RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA mutated breast cancer

Abstract

Background

BRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) and enhanced sensitivity to DNA damaging agents or to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed in clinical trials. Numerous mechanisms of PARPi resistance have been described, whose clinical relevance in gBRCA-mutated breast cancer is unknown. This highlights the need to identify functional biomarkers to better predict PARPi sensitivity.

Patients and Methods

We investigated the in vivo mechanisms of PARPi resistance in gBRCA1 patient-derived tumor xenografts (PDXs) exhibiting differential response to PARPi. Analysis included exome sequencing and immunostaining of DNA damage response proteins to functionally evaluate HRR. Findings were validated in a retrospective sample set from gBRCA1/2-cancer patients treated with PARPi.

Results

RAD51 nuclear foci, a surrogate marker of HRR functionality, was the only common feature in PDX and patient samples with primary or acquired PARPi resistance. Consistently, low RAD51 was associated with objective response to PARPi. Evaluation of the RAD51 biomarker in untreated tumors was feasible due to endogenous DNA damage. In PARPi-resistant gBRCA1 PDXs, genetic analysis found no in-frame secondary mutations, but BRCA1 hypomorphic proteins in 60% of the models, TP53BP1-loss in 20% and RAD51-amplification in one sample, none mutually exclusive. Conversely, one of three PARPi-resistant gBRCA2 tumors displayed BRCA2 restoration by exome sequencing. In PDXs, PARPi resistance could be reverted upon combination of a PARPi with an ATM inhibitor.

Conclusion

Detection of RAD51 foci in gBRCA tumors correlates with PARPi resistance regardless of the underlying mechanism restoring HRR function. This is a promising biomarker to be used in the clinic to better select patients for PARPi therapy. Our study also supports the clinical development of PARPi combinations such as those with ATM inhibitors.

Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Role, Controversy, and Future Directions

Abstract

Background

The value of induction chemotherapy (ICT) remains under investigation despite decades of research. New advancements in the field, specifically regarding the induction regimen of choice, have reignited interest in this approach for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Sufficient evidence has accumulated regarding the benefits and superiority of TPF (docetaxel, cisplatin, and fluorouracil) over the chemotherapy doublet PF (cisplatin and fluorouracil). We therefore sought to collate and interpret the available data and further discuss the considerations for delivering ICT safely and optimally selecting suitable post-ICT regimens.

Design

We nonsystematically reviewed published phase 3 clinical trials on TPF ICT in a variety of LA SCCHN patient populations conducted between 1990 and 2017.

Results

TPF may confer survival and organ preservation benefits in a subgroup of patients with functionally inoperable or poor-prognosis LA SCCHN. Additionally, patients with operable disease or good prognosis (who are not candidates for organ preservation) may benefit from TPF induction in terms of reducing local and distant failure rates and facilitating treatment deintensification in selected populations. The safe administration of TPF requires treatment by a multidisciplinary team at an experienced institution. The management of adverse events associated with TPF and post-ICT radiotherapy-based treatment is crucial. Finally, post-ICT chemotherapy alternatives to cisplatin concurrent with radiotherapy (ie, cetuximab or carboplatin plus radiotherapy) appear promising and must be investigated further.

Conclusions

TPF is an evidence-based ICT regimen of choice in LA SCCHN and confers benefits in suitable patients when it is administered safely by an experienced multidisciplinary team and paired with the optimal post-ICT regimen, for which, however, no consensus currently exists.

Should decisions on adding adjuvant chemotherapy in early stage ER positive breast cancer be based on gene expression testing or clinicopathologic factors or both?

Neo-adjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08)

Abstract

Background

This open-label, phase lll trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma.

Patients and Methods

Patients were randomly assigned (1:1) to 2 cycles of chemotherapy (docetaxel 75 mg/m², cisplatin 75 mg/m²) followed by chemoradiation (45 Gy, docetaxel 20 mg/m² and cisplatin 25 mg/m², weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m² weekly and adjuvant cetuximab 500 mg/m² fortnightly for 3 months. The primary endpoint was progression-free survival (PFS).

Results

In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years (95% CI, 2.0 to not reached) with cetuximab and 2.0 years (95% CI, 1.5 to 2.8) with control (HR, 0.79; 95% CI, 0.58 to 1.07; P = .13). Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2 to 4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52 to 1.01; P = .055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31 to 0.90; P = .017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64 to 1.59, P = .97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings.

Conclusion

Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma.

Clinical trial information

NCT01107639

Circulating tumor DNA detection in hepatocellular carcinoma

Eribulin in BRAF V600E mutant metastatic colorectal cancer: Case series and potential rationale

Cutis laxa in a patient with 1p36 deletion syndrome

The Journal of Dermatology, EarlyView.

Herpes vegetans accompanied by Good's syndrome

The Journal of Dermatology, EarlyView.

Pigmented dermatofibrosarcoma protuberans associated with dermal melanocytosis

The Journal of Dermatology, EarlyView.

Relationship between environmental factors, age of onset and familial history in Japanese patients with psoriasis

The Journal of Dermatology, EarlyView.

Review on applications of artificial intelligence methods for dam and reservoir-hydro-environment models

Abstract

Efficacious operation for dam and reservoir system could guarantee not only a defenselessness policy against natural hazard but also identify rule to meet the water demand. Successful operation of dam and reservoir systems to ensure optimal use of water resources could be unattainable without accurate and reliable simulation models. According to the highly stochastic nature of hydrologic parameters, developing accurate predictive model that efficiently mimic such a complex pattern is an increasing domain of research. During the last two decades, artificial intelligence (AI) techniques have been significantly utilized for attaining a robust modeling to handle different stochastic hydrological parameters. AI techniques have also shown considerable progress in finding optimal rules for reservoir operation. This review research explores the history of developing AI in reservoir inflow forecasting and prediction of evaporation from a reservoir as the major components of the reservoir simulation. In addition, critical assessment of the advantages and disadvantages of integrated AI simulation methods with optimization methods has been reported. Future research on the potential of utilizing new innovative methods based AI techniques for reservoir simulation and optimization models have also been discussed. Finally, proposal for the new mathematical procedure to accomplish the realistic evaluation of the whole optimization model performance (reliability, resilience, and vulnerability indices) has been recommended.

The role of the water footprint in the context of green marketing

Abstract

The environmental degradation, because of various factors, such as climate change, human activities, increase of population globally, etc. have brought on pressures on the fresh water supplies that vary on time and space. Consequently, economic, environmental, and social tools have emerged known as footprints, in an effort to examine and measure the needs and consequences of humanity on the Earth's life support systems and take measures towards sustainable development. Furthermore, the constantly worsening environmental conditions have resulted in the cultivation of a green culture among society stakeholders that brought on terms such as green marketing and green products. This paper deals with the water footprint (WF) concept and an effort is performed, to explore through a literature review, in which ways it can contribute to the sustainable development of water use, in the context of green marketing (GM) strategies. The approach of the analysis is based on the discrimination to the following aspects: international scale, national and subnational scale, farmers, business, and consumers, in order to track the affection of each part in water issues. The main findings of the literature review showed that the aforementioned factors are playing a key role in protecting water recourses, by the way they formulate their water use and they are interrelated and interdependent. WFs can be useful in the context of GM, by providing helpful information about direct and indirect water consumption, to every contributor factor in supply chains, to consumers, governments, and water managers.

Official control of plant protection products in Poland: detection of illegal products

Abstract

Market presence of illegal and counterfeit pesticides is now a global problem. According to data published in 2012 by the European Crop Protection Association (ECPA), illegal products represent over 10% of the global market of plant protection products. Financial benefits are the main reason for the prevalence of this practice. Counterfeit and illegal pesticides may contain substances that may pose a threat to the environment, crops, animals, and humans, inconsistent with the label and registration dossier. In Poland, action against illegal and counterfeit plant protection products is undertaken by the Main Inspectorate of Plant Health and Seed Inspection (PIORiN), the police, the prosecution, and the pesticide producers. Results of chemical analyses carried out by the Institute of Plant Protection - National Research Institute Sośnicowice Branch, Pesticide Quality Testing Laboratory (PQTL IPP-NRI Sosnicowice Branch) indicate that a majority of illegal pesticides in Poland are detected in the group of herbicides. Products from parallel trade tend to have the most irregularities. This article describes the official quality control system of plant protection products in Poland and presents the analytical methods for testing pesticides suspected of adulteration and recent test results.

Does biologic treatment of psoriasis lower the risk of cardiovascular events and mortality? A critical question that we are only just beginning to answer

Modernizing Regulation of Cosmetic Products: Reintroduction of the Personal Care Products Safety Act

Can We Perform CT of the Appendix with Less Than 1 mSv? A De-escalating Dose-simulation Study

Abstract

Objectives

To systematically explore the lowest reasonably achievable radiation dose for appendiceal CT using an iterative reconstruction (IR) in young adults.

Methods

We prospectively included 30 patients who underwent 2.0-mSv CT for suspected appendicitis. From the helical projection data, 1.5-, 1.0- and 0.5-mSv CTs were generated using a low-dose simulation tool and the knowledge-based IR. We performed step-wise non-inferiority tests sequentially comparing 2.0-mSv CT with each of 1.5-, 1.0- and 0.5-mSv CT, with a predetermined non-inferiority margin of 0.06. The primary end point was the pooled area under the receiver-operating-characteristic curve (AUC) for three abdominal and three non-abdominal radiologists.

Results

For the abdominal radiologists, the non-inferiorities of 1.5-, 1.0- and 0.5-mSv CT to 2.0-mSv CT were sequentially accepted [pooled AUC difference: 2.0 vs. 0.5 mSv, 0.017 (95% CI: -0.016, 0.050)]. For the non-abdominal radiologists, the non-inferiorities of 1.5- and 1.0-mSv CT were accepted; however, the non-inferiority of 0.5-mSv CT could not be proved [pooled AUC difference: 2.0 vs. 1.0 mSv, -0.017 (-0.070, 0.035) and 2.0 vs. 0.5 mSv, 0.045 (-0.071, 0.161)].

Conclusion

The 1.0-mSv appendiceal CT was non-inferior to 2.0-mSv CT in terms of diagnostic performance for both abdominal and non-abdominal radiologists; 0.5-mSv appendiceal CT was non-inferior only for abdominal radiologists.

Key points

• For both abdominal and non-abdominal radiologists, 1.0-mSv appendiceal CT could be feasible.

• The 0.5-mSv CT was non-inferior to 2.0-mSv CT only for expert abdominal radiologists.

• Reader experience is an important factor affecting diagnostic impairment by low-dose CT.

Cervical ultrasonography has no additional value over negative 18 F-FDG PET/CT scans for diagnosing cervical lymph node metastases in patients with oesophageal cancer

Abstract

Objectives

To investigate the additional value of cervical ultrasonography over ¹⁸F-FDG PET/CT for diagnosing cervical lymph node metastases in patients with newly diagnosed oesophageal cancer.

Methods

Between January 2013 and January 2016, 163 patients with newly diagnosed oesophageal cancer underwent both cervical ultrasonography and ¹⁸F-FDG PET/CT at a tertiary referral centre in the Netherlands. Retrospective clinical data analysis was performed to assess the diagnostic value of cervical ultrasonography and ¹⁸F-FDG PET/CT for the detection of cervical lymph node metastases. Fine needle aspiration or clinical follow-up was used as reference standard.

Results

The overall incidence of patients with cervical lymph node metastases was 14%. The sensitivity of ¹⁸F-FDG PET/CT to detect cervical lymph node metastases was 82% (95% CI 59–94%) and specificity was 91% (95% CI 85–95%). The sensitivity and specificity of cervical ultrasonography were 73% (95% CI 50–88%) and 84% (95% CI 77–90%), respectively. In patients with a negative ¹⁸F-FDG PET/CT, 12 of 133 (9%) patients had suspicious nodes on cervical ultrasonography. In all these 12 patients the nodes were confirmed benign.

Conclusions

Cervical ultrasonography has no additional diagnostic value to a negative integrated ¹⁸F-FDG PET/CT for the detection of cervical lymph node metastases in patients with newly diagnosed oesophageal cancer.

Key Points

• Cervical ultrasonography has no value over PET/CT in evaluating cervical node metastases.

• PET/CT provides greater diagnostic confidence compared to cervical ultrasonography.

• Cervical ultrasonography during standard diagnostic work-up may be considered unnecessary.

• Cervical lesions on PET/CT require cytopathological confirmation by FNA.

Round-the-clock performance of coronary CT angiography for suspected acute coronary syndrome: Results from the BEACON trial

Abstract

Objective

To assess the image quality of coronary CT angiography (CCTA) for suspected acute coronary syndrome (ACS) outside office hours.

Methods

Patients with symptoms suggestive of an ACS underwent CCTA at the emergency department 24 hours, 7 days a week. A total of 118 patients, of whom 89 (75 %) presented during office hours (weekdays between 07:00 and 17:00) and 29 (25 %) outside office hours (weekdays between 17:00 and 07:00, weekends and holidays) underwent CCTA. Image quality was evaluated per coronary segment by two experienced readers and graded on an ordinal scale ranging from 1 to 3.

Results

There were no significant differences in acquisition parameters, beta-blocker administration or heart rate between patients presenting during office hours and outside office hours. The median quality score per patient was 30.5 [interquartile range 26.0–33.5] for patients presenting during office hours in comparison to 27.5 [19.75–32.0] for patients presenting outside office hours (p=0.043). The number of non-evaluable segments was lower for patients presenting during office hours (0 [0–1.0] vs. 1.0 [0–4.0], p=0.009).

Conclusion

Image quality of CCTA outside office hours in the diagnosis of suspected ACS is diminished.

Key Points

• Quality scores were higher for coronary-CTA during office hours.

• There were no differences in acquisition parameters.

• There was a non-significant trend towards higher heart rates outside office hours.

• Coronary-CTA on the ED requires state-of-the-art scanner technology and sufficiently trained staff.

• Coronary-CTA on the ED needs preparation time and optimisation of the procedure.

The impact of injector-based contrast agent administration in time-resolved MRA

Abstract

Objectives

Time-resolved contrast-enhanced MR angiography (4D-MRA), which allows the simultaneous visualization of the vasculature and blood-flow dynamics, is widely used in clinical routine. In this study, the impact of two different contrast agent injection methods on 4D-MRA was examined in a controlled, standardized setting in an animal model.

Methods

Six anesthetized Goettingen minipigs underwent two identical 4D-MRA examinations at 1.5 T in a single session. The contrast agent (0.1 mmol/kg body weight gadobutrol, followed by 20 ml saline) was injected using either manual injection or an automated injection system. A quantitative comparison of vascular signal enhancement and quantitative renal perfusion analyses were performed.

Results

Analysis of signal enhancement revealed higher peak enhancements and shorter time to peak intervals for the automated injection. Significantly different bolus shapes were found: automated injection resulted in a compact first-pass bolus shape clearly separated from the recirculation while manual injection resulted in a disrupted first-pass bolus with two peaks. In the quantitative perfusion analyses, statistically significant differences in plasma flow values were found between the injection methods.

Conclusions

The results of both qualitative and quantitative 4D-MRA depend on the contrast agent injection method, with automated injection providing more defined bolus shapes and more standardized examination protocols.

Key points

• Automated and manual contrast agent injection result in different bolus shapes in 4D-MRA.

• Manual injection results in an undefined and interrupted bolus with two peaks.

• Automated injection provides more defined bolus shapes.

• Automated injection can lead to more standardized examination protocols.

Evaluation of an adaptive detector collimation for prospectively ECG-triggered coronary CT angiography with third-generation dual-source CT

Abstract

Objectives

To investigate the impact of an adaptive detector collimation on the dose parameters and accurateness of scan length adaption at prospectively ECG-triggered sequential cardiac CT with a wide-detector third-generation dual-source CT.

Methods

Ideal scan lengths for human hearts were retrospectively derived from 103 triple-rule-out examinations. These measures were entered into the new scanner operated in prospectively ECG-triggered sequential cardiac scan mode with three different detector settings: (1) adaptive collimation, (2) fixed 64 × 0.6-mm collimation, and (3) fixed 96 × 0.6-mm collimation. Differences in effective scan length and deviation from the ideal scan length and dose parameters (CTDIvol, DLP) were documented.

Results

The ideal cardiac scan length could be matched by the adaptive collimation in every case while the mean scanned length was longer by 15.4% with the 64 × 0.6 mm and by 27.2% with the fixed 96 × 0.6-mm collimation. While the DLP was almost identical between the adaptive and the 64 × 0.6-mm collimation (83 vs. 89 mGycm at 120 kV), it was 62.7% higher with the 96 × 0.6-mm collimation (135 mGycm), p < 0.001.

Conclusion

The adaptive detector collimation for prospectively ECG-triggered sequential acquisition allows for adjusting the scan length as accurate as this can only be achieved with a spiral acquisition. This technique allows keeping patient exposure low where patient dose would significantly increase with the traditional step-and-shoot mode.

Key points

• Adaptive detector collimation allows keeping patient exposure low in cardiac CT.

• With novel detectors the desired scan length can be accurately matched.

• Differences in detector settings may cause 62.7% of excessive dose.

Prognostic importance of peritoneal lesion-to-primary tumour standardized uptake value ratio in advanced serous epithelial ovarian cancer

Abstract

Objectives

Using preoperative PET/CT, we evaluated the prognostic value of preoperative [¹⁸F]FDG uptake ratio between various metastatic lesions and primary tumour in patients with advanced serous epithelial ovarian cancer (EOC).

Methods

We retrospectively reviewed patients with International Federation of Gynecology and Obstetrics (FIGO) stage III, IV serous EOC who underwent preoperative [¹⁸F]FDG PET/CT scans. Clinico-pathological variables and PET/CT parameters such as maximum standardized uptake value of the ovarian cancer (SUV_ovary), pelvic or para-aortic LN (SUV_LN), peritoneal (SUV_perit) and distant extra-peritoneal (SUV_dist) metastatic lesions, and the metastatic lesion-to-ovarian cancer standardized uptake value ratio were assessed.

Results

Clinico-pathological data were retrospectively reviewed for 97 eligible patients. The median progression-free survival (PFS) was 18 months (range, 6–90 months) and 59 (60.8 %) patients experienced recurrence. In multivariate regression analysis, older age (p = 0.035, hazard ratio (HR) 1.032, 95 % CI 1.002–1.062), and high SUV_perit/SUV_ovary (p = 0.046, HR 1.755, 95 % CI 1.011–3.047) were independent risk factors of recurrence. Patient group categorized by SUV_perit/SUV_ovary showed significant difference in PFS (Log-Rank test, p = 0.001).

Conclusions

In patients with advanced serous EOC, preoperative SUV_perit/SUV_ovary measured by [¹⁸F]FDG PET/CT provides significant incremental performance for prediction of recurrence.

Key points

• PET/CT data from advanced serous epithelial ovarian cancer patients were analysed.

• Prognostic value of SUV ratio between metastatic and primary tumour was investigated.

• SUV _perit /SUV _ovary provides incremental performance for prediction of recurrence.

Accuracy of computed tomography for selecting the revascularization method based on SYNTAX score II

Abstract

Objectives

The application of SYNTAX score II based on coronary CT angiography (CCTA) for selecting further treatment options has not been studied. This study aimed to investigate the diagnostic performance of CCTA combined with SYNTAX score II for selecting the revascularization method compared with invasive coronary angiography (ICA) based on 2014 European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guidelines.

Methods

From January–May 2011, 160 patients who underwent both CCTA and ICA within 30 interval days were included. The diagnostic performance of CCTA, CCTA plus CT-SYNTAX score I and CT-SYNTAX score II was analysed using ICA counterparts as references.

Results

Overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CCTA plus CT-SYNTAX I for selecting coronary artery bypass grafting (CABG) candidates using ICA plus ICA-SYNTAX I as reference, were 70.6 %, 95.8 %, 66.7 %, 96.5 % and 93.1 %, respectively. The diagnostic performance of CCTA plus CT-SYNTAX II showed improvement with values of 83.3 %, 97.3 %, 71.4 %, 98.6 % and 96.3 %, respectively, using ICA plus ICA-SYNTAX II as reference.

Conclusions

CCTA combined with CT-SYNTAX score II is an accurate method for selecting CABG surgery candidates compared with ICA-SYNTAX score II.

Key points

• SYNTAX plus CCTA can be highly specific for selecting the revascularization method.

• SYNTAX II was complemented by including clinical considerations to SYNTAX I.

• CCTA plus CT-SYNTAX II is an accurate method for selecting CABG candidates.

18 F-fluorodeoxyglucose specimen-positron emission mammography delineates tumour extension in breast-conserving surgery: Preliminary results

Abstract

Objectives

We aimed to determine whether high-resolution specimen-positron emission mammography (PEM) using fluorodeoxyglucose (¹⁸F-FDG) can reveal extension of breast cancer in breast-conserving surgery (BCS), and assess the safety of radiation exposure to medical staff.

Methods

Sixteen patients underwent positron emission tomography, and then BCS with intraoperative frozen section analysis on the same day. Resected specimens with remaining ¹⁸F-FDG accumulation were scanned by high-resolution PEM. At least 1 day after surgery, tumour extension was evaluated by three independent experienced readers and by binarized images from the specimen-PEM data. Intraoperative exposure of medical staff to ¹⁸F-FDG was measured.

Results

Specimen-PEM evaluations of binarized images and the three investigators detected all (100 %, 12/12) invasive lesions and 94.4 % (17/18) of in situ lesions using both methods. The positive predictive value of the accumulated lesions was 74.4 % (29/39) for the binarized images and 82.9 % (29/35) for the three investigators. Analysis of intraoperative frozen sections detected 100 % (2/2) of the margin-positive cases, also detected by both specimen-PEM evaluation methods with no false-positive margin cases. The mean exposure of the medical staff to ¹⁸F was 18 μSv.

Conclusions

Specimen-PEM detected invasive and in situ lesions with high accuracy and allowable radiation exposure.

Key points

• Specimen-PEM detected invasive and in situ lesions with high accuracy.

• Specimen-PEM predicted complete resection with the same accuracy as frozen section analysis.

• Breast-conserving surgery after fluorodeoxyglucose injection was performed with low medical staff exposure.

Validation of goose liver fat measurement by QCT and CSE-MRI with biochemical extraction and pathology as reference

Abstract

Objectives

This study aimed to validate the accuracy and reliability of quantitative computed tomography (QCT) and chemical shift encoded magnetic resonance imaging (CSE-MRI) to assess hepatic steatosis.

Methods

Twenty-two geese with a wide range of hepatic steatosis were collected. After QCT and CSE-MRI examinations, the liver of each goose was removed and samples were taken from the left lobe, upper and lower half of the right lobe for biochemical measurement and histology. Fat percentages by QCT and proton density fat fraction by MRI (MRI-PDFF) were measured within the sample regions of biochemical measurement and histology. The accuracy of QCT and MR measurements were assessed through Spearman correlation coefficients (r) and Passing and Bablok regression equations using biochemical measurement as the "gold standard".

Results

Both QCT and MRI correlated highly with chemical extraction [r = 0.922 (p < 0.001) and r = 0.949 (p < 0.001) respectively]. Chemically extracted triglyceride was accurately predicted by both QCT liver fat percentages (Y = 0.6 + 0.866 × X) and by MRI-PDFF (Y = -1.8 + 0.773 × X).

Conclusions

QCT and CSE-MRI measurements of goose liver fat were accurate and reliable compared with biochemical measurement.

Key Points

• QCT and CSE-MRI can measure liver fat content accurately and reliably

• Histological grading of hepatic steatosis has larger sampling variability

• QCT and CSE-MRI have potential in the clinical setting

Transoesophageal echocardiography prior to catheter ablation could be avoided in atrial fibrillation patients with a low risk of stroke and without filling defects in the late-phase MDCT scan: A retrospective analysis of 783 patients

Abstract

Objectives

To test whether multidetector computed tomography (MDCT) could completely replace transoesophageal echocardiography (TEE) to detect left atrial appendage (LAA) thrombi in atrial fibrillation (AF) patients using a large sample size.

Methods

783 patients with AF who underwent MDCT and TEE before catheter ablation were retrospectively included. Demographic data were obtained. Two radiologists blinded to clinical data made the imaging diagnosis.

Results

Most of the patients (96.2 %) had a CHA₂DS₂-VASc score (congestive heart failure, hypertension, age ≥ 75 years old (doubled), diabetes, stroke/transient ischaemic attack/thromboembolism (doubled), vascular disease, age 65–74 years, female sex) ≤ 3. Eight thrombi were identified by TEE, all of which were detected by MDCT; no thrombus was observed with TEE without the observation of filling defects by late-phase MDCT scanning in any of the patients. Using TEE as reference standard, the sensitivity, specificity, positive predictive value and negative predictive value of MDCT for thrombus detection were 100 %, 95.74 % (95 % CI 94.33 %–97.15 %), 19.51 % (95 % CI 16.73 %–22.29 %) and 100 %, respectively.

Conclusions

For AF patients with low risk of stroke, when MDCT images showed no filling defect in the late phase, TEE prior to catheter ablation can be avoided.

Key Points

• MDCT can help detect the presence of LAA thrombus.

• TEE can be avoided when late-phase MDCT shows no filling defect.

• TEE is required in patients whose MDCT images indicate thrombus.

The efficacy of real-time colour Doppler flow imaging on endoscopic ultrasonography for differential diagnosis between neoplastic and non-neoplastic gallbladder polyps

Abstract

Objectives

We evaluated the usefulness of real-time colour Doppler flow (CDF) endoscopic ultrasonography (EUS) for differentiating neoplastic gallbladder (GB) polyps from non-neoplastic polyps.

Methods

Between August 2014 and December 2016, a total of 233 patients with GB polyps who underwent real-time CDF-EUS were consecutively enrolled in this prospective study. CDF imaging was subjectively categorized for each patient as: strong CDF pattern, weak CDF pattern and no CDF pattern.

Results

Of the 233 patients, 115 underwent surgical resection. Of these, there were 90 cases of non-neoplastic GB polyps and 23 cases of neoplastic GB polyps. In a multivariate analysis, a strong CDF pattern was the most significant predictive factor for neoplastic polyps; sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 52.2 %, 79.4 %, 38.7 %, 86.9 % and 73.9 %, respectively. Solitary polyp and polyp size were associated with an increased risk of neoplasm.

Conclusions

The presence of a strong CDF pattern as well as solitary and larger polyps on EUS may be predictive of neoplastic GB polyps. As real-time CDF-EUS poses no danger to the patient and requires no additional equipment, it is likely to become a supplemental tool for the differential diagnosis of GB polyps.

Key points

• Differential diagnosis between neoplastic polyps and non-neoplastic polyps of GB is limited.

• The use of real-time CDF-EUS was convenient, with high agreement between operators.

• The real-time CDF-EUS is helpful in differential diagnosis of GB polyps.

Hemispherical photoacoustic imaging of myocardial infarction: in vivo detection and monitoring

Abstract

Objectives

This study aimed to demonstrate the capacity for noninvasive localisation and characterisation of myocardial infarction (MI) in vivo using a hemispherical photoacoustic imaging (PAI) system. MI remains a leading cause of morbidity and mortality worldwide. To enable optimal treatment of patients, timely and accurate diagnosis and longitudinal monitoring is critical.

Methods

Ischaemia was induced in Balb/c mice by ligation of the left anterior descending artery. The hemispherical PAI system, equipped with 128 ultrasonic transducers spirally distributed on the surface, along with parallel data acquisition, was applied for imaging of the mouse heart.

Results

Our study showed that hemispherical PAI can delineate thoracic vessels and the morphology of the entire heart. Longitudinal PAI images revealed gradual expansion of the infarcted area along with necrosis and fibrosis, which were quantitatively validated by triphenyltetrazolium chloride staining. After MI modelling, the photoacoustic (PA) signal intensity decreased by 399.1 ± 56.3 (p < 0.001), a ~2.5-fold reduction compared to that of healthy cardiac tissue. The calculated size of the enlarged heart, 10.4 ± 6.0 mm² (p < 0.001), represents an increase of ~18% versus that of a healthy heart.

Conclusions

PAI enables MI diagnosis and injury localisation with its capabilities for both deep organ imaging and lesion region differentiation.

Key Points

• Photoacoustic imaging (PAI), combining optical absorption and ultrasonic resolution, can delineate cardiac anatomy.

• PAI can diagnose myocardial infarction lesions with 10 mm imaging depth in vivo.

• Quantified results are in excellent agreement with enzyme and histological examinations.

• PAI can serve as a complementary modality to SPECT and ultrasound imaging.

• This study will encourage further PAI development for clinical use.

Advanced CT acquisition protocol with a third-generation dual-source CT scanner and iterative reconstruction technique for comprehensive prosthetic heart valve assessment

Abstract

Objectives

Multidetector CT (MDCT) is a valuable tool for functional prosthetic heart valve (PHV) assessment. However, radiation exposure remains a concern. We assessed a novel CT-acquisition protocol for comprehensive PHV evaluation at limited dose.

Methods

Patients with a PHV were scanned using a third-generation dual-source CT scanner (DSCT) and iterative reconstruction technique (IR). Three acquisitions were obtained: a non-enhanced scan; a contrast-enhanced, ECG-triggered, arterial CT angiography (CTA) scan with reconstructions at each 5 % of the R-R interval; and a delayed high-pitch CTA of the entire chest. Image quality was scored on a five-point scale. Radiation dose was obtained from the reported CT dose index (CTDI) and dose length product (DLP).

Results

We analysed 43 CT examinations. Mean image quality score was 4.1±1.4, 4.7±0.5 and 4.2±0.6 for the non-contrast-enhanced, arterial and delayed acquisitions, respectively, with a total mean image quality of 4.3±0.7. Mean image quality for leaflet motion was 3.9±1.4. Mean DLP was 28.2±17.1, 457.3±168.6 and 68.5±47.2 mGy.cm for the non-contrast-enhanced (n=40), arterial (n=43) and delayed acquisition (n=43), respectively. The mean total DLP was 569±208 mGy.cm and mean total radiation dose was 8.3±3.0 mSv (n=43).

Conclusion

Comprehensive assessment of PHVs is possible using DSCT and IR at moderate radiation dose.

Key points

• Prosthetic heart valve dysfunction is a potentially life-threatening condition.

• Dual-source CT can adequately assess valve leaflet motion and anatomy.

• We assessed a comprehensive protocol with three acquisitions for PHV evaluation.

• This protocol is associated with good image quality and limited dose.

Preoperative multiparametric MRI of the prostate for the prediction of lymph node metastases in prostate cancer patients treated with extended pelvic lymph node dissection

Abstract

Objectives

To assess the role of preoperative multiparametric MRI (mpMRI) of the prostate in the prediction of nodal metastases in patients treated with radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).

Methods

We retrospectively analyzed 101 patients who underwent both preoperative mpMRI of the prostate and RP with ePLND at our institution. For each patient, complete preoperative clinical data and tumour characteristics at mpMRI were recorded. Final histopathologic stage was considered the standard of reference. Univariate and multivariate logistic regression analyses were performed.

Results

Nodal metastases were found in 23/101 (22.8%) patients. At univariate analyses, all clinical and radiological parameters were significantly associated to nodal invasion (all p<0.03); tumour volume at MRI (mrV), tumour ADC and tumour T-stage at MRI (mrT) were the most accurate predictors (AUC = 0.93, 0.86 and 0.84, respectively). A multivariate model including PSA levels, primary Gleason grade, mrT and mrV showed high predictive accuracy (AUC = 0.956). Observed prevalence of nodal metastases was very low among tumours with mrT2 stage and mrV<1cc (1.8%).

Conclusion

Preoperative mpMRI of the prostate can predict nodal metastases in prostate cancer patients, potentially allowing a better selection of candidates to ePLND.

Key points

• Multiparametric-MRI of the prostate can predict nodal metastases in prostate cancer

• Tumour volume and stage at MRI are the most accurate predictors

• Prevalence of nodal metastases is low for T2-stage and <1cc tumours

• Preoperative mpMRI may allow a better selection of candidates to lymphadenectomy

Diagnostic accuracy of low and high tube voltage coronary CT angiography using an X-ray tube potential-tailored contrast medium injection protocol

Abstract

Objectives

To compare the diagnostic accuracy between low-kilovolt peak (kVp) (≤ 100) and high-kVp (> 100) third-generation dual-source coronary CT angiography (CCTA) using a kVp-tailored contrast media injection protocol.

Methods

One hundred twenty patients (mean age = 62.6 years, BMI = 29.0 kg/m²) who underwent catheter angiography and CCTA with automated kVp selection were separated into two cohorts (each n = 60, mean kVp = 84 and 117). Contrast media dose was tailored to the kVp level: 70 = 40 ml, 80 = 50 ml, 90 = 60 ml, 100 = 70 ml, 110 = 80 ml, and 120 = 90 ml. Contrast-to-noise ratio (CNR) was measured. Two observers evaluated image quality and the presence of significant coronary stenosis (> 50% luminal narrowing).

Results

Diagnostic accuracy (sensitivity/specificity) with ≤ 100 vs. > 100 kVp CCTA was comparable: per patient = 93.9/92.6% vs. 90.9/92.6%, per vessel = 91.5/97.8% vs. 94.0/96.8%, and per segment = 90.0/96.7% vs. 90.7/95.2% (all P > 0.64). CNR was similar (P > 0.18) in the low-kVp vs. high-kVp group (12.0 vs. 11.1), as ws subjective image quality (P = 0.38). Contrast media requirements were reduced by 38.1% in the low- vs. high-kVp cohort (53.6 vs. 86.6 ml, P < 0.001) and radiation dose by 59.6% (4.3 vs. 10.6 mSv, P < 0.001).

Conclusions

Automated tube voltage selection with a tailored contrast media injection protocol allows CCTA to be performed at ≤ 100 kVp with substantial dose reductions and equivalent diagnostic accuracy for coronary stenosis detection compared to acquisitions at > 100 kVp.

Key points

• Low-kVp coronary CT angiography (CCTA) enables reduced contrast and radiation dose.

• Diagnostic accuracy is comparable between ≤ 100 and > 100 kVp CCTA.

• Image quality is similar for low- and high-kVp CCTA.

• Low-kVp image acquisition is facilitated by automated tube voltage selection.

• Tailoring contrast injection protocols to the automatically selected kVp-level is feasible.

Optimisation of sonourethrography: the clamp method

Abstract

Purpose

To describe the clamp method for performing retrograde sonourethrography (RSUG) and contrast-enhanced voiding sonourethrography (CE-VSUG) via the transperineal approach in male adults.

Materials and methods

Prospective study of 113 males (14-86 years) with urethral strictures confirmed by urethrography who received sonourethrography via the clamp method between 2011 and 2015. The characteristic parameters of the quantitative variables were calculated and a comparative analysis of the qualitative variables was conducted using the McNemar test.

Results

RSUG was performed successfully in all the cases (n = 113) and detected 49 cases with anterior urethral strictures; the strictures in the proximal bulbar cone in five of them (10.2%) were not visualised on retrograde urethrography (RUG) (p < 0.05). CE-VSUG was performed successfully in 97 cases and observed posterior urethral strictures in 82; the bladder neck strictures in 6 of them (7.3%) were not observed on voiding cystourethrography (VCUG) (p < 0.05). Retrograde bladder filling was achieved in approximately 6 min.

Conclusion

The clamp method enables RSUG and CE-VSUG to be performed simply, effectively and painlessly by a single operator. It also allows the evaluation of cases with urethromeatal alterations (stricture, hypospadias and meatotomy).

Key Points

• The clamp method enables RSUG to be performed simply and painlessly.

• The clamp method requires only one operator and allows assessing urethromeatal alterations.

• RSUG shows greater capacity for detecting anterior urethral strictures than RUG.

• The clamp method achieves retrograde bladder filling in approximately 6 min.

• CE-VSUG shows greater capacity for detecting strictures than VCUG.

Chemical shift magnetic resonance imaging for distinguishing minimal-fat renal angiomyolipoma from renal cell carcinoma: a meta-analysis

Abstract

Objectives

To determine the performance of chemical shift signal intensity index (CS-SII) values for distinguishing minimal-fat renal angiomyolipoma (mfAML) from renal cell carcinoma (RCC) and to assess RCC subtype characterisation.

Methods

We identified eligible studies on CS magnetic resonance imaging (CS-MRI) of focal renal lesions via PubMed, Embase, and the Cochrane Library. CS-SII values were extracted by lesion type and evaluated using linear mixed model-based meta-regression. RCC subtypes were analysed. Two-sided p value <0.05 indicated statistical significance. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.

Results

Eleven articles involving 850 patients were included. Minimal-fat AML had significantly higher CS-SII value than RCC (p < 0.05); there were no significant differences between mfAML and clear cell RCC (cc-RCC) (p = 0.112). Clear cell RCC had a significantly higher CS-SII value than papillary RCC (p-RCC) (p < 0.001) and chromophobe RCC (ch-RCC) (p = 0.045). The methodological quality was relatively high, and Begg's test data points indicated no obvious publication bias.

Conclusions

The CS-SII value for differentiating mfAML from cc-RCC remains unproven, but is a promising method for differentiating cc-RCC from p-RCC and ch-RCC.

Key Points

• RCC CS-SII values are significantly lower than those of mfAML overall.

• CS-SII values cannot aid differentiation between mfAML and cc-RCC.

• CS-SII values might help characterise RCC subtypes.

Breast lesions classified as probably benign (BI-RADS 3) on magnetic resonance imaging: a systematic review and meta-analysis

Abstract

Purpose

To investigate prevalence, malignancy rates, imaging features, and follow-up intervals for probably benign (BI-RADS 3) lesions on breast magnetic resonance imaging (MRI).

Methods

A systematic database-review of articles published through 22/06/2016 was performed. Eligible studies reported BI-RADS 3 lesions on breast MRI. Two independent reviewers performed a literature review and data extraction. Data collection included study characteristics, number/type of BI-RADS 3 lesions, final diagnosis (histopathology and/or follow-up). Sources of bias (QUADAS-2) were assessed. Meta-analysis included data-pooling, heterogeneity testing, and meta-regression.

Results

Fifteen studies were included. Prevalence was reported in 11 studies (range: 1.2-24.3%). Malignancy rates ranged between 0.5-10.1% (pooled 61/2814, 1.6%, 95%-CI:0.9-2.3% (random-effects-model), I²=53%, P=0.007). In a subgroup of 11 studies (2183 lesions), highest malignancy rates were observed in non-mass lesions (pooled 25/714, 2.3%, 95%-CI:0.8-3.9%, I²=52%, P=0.021) followed by mass lesions (pooled 15/771, 1.5%, 95%-CI:0.7-2.4%, I²=0%, P=0.929), and foci (pooled 10/698, 1%, 95%-CI:0.3-1.7%, I²=0%, P=0.800). There was non-significant negative association between prevalence and malignancy rates (P=0.077). Malignant lesions were diagnosed at all follow-up time points.

Conclusion

While prevalence of MRI BI-RADS 3 lesions was strongly heterogeneous, pooled malignancy rates met BI-RADS benchmarks (<2%). Malignancy rates varied, exceeding 2% in non-mass lesions. Twenty-four-month surveillance is required to detect all malignant lesions.

Key points

• Probably benign (BI-RADS 3) lesions showed a pooled malignancy-rate of 1.6% (95%-CI:0.9-2.3%).

• Malignancy rates differ and are highest in non-mass lesions (2.3%, 95%-CI:0.8-3.9%).

• The prevalence of BI-RADS 3 lesions on breast MRI ranged from 1.2-24.3%.

• Malignant lesions were diagnosed at follow-up time points up to 24 months.

The Fascist Seduction of Narrative: Walter Benjamin’s Historical Materialism Beyond Counter-Narrative

Abstract

This essay introduces Walter Benjamin's historical materialism to illuminate how history teachers may invoke a critique of the past and present through democratizing the production of knowledge in the classroom. Historical materialism gives students access to the means of knowledge production and entrusts them with the task of generating a critique of politics though encounters with historical objects. The rise of the alt-right, alternative facts, and fake news sites necessitates social studies methods that intervene into the fascist seductions of narrative in history. A Benjaminian pedagogy emphasizes reading practices that acknowledge the political layers of history inscribed within the objects. This generates space for forms of pessimism and dialectic critiques of barbarism that students may experience with history beyond the teacher's capacity for understanding. In the name of democracy over fascism, the article adds a political critique to students' historical and critical thinking skills.

Effect of Fluid Intake on Hydration Status and Skin Barrier Characteristics in Geriatric Patients: An Explorative Study

Background/Aim: Inadequate fluid intake is assumed to be a trigger of water-loss dehydration, which is a major health risk in aged and geriatric populations. Thus, there is a need to search for easy to use diagnostic tests to identify dehydration. Our overall aim was to investigate whether skin barrier parameters could be used for predicting fluid intake and/or hydration status in geriatric patients. Methods: An explorative observational comparative study was conducted in a geriatric hospital including patients aged 65 years and older. We measured 3-day fluid intake, skin barrier parameters, Overall Dry Skin Score, serum osmolality, cognitive and functional health, and medications. Results: Forty patients were included (mean age 78.45 years and 65% women) with a mean fluid intake of 1,747 mL/day. 20% of the patients were dehydrated and 22.5% had an impending dehydration according to serum osmolality. Multivariate analysis suggested that skin surface pH and epidermal hydration at the face were associated with fluid intake. Serum osmolality was associated with epidermal hydration at the leg and skin surface pH at the face. Fluid intake was not correlated with serum osmolality. Diuretics were associated with high serum osmolality. Conclusions: Approximately half of the patients were diagnosed as being dehydrated according to osmolality, which is the current reference standard. However, there was no association with fluid intake, questioning the clinical relevance of this measure. Results indicate that single skin barrier parameters are poor markers for fluid intake or osmolality. Epidermal hydration might play a role but most probably in combination with other tests.
Skin Pharmacol Physiol 2018;31:155–162

Contribution to the understanding of biologic concentrations of arsenic in children living in an urban area from Rio de Janeiro, Brazil

Abstract

There are few studies about children's environmental exposure to arsenic (As) in Brazil, most of them being in mining regions. The objective of this study was to contribute to the understanding of biologic concentrations of arsenic in children living in an urban area, in Brazil. A study of arsenic concentrations in capillary blood (n = 270), nail (n = 261), and urine (n = 99) samples, in male and female children, 8 to 10 years old, from two public schools in Rio de Janeiro, was conducted. Socio-economic and health data were obtained through questionnaires. The nail and capillary blood analysis were performed by inductively coupled plasma mass spectrometry (ICP-MS), while urine samples were analyzed using hydride generation atomic absorption spectrometry (HG-AAS). The median, geometric mean, and 95th percentiles of total arsenic concentrations were, respectively, 2.53, 2.40, and 3.58 μg/L in capillary blood; 0.09, 0.10, and 0.24 μg/g in nails; and 12.50, 10.97, and 39.45 μg/L in urine. The geometric mean of urinary arsenic level was above the values reported by international surveys for non-exposed populations. The arsenic concentrations in nails were compatible with the values found in national studies. These outcomes can contribute to the increase of knowledge on biologic concentrations of arsenic in children living in urban areas, in Brazil.

Characterization of toluene metabolism by methanotroph and its effect on methane oxidation

Abstract

Methanotrophs not only oxidize CH₄, but also can oxidize a relatively broad range of other substrates, including trichloroethylene, alkanes, alkenes, and aromatic compounds. In this study, Methylosinus sporium was used as a model organism to characterize toluene metabolism by methanotrophs. Reverse transcription quantitative PCR analysis showed that toluene enhanced the mmoX expression of M. sporium. When the toluene concentration was below 2000 mg m⁻³, the kinetics of toluene metabolism by M. sporium conformed to the Michaelis-Menten equation (V_max = 0.238 g g_{dry weight}⁻¹ h⁻¹, K_m  = 545.2 mg m⁻³). The use of a solid-phase extraction technique followed by a gas chromatography-mass spectrometry analysis and molecular docking calculation showed that toluene was likely to primarily bind the di-iron center structural region of soluble methane monooxygenase (sMMO) hydroxylase and then be oxidized to o-cresol. Although M. sporium oxidized toluene, it did not incorporate toluene into its biomass. The coexistence of toluene and CH₄ could influence CH₄ oxidation, the growth of methanotrophs, and the distribution of CH₄-derived carbon, which were related to the ratio of the toluene concentration to biomass. These results would be helpful to understand the metabolism of CH₄ and non-methane volatile organic compounds in the environment.

Variation laws and release characteristics of phosphorus on surface sediment of Dongting Lake

Abstract

The variation trend and growth rate of P were analyzed by the concentration of the phosphorus fraction on surface sediment of Dongting Lake from 2012 to 2016, to reveal the cumulative effect of P in the actual environment. Meanwhile, the adsorption kinetics and adsorption isotherm were employed to examine the P-release possibility of sediment, which predicts the yearly released sediment phosphorus in Dongting Lake. The actual growth rate of TP (Total Phosphorus) is 53 mg·(kg·year)⁻¹ in East Dongting Lake, 39 mg·(kg·year)⁻¹ in South Dongting Lake, and 29 mg·(kg·year)⁻¹ in West Dongting Lake, while the sum of the phosphorus fraction growth rates has little difference from the rate of TP in sediments of the three areas of Dongting Lake. Furthermore, the Elovich model and the Langmuir crossover-type equations are established to present the adsorption characteristic of sediment in Dongting Lake; the result shows that the sediments play a source role for phosphorus in East and South Dongting Lake from zero equilibrium phosphorus concentration (EPC₀) in the present situation, but an adsorption effect on TP is shown in West Dongting Lake. When the conditions of environment change are ignored, the maximum P-sorption level in sediments of East Dongting Lake will reach in 2040 according to the actual growth rate of sediments, while that in West Dongting Lake and South Dongting Lake will be in 2046 and 2061, respectively.

Ipseity at the Intersection of Phenomenology, Psychiatry and Philosophy of Mind: Are we Talking about the Same Thing?

Abstract

In recent years, phenomenologically informed philosophers, psychologists and psychiatrists have attempted to import philosophical notions associated with the self into the empirical study of pathological (self-)experience. In particular, so-called ipseity disturbances have been put forward as generative of symptoms of schizophrenia, and several attempts have been made to operationalize and measure kinds and degrees of ipseity disturbances in schizophrenia. However, we find that this work faces challenges caused by the fact that (a) the notion of ipseity is used ambiguously, both in the philosophical and in the empirical discussion, and (b) the methods employed to operationalize ipseity often portray a rather different understanding of the notion from that found in the (phenomenological) literature that is cited as providing the philosophical foundation for the studies in question. In particular, according to the definitions found in the philosophical literature, while being phenomenologically available, the self is not represented in ipseity. However, when it comes to the empirical study of ipseity and its disturbances, the object of investigation is often a kind of explicit self-representation. As a result, it is unclear whether different researchers are really talking about the same thing. Future progress in this area will require more careful conceptual distinctions; the present article aims to contribute to this task.

The Microbiome and Population Health: Considerations to Enhance Study Design and Data Analysis in Observational and Interventional Epidemiology

Abstract

Measurement and characterization of the human microbiome in large population-based human studies has recently become a reality secondary to technological advances in high throughput DNA sequencing. These advances bring new challenges and knowledge gaps for study planning, data analysis and interpretation that are novel to large-scale epidemiological studies. In this issue of The Journal, Sinha et al. have provided data to inform statistical power and sample size requirements for microbiome studies in population-based settings. This work serves as a helpful starting point for study planning while also serving as a springboard for discussion regarding additional considerations for improving microbiome research. This commentary emphasizes the importance of selecting microbiome metrics appropriate for the biological hypothesis under investigation as well as the need for new analytical tools that can better capitalize on the unique, yet rich, information contained in microbiome data sets.

Commentary on the “Evidence- and Consensus-Based (S3) Guidelines for the Treatment of Actinic Keratosis” Published by the International League of Dermatological Societies in Cooperation with the European Dermatology Forum

In 2015, the International League of Dermatological Societies and the European Dermatology Forum published a guideline for the treatment of actinic keratosis, which is classified as an evidence- and consensus-based S3 guideline. From the point of view of the GD Task Force "Licht.Hautkrebs.Prävention," an interdisciplinary expert panel of the Society for Dermopharmacy for the prevention and treatment of skin cancer, this guideline reveals strengths and weaknesses but, in summary, does not meet the claim for an evidence- and consensus-based S3 guideline.
Skin Pharmacol Physiol 2018;31:144–146

Correction to: On Harman’s theory of knowledge

Abstract

In the original publication of the article, the corresponding author used pseudonym as 'M. Lisagor'. The correct name is given in this correction.

Cutis laxa associated monoclonal gammopathy: 14 new cases and review of the literature

Publication date: Available online 3 April 2018
Source:Journal of the American Academy of Dermatology
Author(s): Marie Jachiet, Stéphanie Harel, Anne Saussine, Maxime Battistella, Michel Rybojad, Bouchra Asli, Djaouida Bengoufa, Thibault Mahevas, Didier Bessis, Lionel Galicier, Jean-Luc Schmutz, Smail Hadj-Rabia, David Boutboul, Céleste Lebbé, Martine Bagot, Marion Malphettes, Dan Lipsker, Jean-Paul Fermand, Jean-David Bouaziz, Bertrand Arnulf

Adding A New Analytical Procedure With Clinical Interpretation in the Tool Box of Survival Analysis

The Way Things Look: a Defence of Content

Abstract

How does perceptual experience disclose the world to our view? In the first introductory section, I set up a contrast between the representational and the purely relational conception of perceptual experience. In the second section, I discuss an argument given by Charles Travis (Mind 113: 57–94, 2004) against perceptual content. The third section is devoted to the phenomenon of perceptual constancy: in 3.1 I describe the phenomenon. In 3.2 I argue that the description given suggests a phenomenological distinction that can be deployed for a defence of content. In 3.3 I compare and contrast my view of perceptual content with that of Susanna Schellenberg (The Journal of Philosophy 105(02): 55–84, 2008). Finally (3.4), I support my conception of content by means of an argument that links content to the way in which the mind-independent nature of material objects is manifest in perceptual experience.

Optimizing the use of topical retinoids in Asian acne patients

The Journal of Dermatology, EarlyView.