Selenium (Se) uptake and dynamic changes of Se content in soil–plant systems

Abstract

In this study, we collected crop plants and associated soil samples and determined these for selenium (Se) content to analyze the uptake, enrichment, and translocation of Se in the different soil–plant systems of an agricultural production area, elucidate the dynamic mechanisms relating to Se content in plants and soil during different growth periods, and screen plants for high Se enrichment ability. Bioconcentration factor determinations indicated that the grains of rice have the strongest Se enrichment ability, followed by soybean and corn. Translocation factor analysis indicated that the grains of rice and corn have similar low translocation abilities for Se compared with soybean. Within the study area, the Se content in plants was closely related to the soil available Se content and varied considerably among different growth periods and plant organs. This study provides a theoretical basis for the development and utilization of local agricultural products.

European headache federation guideline on idiopathic intracranial hypertension

Idiopathic Intracranial Hypertension (IIH) is characterized by an elevation of intracranial pressure (ICP no identifiable cause. The aetiology remains largely unknown, however observations made in a number of ...

Characterization of composted sewage sludge during the maturation process: a pilot scale study

Abstract

This paper determines the impact of the maturation process of composted sewage sludge on the quality of the final product and assesses the stabilization effect. The samples of composted sewage sludge were taken from a wastewater treatment plant located in Pomerania in northern Poland. The sewage sludge was composted in an open windrow composting plant with the addition of straw and wood chips in the turning windrow. The aeration of the sewage sludge mixture was conducted based on two methods. The first phase (intensive degradation phase of 6 to 8 weeks) was characterized by frequently turning; the second phase for maturation used aeration channels (2 to 3 months). In three sampling campaigns samples were taken from the same windrow after 2 (no. 1), 8 (no. 2), and 12 weeks (no. 3) of maturation. Fresh samples were used for analyzing the stabilization parameter as static respiration activity (AT₄). Furthermore, the values of pH, organic matter (OM), total organic carbon (TOC), elementary composition, nutrients, total content, and mobile forms of heavy metals were analyzed in the compost samples. A significant decrease was found in the stabilization parameter (AT₄) during the maturation of tested materials. In turn, no significant differences were found in the elementary composition. The concentration of most metals increased in the final product. The total content of heavy metals in the final product did not exceed the limit values for the agricultural use of sewage sludge, compost from municipal waste, and for organic fertilizers. There were no significant changes in the percentage of bioavailable and mobile forms of heavy metals during compost maturation. Zinc was characterized by the highest level of mobile and bioavailable forms, which may cause bioaccumulation after the fertilization of soil. The study has shown that the process of maturation of compost from sewage sludge not affects changes in the content of heavy metal forms. The scope of this study has been planned on a wider scale for different variants of sewage sludge composting, in order to evaluate the process.

Managing Periocular Filler-Related Syndrome Prior to Lower Blepharoplasty

Abstract

Background

Hyaluronic acid (HA) fillers are extensively used in periocular volume augmentation. Although they have an excellent safety profile, filler-related issues such as visibility/palpability, contour abnormalities, malar edema, and blue-gray dyschromia can occur. Recognition and management of filler-related issues are critical prior to subsequent procedures. The clinical course of patients who had periocular HA filler-related issues and subsequently underwent lower eyelid blepharoplasty is described.

Methods

HA filler was dissolved with hyaluronidase (15–30 U/cm²) treatment. Visible lower eyelid fat prolapse after filler removal was corrected with transconjunctival blepharoplasty with fat repositioning and skin resurfacing. Complications and outcome were assessed and recorded.

Results

Twenty-three patients (46 eyelids) were treated. All presented with contour abnormalities, 19 with contour abnormalities and malar edema, and seven with blue-gray dyschromia. In 15 patients, one session of hyaluronidase completely dissolved the filler, and in eight patients, two sessions were required. Of these eight patients, edema resolved after the second hyaluronidase injection in four; in the remaining four, mild edema persisted despite absence of visible/palpable filler. Postblepharoplasty, 19 patients had an acceptable outcome with no complications (82.6%). Four patients had prolonged edema postoperatively; three had a resolution by 6 months. In 23 patients who had skin resurfacing procedures, there was no incidence of postinflammatory hyperpigmentation.

Conclusions

HA filler-related issues need to be identified and managed prior to further intervention. Hyaluronidase treatment effectively dissolves the filler, but mild malar edema can persist. Outcomes are acceptable after subsequent blepharoplasty, but adequate patient counseling is necessary about expectations and limitations.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Refinements in Tear Trough Deformity Correction: Intraoral Release of Tear Trough Ligaments: Anatomical Consideration and Clinical Approach

Abstract

Background

Correction of tear trough (TT) deformity is a crucial aspect of facial rejuvenation. Because the anatomical origins of TT deformity lie in the TT ligaments, which firmly attach the dermis to the periosteum, the release of TT ligaments should be considered when performing an etiological correction. The aim of this paper is to propose an alternative method for TT deformity correction, comprising use of filler together with the release of TT ligaments. This technique was compared to the procedure of only percutaneous filler.

Methods

From January 2014 to December 2015, 10 patients were enrolled in the study for recurrence of TT deformity. All the patients underwent TT ligament release and filler injections; all had been previously treated with percutaneous hyaluronic acid injection without ligament release. Under local anesthesia, the TT ligaments were detached using a blunt cannula introduced directly in the supra periosteal plane through an intraoral access. Once the ligament was released, the TT depression was evenly recontoured with a very small amount of filler. The clinical data, digital images, evaluations of outcomes, including patient satisfaction rates were collected and compared.

Results

Adding the procedure of TT ligament release to filler injections showed satisfactory results, avoiding an unnatural puffy appearance. The comparison between the two different methods showed improved outcomes and increased patient satisfaction with minor patient discomfort among those who underwent TT ligament release.

Conclusion

Because TT ligaments are among the etiologic factors of TT deformity, they have a strong impact on procedures that are designed to improve TT deformity; therefore, TT ligament release should always be considered to obtain satisfactory, natural results.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Studying Controversies: Unification, Contradiction, Integration

Abstract

My aim here is to show that approximate truth as a paraconsistent notion (neutral to the realism/anti-realism debate) can be successfully incorporated into the analysis of scientific unification, thus advancing towards a more realistic representation of theory development that takes into account the controversies that often loom alongside the progress of research programmes. I support my analysis with a case study of the recent debate in ecology centred around the existence of the paradox of enrichment and the controversy between ecological models of predation that employ prey-dependent and ratio-dependent functional responses. These models were initially proposed as equally good representations of the basic aspects of predator–prey dynamics. However, both models generated inconsistent observational consequences and, therefore, introduced a contradiction within predator–prey theory. I argue that by accepting these models as approximately true representations of predator–prey dynamics we can convey how the available observational data have been successfully systematized in a consistent way under them. This first step in resolving the controversy relied on building a series of contrastive arguments based on both models' derivations about population dynamics and the available empirical data. The heightening of this contrast between the models, in turn, was also essential in defining a limiting function which can be used to integrate both models and reach a new unified expression of predator–prey dynamics.

Evaluation of Escherichia coli pathotypes associated with Irritable Bowel Syndrome

Abstract

Irritable Bowel Syndrome (IBS) affects 10–20% of people. Increased numbers of Escherichia coli (E. coli) correlate with symptoms, and patients respond to antimicrobials targeting E. coli. We examined whether specific E. coli strains, phylogroups and pathotypes are associated with IBS. We evaluated 218 E. coli isolates from 33 IBS patients and 23 healthy controls. RAPD analysis revealed 89 E. coli strains (29 controls, 60 IBS), spanning the A, B1, B2, D phylogroups. Strains were similarly enriched in virulence genes associated with extraintestinal pathogenic E.coli (ExPEC) and/or adherent-invasive E.coli (AIEC). Three strains harbored a diarrheagenic virulence gene (2 IBS, 1 control). E. coli capable of invading epithelial cells or replicating in macrophages were detected in 53% of IBS and 50% controls, and 67% IBS and 45% controls respectively (P>0.05). AIEC were identified in 33% of IBS patients vs. 20% of controls (P=0.35). Virulence genes ibeA, ColV and pduC were associated with intramacrophage persistence; ibeA and ColV were associated with epithelial invasion and AIEC pathotype (P<0.05). IBS patients and controls are commonly colonized by E. coli that resemble ExPEC and display pathogen-like behavior in vitro, similar to CD-associated AIEC. The relationship of these resident pathosymbiont E. coli to IBS warrants further investigation.

Quantitative proteomic analysis of xylose fermentation strain Pichia stipitis CBS 5776 to lignocellulosic inhibitors acetic acid, vanillin, and 5-hydroxymethylfurfural

Abstract

To obtain a global insight into the dynamic protein expression pattern in Pichia stipitis during xylose fermentation in the presence of three representative inhibitors (acetic acid, vanillin, and 5-hydroxymethylfurfural), proteins were extracted for quantitative proteomic analysis using 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) on a liquid chromatography-mass/mass spectrometry (LC-MS/MS) instrument. Interestingly, aconitase (Aco1p) and NAD-isocitrate dehydrogenase (Idh1p), were upregulated during the middle exponential phase in the presence of the three inhibitors during tricarboxylic acid (TCA) cycle. We speculated that yeast cells adaptively increased the expression of the TCA cycle proteins to compensate for low NADH derived from glycolysis in the presence of the three inhibitors. Proteins related to amino acid metabolism, aminoacyl tRNA synthesis, and stress response were also significantly affected in the presence of the three inhibitors. Taken together, quantitative proteomic analysis is capable of monitoring P. stipitis xylose fermentation under inhibitor conditions and identifying physiological changes, such as stress response.

Streptomyces protein secretion and its application in biotechnology

Abstract

Bacteria are of tremendous importance in the pharma- and bio-industry as producers of a broad range of economically interesting metabolites and proteins. Gram-positive bacteria are valuable hosts for the production of heterologous proteins for obvious reasons. Contrary to Gram-negative bacteria, Gram-positive bacteria release their secreted proteins immediately into the spent culture broth as they are not hindered by an outer membrane. Secretory protein production also avoids the formation of inclusion bodies, hence facilitating downstream processing. Eight protein secretion pathways have been described in Gram-positive bacteria, but solely the general secretion or Sec pathway, and to a lesser extent, the Twin-arginine pathway are used for the recombinant protein production. This process is not always successful, but might be hampered by inefficient secretion, misfolding of the recombinant protein, its degradation by proteases and metabolic burden by the host hindering proper growth and diminishing product yield. In this review, the different protein export avenues will be briefly discussed, and the potential means to optimize protein secretion and yields for the Streptomyces lividans model presented. The proposed approaches are largely applicable for other Streptomyces host systems.

Extraction of open-state mitral valve geometry from CT volumes

Abstract

Purpose

The importance of mitral valve therapies is rising due to an aging population. Visualization and quantification of the valve anatomy from image acquisitions is an essential component of surgical and interventional planning. The segmentation of the mitral valve from computed tomography (CT) acquisitions is challenging due to high variation in appearance and visibility across subjects. We present a novel semi-automatic approach to segment the open-state valve in 3D CT volumes that combines user-defined landmarks to an initial valve model which is automatically adapted to the image information, even if the image data provide only partial visibility of the valve.

Methods

Context information and automatic view initialization are derived from segmentation of the left heart lumina, which incorporates topological, shape and regional information. The valve model is initialized with user-defined landmarks in views generated from the context segmentation and then adapted to the image data in an active surface approach guided by landmarks derived from sheetness analysis. The resulting model is refined by user landmarks.

Results

For evaluation, three clinicians segmented the open valve in 10 CT volumes of patients with mitral valve insufficiency. Despite notable differences in landmark definition, the resulting valve meshes were overall similar in appearance, with a mean surface distance of \(1.62 \pm 2.10\) mm. Each volume could be segmented in 5–22 min.

Conclusions

Our approach enables an expert user to easily segment the open mitral valve in CT data, even when image noise or low contrast limits the visibility of the valve.

A patient-specific haptic drilling simulator based on virtual reality for dental implant surgery

Abstract

Purpose

In the dental implant surgery, there are inevitable risks due to the anatomically complex operation in the cranio-maxillofacial region. Therefore, there is a trend to use computer-aided technology to simulate the process of the implant surgery. In this study, we present a haptic simulator for trainees to study and rehearse the drilling performance of dental implant surgery.

Materials and methods

The dental implant surgery simulator (DISS) is developed based on the haptic force-feedback device Omega.6, and some free open-source software libraries such as Computer Haptics and Active Interface (CHAI3D), Qt and Visualization Toolkit. To achieve the desired effects of drilling, the meshes are subdivided with a recursive algorithm which breaks down a triangular patch into 4 sub-triangles. The drilling operation can be implemented at any specified location of the model. Once the drilling direction is determined, the position and rotation of the haptic device tool are constrained to the orientation through a dimension reduction algorithm. The driller diameter and drill speed are tunable to implement stepwise drilling for the patient-specific models.

Results

A patient-specific drilling simulator based on virtual reality for dental implant surgery is presented. The simulation of stepwise drilling was conducted, and three patient-specific models reconstructed by Computed Tomography data were employed to help the novices to find the suitable drilling parameter.

Conclusion

The obtained results showed that the haptic-based DISS could simulate various dental implant surgeries with different driller diameter and drill speed which takes patient-specific models as input. The evaluation of the DISS proves its good performance and it could provide an effective method to improve the skills and experiences of trainees.

Accuracy of computer-aided design models of the jaws produced using ultra-low MDCT doses and ASIR and MBIR

Abstract

Purpose

To compare the surface of computer-aided design (CAD) models of the maxilla produced using ultra-low MDCT doses combined with filtered backprojection (FBP), adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR) reconstruction techniques with that produced from a standard dose/FBP protocol.

Methods

A cadaveric completely edentulous maxilla was imaged using a standard dose protocol (CTDIvol: 29.4 mGy) and FBP, in addition to 5 low dose test protocols (LD1-5) (CTDIvol: 4.19, 2.64, 0.99, 0.53, and 0.29 mGy) reconstructed with FBP, ASIR 50, ASIR 100, and MBIR. A CAD model from each test protocol was superimposed onto the reference model using the 'Best Fit Alignment' function. Differences between the test and reference models were analyzed as maximum and mean deviations, and root-mean-square of the deviations, and color-coded models were obtained which demonstrated the location, magnitude and direction of the deviations.

Results

Based upon the magnitude, size, and distribution of areas of deviations, CAD models from the following protocols were comparable to the reference model: FBP/LD1; ASIR 50/LD1 and LD2; ASIR 100/LD1, LD2, and LD3; MBIR/LD1. The following protocols demonstrated deviations mostly between 1–2 mm or under 1 mm but over large areas, and so their effect on surgical guide accuracy is questionable: FBP/LD2; MBIR/LD2, LD3, LD4, and LD5. The following protocols demonstrated large deviations over large areas and therefore were not comparable to the reference model: FBP/LD3, LD4, and LD5; ASIR 50/LD3, LD4, and LD5; ASIR 100/LD4, and LD5.

Conclusions

When MDCT is used for CAD models of the jaws, dose reductions of 86% may be possible with FBP, 91% with ASIR 50, and 97% with ASIR 100. Analysis of the stability and accuracy of CAD/CAM surgical guides as directly related to the jaws is needed to confirm the results.

Modular force approximating soft robotic pneumatic actuator

Abstract

Purpose

Soft robots are highly flexible and adaptable instruments that have proven extremely useful, especially in the surgical environment where compliance allows for improved maneuverability throughout the body. Endoscopic devices are a primary example of an instrument that physicians use to navigate to difficult-to-reach areas inside the body. This paper presents a modular soft robotic pneumatic actuator as a proof of concept for a compliant endoscopic device.

Methods

The actuator is 3D printed using an FDM printer. Maximum bending angle is measured using image processing in MATLAB at a gauge pressure level of 35 psi. End-effector displacement is measured using electromagnetic tracking as gauge pressure ranges from 10 to 35 psi, and uniaxial tensile loading ranges from 0 to 120 g.

Results

The actuator achieves a maximum bending angle of 145°. Fourth-order polynomial regression is used to model the actuator displacement upon inflation and tensile loading with an average coefficient of correlation value of 0.998. We also develop a feedforward neural network as a robust computer-assisted method for controlling the actuator that achieves a coefficient of correlation value of 0.996.

Conclusion

We propose a novel modular soft robotic pneumatic actuator that is developed via rapid prototyping and evaluated using image processing and machine learning models. The curled resting shape allows for simple manufacturing and achieves a greater range of bending than other actuators of its kind. A feedforward neural network provides accurate prediction of end-effector displacement upon inflation and loading to deliver precise manipulation and control.

Development of a shoulder-mounted robot for MRI-guided needle placement: phantom study

Abstract

Purpose

This paper presents new quantitative data on a signal-to-noise ratio (SNR) study, distortion study, and targeting accuracy phantom study for our patient-mounted robot (called Arthrobot). Arthrobot was developed as an MRI-guided needle placement device for diagnostic and interventional procedures such as arthrography.

Methods

We present the robot design and inverse kinematics. Quantitative assessment results for SNR and distortion study are also reported. A respiratory motion study was conducted to evaluate the shoulder mounting method. A phantom study was conducted to investigate end-to-end targeting accuracy. Combined error considering targeting accuracy, respiratory motion, and structure deformation is also reported.

Results

The SNR study showed that the SNR changes only 2% when the unpowered robot was placed on top of a standard water phantom. The distortion study showed that the maximum distortion from the ground truth was 2.57%. The average error associated with respiratory motion was 1.32 mm with standard deviation of 1.38 mm. Results of gel phantom targeting studies indicate average needle placement error of 1.64 mm, with a standard deviation of 0.90 mm.

Conclusions

Noise and distortion of the MR images were not significant, and image quality in the presence of the robot was satisfactory for MRI-guided targeting. Combined average total error, adding mounting stability errors and structure deformation errors to targeting error, is estimated to be 3.4 mm with a standard deviation of 1.65 mm. In clinical practice, needle placement accuracy under 5 mm is considered sufficient for successful joint injection during shoulder arthrography. Therefore, for the intended clinical procedure, these results indicate that Arthrobot has sufficient positioning accuracy.

Deep dense multi-path neural network for prostate segmentation in magnetic resonance imaging

Abstract

Purpose

We propose an approach of 3D convolutional neural network to segment the prostate in MR images.

Methods

A 3D deep dense multi-path convolutional neural network that follows the framework of the encoder–decoder design is proposed. The encoder is built based upon densely connected layers that learn the high-level feature representation of the prostate. The decoder interprets the features and predicts the whole prostate volume by utilizing a residual layout and grouped convolution. A set of sub-volumes of MR images, centered at the prostate, is generated and fed into the proposed network for training purpose. The performance of the proposed network is compared to previously reported approaches.

Results

Two independent datasets were employed to assess the proposed network. In quantitative evaluations, the proposed network achieved 95.11 and 89.01 Dice coefficients for the two datasets. The segmentation results were robust to variations in MR images. In comparison experiments, the segmentation performance of the proposed network was comparable to the previously reported approaches. In qualitative evaluations, the segmentation results by the proposed network were well matched to the ground truth provided by human experts.

Conclusions

The proposed network is capable of segmenting the prostate in an accurate and robust manner. This approach can be applied to other types of medical images.

Real-time microrobot posture recognition via biplane X-ray imaging system for external electromagnetic actuation

Abstract

Purpose

As a promising intravascular therapeutic approach for autonomous catheterization, especially for thrombosis treatment, a microrobot or robotic catheter driven by an external electromagnetic actuation system has been recently investigated. However, the three-dimensional (3D) real-time position and orientation tracking of the microrobot remains a challenge for precise feedback control in clinical applications owing to the micro-size of the microrobot geometry in vessels, along with bifurcation and vulnerability. Therefore, in this paper, we propose a 3D posture recognition method for the unmanned microrobotic surgery driven by an external electromagnetic actuator system.

Methods

We propose a real-time position and spatial orientation tracking method for a millimeter-sized intravascular object or microrobot using a principal component analysis algorithm and an X-ray reconstruction. The suggested algorithm was implemented to an actual controllable wireless microrobot system composed of a bullet-shaped object, a biplane X-ray imaging device, and an electromagnetic actuation system. Numerical computations and experiments were conducted for the performance verification.

Results

The experimental results showed a good performance of the implemented system with tracking errors less than 0.4 mm in position and 2° in orientation. The proposed tracking technique accomplished a fast processing time, ~ 0.125 ms/frame, and high-precision recognition of the micro-sized object.

Conclusions

Since the suggested method does not require pre-information of the object geometry in the human body for its 3D shape and position recognition, it could be applied to various elliptical shapes of the microrobot system with computation time efficacy and recognition accuracy. Hence, the method can be used for therapeutic millimeter- or micron-sized manipulator recognition in vascular, as well as implanted objects in the human body.

Development and internal validation of an aneurysm rupture probability model based on patient characteristics and aneurysm location, morphology, and hemodynamics

Abstract

Purpose

Unruptured cerebral aneurysms pose a dilemma for physicians who need to weigh the risk of a devastating subarachnoid hemorrhage against the risk of surgery or endovascular treatment and their complications when deciding on a treatment strategy. A prediction model could potentially support such treatment decisions. The aim of this study was to develop and internally validate a model for aneurysm rupture based on hemodynamic and geometric parameters, aneurysm location, and patient gender and age.

Methods

Cross-sectional data from 1061 patients were used for image-based computational fluid dynamics and shape characterization of 1631 aneurysms for training an aneurysm rupture probability model using logistic group Lasso regression. The model's discrimination and calibration were internally validated based on the area under the curve (AUC) of the receiver operating characteristic and calibration plots.

Results

The final model retained 11 hemodynamic and 12 morphological variables, aneurysm location, as well as patient age and gender. An adverse hemodynamic environment characterized by a higher maximum oscillatory shear index, higher kinetic energy and smaller low shear area as well as a more complex aneurysm shape, male gender and younger age were associated with an increased rupture risk. The corresponding AUC of the model was 0.86 (95% CI [0.85, 0.86], after correction for optimism 0.84).

Conclusion

The model combining variables from various domains was able to discriminate between ruptured and unruptured aneurysms with an AUC of 86%. Internal validation indicated potential for the application of this model in clinical practice after evaluation with longitudinal data.

Semiautomatic neck curve reconstruction for intracranial aneurysm rupture risk assessment based on morphological parameters

Abstract

Purpose

Morphological parameters of intracranial aneurysms (IAs) are well established for rupture risk assessment. However, a manual measurement is error-prone, not reproducible and cumbersome. For an automatic extraction of morphological parameters, a 3D neck curve reconstruction approach to delineate the aneurysm from the parent vessel is required.

Methods

We present a 3D semiautomatic aneurysm neck curve reconstruction for the automatic extraction of morphological parameters which was developed and evaluated with an experienced neuroradiologist. We calculate common parameters from the literature and include two novel angle-based parameters: the characteristic dome point angle and the angle difference of base points.

Results

We applied our method to 100 IAs acquired with rotational angiography in clinical routine. For validation, we compared our approach to manual segmentations yielding highly significant correlations. We analyzed 95 of these datasets regarding rupture state. Statistically significant differences were found in ruptured and unruptured groups for maximum diameter, maximum height, aspect ratio and the characteristic dome point angle. These parameters were also found to statistically significantly correlate with each other.

Conclusions

The new 3D neck curve reconstruction provides robust results for all datasets. The reproducibility depends on the vessel tree centerline and the user input for the initial dome point and parameters characterizing the aneurysm neck region. The characteristic dome point angle as a new metric regarding rupture risk assessment can be extracted. It requires less computational effort than the complete neck curve reconstruction.

Model checking for trigger loss detection during Doppler ultrasound-guided fetal cardiovascular MRI

Abstract

Purpose

Ultrasound (US) is the state of the art in prenatal diagnosis to depict fetal heart diseases. Cardiovascular magnetic resonance imaging (CMRI) has been proposed as a complementary diagnostic tool. Currently, only trigger-based methods allow the temporal and spatial resolutions necessary to depict the heart over time. Of these methods, only Doppler US (DUS)-based triggering is usable with higher field strengths. DUS is sensitive to motion. This may lead to signal and, ultimately, trigger loss. If too many triggers are lost, the image acquisition is stopped, resulting in a failed imaging sequence. Moreover, losing triggers may prolong image acquisition. Hence, if no actual trigger can be found, injected triggers are added to the signal based on the trigger history.

Method

We use model checking, a technique originating from the computer science domain that formally checks if a model satisfies given requirements, to simultaneously model heart and respiratory motion and to decide whether respiration has a prominent effect on the signal. Using bounds on the physiological parameters and their variability, the method detects when changes in the signal are due to respiration. We use this to decide when to inject a trigger.

Results

In a real-world scenario, we can reduce the number of falsely injected triggers by 94% from more than 87% to less than 5%. On a subset of motion that would allow CMRI, the number can be further reduced to below 0.2%. In a study using simulations with a robot, we show that our method works for different types of motions, motion ranges, starting positions and heartbeat traces.

Conclusion

While DUS is a promising approach for fetal CMRI, correct trigger injection is critical. Our model checking method can reduce the number of wrongly injected triggers substantially, providing a key prerequisite for fast and artifact free CMRI.

Priority monism, dependence and fundamentality

Abstract

Priority monism (PM) is roughly the view that the universe is the only fundamental object, that is, a concrete object that does not depend on any other concrete object. Schaffer, the main advocate of PM, claims that PM is compatible with dependence having two different directions: from parts to wholes for subcosmic wholes, and from whole to parts for the cosmic whole. Recently it has been argued that this position is untenable. Given plausible assumptions about dependence, PM entails that dependence has only one direction, it always goes from wholes to parts. One such plausible assumption is a principle of Isolation. I argue that, given all extant accounts of dependence on the market, PM entails No Isolation. The argument depends upon a particular feature of the dependence relation, namely, necessitation and its direction. In the light of this, I contend that the argument is important, insofar as it suggests that we should distinguish dependence from other cognate notions, e.g. grounding. Once this distinction is made, I suggest we should also distinguish between two different notions of fundamentality that might turn out to be not-coextensive.

Longitudinal Findings of MRI and PET in West Syndrome with Subtle Focal Cortical Dysplasia [PEDIATRICS]

BACKGROUND AND PURPOSE:

Despite the development of neuroimaging, identification of focal cortical dysplasia remains challenging. The purpose of this study was to show the longitudinal changes of MR imaging and FDG-PET in patients with West syndrome and subtle focal cortical dysplasia.

MATERIALS AND METHODS:

Among 52 consecutive patients with West syndrome, 4 were diagnosed with subtle focal cortical dysplasia on 3T MR imaging. MR imaging and PET findings were evaluated longitudinally at onset and at 12 and 24 months of age.

RESULTS:

At the onset of West syndrome, MR imaging demonstrated focal signal abnormalities of the subcortical white matter in 2 patients. In the other 2 patients, focal subcortical high-intensity signals became visible on follow-up T2WI as myelination progressed. PET at onset showed focal cortical hypometabolism in 3 patients, with 1 of these patients also having focal hypermetabolism and 1 having normal findings. On PET at 24 months, hypometabolism persisted in 2 patients and disappeared in 1, and hypermetabolism disappeared in 1. In 1 patient with normal MR imaging and PET findings at onset, focal hyperintensity and hypometabolism first appeared at 24 months of age. The findings on MR imaging and PET in these patients evolved differently with brain maturation and the clinical course.

CONCLUSIONS:

Subtle focal cortical dysplasia can be undetectable on MR imaging at the onset of West syndrome and is not always accompanied by hypometabolism or hypermetabolism on PET. Longitudinal MR imaging and PET studies may be useful for detecting such lesions. Even in West syndrome with a congenital structural abnormality, PET findings evolve differently with brain maturation and the clinical condition.

Reply: [LETTERS]

Negative Predictive Value of NI-RADS Category 2 in the First Posttreatment FDG-PET/CT in Head and Neck Squamous Cell Carcinoma [HEAD & NECK]

BACKGROUND AND PURPOSE:

FDG PET/CT has a high negative predictive value in patients with head and neck squamous cell carcinoma who responds completely to non-operative therapy. However, the treatment failure rate in patients with a partial but incomplete response is unclear. Our aim was to investigate the negative predictive value of the first posttreatment FDG-PET/CT in patients with head and neck squamous cell carcinoma with incomplete response interpreted as Neck Imaging Reporting and Data System (NI-RADS) category 2.

MATERIALS AND METHODS:

We retrospectively identified patients with head and neck squamous cell carcinoma treated with chemoradiation or radiation therapy with curative intent in our institution between 2008 and 2016. We included patients whose first posttreatment FDG-PET/CT was interpreted as showing marked improvement of disease but who had a mild residual mass or FDG avidity in either the primary tumor bed or lymph nodes (NI-RADS 2). The negative predictive value of FDG-PET/CT was calculated, including the 95% CI, using the Newcombe method. Two-year disease-free survival was the reference standard.

RESULTS:

Seventeen of 110 patients (15%) experienced locoregional treatment failure within 2 years of completing treatment, yielding a negative predictive value of 85% (95% Cl, 77%–90%). The most common location of tumor recurrence was the cervical lymph nodes (59%). The median time interval between completion of therapy and treatment failure was 10 months (range, 5–24 months).

CONCLUSIONS:

In patients with an incomplete response after treatment of head and neck squamous cell carcinoma, the negative predictive value of the first posttreatment FDG-PET/CT was 85%, which is lower than the 91% negative predictive value of FDG-PET/CT in patients with an initial complete response. Patients with an incomplete response (NI-RADS 2) should undergo more frequent clinical and imaging surveillance than patients with an initial complete response (NI-RADS 1).

Quality-Control Assessment to Improve the Accuracy of Dynamic Contrast-Enhanced MR Imaging Perfusion [LETTERS]

Identification of Hostile Hemodynamics and Geometries of Cerebral Aneurysms: A Case-Control Study [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Hostile hemodynamic conditions and geometries are thought to predispose aneurysms for instability and rupture. This study compares stable, unstable, and ruptured aneurysms while controlling for location and patient characteristics.

MATERIALS AND METHODS:

The hemodynamics and geometries of 165 stable, 65 unstable, and 554 ruptured aneurysms were compared. Hemodynamics was modeled using image-based computational fluid dynamics. Case-control pairs were selected matching aneurysm location, patient age, and sex. Paired Wilcoxon tests were used to compare hemodynamic and geometric variables among different aneurysm groups. The pairing was repeated 100 times, and the combined P values were calculated and adjusted for multiple testing.

RESULTS:

Ruptured aneurysms had lower minimum wall shear stress (P = .03), higher maximum wall shear stress (P = .03), more concentrated (P = .03) and mean oscillatory shear stress (P = .03), higher maximum velocity (P = .03), and more complex flows (vortex core-line length, P = .03) than stable aneurysms. Similarly, unstable aneurysms had more concentrated shear stress (P = .04) and more complex flows (vortex core-line length, P = .04) than stable aneurysms. Compared with stable aneurysms, ruptured aneurysms were larger (size ratio, aneurysm size/vessel size, P = .03), more elongated (aspect ratio, P = .03), and irregular (nonsphericity index, P = .03). Similarly, unstable aneurysms were larger (size ratio, P = .04), more elongated (aspect ratio, P = .04), and irregular (bulge location, P = .04; area-weighted Gaussian curvature; P = .04) than stable aneurysms. No significant differences were found between unstable and ruptured aneurysms.

CONCLUSIONS:

Unstable and ruptured aneurysms have more complex flows with concentrated wall shear stress and are larger, more elongated, and irregular than stable aneurysms, independent of aneurysm location and patient sex and age.

Reply: [LETTERS]

CT versus MR Imaging in Estimating Cochlear Radiation Dose during Gamma Knife Surgery for Vestibular Schwannomas [PATIENT SAFETY]

BACKGROUND AND PURPOSE:

Leksell stereotactic radiosurgery is an effective option for patients with vestibular schwannomas. Some centers use a combination of stereotactic CT fused with stereotactic MR imaging to achieve an optimal target definition as well as minimize the radiation dose delivered to adjacent structures that correlate with hearing outcomes. The present prospective study was designed to determine whether there is cochlear dose variability between MR imaging and CT.

MATERIALS AND METHODS:

Fifty consecutive patients underwent stereotactic radiosurgery for vestibular schwannomas. Dose-planning was performed using high-definition fused stereotactic MR imaging and stereotactic CT images. The 3D cochlear volume was determined by delineating the cochlea on both CT and T2-weighted MR imaging. The mean radiation dose, maximum dose, and 3- and 4.20-Gy cochlear volumes were identified using standard Leksell Gamma Knife software.

RESULTS:

The median mean radiation dose delivered to the cochlea was 3.50 Gy (range, 1.20–6.80 Gy) on CT and 3.40 Gy (range, 1–6.70 Gy) on MR imaging (concordance correlation coefficient = 0.86, r² = 0.9, P ≤ .001). The median maximum dose delivered to the cochlea was 6.7 Gy on CT and 6.6 Gy on MR imaging (concordance correlation coefficient = 0.89, r² = 0.90, P ≤ .001). Dose-volume histograms generated from CT and MR imaging demonstrated a strong level of correlation in estimating the 3- and 4.20-Gy volumes (concordance correlation coefficient = 0.81, r² = 0.82, P ≤ .001 and concordance correlation coefficient = 0.87, r² = 0.89, P ≤ .001).

CONCLUSIONS:

Both MR imaging and CT provide similar cochlear dose parameters. Despite the reported superiority of CT in identifying bony structures, high-definition MR imaging alone is sufficient to identify the radiation doses delivered to the cochlea.

Vertebroplasty: Expectation or Evidence-Based Interventional Radiology? [LETTERS]

Dilated Vein of the Filum Terminale on MRI: A Marker for Deep Lumbar and Sacral Dural and Epidural Arteriovenous Fistulas [SPINE]

BACKGROUND AND PURPOSE:

Conventional MR imaging can provide important clues regarding the location of a spinal vascular malformation. We hypothesized that a dilated vein of the filum terminale, identified as a curvilinear flow void on T2WI, could be an imaging marker for a lower lumbar (L3–L5) or sacral fistula.

MATERIALS AND METHODS:

We retrospectively identified all spinal dural and spinal epidural arteriovenous fistulas from 2 large tertiary referral centers from 2005 to 2018. All patients had a lumbar spinal MR imaging and a conventional spinal angiography. Images were reviewed by 2 neuroradiologists who categorized the level of the arterial feeder to the fistula and the presence or absence of a dilated vein of the filum terminale on T2WI and T1 postcontrast images. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the presence of a dilated filum terminale vein for a deep lumbar or sacral fistula.

RESULTS:

One hundred sixty-two patients were included. An enlarged filum terminale vein was identified in 39 patients. Sensitivity, specificity, positive predictive value, and negative predictive value of the presence of a dilated filum terminale vein for a deep lumbar or sacral fistula were 86%, 98.3%, 94.9%, and 95.1%, respectively.

CONCLUSIONS:

The presence of a dilated vein of the filum terminale can accurately localize a spinal dural arteriovenous fistula/spinal epidural arteriovenous fistula to the lower lumbar or sacral spine in patients being evaluated for such lesions. This finding can be used to facilitate both noninvasive and conventional spinal angiography.

Reply: [LETTERS]

Quantification of Blood Velocity with 4D Digital Subtraction Angiography Using the Shifted Least-Squares Method [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

4D-DSA provides time-resolved 3D-DSA volumes with high temporal and spatial resolutions. The purpose of this study is to investigate a shifted least squares method to estimate the blood velocity from the 4D DSA images. Quantitative validation was performed using a flow phantom with an ultrasonic flow probe as ground truth. Quantification of blood velocity in human internal carotid arteries was compared with measurements generated from 3D phase-contrast MR imaging.

MATERIALS AND METHODS:

The centerlines of selected vascular segments and the time concentration curves of each voxel along the centerlines were determined from the 4D-DSA dataset. The temporal shift required to achieve a minimum difference between any point and other points along the centerline of a segment was calculated. The temporal shift as a function of centerline point position was fit to a straight line to generate the velocity. The proposed shifted least-squares method was first validated using a flow phantom study. Blood velocities were also estimated in the 14 ICAs of human subjects who had both 4D-DSA and phase-contrast MR imaging studies. Linear regression and correlation analysis were performed on both the phantom study and clinical study, respectively.

RESULTS:

Mean velocities of the flow phantom calculated from 4D-DSA matched very well with ultrasonic flow probe measurements with 11% relative root mean square error. Mean blood velocities of ICAs calculated from 4D-DSA correlated well with phase-contrast MR imaging measurements with Pearson correlation coefficient r = 0.835.

CONCLUSIONS:

The availability of 4D-DSA provides the opportunity to use the shifted least-squares method to estimate velocity in vessels within a 3D volume.

[other]

Radiologic-Pathologic Correlation of Tumor Thickness and Its Prognostic Importance in Squamous Cell Carcinoma of the Oral Cavity: Implications for the Eighth Edition Tumor, Node, Metastasis Classification [HEAD & NECK]

BACKGROUND AND PURPOSE:

Addressing the performance of an imaging-based parameter compared to a "gold standard" pathologic measurement is essential to achieve accurate clinical T-classification. Our aim was to determine the radiologic-pathologic tumor thickness correlation and its prognostic value in oral squamous cell carcinoma.

MATERIALS AND METHODS:

All pathologic T1–T3 (seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer) oral squamous cell carcinomas diagnosed between 2010 and 2015 were reviewed. Radiologic tumor thickness was measured on preoperative CT or MR imaging blinded to pathology. The radiologic-pathologic tumor thickness correlation was calculated. The impact of the imaging-to-surgery time interval and imaging technique on the correlation was explored. Intra-/interrater reliability on radiologic tumor thickness was calculated. The correlation of radiologic-versus-pathologic tumor thickness and its performance as the seventh edition T-category modifier was evaluated. Multivariable analysis assessed the prognostic value of the radiologic tumor thickness for overall survival adjusted for age, seventh edition T-category, and performance status.

RESULTS:

For 354 consecutive patients, the radiologic-pathologic tumor thickness correlation was similar for the image-to-surgery interval of ≤4.0 weeks ( = 0.76) versus 4–8 weeks ( = 0.80) but lower in those with more than an 8-week interval ( = 0.62). CT and MR imaging had similar correlations (0.76 and 0.80). Intrarater and interrater reliability was excellent (0.88 and 0.84). Excluding 19 cases with an imaging-to-surgery interval of >8 weeks, 335 patients were eligible for further analysis. The radiologic-pathologic tumor thickness correlation was 0.78. The accuracy for upstaging the T-classification based on radiologic tumor thickness was 83% for pathologic T1 and 74% for pathologic T2 tumors. Multivariable analysis confirmed the prognostic value of radiologic tumor thickness (hazard ratio = 1.5, P = .02) for overall survival.

CONCLUSIONS:

This study demonstrates a good radiologic-pathologic tumor thickness correlation. Intrarater and interrater reliability for radiologic tumor thickness was excellent. Radiologically thicker tumor was predictive of inferior survival.

Deep Learning in Neuroradiology [ADULT BRAIN]

SUMMARY:

Deep learning is a form of machine learning using a convolutional neural network architecture that shows tremendous promise for imaging applications. It is increasingly being adapted from its original demonstration in computer vision applications to medical imaging. Because of the high volume and wealth of multimodal imaging information acquired in typical studies, neuroradiology is poised to be an early adopter of deep learning. Compelling deep learning research applications have been demonstrated, and their use is likely to grow rapidly. This review article describes the reasons, outlines the basic methods used to train and test deep learning models, and presents a brief overview of current and potential clinical applications with an emphasis on how they are likely to change future neuroradiology practice. Facility with these methods among neuroimaging researchers and clinicians will be important to channel and harness the vast potential of this new method.

The Impact of Persistent Leukoencephalopathy on Brain White Matter Microstructure in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Chemotherapy Only [PEDIATRICS]

BACKGROUND AND PURPOSE:

Survivors of acute lymphoblastic leukemia are at risk for neurocognitive deficits and leukoencephalopathy. We performed a longitudinal assessment of leukoencephalopathy and its associations with long-term brain microstructural white matter integrity and neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia treated on a modern chemotherapy-only protocol.

MATERIALS AND METHODS:

One hundred seventy-three survivors of acute lymphoblastic leukemia (49% female), treated on a chemotherapy-only protocol, underwent brain MR imaging during active therapy and repeat imaging and neurocognitive testing at follow-up (median, 13.5 years of age; interquartile range, 10.7–17.6 years; median time since diagnosis, 7.5 years; interquartile range, 6.3–9.1 years). Persistence of leukoencephalopathy was examined in relation to demographic and treatment data and to brain DTI in major fiber tracts and neurocognitive testing at follow-up.

RESULTS:

Leukoencephalopathy was found in 52 of 173 long-term survivors (30.0%) and persisted in 41 of 52 (78.8%) who developed it during therapy. DTI parameters were associated with leukoencephalopathy in multiple brain regions, including the corona radiata (fractional anisotropy, P = .001; mean diffusivity, P < .001), superior longitudinal fasciculi (fractional anisotropy, P = .02; mean diffusivity, P < .001), and superior fronto-occipital fasciculi (fractional anisotropy, P = .006; mean diffusivity, P < .001). Mean diffusivity was associated with neurocognitive impairment including in the genu of the corpus callosum (P = .04), corona radiata (P = .02), and superior fronto-occipital fasciculi (P = .02).

CONCLUSIONS:

Leukoencephalopathy during active therapy and neurocognitive impairment at long-term follow-up are associated with microstructural white matter integrity. DTI may be more sensitive than standard MR imaging for detection of clinically consequential white matter abnormalities in childhood acute lymphoblastic leukemia survivors treated with chemotherapy and in children undergoing treatment.

Comparison of Advanced Imaging Resources, Radiology Workforce, and Payment Methodologies between the United States and Canada [research-article]

SUMMARY:

The purpose of this Practice Perspectives was to review the United States and Canadian approaches to health care access and payment for advanced imaging. The historical background, governmental role, workforce, coding, payment, radiologic challenges, cost, resource intensity, and overall outcomes in longevity are reviewed.

Multiple Brain Developmental Venous Anomalies as a Marker for Constitutional Mismatch Repair Deficiency Syndrome [PEDIATRICS]

BACKGROUND AND PURPOSE:

Biallelic constitutional mutations in DNA mismatch repair genes cause a distinct syndrome, constitutional mismatch repair deficiency syndrome (CMMRD), characterized by cancers from multiple organs, most commonly brain tumors, during childhood. Surveillance protocols include total and brain MR imaging among other modalities to enable early detection of tumors. Brain surveillance scans revealed prominent brain developmental venous anomalies (DVAs) in some patients. DVAs are benign vascular anomalies, and their incidence in the general population is 2.6%–6.4%. Most developmental venous anomalies are asymptomatic and are found incidentally. Our purpose was to assess the prevalence of DVAs in CMMRD patients and describe their phenotype.

MATERIALS AND METHODS:

A retrospective descriptive analysis of brain MR imaging studies from 10 patients from 3 families with CMMRD was performed. Analysis included the number of developmental venous anomalies, location, draining vessels, and associated vascular anomalies (ie, cavernomas), with clinical correlation of symptoms and tumors.

RESULTS:

All 10 patients had ≥2 developmental venous anomalies, and 2 had, in addition, non-therapy-induced cavernomas. There was no clinically symptomatic intracranial bleeding from developmental venous anomalies. Six patients had malignant brain tumors. The location of brain tumors was not adjacent to the developmental venous anomalies. No new developmental venous anomalies developed during follow-up.

CONCLUSIONS:

The occurrence of multiple developmental venous anomalies in all our patients with CMMRD suggests that developmental venous anomalies may be a characteristic of this syndrome that has not been previously described. If confirmed, this quantifiable feature can be added to the current scoring system and could result in early implementation of genetic testing and surveillance protocols, which can be life-saving for these patients.

Clinical Value of Hybrid TOF-PET/MR Imaging-Based Multiparametric Imaging in Localizing Seizure Focus in Patients with MRI-Negative Temporal Lobe Epilepsy [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Temporal lobe epilepsy is the most common type of epilepsy. Early surgical treatment is superior to prolonged medical therapy in refractory temporal lobe epilepsy. Successful surgical operations depend on the correct localization of the epileptogenic zone. This study aimed to evaluate the clinical value of hybrid TOF-PET/MR imaging–based multiparametric imaging in localizing the epileptogenic zone in patients with MR imaging-negative for temporal lobe epilepsy.

MATERIALS AND METHODS:

Twenty patients with MR imaging-negative temporal lobe epilepsy who underwent preoperative evaluation and 10 healthy controls were scanned using PET/MR imaging with simultaneous acquisition of PET and arterial spin-labeling. On the basis of the standardized uptake value and cerebral blood flow, receiver operating characteristic analysis and a logistic regression model were used to evaluate the predictive value for the localization. Statistical analyses were performed using statistical parametric mapping. The values of the standardized uptake value and cerebral blood flow, as well as the asymmetries of metabolism and perfusion, were compared between the 2 groups. Histopathologic findings were used as the criterion standard.

RESULTS:

Complete concordance was noted in lateralization and localization among the PET, arterial spin-labeling, and histopathologic findings in 12/20 patients based on visual assessment. Concordance with histopathologic findings was also obtained for the remaining 8 patients based on the complementary PET and arterial spin-labeling information. Receiver operating characteristic analysis showed that the sensitivity and specificity of PET, arterial spin-labeling, and combined PET and arterial spin-labeling were 100% and 81.8%, 83.3% and 54.5%, and 100% and 90.9%, respectively. When we compared the metabolic abnormalities in patients with those in healthy controls, hypometabolism was detected in the middle temporal gyrus (P < .001). Metabolism and perfusion asymmetries were also located in the temporal lobe (P < .001).

CONCLUSIONS:

PET/MR imaging–based multiparametric imaging involving arterial spin-labeling may increase the clinical value of localizing the epileptogenic zone by providing concordant and complementary information in patients with MR imaging-negative temporal lobe epilepsy.

Comment on "Common Origin of Brachiocephalic and Left Common Carotid Arteries: Proposal of New Terminology" [LETTERS]

Longitudinal Persistence of Meningeal Enhancement on Postcontrast 7T 3D-FLAIR MRI in Multiple Sclerosis [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Preliminary research has demonstrated that postgadolinium 3D-FLAIR MR imaging at 7T may be a valuable tool for detecting abnormal meningeal enhancement and inflammation in MS; however, researchers have not systematically investigated its longitudinal persistence. We hypothesized that persistence of meningeal enhancement in MS varies on the basis of pattern of enhancement as well as demographic and clinical factors such as treatment status, disease phenotype, and disability score.

MATERIALS AND METHODS:

Thirty-one subjects with MS were prospectively scanned before and after intravenous contrast administration at 2 time points, approximately 1 year apart. Fifteen subjects in the cohort were scanned at another time approximately 1 year later. Foci of enhancement were categorized into 4 subtypes: subarachnoid spread/fill, subarachnoid nodular, vessel wall, and dural foci. We reviewed follow-up scans to determine whether foci changed between time points and then compared persistence with demographic and clinical variables.

RESULTS:

Persistence ranged from 71% to 100% at 1 year and 73% to 100% at 2 years, depending on the enhancement pattern. Subarachnoid spread/fill and subarachnoid nodular subtypes persisted less often than vessel wall and dural foci. Persistence was not significantly different between those on/off treatment and those with progressive/nonprogressive disease phenotypes. The number of persisting foci was significantly different in subjects with/without increasing Expanded Disability Status Scale scores (median, 12 versus 7.5, P = .04).

CONCLUSIONS:

Longitudinal persistence of meningeal enhancement on 3D-FLAIR at 7T in MS varies by pattern of enhancement and correlates with worsening disability; however, it is not significantly different in those on/off treatment or in those with progressive/nonprogressive disease phenotypes.

Starting the Fight in the Tumor: Expert Recommendations for the Development of Human Intratumoral Immunotherapy (HIT-IT)

Abstract

A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 08 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and two clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members, that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities, and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators, but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved.

Collagenous and elastotic marginal plaques of the hand: a potential clue to the diagnosis of alkaptonuria

Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.

Effect of methotrexate monotherapy on T‐cell subsets in the peripheral circulation in psoriasis

Clinical and Experimental Dermatology, EarlyView.

Linear nail bed dyschromia: a distinctive dermoscopic feature of nail lichen planus

Clinical and Experimental Dermatology, EarlyView.

Asymptomatic solitary mass on the sacral region

Clinical and Experimental Dermatology, EarlyView.

Acitretin: a promising therapy for localized childhood lichen myxoedematosus

Clinical and Experimental Dermatology, EarlyView.

Hypopigmented patches in childhood: do not forget mycosis fungoides

Clinical and Experimental Dermatology, EarlyView.

Bullous pyoderma gangrenosum secondary to underlying multiple myeloma: treated with ciclosporin

Clinical and Experimental Dermatology, EarlyView.

Sporadic case of Darier disease caused by a novel splice‐site mutation in the ATP2A2 gene

Clinical and Experimental Dermatology, EarlyView.

A survey of the treatment and management of patients with severe chronic spontaneous urticaria

Clinical and Experimental Dermatology, EarlyView.

Alteration of serum and tissue tumor necrosis factor alpha levels: A possible mechanism of action of oral pulse steroids in the treatment of alopecia areata

Journal of Cosmetic Dermatology, EarlyView.

Issue Information

International Journal of Dermatology, Volume 57, Issue 11, Page i-iii,1273-1274, November 2018.

Improvement of alopecia areata with apremilast

Australasian Journal of Dermatology, EarlyView.

Chondrodysplasia punctata (CDPX2) in a male caused by single‐gene mosaicism: A 20‐year follow‐up

Australasian Journal of Dermatology, EarlyView.

Sentinel lymph node biopsy remains the most accurate method of obtaining staging and prognostic information for patients with primary cutaneous melanomas

Australasian Journal of Dermatology, EarlyView.

Primary cutaneous lymphoma in Argentina: a report of a nationwide study of 416 patients

International Journal of Dermatology, EarlyView.