Genetic Overview of Syndactyly and Polydactyly

Summary: Syndactyly and polydactyly—respectively characterized by fused and supernumerary digits—are among the most common congenital limb malformations, with syndactyly presenting at an estimated incidence of 1 in 2,000–3,000 live births and polydactyly at a frequency of 1 in approximately 700–1,000 live births. Despite their relatively regular manifestation in the clinic, the etiologies of syndactyly and polydactyly remain poorly understood because of their phenotypic and genetic diversity. Further, even though concrete knowledge of genotypic links has been established for some variants of syndactyly and polydactyly, there appears to be no single comprehensive published summary of all syndromic and nonsyndromic syndactyly and polydactyly presentations, and there is decidedly no resource that maps all syndromic and nonsyndromic syndactylies and polydactylies to their genetic bases. This gap in the literature problematizes comprehensive carrier screening and prenatal diagnosis and complicates novel diagnostic attempts. This review thus attempts to collect all that is known about the genetic bases of syndromic and nonsyndromic syndactylies and polydactylies, as well as to highlight the dactyly manifestations for which no genetic bases are as yet known. Then, having established a summation of existing and missing knowledge, this work briefly outlines the diagnostic techniques that a genetics-reinforced understanding of syndactyly and polydactyly could inform.

Tratamiento de la enfermedad de injerto contra huésped crónica esclerodermiforme con imatinib: una perspectiva dermatológica

Publication date: Available online 15 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): P. Molés-Poveda, P. Montesinos, J. Sanz-Caballer, B. de Unamuno, J.L. Piñana, A. Sahuquillo, R. Botella-Estrada
IntroducciónLa enfermedad de injerto contra huésped crónica (EICHc) es la causa más importante de mortalidad tardía no relacionada con la recidiva del trasplante alogénico de células progenitoras hematopoyéticas. La EICHc esclerodermiforme suele ser refractaria a los corticosteroides y supone todo un reto terapéutico. Se han descrito anticuerpos activadores contra el RFCDP en pacientes con EICHc esclerodermiforme. Estos anticuerpos inducen la fosforilación del RFCDP, produciendo fibrosis. Hay cada vez más evidencias de la efectividad de imatinib, un inhibidor de la tirosina cinasa, en el tratamiento de la EICHc esclerodermiforme.ObjetivoEvaluar la respuesta de la EICHc esclerodermiforme al imatinib.Materiales y métodosEstudio retrospectivo de 18 pacientes con EICHc cutánea esclerodermiforme refractaria a inmunosupresores tratada con imatinib en un único centro. La evaluación de la respuesta al tratamiento se realizó mediante valoración clínica del dermatólogo y percepción subjetiva del paciente tras uno, 3, 6, 9, 12 y 18 meses de iniciar el tratamiento con imatinib. La respuesta fue valorada como completa, parcial, significativa, sin cambios o progresión. El descenso de la dosis de esteroides se catalogó como completo, parcial o no posible.ResultadosEn nuestra serie, 4 (22%) pacientes lograron una respuesta completa, 9 (50%) alcanzaron una respuesta parcial, 2 (11%) tuvieron un grado significativo de respuesta, 2 (11%) no presentaron ningún cambio y uno (6%) experimentó avance de la enfermedad en el último seguimiento que se llevó a cabo. El tiempo medio transcurrido desde el inicio del imatinib hasta mostrar algún grado de respuesta fue de 2,75 meses (rango 1-9 meses).ConclusionesEste estudio apoya la evidencia de la utilidad del imatinib en el tratamiento de la EICHc esclerodermiforme.IntroductionChronic graft-versus-host disease (cGVHD) is the most important cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Sclerodermatous cGVHD is usually steroid refractory and remains a therapeutic challenge. Activating antibodies against the PDGFR have been reported in patients with sclerodermatous cGVHD. These antibodies induce PDGFR phosphorylation and lead to fibrosis. There is increasing evidence of successful treatment of sclerodermatous cGVHD with imatinib, a tyrosine kinase inhibitor.ObjectiveTo evaluate the response of cutaneous sclerodermatous cGVHD to imatinib.Materials and methodsRetrospective study of 18 patients with sclerodermatous cGVHD refractory to immunosuppressants treated with imatinib in a single center. Evaluation of treatment response was performed by clinicians' assessment and patients' subjective response at one, 3, 6, 9, 12 and 18 months after initiation of imatinib. Response was assessed as complete, partial, significant, no change or progression. Tapper off steroids was complete, partial or not possible.ResultsIn our series, 4 (22%) patients achieved complete response, 9 (50%) patients partial response, 2 (11%) patients significant response, 2 (11%) patients had no change and one (6%) patient progressive disease at last follow-up. Mean time from initiation of imatinib to any degree of response was 2,75 months (range 1-9 months).ConclusionsThis study provides further evidence of the role of imatinib for the treatment of steroid refractory sclerodermatous cGVHD.

High fat diet exacerbates imiquimod-induced psoriasis-like dermatitis in mice

Abstract

Psoriasis, a chronic inflammatory skin disease, is closely related to systemic metabolism. An elevated body mass index (BMI) is a risk factor for psoriasis; inflammasomes are activated by adipose tissue macrophages in obese subjects. We hypothesized that hyperlipidemia is involved in the pathogenesis of psoriasis and examined the role of a high fat diet (HFD) in the development of psoriasis in imiquimod (IMQ)-treated mice. The body weight and serum level of cholesterol were significantly higher in mice fed an HFD than a regular diet (RD). HFD mice had higher psoriasis skin scores and the number of neutrophils infiltrating into the lesional skin was elevated. IL-17A mRNA expression was significantly increased in the skin of IMQ-treated HFD mice; the expression of IL-22, IL-23, and TNF-α mRNA was not enhanced. Caspase-1 and IL-1β were activated in the skin of IMQ-treated HFD mice and their serum level of IL-17A, TNF-α, and IL-1β was significantly upregulated. Our findings strongly suggest that hyperlipidemia is involved in the development and progression of psoriasis via systemic inflammation and inflammasome activation.

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(−)-Epigallocatechin-3-gallate, the major green tea catechin, regulates the desensitization of β1 adrenoceptor via GRK2 in experimental heart failure

Abstract

Objective

We investigated the effect of (−)-epigallocatechin-3-gallate (EGCG) on cardiac function and its mechanism, which focused on the desensitization of β1-AR and GRK2 in heart failure (HF) rats.

Methods

HF was induced by abdominal aortic coarctation. Four weeks after HF induction, the rats were given EGCG (25, 50, 100 mg/kg/day). Cardiac function was assessed by measuring haemodynamic parameters. Histological changes were analyzed by HE and Masson's trichrome staining. The expression of β1-AR was detected by immunohistochemistry and immunofluorescence. The membrane expression of β1-AR and GRK2 was detected by western blot. The expression levels of β1-AR mRNA and GRK2 mRNA were evaluated by Q-PCR.

Result

Compared to the control group, the left ventricular end diastolic pressure, mean blood pressure, heart weight/body weight, and posterior wall thickness in the HF group were significantly increased, whereas the left ventricular systolic pressure, maximum rate of left ventricular pressure rise (+ dP/dt _max) and maximum rate of left ventricular pressure fall (− dP/dt _max) were clearly decreased. EGCG could improve cardiac function by regulating these parameters. Inflammatory cell infiltration, irregularly arranged cardiomyocytes, swelling of cardiomyocytes and myocardial fibrosis were observed in HF rats' myocardial morphology, and EGCG obviously improved the morphological signs. The expression of β1-AR was significantly decreased in the left ventricle tissue of HF rats by immunohistochemistry and immunofluorescence. The membrane expression of β1-AR decreased, whereas GRK2 increased in vivo and in vitro by western blot. EGCG could down-regulate the membrane expression of GRK2 and up-regulate the expression of β1-AR. There were no significant differences in the total expression of β1-AR mRNA and GRK2 mRNA.

Conclusions

EGCG has therapeutic effects on the heart function of HF rats. The mechanism might be related to the inhibition of the transfer membrane of GRK2 and to the reduction of the desensitization of β1-AR.

Chronic Long-Standing Temporomandibular Joint Dislocation: Report of Three Cases and Review of Literature

Abstract

Purpose

To present three cases of chronic long-standing TMJ dislocation and discuss our treatment protocol with other options in the literature.

Patients and methods

Three cases of chronic TMJ dislocation (more than 4 months) that has never been reduced previously were treated by open reduction, meniscectomy or meniscoplasty and lateral pterygoid muscle myotomy. After a short period of MMF, TMJ physiotherapy was performed.

Results

During 3 years of follow-up, the condition had not recurred at all and all patients were functional and symptom free.

Conclusion

Based on other therapeutic options in the literature, our treatment protocol seems to be an effectual operation with fewer complications.

Pityriasis rubra pilaris: Algorithms for diagnosis and treatment

Abstract

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease that affects men and women of all ages and also children. The clinical appearance of PRP is highly variable, as is the individual prognosis. Therefore, stratifying PRP into six disease subtypes represents a first step to personalized medicine for this rare inflammatory skin disease. The next step should be to associate specific therapeutic strategies with these subtypes of PRP. However, no randomized, controlled trials on the treatment of PRP have been performed. Consequently, the actual treatment algorithm for PRP will be based on clinical experience, small case series, and case reports. The majority of published evidence is on type I PRP, whereas the treatment experience for other clinical types of PRP is still sparse and has to be gained. Nevertheless, it is now time to start developing valid algorithms as a basis for the diagnosis and treatment of PRP based on the data available.

This review makes use of algorithms developed in psoriasis and atopic eczema and puts together recent insights into the pathogenesis, diagnosis and treatment experience of PRP. The innovative intention of this appraisal is to develop a structured algorithm for PRP treatment that should be further developed going forward.

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The many faces of tuberculosis of the oral mucosa- Three cases with distinct pathomechanisms

Abstract

Tuberculosis (TB) is a chronic infectious disease caused by the acid-fast bacillus Micobacterium tuberculosis. Increased risk of infection occurs with HIV disease, intravenous drug abuse, malignancies, and treatment with immunosuppressants and immunobiologics ¹

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Presenting symptoms and long term survival in Head and Neck cancer

Abstract

Objectives

To assess how type and number of symptoms are related to survival in head and neck cancer patients.

Design

Patients were followed-up for over 10 years from the Scottish Audit of Head and Neck Cancer; (national cohort of head and neck cancer patients in Scotland 1999 – 2001). September 2013, cohort was linked to national mortality data. First, second and third presenting symptoms were recorded at diagnosis.

Setting

National prospective audit – Scotland.

Participants

A subset of 1589 patients, from the original cohort of 1895, who had cancer arising from one of the four main subsites; larynx, oropharynx, oral cavity and hypopharynx.

Main outcome measures

Median survival in relation to patients' presenting symptoms.

Results

1146 (72%) males and 443 (28%) females, mean age at diagnosis 64 years (13 – 95). There was a significant difference in survival in relation to the number of the patient's presenting symptoms; one symptom had a median survival of 5.3 years compared with 1.1 years for three symptoms. Patients who presented with weight loss had a median survival of 0.8 years, compared to 4.2 years if they did not (p<0.001). Patients who presented with hoarseness had a median survival of 5.9 years compared to 2.6 years without (p<0.001). There was no significant difference in long term survival for patients who presented with an ulcer, compared to those that did not (p=0.105).

Conclusions

This study highlights the importance of patients' presenting symptoms, giving valuable information in highlighting appropriate "red flag" symptoms and subsequent treatment planning and prognosis.

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Shifts from methyl chloride sink to source functions within a coastal salt marsh in eastern China: an examination of the effects of biomass burning prohibition policies

Abstract

Our previous study found that a salt marsh in eastern China can act as a large CH₃Cl sink. One striking finding of this previous study was a strong relationship between high-ambient CH₃Cl concentrations and fluxes during the growing season. Moreover, the high-ambient CH₃Cl concentration was likely to be related to local biomass burning. However, implementation of biomass burning prohibition policies has effectively reduced biomass burning. Therefore, we predicted that the prohibition of biomass burning would alter CH₃Cl concentration and flux within the eastern Chinese coastal salt marsh. In this study, we used static flux chambers to measure CH₃Cl fluxes in the early (July of 2004 and January of 2005) and middle-late stages (August and December of 2013) of biomass burning prohibition of along a creek and vegetation transects of the salt marsh. After implementation of the biomass burning prohibition, the concentration and flux of CH₃Cl directly related to biomass burning changed remarkably. During the middle-late stage of prohibition, the initial CH₃Cl concentration was significantly reduced compared to during the early stage of prohibition. Reductions in atmospheric CH₃Cl concentration were especially apparent during the growing season, when biomass burning was prohibited and atmospheric CH₃Cl concentration dropped to levels nearly as low as the Northern Hemisphere background concentration. Atmospheric CH₃Cl concentration significantly varied throughout the salt marsh, with the highest concentrations appearing over the inland areas and mudflat and lower values occurring over the middle locations. This spatial distribution of CH₃Cl may have been directly related to the existence and distribution of potential CH₃Cl sources, such as coastal seawater, terrestrial biomass burning, and senescent and decaying aboveground biomass. These changes in initial CH₃Cl concentration caused by the biomass burning prohibition may eventually lead to shift in the salt marsh from the tendency to act as a CH₃Cl sink to the tendency to act as a CH₃Cl source. When the initial atmospheric CH₃Cl concentration was high, the vegetation stands acted as CH₃Cl sinks. Conversely, they became CH₃Cl sources. Therefore, we conclude that the biomass burning prohibition altered the ecosystem–atmosphere exchange of CH₃Cl within the studied eastern Chinese coastal salt marsh.

Practical Immunodermatology

Clinical and Basic Immunodermatology, 2nd edition Anthony A. Gaspari, Stephen K. Tyring and Daniel H. Kaplan, (Eds.). 2017, Springer. 895 pages. $249.00 (eBook $189.00). ISBN 978-3-319-29785-9

Emerging Therapies for Atopic Dermatitis: TRPV1 Antagonists

Transient receptor potential (TRP) ion channels are important mediators of somatosensory signaling throughout the body. Our understanding of the contribution of TRPs to a multitude of cutaneous physiologic processes has grown substantially in the past decade. TRPV1, one of the better-understood members of this large family of ion channels, impacts multiple pathways involved in pruritus. Further, TRPV1 appears to play a role in maintaining skin barrier function. Together, these properties make TRPV1 a ripe target for new therapies in atopic dermatitis.

Interferonregulatoryfactor-8(IRF-8) regulates the expression of matrix metalloproteinase-13 (MMP-13) in chondrocytes

Abstract

Low levels of inflammation-induced expression of matrix metalloproteinase (MMP) play a crucial role in articular cartilage matrix destruction in osteoarthritis (OA) patients. Interferon regulatory factor-8 (IRF-8), an important member in the IRF family, plays a key role in regulating the inflammation-related signaling pathway. The aim of this study is to investigate the physiological roles of IRF-8 in the pathological progression of OA. We found that IRF-8 was expressed in human primary chondrocytes. Interestingly, the expression of IRF-8 was upregulated in OA chondrocytes. In addition, IRF-8 was increased in response to interleukin-1β (IL-1β) treatment, mediated by the Janus kinase 2 (JAK2) pathway. Overexpression of IRF-8 in human chondrocytes by transduction with lentiviral-IRF-8 exacerbated IL-1β-induced expression of matrix metalloproteinase-13 (MMP-13) in human chondrocytes. In contrast, knockdown of IRF-8 inhibited IL-1β-induced expression of MMP-13. Importantly, IRF-8 could bind to the promoter of MMP-13 and stimulate its activity. Additionally, overexpression of IRF-8 exacerbated IL-1β-induced degradation of type II collagen. However, silencing IRF-8 abrogated the degradation of type II collagen. Taken together, our findings identified a novel function of IRF-8 in regulating articular cartilage matrix destruction by promoting the expression of MMP-13.

Heavy metal pollution in immobile and mobile components of lentic ecosystems—a review

Abstract

With growing population and urbanization, there is an increasing exploitation of natural resources, and this often results to environmental pollution. In this review, the levels of heavy metal in lentic compartments (water, sediment, fishes, and aquatic plants) over the past two decades (1997–2017) have been summarized to evaluate the current pollution status of this ecosystem. In all the compartments, the heavy metals dominated are zinc followed by iron. The major reason could be area mineralogy and lithogenic sources. Enormous quantity of metals like iron in estuarine sediment is a very natural incident due to the permanently reducing condition of organic substances. Contamination of cadmium, lead, and chromium was closely associated with anthropogenic origin. In addition, surrounding land use and atmospheric deposition could have been responsible for substantial pollution. The accumulation of heavy metals in fishes and aquatic plants is the result of time-dependent deposition in lentic ecosystems. Moreover, various potential risk assessment methods for heavy metals were discussed. This review concludes that natural phenomena dominate the accumulation of essential heavy metals in lentic ecosystems compared to anthropogenic sources. Amongst other recent reviews on heavy metals from other parts of the world, the present review is executed in such a way that it explains the presence of heavy metals not only in water environment, but also in the whole of the lentic system comprising sediment, fishes, and aquatic plants.

Rethinking moral distress: conceptual demands for a troubling phenomenon affecting health care professionals

Abstract

Recent medical and bioethics literature shows a growing concern for practitioners' emotional experience and the ethical environment in the workplace. Moral distress, in particular, is often said to result from the difficult decisions made and the troubling situations regularly encountered in health care contexts. It has been identified as a leading cause of professional dissatisfaction and burnout, which, in turn, contribute to inadequate attention and increased pain for patients. Given the natural desire to avoid these negative effects, it seems to most authors that systematic efforts should be made to drastically reduce moral distress, if not altogether eliminate it from the lives of vulnerable practitioners. Such efforts, however, may be problematic, as moral distress is not adequately understood, nor is there agreement among the leading accounts regarding how to conceptualize the experience. With this article I make clear what a robust account of moral distress should be able to explain and how the most common notions in the existing literature leave significant explanatory gaps. I present several cases of interest and, with careful reflection upon their distinguishing features, I establish important desiderata for an explanatorily satisfying account. With these fundamental demands left unsatisfied by the leading accounts, we see the persisting need for a conception of moral distress that can capture and delimit the range of cases of interest.

The immune checkpoint molecule VISTA regulates allergen-specific Th2-mediated immune responses

Abstract

V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint receptor and ligand that regulates T cell activation. We investigated the functional involvement of VISTA in Th2 cell-mediated immune responses using an ovalbumin (OVA)-induced allergic asthma model. Treatment with an anti-VISTA monoclonal antibody (mAb) during allergen sensitization increased the production of antibodies, including total IgE, OVA-specific IgG1 and IgG2a, and allergen-specific interleukin (IL)-5 and IL-13; it also increased the expression of IL-13 by splenic CD4 ⁺ T cells. However, treatment with the anti-VISTA mAb during sensitization did not accelerate asthmatic responses, including airway hyper-responsiveness (AHR) or the number of eosinophils in bronchoalveolar lavage (BAL) fluid. In contrast, treatment with the anti-VISTA mAb during allergen challenge significantly augmented AHR and BAL fluid eosinophilia. This treatment also increased the production of IL-5 and IL-13 in BAL fluid and the expression of IL-13 by CD4 ⁺ T cells in draining lymph nodes. These results suggest that VISTA is involved in the regulation of Th2 cell generation and Th2 cell-mediated antibody production, and regulates asthmatic responses, especially in the effector phase.

Elemental composition in rainbow trout tissues from a fish farm from Patagonia, Argentina

Abstract

Rainbow trout is a salmonid specie of commercial importance raised in hatcheries in many countries. Studies over mineral requirements have being perform to guarantee the fulfillment of the nutritional needs and therefore improving the fish farm productions. The aim of this work was to investigate the performance of the elements like Ag, As, Br, Ca, Cr, Cs, Fe, Hg, K, Na, Rb, Se, and Zn, in rainbow trout from a Patagonian fish farming. Body burden of each element in relation to weight were analyzed for identifying potential bioaccumulation or dilution processes. Our results indicated that water and food were the sources for most of the elements, except Se and Ag. Selenium showed the highest value in unfertilized eggs, and Ag was detected in larvae newly after feeding. Toxic elements as Ag, Cr, and Hg were below the regulation standards for human consumption but tend to bioconcentrate in the juvenile state, and the As was during all the growth studied. The macro and micro nutrients assemble the daily requirements for the humans consume, excepting the K.

Technology acceptance perception for promotion of sustainable consumption

Abstract

Economic growth in the past decades has resulted in change in consumption pattern and emergence of tech-savvy generation with unprecedented increase in the usage of social network technology. In this paper, the technology acceptance value gap adapted from the technology acceptance model has been applied as a tool supporting social network technology usage and subsequent promotion of sustainable consumption. The data generated through the use of structured questionnaires have been analyzed using structural equation modeling. The validity of the model and path estimates signifies the robustness of Technology Acceptance value gap in adjudicating the efficiency of social network technology usage in augmentation of sustainable consumption and awareness. The results indicate that subjective norm gap, ease-of-operation gap, and quality of green information gap have the most adversarial impact on social network technology usage. Eventually social networking technology usage has been identified as a significant antecedent of sustainable consumption.

β-carotene and retinol reduce benzo[a]pyrene-induced mutagenicity and oxidative stress via transcriptional modulation of xenobiotic metabolizing enzymes in human HepG2 cell line

Abstract

Benzo[a]pyrene (B[a]P) is one of the polycyclic aromatic hydrocarbons which is formed due to smoking of foods, incomplete combustion of woods, vehicle exhausts, and cigarettes smokes. B[a]P gets entry into human and animal bodies mainly through their diets. Metabolic activation of B[a]P is required to induce mutagenesis and carcinogenesis in animal and human studies. Carotenoids and retinoids are phytochemicals that if ingested have multiple physiological interferences in the human and animal bodies. In this study, we firstly investigated the protective effects of β-carotene, β-apo-8-carotenal, retinol, and retinoic acid against B[a]P-induced mutagenicity and oxidative stress in human HepG2 cells. Secondly, we tested the hypothesis of modulating xenobiotic metabolizing enzymes (XMEs) by carotenoids and retinoids as a possible mechanism of protection by these micronutrients against B[a]P adverse effects. The obtained results declared that β-carotene and retinol significantly reduced B[a]P-induced mutagenicity and oxidative stress. Tested carotenoids and retinoids reduced B[a]P-induced phase I XMEs and induced B[a]P reduced phase II and III XMEs. Thus, the protective effects of these micronutrients are probably due to their ability of induction of phase II and III enzymes and interference with the induction of phase I enzymes by the promutagen, B[a]P. It is highly recommended to consume foods rich in these micronutrients in the areas of high PAH pollution.

Correctness of Self-Reported Task Durations: A Systematic Review

Abstract

Objectives

Duration of tasks in a job is an essential interest in occupational epidemiology. Such duration is frequently measured using self-reports, which may, however, be associated with both bias and random errors. The present systematic literature review examines the correctness of self-reported durations of tasks, i.e. the extent to which they differ from more valid reference data due to either systematic or random errors, and factors influencing this correctness, with particular emphasis on the assessment of exposures of relevance to musculoskeletal disorders.

Methods

The search for relevant studies included the databases ISI Web of Science, MEDLINE, EBSCO HOST, Proquest, and Psycnet.

Results

Thirty-two articles were identified; of which, 23 examined occupational tasks and 9 examined non-occupational tasks. Agreement between self-reports and a more correct reference was reported for, in total, 182 tasks. Average proportional errors were, for most tasks, between −50% (i.e. underestimations) and +100%, with a dominance of overestimations; 22% of all results considered overestimations of 100% or more. For 15% of the 182 reported tasks, the mean difference between the self-reported and the reference duration value was <5%, and 20% of the 182 mean differences were between 5 and 20%. In general, respondents were able to correctly distinguish tasks of a longer duration from shorter tasks, even though the actual durations were not correct. A number of factors associated with the task per se appeared to influence agreement between self-reports and reference data, including type of task, true task duration, task pattern across time (continuous versus discontinuous), and whether the addressed task is composed of subtasks. The musculoskeletal health status of the respondent did not have a clear effect on the ability to correctly report task durations. Studies differed in key design characteristics and detail of information reported, which hampers a formal aggregation of results.

Conclusions

The correctness of self-reported task durations is, at the best, moderate at the individual level, and this may present a significant problem when using self-reports in task-based assessment of individual job exposures. However, average self-reports at the group level appear reasonably correct and may thus be a viable method in studies addressing, for instance, the relative occurrence of tasks in a production system. Due to the disparity of studies, definite conclusions on the quantitative effect on agreement of different modifiers are not justified, and we encourage future studies specifically devoted to understanding and controlling sources of bias in self-reported task durations. We also encourage studies developing decision support for when to apply or avoid self-reports to measure task durations, depending on study purpose and occupational setting.

Toenail Manganese: A Sensitive and Specific Biomarker of Exposure to Manganese in Career Welders

Abstract

Manganese (Mn) is an essential trace metal. It is also a component of welding fume. Chronic inhalation of manganese from welding fume has been associated with decreased neurological function. Currently, there is not a universally recognized biomarker for Mn exposure; however, hair and toenails have shown promise. In a cohort of 45 male welders and 35 age-matched factory control subjects, we assessed the sensitivity and specificity of toenail Mn to distinguish occupationally exposed subjects from unexposed controls. Further we examined the exposure time window that best correlates with the proposed biomarker, and investigated if non-occupational exposure factors impacted toenail Mn concentrations. Toenail clippings were analyzed for Mn using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Exposure to respirable Mn-containing particles (<4 µm) was estimated using an exposure model that combines personal air monitoring, work history information, and dietary intake to estimate an individual's exposure to Mn from inhalation of welding fume. We assessed the group differences in toenail concentrations using a Student's t-test between welders and control subjects and performed a receiver operating characteristic (ROC) curve analysis to identify a threshold in toenail concentration that has the highest sensitivity and specificity in distinguishing welders from control subjects. Additionally, we performed mixed-model regressions to investigate the association between different exposure windows and toenail Mn concentrations. We observed that toenail Mn concentrations were significantly elevated among welders compared to control subjects (6.87 ± 2.56 versus 2.70 ± 1.70 µg g⁻¹; P < 0.001). Our results show that using a toenail Mn concentration of 4.14 µg g⁻¹ as cutoff allows for discriminating between controls and welders with 91% specificity and 94% sensitivity [area under curve (AUC) = 0.98]. Additionally, we found that a threshold of 4.66 µg g⁻¹ toenail Mn concentration enables a 90% sensitive and 90% specific discrimination (AUC = 0.96) between subjects with average exposure above or below the American Conference of Governmental Industrial Hygienist (ACGIH) Threshold Limit Value (TLV) of 0.02 mg m⁻³ during the exposure window of 7–12 months prior to the nail being clipped. Investigating which exposure window was best reflected by toenail Mn reproduced the result from another study of toenail Mn being significantly (P < 0.001) associated with exposure 7–12 months prior to the nail being clipped. Lastly, we found that dietary intake, body mass index, age, smoking status, and ethnicity had no significant effect on toenail Mn concentrations. Our results suggest that toenail Mn is a sensitive, specific, and easy-to-acquire biomarker of Mn exposure, which is feasible to be used in an industrial welder population.

Predicting Forearm Physical Exposures During Computer Work Using Self-Reports, Software-Recorded Computer Usage Patterns, and Anthropometric and Workstation Measurements

Abstract

Objectives

Alternative techniques to assess physical exposures, such as prediction models, could facilitate more efficient epidemiological assessments in future large cohort studies examining physical exposures in relation to work-related musculoskeletal symptoms. The aim of this study was to evaluate two types of models that predict arm-wrist-hand physical exposures (i.e. muscle activity, wrist postures and kinematics, and keyboard and mouse forces) during computer use, which only differed with respect to the candidate predicting variables; (i) a full set of predicting variables, including self-reported factors, software-recorded computer usage patterns, and worksite measurements of anthropometrics and workstation set-up (full models); and (ii) a practical set of predicting variables, only including the self-reported factors and software-recorded computer usage patterns, that are relatively easy to assess (practical models).

Methods

Prediction models were build using data from a field study among 117 office workers who were symptom-free at the time of measurement. Arm-wrist-hand physical exposures were measured for approximately two hours while workers performed their own computer work. Each worker's anthropometry and workstation set-up were measured by an experimenter, computer usage patterns were recorded using software and self-reported factors (including individual factors, job characteristics, computer work behaviours, psychosocial factors, workstation set-up characteristics, and leisure-time activities) were collected by an online questionnaire. We determined the predictive quality of the models in terms of R² and root mean squared (RMS) values and exposure classification agreement to low-, medium-, and high-exposure categories (in the practical model only).

Results

The full models had R² values that ranged from 0.16 to 0.80, whereas for the practical models values ranged from 0.05 to 0.43. Interquartile ranges were not that different for the two models, indicating that only for some physical exposures the full models performed better. Relative RMS errors ranged between 5% and 19% for the full models, and between 10% and 19% for the practical model. When the predicted physical exposures were classified into low, medium, and high, classification agreement ranged from 26% to 71%.

Conclusion

The full prediction models, based on self-reported factors, software-recorded computer usage patterns, and additional measurements of anthropometrics and workstation set-up, show a better predictive quality as compared to the practical models based on self-reported factors and recorded computer usage patterns only. However, predictive quality varied largely across different arm-wrist-hand exposure parameters. Future exploration of the relation between predicted physical exposure and symptoms is therefore only recommended for physical exposures that can be reasonably well predicted.

Solvent Transfer—Efficiency of Risk Management Measures

Abstract

A series of laboratory simulations were conducted in order to determine the airborne protection that might be afforded by different combinations of workplace exposure controls typically encountered when handling volatile solvents (e.g. solvent transfer). These conditions, referred to as risk management measures (RMMs) under the Registration, Evaluation and Authorisation of Chemicals Regulation (REACH), are typically described using standard phrases in safety data sheets [and specifically those of the European Phrase Catalogue (EUPhraC)]. Ethanol was used as a model compound and its emissions were monitored continuously with a portable IR spectrometer at 3000 cm⁻¹. The average emission reduction performance of the investigated RMMs (e.g. containment, extract ventilation, drum pump) exceeded 90%. They present suitable ways to reduce airborne solvent exposure in a workplace and confirmed the initial expectations derived at by the European Solvents Industry Group (ESIG) and the European Centre For Ecotoxicology and toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) model.

Sarin Exposures in A Cohort of British Military Participants in Human Experimental Research at Porton Down 1945–1987

Abstract

Background

The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK's centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken.

Objectives

Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis.

Methods

In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular.

Results

Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28–51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present.

Conclusions

These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans.

Comparison of Respirable Mass Concentrations Measured by a Personal Dust Monitor and a Personal DataRAM to Gravimetric Measurements

Abstract

In 2016, the Mine Safety and Health Administration required the use of continuous monitors to measure respirable dust in mines and better protect miner health. The Personal Dust Monitor, PDM3700, has met stringent performance criteria for this purpose. In a laboratory study, respirable mass concentrations measured with the PDM3700 and a photometer (personal DataRam, pDR-1500) were compared to those measured gravimetrically for five aerosols of varying refractive index and density (diesel exhaust fume, welding fume, coal dust, Arizona road dust (ARD), and salt [NaCl] aerosol) at target concentrations of 0.38, 0.75, and 1.5 mg m⁻³. For all aerosols except coal dust, strong, near-one-to-one, linear relationships were observed between mass concentrations measured with the PDM3700 and gravimetrically (diesel fume, slope = 0.99, R² = 0.99; ARD, slope = 0.98, R² = 0.99; and NaCl, slope = 0.95, R² = 0.99). The slope deviated substantially from unity for coal dust (slope = 0.55; R² = 0.99). Linear relationships were also observed between mass concentrations measured with the pDR-1500 and gravimetrically, but one-to-one behavior was not exhibited (diesel fume, slope = 0.23, R² = 0.76; coal dust, slope = 0.54, R² = 0.99; ARD, slope = 0.61, R² = 0.99; NaCl, slope = 1.14, R² = 0.98). Unlike the pDR-1500, mass concentrations measured with the PDM3700 appear independent of refractive index and density, suggesting that it could have applications in a variety of occupational settings.

Relationship Between Exposure to Second-Hand Smoke in the Workplace and Occupational Injury in the Republic of Korea

Abstract

Background

Most studies in the field of smoking exposure in the workplace linked to occupational safety have only focused on active smoking. Few studies have reported that exposure to second-hand smoke in the workplace is a possible factor increasing the risk of occupational injury without considering occupational characteristics. The aim of this study was to determine the association between occupational injury and level of exposure to second-hand smoke at the workplace among Korean workers, after taking into account occupational characteristics.

Method

Using data from the third Korean Working Conditions Survey, levels of exposure to second-hand smoke were categorized as none, moderate, and high. We investigated the influence of exposure to second-hand smoke on occupational injury using logistic regression analysis with stratification by sex, smoking status, smoke-free policy in the workplace, and occupational characteristics. Occupational characteristics (occupational classification, working schedule, length of working day, and co-exposure to occupational hazards in the workplace) were stratified and analyzed using logistic regression models to estimate the risk of occupational injury linked to exposure to second-hand smoke.

Results

Among all participants, there was a significant dose-dependent association between risk of occupational injury and level of exposure level to second-hand smoke. After stratification by sex and smoking status, there was a significant association between risk of occupational injury and exposure level to second-hand smoke. Moreover, there was a significant relationship between exposure to second-hand smoke in the workplace and occupational injury, depending on the smoking-free policy at workplace (odds ratio [OR] in completely non-smoking workplace, 4.23; OR in non-smoking workplace with separate smoking area, 2.98; OR in smoking workplace 2.84). Additionally, there was a significant relationship between risk of occupational injury and exposure to second-hand smoke after stratification by occupational classification, working schedule, long working hours, and co-exposure to hazards in the workplace.

Discussion

There was a dose–response relationship between occupational injury and exposure to second-hand smoke, even after stratification to reduce the impact of various potential confounders and after taking into account occupational characteristics. These findings provide greater insight into the effects of exposure to second-hand smoke on the working population and may direct further research and policy-making in this field.

Taking Multiple Exposure Into Account Can Improve Assessment of Chemical Risks

Abstract

During work, operators may be exposed to several chemicals simultaneously. Most exposure assessment approaches only determine exposure levels for each substance individually. However, such individual-substance approaches may not correctly estimate the toxicity of 'cocktails' of chemicals, as the toxicity of a cocktail may differ from the toxicity of substances on their own. This study presents an approach that can better take into account multiple exposure when assessing chemical risks. Almost 30000 work situations, monitored between 2005 and 2014 and recorded in two French databases, were analysed using MiXie software. The algorithms employed in MiXie can identify toxicological classes associated with several substances, based on the additivity of the selected effects of each substance. The results of our retrospective analysis show that MiXie was able to identify almost 20% more potentially hazardous situations than identified using a single-substance approach. It therefore appears essential to review the ways in which multiple exposure is taken into account during risk assessment.

Respiratory Symptoms in Hospital Cleaning Staff Exposed to a Product Containing Hydrogen Peroxide, Peracetic Acid, and Acetic Acid

Abstract

Cleaning and disinfecting products consisting of a mixture of hydrogen peroxide (HP), peracetic acid (PAA), and acetic acid (AA) are widely used as sporicidal agents in health care, childcare, agricultural, food service, and food production industries. HP and PAA are strong oxidants and their mixture is a recognized asthmagen. However, few exposure assessment studies to date have measured HP, PAA, and AA in a health care setting. In 2015, we performed a health and exposure assessment at a hospital where a new sporicidal product, consisting of HP, PAA, and AA was introduced 16 months prior. We collected 49 full-shift time-weighted average (TWA) air samples and analyzed samples for HP, AA, and PAA content. Study participants were observed while they performed cleaning duties, and duration and frequency of cleaning product use was recorded. Acute upper airway, eye, and lower airway symptoms were recorded in a post-shift survey (n = 50). A subset of 35 cleaning staff also completed an extended questionnaire that assessed symptoms reported by workers as regularly occurring or as having occurred in the previous 12 months. Air samples for HP (range: 5.5 to 511.4 ppb) and AA (range: 6.7 to 530.3 ppb) were all below established US occupational exposure limits (OEL). To date, no full-shift TWA OEL for PAA has been established in the United States, however an OEL of 0.2 ppm has been suggested by several research groups. Air samples for PAA ranged from 1.1 to 48.0 ppb and were well below the suggested OEL of 0.2 ppm. Hospital cleaning staff using a sporicidal product containing HP, PAA, and AA reported work-shift eye (44%), upper airway (58%), and lower airway (34%) symptoms. Acute nasal and eye irritation were significantly positively associated with increased exposure to the mixture of the two oxidants: HP and PAA, as well as the total mixture (TM)of HP, PAA, and AA. Shortness of breath when hurrying on level ground or walking up a slight hill was significantly associated with increased exposure to the oxidant mixture (P = 0.017), as well as the TM (P = 0.026). Our results suggest that exposure to a product containing HP, PAA, and AA contributed to eye and respiratory symptoms reported by hospital cleaning staff at low levels of measured exposure.

Job Tasks as Determinants of Thoracic Aerosol Exposure in the Cement Production Industry

Abstract

Background

The aims of this study were to identify important determinants and investigate the variance components of thoracic aerosol exposure for the workers in the production departments of European cement plants.

Methods

Personal thoracic aerosol measurements and questionnaire information (Notø et al., 2015) were the basis for this study. Determinants categorized in three levels were selected to describe the exposure relationships separately for the job types production, cleaning, maintenance, foreman, administration, laboratory, and other jobs by linear mixed models. The influence of plant and job determinants on variance components were explored separately and also combined in full models (plant&job) against models with no determinants (null). The best mixed models (best) describing the exposure for each job type were selected by the lowest Akaike information criterion (AIC; Akaike, 1974) after running all possible combination of the determinants.

Results

Tasks that significantly increased the thoracic aerosol exposure above the mean level for production workers were: packing and shipping, raw meal, cement and filter cleaning, and de-clogging of the cyclones. For maintenance workers, time spent with welding and dismantling before repair work increased the exposure while time with electrical maintenance and oiling decreased the exposure. Administration work decreased the exposure among foremen. A subjective tidiness factor scored by the research team explained up to a 3-fold (cleaners) variation in thoracic aerosol levels. Within-worker (WW) variance contained a major part of the total variance (35–58%) for all job types. Job determinants had little influence on the WW variance (0–4% reduction), some influence on the between-plant (BP) variance (from 5% to 39% reduction for production, maintenance, and other jobs respectively but an 79% increase for foremen) and a substantial influence on the between-worker within-plant variance (30–96% for production, foremen, and other workers). Plant determinants had little influence on the WW variance (0–2% reduction), some influence on the between-worker variance (0–1% reduction and 8% increase), and considerable influence on the BP variance (36–58% reduction) compared to the null models.

Conclusion

Some job tasks contribute to low levels of thoracic aerosol exposure and others to higher exposure among cement plant workers. Thus, job task may predict exposure in this industry. Dust control measures in the packing and shipping departments and in the areas of raw meal and cement handling could contribute substantially to reduce the exposure levels. Rotation between low and higher exposed tasks may contribute to equalize the exposure levels between high and low exposed workers as a temporary solution before more permanent dust reduction measures is implemented. A tidy plant may reduce the overall exposure for almost all workers no matter of job type.

ART, Stoffenmanager, and TRA: A Systematic Comparison of Exposure Estimates Using the TREXMO Translation System

Abstract

Several occupational exposure models are recommended under the EU's REACH legislation. Due to limited availability of high-quality exposure data, their validation is an ongoing process. It was shown, however, that different models may calculate significantly different estimates and thus lead to potentially dangerous conclusions about chemical risk. In this paper, the between-model translation rules defined in TREXMO were used to generate 319000 different in silico exposure situations in ART, Stoffenmanager, and ECETOC TRA v3. The three models' estimates were computed and the correlation and consistency between them were investigated. The best correlated pair was Stoffenmanager–ART (R, 0.52–0.90), whereas the ART–TRA and Stoffenmanager–TRA correlations were either lower (R, 0.36–0.69) or no correlation was found. Consistency varied significantly according to different exposure types (e.g. vapour versus dust) or settings (near-field versus far-field and indoors versus outdoors). The percentages of generated situations for which estimates differed by more than a factor of 100 ranged from 14 to 97%, 37 to 99%, and 1 to 68% for Stoffenmanager–ART, TRA–ART, and TRA–Stoffenmanager, respectively. Overall, the models were more consistent for vapours than for dusts and solids, near-fields than for far-fields, and indoor than for outdoor exposure. Multiple linear regression analyses evidenced the relationship between the models' parameters and the relative differences between the models' predictions. The relative difference can be used to estimate the consistency between the models. Furthermore, the study showed that the tiered approach is not generally applicable to all exposure situations. These findings emphasize the need for a multiple-model approach to assessing critical exposure scenarios under REACH. Moreover, in combination with occupational exposure measurements, they might also be used for future studies to improve prediction accuracy.

Efficacy and Safety of Ethanol Ablation for Branchial Cleft Cysts [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst.

MATERIALS AND METHODS:

Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%–80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated.

RESULTS:

The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8–49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0–3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%–100.0%; P < .001). Therapeutic success was achieved in all nodules (20/20, 100%), and the symptomatic (P < .001) and cosmetic (P < .001) scores had improved significantly by the last follow-up. In 1 patient, intracystic hemorrhage developed during the aspiration; however, no major complications occurred in any patient.

CONCLUSIONS:

Ethanol ablation is an effective and safe treatment for patients with branchial cleft cysts who refuse, or are ineligible for, an operation.

Hemodynamic Characteristics of Ruptured and Unruptured Multiple Aneurysms at Mirror and Ipsilateral Locations [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Different hemodynamic patterns have been associated with aneurysm rupture. The objective was to test whether hemodynamic characteristics of the ruptured aneurysm in patients with multiple aneurysms were different from those in unruptured aneurysms in the same patient.

MATERIALS AND METHODS:

Twenty-four mirror and 58 ipsilateral multiple aneurysms with 1 ruptured and the others unruptured were studied. Computational fluid dynamics models were created from 3D angiographies. Case-control studies of mirror and ipsilateral aneurysms were performed with paired Wilcoxon tests.

RESULTS:

In mirror pairs, the ruptured aneurysm had more oscillatory wall shear stress (P = .007) than the unruptured one and tended to be more elongated (higher aspect ratio), though this trend achieved only marginal significance (P = .03, 1-sided test). In ipsilateral aneurysms, ruptured aneurysms had larger maximum wall shear (P = .05), more concentrated (P < .001) and oscillatory wall shear stress (P < .001), stronger (P < .001) and more concentrated inflow jets (P < .001), larger maximum velocity (P < .001), and more complex flow patterns (P < .001) compared with unruptured aneurysms. Additionally, ruptured aneurysms were larger (P < .001) and more elongated (P < .001) and had wider necks (P < .001) and lower minimum wall shear stress (P < .001) than unruptured aneurysms.

CONCLUSIONS:

High wall shear stress oscillations and larger aspect ratios are associated with rupture in mirror aneurysms. Adverse flow conditions characterized by high and concentrated inflow jets; high, concentrated, and oscillatory wall shear stress; and strong, complex and unstable flow patterns are associated with rupture in ipsilateral multiple aneurysms. In multiple ipsilateral aneurysms, these unfavorable flow conditions are more likely to develop in larger, more elongated, more wide-necked, and more distal aneurysms.

Regarding "Perfusion MR Imaging Using a 3D Pulsed Continuous Arterial Spin-Labeling Method for Acute Cerebral Infarction Classified as Branch Atheromatous Disease Involving the Lenticulostriate Artery Territory" [LETTERS]

Zika Virus Iceberg: Very Large [LETTERS]

Reply: [LETTERS]

Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy.

MATERIALS AND METHODS:

Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping–oxygen extraction fraction images.

RESULTS:

Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping–oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5–249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping–oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively.

CONCLUSIONS:

Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy.

Regarding "Determining the Orientation of Directional Deep Brain Stimulation Electrodes Using 3D Rotational Fluoroscopy" [LETTERS]

Basion-Cartilaginous Dens Interval: An Imaging Parameter for Craniovertebral Junction Assessment in Children [PEDIATRICS]

BACKGROUND AND PURPOSE:

Widening of the basion-dens interval is an important sign of cranioverterbral junction injury. The current literature on basion-dens interval in children is sparse and based on bony measurements with variable values. Our goal was to establish the normal values of a recently described new imaging parameter, the basion–cartilaginous dens interval in children.

MATERIALS AND METHODS:

Three hundred healthy pediatric patients (0–10 years of age) were selected retrospectively. These patients were divided into 3 different groups: A (0–3 years), B (3–6 years), and C (6–10 years). The basion–cartilaginous dens interval was calculated on the sagittal MPR image of cervical spine CT in a soft-tissue window. The mean, SD, and the upper limit of normal (mean +2 SDs) of the 3 groups were calculated, and statistical tests were used to check for significant differences of the basion–cartilaginous dens interval among these 3 groups.

RESULTS:

The upper limits of the basion–cartilaginous dens interval for the 3 groups were 5.34 mm in group A, 5.64 mm in group B, and 7.24 mm in group C. There were statistically significant differences in the basion–cartilaginous dens interval values among the 3 groups. There was no statistically significant difference in basion–cartilaginous dens interval values between groups A and B; however, values in group C were significantly different from those in both A and B. There was no statistically significant difference in the basion–cartilaginous dens interval values between males and females.

CONCLUSIONS:

The basion–cartilaginous dens interval is a novel imaging parameter to assess cranioverterbral junction integrity in children, which includes the nonossified cartilage in the measurement.

Reply: [LETTERS]

Treatment of Middle Cerebral Artery Aneurysms with Flow-Diverter Stents: A Systematic Review and Meta-Analysis [INTERVENTIONAL]

BACKGROUND:

The safety and efficacy of flow-diversion treatment of MCA aneurysms have not been well-established.

PURPOSE:

Our aim was to evaluate angiographic and clinical outcomes after flow diversions for MCA aneurysms.

DATA SOURCES:

A systematic search of PubMed, MEDLINE, and Embase was performed for studies published from 2008 to May 2017.

STUDY SELECTION:

According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we selected studies with >5 patients describing angiographic and clinical outcomes after flow-diversion treatment of MCA aneurysms.

DATA ANALYSIS:

Random-effects meta-analysis was used to pool the following outcomes: aneurysm occlusion rate, procedure-related complications, rupture rate of treated aneurysms, and occlusion of the jailed branches.

DATA SYNTHESIS:

Twelve studies evaluating 244 MCA aneurysms were included in this meta-analysis. Complete/near-complete occlusion was obtained in 78.7% (95% CI, 67.8%–89.7%) of aneurysms. The rupture rate of treated aneurysms during follow-up was 0.4% per aneurysm-year. The rate of treatment-related complications was 20.7% (95% CI, 14%–27.5%), and approximately 10% of complications were permanent. The mortality rate was close to 2%. Nearly 10% (95% CI, 4.7%–15.5%) of jailed arteries were occluded during follow-up, whereas 26% (95% CI, 14.4%–37.6%) had slow flow. Rates of symptoms related to occlusion and slow flow were close to 5%.

LIMITATIONS:

Small and retrospective series could affect the strength of the reported results.

CONCLUSIONS:

Given the not negligible rate of treatment-related complications, flow diversion for MCA aneurysms should be considered an alternative treatment when traditional treatment methods are not feasible. However, when performed in this select treatment group, high rates of aneurysm occlusion and protection against re-rupture can be achieved.

Safety and Efficacy of Aneurysm Treatment with the WEB [LETTERS]

Pial Artery Supply as an Anatomic Risk Factor for Ischemic Stroke in the Treatment of Intracranial Dural Arteriovenous Fistulas [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Although intracranial dural arteriovenous fistulas are principally supplied by dural branches of the external carotid, internal carotid, and vertebral arteries, they can also be fed by pial arteries that supply the brain. We sought to determine the frequency of neurologic deficits following treatment of intracranial dural arteriovenous fistulas with and without pial artery supply.

MATERIALS AND METHODS:

One hundred twenty-two consecutive patients who underwent treatment for intracranial dural arteriovenous fistulas at our hospital from 2008 to 2015 were retrospectively reviewed. Patient data were examined for posttreatment neurologic deficits; patients with such deficits were evaluated for imaging evidence of cerebral infarction. Data were analyzed with multivariable logistic regression.

RESULTS:

Of 122 treated patients, 29 (23.8%) had dural arteriovenous fistulas with pial artery supply and 93 (76.2%) had dural arteriovenous fistulas without pial arterial supply. Of patients with pial artery supply, 4 (13.8%) had posttreatment neurologic deficits, compared with 2 patients (2.2%) without pial artery supply (P = .04). Imaging confirmed that 3 patients with pial artery supply (10.3%) had cerebral infarcts, compared with only 1 patient without pial artery supply (1.1%, P = .03). Increasing patient age was also positively associated with pial supply and treatment-related complications.

CONCLUSIONS:

Patients with dural arteriovenous fistulas supplied by the pial arteries were more likely to experience posttreatment complications, including ischemic strokes, than patients with no pial artery supply. The approach to dural arteriovenous fistula treatment should be made on a case-by-case basis so that the risk of complications can be minimized.

Reply: [LETTERS]

CT Texture Analysis: Defining and Integrating New Biomarkers for Advanced Oncologic Imaging in Precision Medicine: A Comment on "CT Texture Analysis Potentially Predicts Local Failure in Head and Neck Squamous Cell Carcinoma Treated with Chemoradiotherapy" [article-commentary]

[other]

Quantitative Synthetic MRI in Children: Normative Intracranial Tissue Segmentation Values during Development [PEDIATRICS]

BACKGROUND AND PURPOSE:

Synthetic MR imaging is a new technique to create absolute R1 relaxivity (1/T1), R2 relaxivity (1/T2), and proton-density maps using a single multiple-spin-echo saturation recovery sequence. These relaxivity maps allow rapid automated intracranial segmentation of tissue types. To assess its utility in children, we created a normative data base of intracranial volume and brain parenchymal, GM, WM, CSF, and myelin volumes in a pediatric population with normal brain MRI findings using synthetic MR imaging.

MATERIALS AND METHODS:

All multiple-spin-echo saturation recovery sequences containing brain MR imaging examinations performed during 34 months were retrospectively reviewed. Abnormal examination findings were excluded following a detailed radiographic and clinical chart review. The remaining normal examination findings were then quantitatively analyzed with synthetic MR imaging. Intracranial, brain parenchymal, GM, WM, CSF, and myelin volumes were plotted versus age. Qualitative assessment of segmentation accuracy was performed. Selected abnormal examination findings were compared with these normative curves.

RESULTS:

One hundred twenty-two MRI examinations with normal findings were included of individuals ranging from 0.1 to 21.5 years of age (median, 11.8 years). Resulting normative data plots compared favorably with previously published data obtained using more onerous techniques. Differentiation from pathologic states was possible using quantitative values in select cases.

CONCLUSIONS:

A pediatric data base of normal intracranial tissue volumes using a single sequence and rapid software analysis has been compiled and correlates with previously published data. This provides a framework for clinical interpretation of quantitative synthetic MR images during development. Improved age-based segmentation algorithms in young children are needed.

Bring Back the Joy in Neuroradiology [editorial]

Predictive Models in Differentiating Vertebral Lesions Using Multiparametric MRI [SPINE]

BACKGROUND AND PURPOSE:

Conventional MR imaging has high sensitivity but limited specificity in differentiating various vertebral lesions. We aimed to assess the ability of multiparametric MR imaging in differentiating spinal vertebral lesions and to develop statistical models for predicting the probability of malignant vertebral lesions.

MATERIALS AND METHODS:

One hundred twenty-six consecutive patients underwent multiparametric MRI (conventional MR imaging, diffusion-weighted MR imaging, and in-phase/opposed-phase imaging) for vertebral lesions. Vertebral lesions were divided into 3 subgroups: infectious, noninfectious benign, and malignant. The cutoffs for apparent diffusion coefficient (expressed as 10^–3 mm²/s) and signal intensity ratio values were calculated, and 3 predictive models were established for differentiating these subgroups.

RESULTS:

Of the lesions of the 126 patients, 62 were infectious, 22 were noninfectious benign, and 42 were malignant. The mean ADC was 1.23 ± 0.16 for infectious, 1.41 ± 0.31 for noninfectious benign, and 1.01 ± 0.22 mm²/s for malignant lesions. The mean signal intensity ratio was 0.80 ± 0.13 for infectious, 0.75 ± 0.19 for noninfectious benign, and 0.98 ± 0.11 for the malignant group. The combination of ADC and signal intensity ratio showed strong discriminatory ability to differentiate lesion type. We found an area under the curve of 0.92 for the predictive model in differentiating infectious from malignant lesions and an area under the curve of 0.91 for the predictive model in differentiating noninfectious benign from malignant lesions. On the basis of the mean ADC and signal intensity ratio, we established automated statistical models that would be helpful in differentiating vertebral lesions.

CONCLUSIONS:

Our study shows that multiparametric MRI differentiates various vertebral lesions, and we established prediction models for the same.

Pacemakers in MRI for the Neuroradiologist [review-article]

SUMMARY:

Cardiac implantable electronic devices are frequently encountered in clinical practice in patients being screened for MR imaging examinations. Traditionally, the presence of these devices has been considered a contraindication to undergoing MR imaging. Growing evidence suggests that most of these patients can safely undergo an MR imaging examination if certain conditions are met. This document will review the relevant cardiac implantable electronic devices encountered in practice today, the background physics/technical factors related to scanning these devices, the multidisciplinary screening protocol used at our institution for scanning patients with implantable cardiac devices, and our experience in safely performing these examinations since 2010.

WEB Device: Ready for Ruptured Aneurysms? [article-commentary]

Financial development, income inequality, and CO 2 emissions in Asian countries using STIRPAT model

Abstract

The main purpose of this paper is to find the effects of financial development, income inequality, energy usage, and per capita GDP on carbon dioxide (CO₂) emissions as well the environmental Kuznets curve (EKC) for the three developing Asian countries—Bangladesh, India, and Pakistan. Panel data during the period 1980–2014 and the Stochastic Impacts by Regression on Population, Affluence, and Technology model with fully modified ordinary least squares (FMOLS) are employed for empirical investigation. The results show that financial development has a significant negative relationship with CO₂ emission in the three selected Asian countries with the exception of India. The results further reveal that income inequality in Pakistan and India reduce CO₂ emission, while the result for Bangladesh is opposite. Likewise, energy usage has a significant positive effect on CO₂ emission in Bangladesh, Pakistan, and India. Our empirical analysis based on long-run and short-run elasticity appraisal suggests the validation of the EKC in Pakistan and India. The study findings recommend an important policy insinuation. The study suggests introducing a motivational campaign for the inhabitant towards utilization of high-efficiency electrical appliances, constructing mutual cooperation for economic development rather involve in winning development race, and introducing effective pollution absorption measures along with big projects.

Passende Verordnungsmenge und Applikation von Topika

Zusammenfassung

Hintergrund

Die Abschätzung der notwendigen Verordnungsmenge sowie der Anwendungsmenge von Topika durch den Patienten bereitet in der Versorgung nicht selten Schwierigkeiten. Unzureichende oder unwirtschaftliche Versorgung kann die Folge sein. Um beide Fehlerbereiche zu minimieren, sind einfache Methoden und eine hinreichende Erfahrung in der Abschätzung passender Verordnungsmengen und der Vermittlung verständlicher Applikationsvorgaben wichtig.

Ziel der Arbeit

Es erfolgten die Aufzeigung des aktuellen Publikationsstandes und die Prüfung der Evidenz zur sachgerechten topischen Verordnungsmenge und deren Anwendung durch den Patienten.

Material und Methoden

Es wurde ein Literaturreview auf der Basis einer strukturierten Literaturrecherche in PubMed mit den einzeln und gepoolt eingesetzten Suchbegriffen „local therapy", „topical treatment", „prescription", „amount of ointment needed", „involved area", „BSA", „finger-tip-unit", „Rule of Hand", „calculated dosage" und „rule of nines" durchgeführt. Eingeschlossen wurden wissenschaftliche Originalarbeiten nach manuellem Screening des Titels und Abstracts hinsichtlich der Relevanz.

Ergebnisse

Die Suchstrategie identifizierte nach manueller Selektion 19 relevante Publikationen. Als Maß der genaueren Applikation wurde am häufigsten das Prinzip der Fingertip-Unit (Fingerspitzeneinheit; FTU) eingesetzt. Die sachgerechte Verordnungsmenge wird in Abhängigkeit des Bedarfs pro befallener Fläche berechnet.

Diskussion

Es besteht in Deutschland weiterhin Klärungsbedarf, inwieweit in der Versorgungsroutine optimierte Mengen verordnet und zur Anwendung empfohlen werden. Für die Patienteninstruktion ist die FTU in Verbindung mit der Handflächenregel („Rule of Hand") ein geeignetes Maß zur Selbstapplikation.

Cartilage Analogue of Fibromatosis in the Maxillary Alveolar Bone

Abstract

Cartilage analogue of fibromatosis is a relatively common tumor in the palms and soles of young children and adolescence. The characteristic histological finding of the tumor is the differentiation toward cartilage formation within a background of fibromatosis-like growth. Therefore, the tumor may cause potential diagnostic problems in the maxillofacial bones where it has not been described. The purpose of the present report is to describe the imaging characteristics, histological and immunohistochemical features of an extremely rare case of cartilage analogue of fibromatosis in the maxillary alveolar bone of a 25-year-old female.

Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial

Abstract

Background

Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus.

Patients and Methods

Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival (OS), lymphoma-specific survival (LSS), and safety.

Results

Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0 to 76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% v 12%) and relapsed disease (6% v 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI, 0.69 to 1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI, 72.7 to 82.1) with everolimus and 77.0% (95% CI, 72.1 to 81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes.

Conclusions

Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained.

ClinicalTrials.gov

NCT00790036

Funding sources of practice changing trials

Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study

Abstract

Background

Anti-HER2 therapies are associated with a risk of increased cardiac toxicity, particularly when part of anthracycline-containing regimens. We report cardiac safety of pertuzumab, trastuzumab, and chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer.

Patients and methods

BERENICE (NCT02132949) is a nonrandomized, phase II, open-label, multicenter, multinational study in patients with normal cardiac function. In the neoadjuvant period, Cohort A patients received four cycles of dose-dense doxorubicin and cyclophosphamide, then 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles. Cohort B patients received four standard fluorouracil/epirubicin/cyclophosphamide cycles, then four docetaxel cycles with four standard trastuzumab and pertuzumab cycles. The primary endpoint was cardiac safety during neoadjuvant treatment, assessed by the incidence of New York Heart Association (NYHA) Class III/IV heart failure and of left ventricular ejection fraction (LVEF) declines (≥10 percentage points from baseline and to a value of < 50%). The main efficacy endpoint was pathological complete response (pCR, ypT0/is ypN0). Results are descriptive.

Results

Safety populations were 199 and 198 patients in Cohorts A and B, respectively. Three patients (1.5%; 95% confidence interval [CI]: 0.31–4.34) in Cohort A experienced four NYHA Class III/IV heart failure events. Thirteen patients (6.5%; 95% CI: 3.5–10.9) in Cohort A and four (2.0%; 95% CI: 0.6–5.1) in Cohort B experienced at least one LVEF decline. No new safety signals were identified. pCR rates were 61.8% and 60.7% in Cohorts A and B, respectively. The highest pCR rates were in the HER2-enriched PAM50 subtype (75.0% and 73.7%, respectively).

Conclusion

Treatment with pertuzumab, trastuzumab, and common anthracycline-containing regimens for the neoadjuvant treatment of early breast cancer resulted in cardiac and general safety profiles, and pCR rates, consistent with prior studies with pertuzumab.

Clinical Trial Information

NCT02132949

Role of up-front autologous stem cell transplantation in peripheral T-cell lymphoma for patients in response after induction: An analysis of patients from LYSA centers

Abstract

Background

Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem cell transplant (ASCT) is, therefore, still intensely debated.

Patients and methods

In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT).

Results

Among 527 patients screened from 14 centers in France, Belgium, and Portugal, a final cohort of 269 patients ≤ 65 years old with PTCL-NOS (N=78, 29%), AITL (N=123, 46%) and ALK-ALCL (N=68, 25%) with partial (N=52, 19%) or complete responses (N=217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI 0.69-1.50 for PFS and HR = 1.08; 95% CI 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P=0.90 and 0.66 for PFS and OS respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category.

Conclusions

The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL or ALK- ALCL with partial or complete response after induction.

Circulating cell-free DNA as predictor of treatment failure after neo-adjuvant chemo-radiotherapy before surgery in patients with locally advanced rectal cancer

Abstract

Background

Treatment of patients with locally advanced rectal cancer (LARC) is based on a combination of chemo-radiotherapy (CRT) and surgery. The rate of distant recurrences remains over 25%. Circulating cell-free DNA (cfDNA) in plasma is a mixture of normal and cancer-specific DNA segments, and is a promising biomarker in patients with colorectal cancer. The aim of our study was to investigate plasma cfDNA as a prognostic marker for outcome in patients with LARC treated with neoadjuvant CRT and surgery.

Patients and Methods

123 patients with LARC were included in two biomarker studies. Patients were treated with neoadjuvant CRT before TME surgery. Fifty-two (42%) of the patients received induction chemotherapy (ICT) with capecitabine + oxaliplatin. Total cfDNA was measured by direct fluorescent assay in EDTA plasma samples obtained at baseline, after ICT, and after CRT. Serial samples 5 years after surgery were collected in 51 patients (41%).

Results

Median follow-up was 55 months. Distant or local recurrence were seen in 30.9% of the patients. Patients with baseline cfDNA levels above the 75th quartile had a higher risk of local or distant recurrence and shorter time to recurrence compared to patients with plasma cfDNA below the 75^th percentile (HR = 2.48, 95%CI:1.3–4.8, P = 0.007). The same applied to disease free survival (DFS) (HR = 2.43, 95%CI:1.27–4.7, P = 0.015). In multivariate analysis, a high cfDNA level was significantly associated with time to progression and DFS. During follow-up, the association remained significant regardless of time point for sample analysis.

Conclusion

We have demonstrated an association between a high baseline plasma level of cfDNA and increased risk of recurrence, shorter time to recurrence, and shorter DFS in patients with LARC. Consequently, cfDNA could potentially improve pre- and posttreatment risk assessment and facilitate individualized therapy for patients with LARC.

Respiratory syncytial virus during pregnancy

Burden of respiratory syncytial virus infection in South African HIV-infected and HIV-uninfected pregnant and post-partum women: A longitudinal cohort study

Abstract

Background

There are limited data on the burden of respiratory syncytial virus (RSV) illness among pregnant and post-partum women, to determine their potential benefit from maternal RSV vaccination aimed primarily at protecting their probands. We evaluated the incidence of RSV-illness from mid-pregnancy until 24-weeks post-partum in HIV-uninfected and HIV-infected women and their infants.

Methods

Mother-infant dyads were enrolled in phase-III maternal influenza vaccine efficacy trials. These included 1060 and 1056 HIV-uninfected pregnant women in 2011 and 2012, respectively, 194 HIV-infected pregnant women in 2011, and their infants. Upper respiratory tract samples obtained at illness visits were tested for RSV by PCR.

Results

The incidence (per 1000 person-months) of RSV-illness (n=43 overall) among HIV-uninfected women was lower in 2011 (1.2; 95%CI: 0.6, 2.2) than in 2012 (4.0; 95%CI: 2.8, 5.6; p=0.001). The incidence of RSV-illness (n=5) in HIV-infected women was 3.4 (95%CI: 1.4, 8.1) in 2011. Maternal RSV-infection was associated with respiratory symptoms including cough (72.1%), rhinorrhoea (39.5%), sore-throat (37.2%); and headache (42%), but fever was absent in all cases. RSV-infection during pregnancy was not associated with adverse pregnancy outcomes. Post-partum, RSV-infection in mothers (n=27) was associated with concurrent infection among 51.9% of their infants; and conversely 29.8% of mothers with an investigated respiratory illness within 7 days of their infants having a RSV illness also tested positive for RSV.

Conclusions

RSV-infection is associated with respiratory illness during pregnancy and post-partum in women. Vaccination of pregnant women against RSV could benefit the mother, albeit primarily against non-febrile illness, and her infant.

ACTG A5353: A pilot study of dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA < 500,000 copies/mL

Abstract

Background

Limited data exist on initial HIV-1 treatment with dolutegravir plus lamivudine , particularly for pre-treatment HIV-1 RNA >100,000 copies/mL.

Materials and Methods

A5353 is a phase II, single-arm, pilot study of once-daily dolutegravir (50mg) plus lamivudine (300 mg) in treatment-naïve participants with HIV-1 RNA ≥1000 and < 500,000 copies/mL. Exclusion criteria included active hepatitis B, or major protease, reverse transcriptase, or integrase resistance. The primary efficacy measure was proportion with HIV-1 RNA < 50 copies/mL (FDA snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA >400 copies/mL at week 16/20, or >200 copies/mL at/after week 24. Dolutegravir levels and drug resistance testing were performed at VF.

Results

One hundred and twenty participants (87% male, median age 30 years, 37 (31%) HIV-1 RNA > 100,000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log10 copies/mL and 387 cells/mm ³. Virologic efficacy by FDA snapshot at week 24 was 108/120 (90%, CI [83%, 95%]) with comparable results in the >100,000 copies/mL and ≤100,000 copies/mL strata: 89% [75%, 97%] and 90% [82%, 96%], respectively. Three participants had VF, each with undetected plasma dolutegravir at ≥1 timepoints; the M184V reverse transcriptase and R263R/K integrase mutations developed in one participant. Two participants experienced Grade 3 possibly/probably treatment-related adverse events; none discontinued treatment due to adverse events.

Conclusion

Dolutegravir plus lamivudine demonstrated efficacy in individuals with pre-treatment HIV-1 RNA up to 500,000 copies/mL in this pilot trial, but a participant selected resistance mutations to lamivudine and dolutegravir

Surface properties of PM2.5 calcite fine particulate matter in the presence of same size bacterial cells and exocellular polymeric substances (EPS) of Bacillus mucitaginosus

Abstract

Microorganism cells and spores are the main components of PM2.5 (fine particulate matter) as well as fine mineral particles. In the microscopic system, the microorganisms will affect the minerals through attachment, charge neutralization, and dissolution related to the cell surface structure and metabolite. To explore the process and the results of microbial cells and their extracellular polymeric substances (EPS) acting on the surface properties of minerals of PM2.5 through the metabolism, a common native soil bacterium Bacillus mucitaginosus with abundant extracellular polymers was chosen as the tested strain. Meanwhile, as one of the PM2.5 common minerals, calcite fine particles were taken as the research object to explore the influence of microbial cells and extracellular polymers on its surface properties. High performance liquid chromatography (HPLC), inductively coupled plasma spectrometry (ICP), Zeta potential analysis, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), and scanning electron microscopy (SEM) were used to characterize the composition of EPS, the soluble ions, surface charge, surface groups, crystal form, and surface morphology of calcite residual solid after being treated by the bacterial cells and EPS. The results revealed the EPS of B. mucitaginosus mainly consisted of protein and polysaccharides. Both the whole cell and its EPS could promote the dissolution of calcite particles into calcium ions. Due to the adhesion of organic groups on the calcite surface, the surface potential shifted significantly in the negative direction and the solution pH was clearly increased. The morphology of calcite surface was significantly changed after dissolution and re-crystallization. Experimental results also showed that the existence of the bacteria cells and EPS significantly affected the surface properties of calcite and provide a theoretical basis for the mechanism of PM fine particulate matter on human health impact for further study.

Combination of in situ spectroscopy and chemometric techniques to discriminate different types of Roman bricks and the influence of microclimate environment

Abstract

Red and yellow bricks are the wall-building materials generally used in Roman masonries. The reasons for the different coloration are not always understood, causing loss of crucial information both for the conservation and for the archaeological knowledge of the cultural sites. In this work, a combination of in situ analyses, employing portable Raman spectroscopy and handheld energy dispersive X-ray fluorescence (HH-ED-XRF) spectroscopy along with chemometric analysis, was carried out on ancient Roman bricks of the "Casa di Diana" building (Ostia Antica, Italy-130 CE). Specifically, the compounds and the characteristic elements, which describe each type of brick (red and yellow), were studied avoiding destructive or invasive sampling. The molecular analysis allowed us to identify the major and minor compounds that characterise the bricks (anatase, hematite, quartz, calcite and silicates). However, the elemental analysis gave more useful information. Thus, the complex HH-ED-XRF data matrix generated was treated by a specific principal component analysis (PCA) to identify behavioural differences of the coloured bricks. The results revealed that Ca and Fe are the discriminatory elements for the two types of bricks. The PCA outcomes suggest that the contribution of certain elements is different in the bricks (mainly Ca, P, Sr, As and S, for yellow bricks), which could indicate different raw materials. Even among bricks with the same red colour (Al, Si, Ti, K, Fe, Cr, Mn, Ni, Zn, Cu, Rb and Zr, seemed to be the elements linked to raw materials), as a function of the surface impacts (orientation and microclimate affect the salts' formation), a distinction was made. Furthermore, the PCA pointed out that the yellow bricks are those more affected by decaying processes (related with Ca, P and S), complying with the Raman spectroscopy results in which the efflorescences (gypsum) affect especially the surface of these types of bricks.

Seasonal and spatial variations of microcystins in Poyang Lake, the largest freshwater lake in China

Abstract

Poyang Lake is the largest freshwater lake in China and an important drinking water source. Since the year 2000, toxic cyanobacteria have been observed frequently in Poyang Lake. In the present study, spatial and seasonal variations of microcystins (MCs; MC-RR, MC-YR, and MC-LR) in water column were examined monthly from January to December (except the months of March, May, and November) in 2013, by using ultra-high-performance liquid chromatography-electrospray ionization tandem triple quadrupole/mass spectrometry (UPLC-MS/MS). MC-RR was the most dominant variant, followed by MC-LR, while MC-YR was detected in low concentration. Total MC concentrations (intracellular + extracellular MCs) ranged from 1.26 to 9916.05 ng/L, with an average of 469.99 ng/L, and only 3.14% (6 out of 192 samples) of the water samples contained MC concentrations that exceeded the drinking water guideline level of 1 μg/L for MC-LR proposed by the World Health Organization (WHO). MC concentrations in water column showed obvious seasonal variations in Poyang Lake. Intracellular and extracellular MCs were both at a low level from January to April but increased quickly from June to August and decreased dramatically thereafter. Intracellular MCs exhibited similar spatial distribution pattern with extracellular MCs. Both intracellular and extracellular MC concentrations in eastern bays and around Songmen Mountain of Poyang Lake were higher than other regions. Intracellular MC concentrations were positively correlated with Chl a (r = 046, P < 0.01), pH (r = 0.25, P < 0.01), cyanobacterial biomass (r = 0.40, P < 0.01), and temperature (r = 0.36, P < 0.01) but negatively correlated with TN (r = − 0.28, P < 0.01), suggesting that TN, cyanobacteria biomass, pH, and temperature might be regulating factors for MC production in Poyang Lake.

The association of windmills with conservation of pollinating insects and wild plants in homogeneous farmland of western Poland

Abstract

Loss of suitable seminatural habitats and homogenization of crop types have led to the population decline of pollinating insects in farmland. As these insects support crop production, many practical efforts aim to sustain pollinator diversity which is especially challenging in intensively managed and homogeneous farmland. However, there are ongoing changes of the farmland toward its multifunctionality that includes, for example, wind farm development. Windmills are often built within crops; thus, we examined if the noncropped area around windmills can be valuable habitats for wild plants and pollinating insects: bees, butterflies, and flies. Species richness, abundances, and species diversity index of plants and pollinators around windmills were similar to those found in grassland patches (a typical habitat for these insects) and higher than in the adjacent crops. Pollinator diversity index and species richness at windmills increased with the distance to the nearest grassland patch and windmill. The population sizes of pollinating insects were also positively associated with plant diversity. Particular groups of pollinators showed specific habitat associations: bees occurred mostly at windmills, butterflies were highly associated with grasslands, while flies occurred in a similar number at windmill and on grasslands. Since windmills are frequently built within extensive homogeneous fields, thus, they introduce pollination services into the interior of cropped areas, contrary to field margins, road verges, or seminatural grasslands. Thus, although the development of wind farms has various negative environmental consequences, they can be alleviated by the increase of the local population size and diversity of wild plants and pollinating insects at windmills.

Testing Pneumonia Vaccines in the Elderly: Determining a Case Definition for Pneumococcal Pneumonia in the Absence of a Gold Standard

Abstract

Clinical assessments of vaccines to prevent pneumococcal (Pnc) community-acquired pneumonia (CAP) require sensitive and specific case definitions, but there is no gold standard diagnostic test. To develop a new case definition suitable for vaccine efficacy studies, we applied latent class analysis (LCA) to the results from seven diagnostic tests for Pnc etiology on clinical specimens from 323 elderly radiologically-confirmed pneumonia cases enrolled in The Finnish Community-Acquired Pneumonia Epidemiology study during 2005–2007. Compared to the conventional use of LCA, which is mainly to determine sensitivities and specificities of different tests, we instead used LCA as an appropriate instrument to predict the probability of Pnc etiology for each CAP case based on their test profiles, and utilized the predictions to minimize the sample size that would be needed for a vaccine efficacy trial. When compared to the conventional laboratory criteria of encapsulated Pnc in blood culture or in high-quality sputum culture or urine antigen positivity, our optimized case definition for PncCAP resulted in a trial sample size which was almost 20,000 subjects smaller. We believe that our novel application of LCA detailed here to determine a case definition for PncCAP could also be similarly applied to other diseases without a gold standard.

Therapeutic patient education in children with moderate to severe atopic dermatitis: A multicenter randomized controlled trial in China

Abstract

Background

Therapeutic patient education is a continuous, systematic, patient-centered learning process to help patients and their families acquire and maintain the skills they need to manage their lives with a chronic disease. It has been proven effective in increasing treatment adherence and improving quality of life for patients with atopic dermatitis (AD) in Western countries. We introduce the first multicenter, randomized controlled clinical trial of therapeutic patient education in Chinese children with AD.

Objectives

To evaluate the effects of therapeutic patient education on the severity of AD, quality of life, and understanding and successful use of emollients in Chinese children with eczema.

Methods

We recruited 580 children, ages 2-14 years, with moderate to severe AD from six hospitals in China. Participants were randomized (1:1) to an intervention (n = 293) or control (n = 249) group. In addition to the severity of AD, data on quality of life and a questionnaire on family and patient knowledge of emollients were evaluated at the 6-month follow-up.

Results

On study completion, we found that the intervention group showed a significantly greater reduction in mean SCORing Atopic Dermatitis (P < .001) and Infant's Dermatology Life Quality Index (P = .030) scores than the control group. In addition, knowledge about the use of emollients improved significantly in the intervention group. There was no significant difference between groups in Children's Dermatology Life Quality Index scores.

Conclusions

The first randomized controlled trial of a therapeutic patient education program in China had positive long-term effects on decreasing eczema severity and improvement of quality of life in children 2-4 years of age with AD, as well as in promoting greater understanding of the use of emollients.

Kenneth Warren and the Great Neglected Diseases of Mankind Programme: The Transformation of Geographical Medicine in the US and BeyondBy Conrad Keating

ISBN 978-3-319-50145-1, Springer International Publishing, Cham, Switzerland (Telephone: 800-777-4643, E-mail: onlineservice@springer.com, Website: http://ift.tt/2lK1H8r), 2016, 150 pp., $29.99 Hardcover

A Decade of War: Prospective Trajectories of Posttraumatic Stress Disorder Symptoms Among Deployed US Military Personnel and the Influence of Combat Exposure

Abstract

Posttraumatic stress disorder (PTSD) is a common psychiatric disorder among service members and veterans. The clinical course of PTSD varies between individuals, and patterns of symptom development have yet to be clearly delineated. Previous studies have been limited by convenience sampling, short follow-up periods, and the inability to account for combat-related trauma. To determine the trajectories of PTSD symptoms among deployed military personnel with and without combat exposure, we used data from a population-based representative sample of 8,178 US service members who participated in the Millennium Cohort Study from 2001 to 2011. Using latent growth mixture modeling, trajectories of PTSD symptoms were determined in the total sample, as well as in individuals with and without combat exposure, respectively. Overall, 4 trajectories of PTSD were characterized: resilient, pre-existing, new-onset, and moderate stable. Across all trajectories, combat-deployed service members diverged from non–combat-deployed service members, even after a single deployment. The former also generally had higher PTSD symptoms. Based on the models, nearly 90% of those without combat exposure remained resilient over the 10-year period, compared with 80% of those with combat exposure. Findings demonstrate that although the clinical course of PTSD symptoms shows heterogeneous patterns of development, combat exposure is uniformly associated with poor mental health.

Best Practices for Gauging Evidence of Causality in Air Pollution Epidemiology

Abstract

The contentious political climate surrounding air pollution regulations has brought some researchers and policy-makers to argue that evidence of causality is necessary before implementing more stringent regulations. Recently, investigators in an increasing number of air pollution studies have purported to have used "causal analysis," generating the impression that studies not explicitly labeled as such are merely "associational" and therefore less rigorous. Using 3 prominent air pollution studies as examples, we review good practices for how to critically evaluate the extent to which an air pollution study provides evidence of causality. We argue that evidence of causality should be gauged by a critical evaluation of design decisions such as 1) what actions or exposure levels are being compared, 2) whether an adequate comparison group was constructed, and 3) how closely these design decisions approximate an idealized randomized study. We argue that air pollution studies that are more scientifically rigorous in terms of the decisions made to approximate a randomized experiment are more likely to provide evidence of causality and should be prioritized among the body of evidence for regulatory review accordingly. Our considerations, although presented in the context of air pollution epidemiology, can be broadly applied to other fields of epidemiology.

Estimating the Comparative Effectiveness of Feeding Interventions in the Pediatric Intensive Care Unit: A Demonstration of Longitudinal Targeted Maximum Likelihood Estimation

Abstract

Longitudinal data sources offer new opportunities for the evaluation of sequential interventions. To adjust for time-dependent confounding in these settings, longitudinal targeted maximum likelihood based estimation (TMLE), a doubly robust method that can be coupled with machine learning, has been proposed. This paper provides a tutorial in applying longitudinal TMLE, in contrast to inverse probability of treatment weighting and g-computation based on iterative conditional expectations. We apply these methods to estimate the causal effect of nutritional interventions on clinical outcomes among critically ill children in a United Kingdom study (Control of Hyperglycemia in Paediatric Intensive Care, 2008–2011). We estimate the probability of a child's being discharged alive from the pediatric intensive care unit by a given day, under a range of static and dynamic feeding regimes. We find that before adjustment, patients who follow the static regime "never feed" are discharged by the end of the fifth day with a probability of 0.88 (95% confidence interval: 0.87, 0.90), while for the patients who follow the regime "feed from day 3," the probability of discharge is 0.64 (95% confidence interval: 0.62, 0.66). After adjustment for time-dependent confounding, most of this difference disappears, and the statistical methods produce similar results. TMLE offers a flexible estimation approach; hence, we provide practical guidance on implementation to encourage its wider use.