bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel concept and assessment method for trustworthiness of prognostics
Authors: Sun Bo , Jiang Xiaopeng , Ye Tianyuan , Feng Qiang
Published: March 2016

The existence of the unavoidable uncertainties has a great effect on the prognostics accuracy and performance. However, their influences are rarely taken into account in the current prognostics performance evaluation. Consequently, the validity and/or trustiness degree of prognostics and health management system has not been comprehensively evaluated or measured. Considering the definition of prognostics performance and the characteristics of uncertainties, four prognostics performance metrics and two kinds of quantitative evaluation methods are proposed. On the basis of prognostics performance definition, a novel trustworthiness of prognostics concept is presented. Then, three kinds of assessment methods for trustworthiness of prognostics are provided. Finally, a case study has been carried out on the aviation hydraulic pump for verification purposes, in which the oil-return flow is monitored for predicting the degradation of the pump. The systematic application of trustworthiness of prognostics assessment is implemented based on the back propagation neural network prognostics algorithm. The results show that the proposed trustworthiness of prognostics concept and assessment methods can contribute to the systematic and comprehensive understanding of the performance of prognostics and health management system.
Working Memory Maturation
Authors: Cowan Nelson
Published: March 2016

The theoretical and practical understanding of cognitive development depends on working memory, the limited information temporarily accessible for such daily activities as language processing and problem solving. In this article, I assess many possible reasons that working memory performance improves with development. A first glance at the literature leads to the weird impression that working memory capacity reaches adult levels during infancy but then regresses during childhood. In place of that unlikely explanation, I consider how infant studies may lead to overestimates of capacity if one neglects supports that the tasks provide, compared with adult-level tasks. Further development of working memory during the school years is also considered. Many investigators have come to suspect that working memory capacity may be constant after infancy because of various factors such as developmental increases in knowledge, filtering out of irrelevant distractions, encoding and rehearsal strategies, and pattern formation. With each of these factors controlled, though, working memory still improves during the school years. Suggestions are made for research to bridge the gap between infant and child developmental research, to understand the focus and control of attention in working memory and how these skills develop, and to pinpoint the nature of capacity and its development from infancy forward.
Why a standard contrast-enhanced MRI might be useful in intracranial internal carotid artery stenosis
Authors: Oeinck Maximilian , Rozeik Christoph , Wattchow Jens , Meckel Stephan , Schlageter Manuel , Beeskow Christel , Reinhard Matthias
Published: March 2016

In patients with ischemic stroke of unknown cause cerebral vasculitis is a rare but relevant differential diagnosis, especially when signs of intracranial artery stenosis are found and laboratory findings show systemic inflammation. In such cases, high-resolution T1w vessel wall magnetic resonance imaging (MRI; ‘black blood’ technique) at 3 T is preferentially performed, but may not be available in every hospital. We report a case of an 84-year-old man with right hemispheric transient ischemic attack and signs of distal occlusion in the right internal carotid artery (ICA) in duplex sonography. Standard MRI with contrast agent pointed the way to the correct diagnosis since it showed an intramural contrast uptake in the right ICA and both vertebral arteries. Temporal artery biopsy confirmed the suspected diagnosis of a giant cell arteritis and dedicated vessel wall MRI performed later supported the suspected intracranial large artery inflammation. Our case also shows that early diagnosis and immunosuppressive therapy may not always prevent disease progression, as our patient suffered several infarcts in the left middle cerebral artery (MCA) territory with consecutive high-grade hemiparesis of the right side within the following four months.
Usefulness of quantitative peritumoural perfusion and proton spectroscopic magnetic resonance imaging evaluation in differentiating brain gliomas from solitary brain metastases
Authors: Sparacia Gianvincenzo , Gadde Judith A , Iaia Alberto , Sparacia Benedetta , Midiri Massimo
Published: March 2016

Objectives

The purpose of our study was to evaluate whether peritumoural perfusion weighted and proton spectroscopic magnetic resonance imaging can be used in differentiating between primary gliomas and solitary metastases.

Methods

Ten low-grade gliomas, eight high-grade gliomas and 10 metastases were prospectively evaluated with magnetic resonance imaging, dynamic susceptibility contrast enhanced perfusion imaging and single-voxel proton magnetic resonance spectroscopy before surgical resection or stereotactic biopsy. Maximal relative cerebral blood volume values were calculated drawing three regions of interest of 2 cm2 in the non-enhancing peritumoural areas. Maximal relative cerebral blood volume values were normalised to that of contralateral normal-appearing white matter. Maximal choline/creatine ratios were calculated from three voxels of 10 cm3 placed in the peritumoural areas defined as non-enhancing peritumoural white matter surrounding the tumour. The tumour grade presumed with these values was compared to histopathological grading. Differences in the study parameters between groups were assessed using the Mann–Whitney test. A receiver operating characteristic analysis was performed to determine cut-off values.

Results

A clear relative cerebral blood volume cut-off value of 1.88 was detected for differentiating low-grade gliomas from high-grade gliomas. A clear relative cerebral blood volume cut-off value of 1.20 was detected for differentiation of metastases from gliomas. The differences in the choline/creatine ratios in the peritumoural regions of high-grade gliomas and of solitary metastasis were statistically significant ( P < 0.001) but a clear cut-off value was not found.

Conclusion

Our preliminary data support the hypothesis that peritumoural perfusion-weighted imaging can assist in preoperative differentiation between a glioma and a solitary metastasis.
Implementation of a care pathway for infantile hypertrophic pyloric stenosis reduces length of stay and increases parent satisfaction
Authors: Wetherill Charlotte V , Melling James D , Rhodes Hannah L , Wilkinson David J , Kenny Simon E
Published: March 2016

Introduction

Infantile hypertrophic pyloric stenosis (IHPS) is a common surgical condition, but there are no guidelines regarding preoperative fluid resuscitation. Our aim was to evaluate a novel consensus care pathway for IHPS, incorporating a standardized fluid and electrolyte replacement regime.

Methods

One hundred patients were initially reviewed and compared to thirty-three patients following the introduction of a clinical pathway, whereby infants requiring electrolyte correction received 150 ml/kg/24 h of 0.45% saline, 5% dextrose and 10 mmol KCl, with systematic blood sampling until correction was achieved. We measured time to electrolyte correction, time to surgery and total length of hospitalization. Data were described using the median and interquartile range, and differences between the groups’ categorical and continuous data were described using Chi-squared and the Mann–Whitney U–tests, respectively.

Results

Time in hours taken to correct electrolytes was reduced: 25(16.5–42) versus 9.5(4.5–24.75) p = 0.004. Time to surgery from admission in uncorrected patients decreased from 50(40.25–66.75) to 39(28.75–41.75) p = 0.018. Subsequently, there was a reduction in total length of stay: 94(71–93.5) versus 75(64.5–93.5) p = 0.025. Parental satisfaction increased from 77% in the pre-pathway group to 83% in the pathway group.

Conclusion

A consensus care pathway for IHPS reduces the time taken to correct preoperative electrolyte abnormalities, decreases length of hospitalization and improves parental satisfaction.
New Fourth Generation of Innovation Management Theory & Practice: Part 2
Authors: Miller William L.
Published: March 2016

This is the second article in a pair of articles in the Journal of Creating Value which identified the root cause of a group of wicked global problems as the lack of value creation from radical innovation. The root cause has existed over the last four decades following the large number of significant radical innovations that launched and initially propelled the Information Age. The first article described the essential part of a solution which is adoption of a new fourth generation of innovation management (4G) which has emerged as best practice since 2000 because 4G effectively enables radical innovation in addition to more effective and efficient incremental innovation.

Radical innovation is required for sustained, adequate rates of economic growth driven by improvements in productivity, quality and cost in industries such as healthcare, education, construction and energy. As a result of inadequate radical innovation over the past four decades, a group of major economic, social and environmental wicked problems are unsolved such as income inequality and global warming and these problems exist in all countries including the United States.

4G is guided by 12 new principles and practices to effectively and efficiently create radical innovation based on new dominant designs while also improving the efficient creation of incremental innovation. The first article, Part 1, described the first four principles of 4G in detail. This article, Part 2, describes the remaining eight principles of 4G in detail.
Follicular lymphoma: evolving therapeutic strategies
Authors: Kahl Brad S. , Yang David T.
Published: March 2016

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. After decades of stagnation, the natural history of FL appears to have been favorably impacted by the introduction of rituximab. Randomized clinical trials have demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Maintenance rituximab strategies can improve progression-free survival. Even chemotherapy platforms have changed in the past 5 years, as bendamustine combined with rituximab has rapidly become a standard frontline strategy in North America and parts of Europe. Recent discoveries have identified patients at high risk for poor outcomes to first-line therapy (m7–Follicular Lymphoma International Prognostic Index [m7-FLIPI]) and for poor outcomes after frontline therapy (National LymphoCare Study). However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation. The development of targeted agents, exploiting our current understanding of FL biology, is a high research priority. A multitude of novel therapies are under investigation in both the frontline and relapsed/refractory settings. It will be critical to identify the most appropriate populations for new agents and to develop validated surrogate end points, so that novel agents can be tested (and adopted, if appropriate) efficiently.
The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance
Authors: Zucca Emanuele , Bertoni Francesco
Published: March 2016

Extranodal marginal zone (MZ) B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. The best evidence of an etiopathogenetic link is provided by the association between Helicobacter pylori–positive gastritis and gastric MALT lymphoma. Indeed, successful eradication of this microorganism with antibiotics can be followed by gastric MALT lymphoma regression in most cases. Other microbial agents have been implicated in the pathogenesis of MZ lymphoma arising at different sites. Apart from gastric MALT lymphoma, antibiotic therapies have been adequately tested only in ocular adnexal MALT lymphomas where upfront doxycycline may be a reasonable and effective initial treatment of patients with Chlamydophila psittaci–positive lymphoma before considering more aggressive strategies. In all other instances, antibiotic treatment of nongastric lymphomas remains investigational. Indeed, there is no clear consensus for the treatment of patients with gastric MALT lymphoma requiring further treatment beyond H pylori eradication or with extensive disease. Both radiotherapy and systemic treatments with chemotherapy and anti-CD20 antibodies are efficacious and thus the experience of individual centers and each patient’s preferences in terms of adverse effects are important parameters in the decision process.
Maximal aerobic capacity in ageing subjects: actual measurementsversuspredicted values
Authors: Pistea Cristina , Lonsdorfer Evelyne , Doutreleau Stéphane , Oswald Monique , Enache Irina , Charloux Anne
Published: March 2016

We evaluated the impact of selection of reference values on the categorisation of measured maximal oxygen consumption (V′O2peak) as “normal” or “abnormal” in an ageing population.

We compared measuredV′O2peakwith predicted values and the lower limit of normal (LLN) calculated with five equations. 99 (58 males and 41 females) disease-free subjects aged ≥70 years completed an incremental maximal exercise test on a cycle ergometer.

MeanV′O2peakwas 1.88 L·min−1in men and 1.26 L·min−1in women.V′O2peakranged from 89% to 108% of predicted in men, and from 88% to 164% of predicted in women, depending on the reference equation used. The proportion of subjects below the LLN ranged from 5% to 14% in men and 0–22% in women, depending on the reference equation. The LLN was lacking in one study, and was unsuitable for women in another. Most LLNs ranged between 53% and 73% of predicted. Therefore, choosing an 80% cut-off leads to overestimation of the proportion of “abnormal” subjects.

To conclude, the proportion of subjects aged ≥70 years with a “low”V′O2peakdiffers markedly according to the chosen reference equations. In clinical practice, it is still relevant to test a sample of healthy volunteers and select the reference equations that better characterise this sample.
Artificial stone dust-induced functional and inflammatory abnormalities in exposed workers monitored quantitatively by biometrics
Authors: Ophir Noa , Shai Amir Bar , Alkalay Yifat , Israeli Shani , Korenstein Rafi , Kramer Mordechai R. , Fireman Elizabeth
Published: March 2016

The manufacture of kitchen and bath countertops in Israel is based mainly on artificial stone that contains 93% silica as natural quartz, and ∼3500 workers are involved in cutting and processing it. Artificial stone produces high concentrations of silica dust. Exposure to crystalline silica may cause silicosis, an irreversible lung disease. Our aim was to screen exposed workers by quantitative biometric monitoring of functional and inflammatory parameters.

68 exposed artificial stone workers were compared to 48 nonexposed individuals (controls). Exposed workers filled in questionnaires, and all participants underwent pulmonary function tests and induced sputum analyses. Silica was quantitated by a Niton XL3 X-ray fluorescence spectrometer.

Pulmonary function test results of exposed workers were significantly lower and induced sputa showed significantly higher neutrophilic inflammation compared to controls; both processes were slowed down by the use of protective measures in the workplace. Particle size distribution in induced sputum samples of exposed workers was similar to that of artificial stone dust, which contained aluminium, zirconium and titanium in addition to silica.

In conclusion, the quantitation of biometric parameters is useful for monitoring workers exposed to artificial stone in order to avoid deterioration over time.
A comparative study of SMILES-based compound similarity functions for drug-target interaction prediction
Authors: Öztürk Hakime , Ozkirimli Elif , Özgür Arzucan
Published: March 2016

Background

Molecular structures can be represented as strings of special characters using SMILES. Since each molecule is represented as a string, the similarity between compounds can be computed using SMILES-based string similarity functions. Most previous studies on drug-target interaction prediction use 2D-based compound similarity kernels such as SIMCOMP. To the best of our knowledge, using SMILES-based similarity functions, which are computationally more efficient than the 2D-based kernels, has not been investigated for this task before.

Results

In this study, we adapt and evaluate various SMILES-based similarity methods for drug-target interaction prediction. In addition, inspired by the vector space model of Information Retrieval we propose cosine similarity based SMILES kernels that make use of the Term Frequency (TF) and Term Frequency-Inverse Document Frequency (TF-IDF) weighting approaches. We also investigate generating composite kernels by combining our best SMILES-based similarity functions with the SIMCOMP kernel. With this study, we provided a comparison of 13 different ligand similarity functions, each of which utilizes the SMILES string of molecule representation. Additionally, TF and TF-IDF based cosine similarity kernels are proposed.

Conclusion

The more efficient SMILES-based similarity functions performed similarly to the more complex 2D-based SIMCOMP kernel in terms of AUC-ROC scores. The TF-IDF based cosine similarity obtained a better AUC-PR score than the SIMCOMP kernel on the GPCR benchmark data set. The composite kernel of TF-IDF based cosine similarity and SIMCOMP achieved the best AUC-PR scores for all data sets.
On the comparison of regulatory sequences with multiple resolution Entropic Profiles
Authors: Comin Matteo , Antonello Morris
Published: March 2016

Background

Enhancers are stretches of DNA (100–1000 bp) that play a major role in development gene expression, evolution and disease. It has been recently shown that in high-level eukaryotes enhancers rarely work alone, instead they collaborate by forming clusters of cis-regulatory modules (CRMs). Although the binding of transcription factors is sequence-specific, the identification of functionally similar enhancers is very difficult and it cannot be carried out with traditional alignment-based techniques.

Results

The use of fast similarity measures, like alignment-free measures, to detect related regulatory sequences is crucial to understand functional correlation between two enhancers. In this paper we study the use of alignment-free measures for the classification of CRMs. However, alignment-free measures are generally tied to a fixed resolution k. Here we propose an alignment-free statistic, called $EP^{*}_{2}$
E

P

2

∗

, that is based on multiple resolution patterns derived from the Entropic Profiles (EPs). The Entropic Profile is a function of the genomic location that captures the importance of that region with respect to the whole genome. As a byproduct we provide a formula to compute the exact variance of variable length word counts, a result that can be of general interest also in other applications.

Conclusions

We evaluate several alignment-free statistics on simulated data and real mouse ChIP-seq sequences. The new statistic, $EP^{*}_{2}$
E

P

2

∗

, is highly successful in discriminating functionally related enhancers and, in almost all experiments, it outperforms fixed-resolution methods. We implemented the new alignment-free measures, as well as traditional ones, in a software called EP-sim that is freely available: http://www.dei.unipd.it/~ciompin/main/EP-sim.html.
The impairment of small nerve fibers in severe sepsis and septic shock
Authors: Axer Hubertus , Grimm Alexander , Pausch Christine , Teschner Ulrike , Zinke Jan , Eisenach Sven , Beck Sindy , Guntinas-Lichius Orlando , Brunkhorst Frank M. , Witte Otto W.
Published: March 2016

Background

A decrease of small nerve fibers in skin biopsies during the course of critical illness has been demonstrated recently. However, the diagnostic use of skin biopsies in sepsis and its time course is not known.

Methods

Patients (n=32) with severe sepsis or septic shock were examined using skin biopsies, neurological examination, nerve conduction studies, and sympathetic skin response in the first week after onset of sepsis, 2 weeks and 4 months later and compared to gender- and age-matched healthy controls.

Results

Skin biopsies at the ankle and thigh revealed a significant decrease of intraepidermal nerve fiber density (IENFD) during the first week of sepsis and 2 weeks later. All patients developed critical illness polyneuropathy (CIP) according to electrophysiological criteria and 11 showed IENFD values lower than the 0.05 quantile. Four patients were biopsied after 4 months and still showed decreased IENFD. Results of nerve conduction studies and IENFD did considerably change over time. No differences for survival time between patients with IEFND lower and larger than 3.5 fibers/mm were found.

Conclusions

Skin biopsy is able to detect an impairment of small sensory nerve fibers early in the course of sepsis. However, it may not be suited as a prognostic parameter for survival.

Trial registration

German Clinical Trials Register, DRKS-ID: DRKS00000642, 12/17/2010
Transcranial direct current stimulation as a memory enhancer in patients with Alzheimer’s disease: a randomized, placebo-controlled trial
Authors: Bystad Martin , Grønli Ole , Rasmussen Ingrid Daae , Gundersen Nina , Nordvang Lene , Wang-Iversen Henrik , Aslaksen Per M.
Published: March 2016

Background

The purpose of this study was to assess the efficacy of transcranial direct current stimulation (tDCS) on verbal memory function in patients with Alzheimer’s disease.

Methods

We conducted a randomized, placebo-controlled clinical trial in which tDCS was applied in six 30-minute sessions for 10 days. tDCS was delivered to the left temporal cortex with 2-mA intensity. A total of 25 patients with Alzheimer’s disease were enrolled in the study. All of the patients were diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association criteria. Twelve patients received active stimulation, and thirteen patients received placebo stimulation. The primary outcome measure was the change in two parallel versions of the California Verbal Learning Test–Second Edition, a standardized neuropsychological memory test normalized by age and gender. The secondary outcome measures were the Mini Mental State Examination, clock-drawing test, and Trail Making Test A and B.

Results

Changes in the California Verbal Learning Test–Second Edition scores were not significantly different between the active and placebo stimulation groups for immediate recall (p = 0.270), delayed recall (p = 0.052), or recognition (p = 0.089). There were nonsignificant differences in score changes on the Mini Mental State Examination (p = 0.799), clock-drawing test (p = 0.378), and Trail Making Test A (p = 0.288) and B (p = 0.093). Adverse effects were not observed.

Conclusions

Compared with placebo stimulation, active tDCS stimulation in this clinical trial did not significantly improve verbal memory function in Alzheimer’s disease. This study differs from previous studies in terms of the stimulation protocol, trial design, and application of standardized neuropsychological memory assessment.

Trial registration

ClinicalTrials.gov identifier NCT02518412. Registered on 10 August 2015.
Aging, inflammation, stem cells, and bone healing
Authors: Gibon Emmanuel , Lu Laura , Goodman Stuart B.
Published: March 2016

Complex interactions among cells of the monocyte-macrophage-osteoclast lineage and the mesenchymal stem cell-osteoblast lineage play a major role in the pathophysiology of bone healing. Whereas the former lineage directs inflammatory events and bone resorption, the latter represents a source of cells for bone regeneration and immune modulation. Both of these lineages are affected by increasing age, which is associated with higher baseline levels of inflammatory mediators, and a significant reduction in osteogenic capabilities. Given the above, fracture healing, osteoporosis, and other related events in the elderly present numerous challenges, which potentially could be aided by new therapeutic approaches to modulate both inflammation and bone regeneration.
A projection method for approximating fixed points of quasinonexpansive mappings in Hadamard spaces
Authors: Huang Shuechin , Kimura Yasunori
Published: March 2016

This work is devoted to analyzing the feasibility study of a Moudafi viscosity projection method with a weak contraction for a finite family of quasinonexpansive mappings in a Hadamard space. To this end, we need to construct a countable family of nonexpansive mappings satisfying AKTT condition with a weak contraction by choosing an appropriate control sequence under certain conditions.
Micro-computed tomography scan and virtual histological slide data for the land planarian Obama otavioi (Platyhelminthes)
Authors: Carbayo Fernando , Lenihan Jennifer Winifred
Published: March 2016

Background:

We investigated whether images obtained through X-ray micro-computed tomography (μCT) can be used in conjunction with traditional methods for morphological studies of soft-bodied land planarians. μCT is non-invasive and provides true-to-scale three-dimensional imagery at high resolution. We compared μCT-based images of a recently described land planarian species of Obama otavioi (Platyhelminthes) with those obtained from light microphotography of histological sections, most of which were also digitized at high magnification.

Findings:

The specimens studied were collected in 2012. Subsequent μCT-based images of the stained body of a paratype show nearly all morphological features provided by traditional histology, with the exception of particularly minute structures, smaller than 5 μm, such as the sensory pits and single muscle fibers, which are best visible on traditional histological sections. Because the technique is non-destructive, the scanned specimen is preserved without damage. The raw and derivative μCT data and virtual histological sections are freely available in GigaDB.

Conclusions:

The μCT datasets of these stained soft-bodied organisms reveal images of external and internal structures that support previous taxonomic studies. This technique can be particularly important for non-destructively revealing internal details of whole museum specimens at a faster rate than histology alone. High-resolution virtual histological slides also allow further searches for new, previously unstudied morphological features. The use of X-ray equipment with higher resolution can enable smaller sensory organ and muscle fiber details to be seen. The image sets, μCT-based images and digitized histological slides can be disseminated without the constraints of specimen loans.
Can linear transportation infrastructure verges constitute a habitat and/or a corridor for biodiversity in temperate landscapes? A systematic review protocol
Authors: Jeusset Arzhvaël , Vargac Marianne , Bertheau Yves , Coulon Aurélie , Deniaud Nadine , Flamerie De Lachapelle Frédérique , Jaslier Emmanuel , Livoreil Barbara , Roy Véronique , Touroult Julien , Vanpeene Sylvie , Witté Isabelle , Sordello Romain
Published: March 2016

Background

The role of linear transportation infrastructures (roads, railways, oil and gas pipelines, power lines, rivers and canals) in fragmenting natural habitats has been demonstrated. Yet, the potential of habitat or corridor of their verges (road and railway embankments, strips of grass under power lines or above buried pipelines, or waterway banks) for biodiversity remains controversial. In a context of decreasing natural habitats, the potential of anthropogenic areas for contributing to wildlife conservation should be considered. Moreover, how linear transportation infrastructure verges should be managed in order to favor biodiversity is a crucial question. The present work describes the protocol of the first systematic synthesis of evidence of the potential of linear transportation infrastructure verges as habitat and/or corridor for biodiversity. Outcomes of the study will be useful for helping managers to improve their practices or for prioritizing actions of ecological restoration.

Methods

The subject population will include both flora and fauna of the temperate climate, either species or communities. Exposures to linear transportation infrastructure verges, interventions of verge management (mowing, pruning, etc.) and environmental disturbances (pollution, wildfires, etc.) will be included. Both temporal and spatial comparators will be considered. Relevant outcomes will include dispersal, species richness and abundance. The scientific literature on the topic of the review may turn out to be very heterogeneous. Various management types, biodiversity outcomes and study designs might be conceived. If any combination of these is covered by a sufficient number of studies, we will perform a meta-analysis. At the least, we will produce a systematic map and a narrative synthesis.
Parental Attitudes to Genetic Testing Differ by Ethnicity and Immigration in Childhood Nephrotic Syndrome: A Cross-Sectional Study
Authors: Borges Karlota , Vasilevska-Ristovska Jovanka , Hussain-Shamsy Neesha , Patel Viral , Banh Tonny , Hebert Diane , Pearl Rachel J. , Radhakrishnan Seetha , Piscione Tino D. , Licht Christoph P. B. , Langlois Valerie , Levin Leo , Strug Lisa , Parekh Rulan S.
Published: March 2016

Background:

Studies in the USA report differences in opinion among parents of different ethnic groups toward genetic testing for their child; however, there are no studies that address this issue in the diverse ethnic and immigrant population in Canada.

Objective:

This study aims to determine whether ethnicity and immigration status influences parental interest in clinical genetic testing for a potentially progressive kidney disease.

Design:

This is a cross-sectional study.

Setting:

Participants were recruited from the Greater Toronto Area, Canada.

Participants:

The study included 320 parents of children ages 1–18 years with nephrotic syndrome enrolled in the Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT) observational cohort study.

Measurements:

Demographic, ethnicity, immigration, and child specific factors as well as interest in genetic testing were collected through self-reported questionnaires administered at baseline study visit.

Methods:

Logistic regression models were used to examine association of ethnicity and immigration status with interest in genetic testing.

Results:

The majority of parents (85 %) were interested in genetic testing for their child. South Asian and East/Southeast Asian parents had 74 and 76 % lower odds of agreeing to genetic testing when compared to Europeans (odds ratio (OR) 0.26, 95 % confidence interval (CI) 0.10–0.68; OR 0.24, 95 % CI 0.07–0.79, respectively) after controlling for age and sex of child, age and education level of parent, initial steroid resistance, and duration of time in Canada. Immigrants to Canada also had significantly lower odds (OR 0.29, 95 % CI 0.12–0.72) of agreeing to genetic testing after similar adjustment. Higher education level was not associated with greater interest in genetic testing (OR 1.24, 95 % CI 0.64–2.42).

Limitations:

Participants have already agreed to aggregate genetic testing for research purposes as part of enrolment in INSIGHT study.

Conclusion:

While majority of parents were interested in genetic testing for their child, immigrants, particularly South Asians and East/Southeast Asians, were more likely to decline genetic testing. Genetic counseling needs to be tailored to address specific concerns in these parental groups to maximize informed decision-making in the clinical setting.

Trial registration:

ClinicalTrials.gov , NCT01605266
The Canadian Experience Using the Expanded Criteria Donor Classification for Allocating Deceased Donor Kidneys for Transplantation
Authors: Young Ann , Dixon Stephanie N. , Knoll Greg A. , Garg Amit X. , Lok Charmaine E. , Lam Ngan N. , Kim S. Joseph
Published: March 2016

Background:

Although the outcomes of transplantation with expanded criteria donor (ECD) kidneys are inferior to non-ECD transplants in the USA, the impact of the ECD classification on Canadian kidney transplant recipients is not known.

Objectives:

The objective of the study was to assess the performance of the US-derived ECD classification among deceased donor kidney transplant recipients in a Canadian setting.

Design:

This study was a population-based cohort study.

Setting:

The study was conducted in all adult kidney transplant centers in the province of Ontario.

Patients:

The patients were incident-deceased donor kidney transplant recipients from January 1, 2005 to March 31, 2011.

Measurements:

Study subjects were identified through the Trillium Gift of Life Network and linked to healthcare databases in Ontario. ECD status was based on age, hypertension, kidney function, and stroke-related death. Outcomes of interest included graft loss, death, and delayed graft function.

Methods:

The Kaplan-Meier product limit method was used to graphically assess time to graft loss or death. Multivariable Cox proportional hazards models were used to assess graft loss or death as a function of ECD status. Multivariable logistic regression models were fitted for the outcome of delayed graft function.

Results:

Of 1422 deceased donor kidney transplants, 325 (23 %) were from ECDs. The median donor age was 63 vs. 42 years for ECD vs. non-ECD, respectively. The 5-year cumulative incidence of total graft loss was 29.2 % in ECD and 20.7 % in non-ECD kidney transplants. The relative hazards for total graft loss (HR 1.48 [95 % CI, 1.10; 2.00]) and death-censored graft loss (HR 1.80 [95 % CI, 1.19, 2.71]) were increased in ECD vs. non-ECD transplants. Increased relative risks were also observed for death and delayed graft function, albeit not statistically significant.

Limitations:

Although comprehensive in coverage and outcome ascertainment, the available details on covariate data may be limited in large healthcare databases.

Conclusions:

The ECD classification identifies kidneys at increased risk for graft loss in Canadian patients. The performance of more granular measures of donor risk (e.g., Kidney Donor Risk Index) and its impact on organ allocation/utilization in Canadian patients requires further study.
Gabapentin for Uremic Pruritus in Hemodialysis Patients: A Qualitative Systematic Review
Authors: Lau Torey , Leung Sharon , Lau Wynnie
Published: March 2016

Purpose of the review:

Uremic pruritus (UP) is a common discomfort of dialysis-dependent end-stage renal disease. Some studies suggest a neuropathic cause of UP. Gabapentin, an anticonvulsant, has shown promising results as an emerging drug to treat this condition.

Objective:

An updated qualitative systematic review was conducted to evaluate its efficacy and safety in hemodialysis patients.

Source of information:

Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov , and Google Scholar through June 2015 were used as sources of information.

Patients:

Patients are adult hemodialysis patients receiving gabapentin for UP.

Methods:

All randomized controlled trials (RCTs), quasi-RCTs, observational studies, open-label studies, and retrospective studies were included. Case series and case reports were excluded. All descriptions and data were extracted independently by two authors.

Results:

Seven studies evaluating gabapentin with a total of 179 patients were included. Most patients were refractory to antihistamines and topical emollients. Statistically significant favorable outcomes on pruritus scores were found in six studies. Five studies evaluated antipruritic efficacy based on a 10-point visual analog scale (VAS), and improvements in the range of an absolute decrease of 5.7 to 9.4 points from baseline were achieved on average by 3–8 weeks of treatment. Side effects are common with six studies reporting at least 26 incidences of side effects such as somnolence, dizziness, and fatigue. A total of four patients reportedly discontinued gabapentin due to intolerability.

Limitations:

Our review is limited by the inclusion of generally small, lower quality studies that lacked comparator groups or were open-label studies. Since the first two randomized controlled trials were published, no further high-quality studies have been conducted.

Implications:

Our review supports a trial of gabapentin for the management of UP in hemodialysis patients refractory to antihistamines and/or emollients. The results should be interpreted cautiously due to the lower quality of included studies. We recommend a starting dose of 100 mg orally after hemodialysis to minimize adverse events in this population.
Epidemiologic characteristics of death by burn injury from 2000 to 2009 in Colombia, South America: a population-based study
Authors: Navarrete Norberto , Rodriguez Nelcy
Published: March 2016

Background

Burns are one of the most severe traumas that an individual can suffer. The World Health Organization (WHO) affirms that injuries related to burns are a global public health problem mainly in low- and middle-income countries. The first step towards reducing any preventable injury is based on accurate information. In Colombia, the basic epidemiological characteristics of burn injuries are unknown. The objectives were establishing the causes, high-risk populations, mortality rate, and tendencies of burn deaths.

Methods

Observational, analytical, population-based study based on official death certificate occurred between 2000 and 2009. All codes of the International Classification of Diseases-10th Revision (ICD-10) related to burns were included. The mortality rates were standardized using the WHO world average age weights 2000–2025. To determine the tendency, an average annual percent change (AACP) was calculated.

Results

A total of 5448 deaths due to burns were identified; 78.4 % were men. The crude and adjusted burn mortality rate was 1.270 and 1.302 per 100,000, respectively. The AACP was −5.25 %. Electrical injury caused the greatest number of deaths (49.5 %), followed by fire and lightning injuries. A total of 1197 (22.1 %) children were under 15 years old. The causes of deaths were different among age groups. 59.4 % deaths occurred outside health institutions.

Conclusions

This study is a first step in identifying the main causes of death and groups with higher mortality rates. Electricity is the main cause of deaths due to burn injury. Further research is required in order to generate awareness among government and community for reducing the number of injuries and burn deaths in our country.
Influence of baseline severity on antidepressant efficacy for anxiety disorders: Meta-analysis and meta-regression
Authors: de Vries Ymkje Anna , de Jonge Peter , van den Heuvel Edwin , Turner Erick H. , Roest Annelieke M.
Published: March 2016

Background

Antidepressants are established first-line treatments for anxiety disorders, but it is not clear whether they are equally effective across the severity range.

Aims

To examine the influence of baseline severity of anxiety on antidepressant efficacy for generalised anxiety disorder (GAD), social anxiety disorder (SAD), obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD) and panic disorder.

Method

Fifty-six trials of second-generation antidepressants for the short-term treatment of an anxiety disorder were included. Baseline and change scores were extracted for placebo and treatment groups in each trial. Mixed effects meta-regression was used to investigate the effects of treatment group, baseline severity and their interaction.

Results

Increased baseline severity did not predict greater improvement in drug groups compared with placebo groups. Standardised regression coefficients of the interaction term between baseline severity and treatment group were 0.04 (95% CI –0.13 to 0.20, P = 0.65) for GAD, –0.06 (95% CI –0.20 to 0.09, P = 0.43) for SAD, 0.04 (95% CI –0.07 to 0.16, P = 0.46) for OCD, 0.16 (95% CI –0.22 to 0.53, P = 0.37) for PTSD and 0.002 (95% CI –0.10 to 0.10, P = 0.96) for panic disorder. For OCD, baseline severity did predict improvement in both placebo and drug groups equally (β = 0.11, 95% CI 0.05 to 0.17, P = 0.001).

Conclusions

No relationship between baseline severity and drug–placebo difference was found for anxiety disorders. These results suggest that if the efficacy of antidepressants is considered clinically relevant, they may be prescribed to patients with anxiety regardless of symptom severity.
Escapism; Or, the Soul of Globalization
Authors: Limon John
Published: March 2016

This essay attempts to define into existence the supergeneric category of “escapism” by way of analyzing Richard Rodgers and Oscar Hammerstein's The Sound of Music. The essay (following the genre-defining procedures of Tzvetan Todorov) argues that there are three rules of escapism: all problems must be solved by personal relations, the escapism must be self-conscious, this self-conscious escapism must be muddled with an actual escape. But the sign of escapism by which it can be initially recognized is inescapability. The opposite of Utopian, escapism is Topian: what is escaped is not a place but the unloveliness of that place. According to the third rule, an actual location must ostensibly be escaped—in The Sound of Music, post-Anschluss Austria. It is, however, the unloveliness of performing in public, as felt by Captain von Trapp on behalf of the musical, that must be transmuted within Austria, and the public stage of escapism is continuous from there to Broadway to (via the film) the world. It is by way of the world reach of The Sound of Music that we can conceive of escapism as the soul of globalization: the essence of globalization is that there is no elsewhere, which means that to escape the profane world can only be to repurpose it as sacredly lovable. When The Sound of Music resorts at the end to the tombs of the abbey, however, it puts a period to its own escapism.
Development of the aboral domain in Nematostella requires β-catenin and the opposing activities of six3/6 and frizzled5/8
Authors: Leclère Lucas , Bause Markus , Sinigaglia Chiara , Steger Julia , Rentzsch Fabian
Published: March 2016

The development of the oral pole in cnidarians and the posterior pole in bilaterians is regulated by canonical Wnt signaling, while a set of transcription factors, including Six3/6 and FoxQ2, controls aboral development in cnidarians and anterior identity in bilaterians. However, it is poorly understood how these two patterning systems are initially set up in order to generate correct patterning along the primary body axis. Investigating the early steps of aboral pole formation in the sea anemone Nematostella vectensis, we found that, at blastula stage, oral genes are expressed before aboral genes and that Nvβ-catenin regulates both oral and aboral development. In the oral hemisphere, Nvβ-catenin specifies all subdomains except the oral-most, NvSnailA expressing domain, which is expanded upon Nvβ-catenin knockdown. In addition, Nvβ-catenin establishes the aboral patterning system by promoting the expression of NvSix3/6 at the aboral pole and suppressing the Wnt receptor NvFrizzled5/8 at the oral pole, whose expression thereby gets restricted to the aboral domain. At gastrula stage, NvSix3/6 and NvFrizzled5/8 are both expressed in the aboral domain, but they have opposing activities, with NvSix3/6 maintaining and NvFrizzled5/8 restricting the size of the aboral domain. At planula stage, NvFrizzled5/8 is required for patterning within the aboral domain and for regulating the size of the apical organ by modulation of a previously characterized FGF feedback loop. Our findings suggest conserved roles for six3/6 and frizzled5/8 in aboral/anterior development and reveal key functions for Nvβ-catenin in the patterning of the entire oral-aboral axis of Nematostella.
Species tailoured contribution of volumetric growth and tissue convergence to posterior body elongation in vertebrates
Authors: Steventon Ben , Duarte Fernando , Lagadec Ronan , Mazan Sylvie , Nicolas Jean-François , Hirsinger Estelle
Published: March 2016

Posterior body elongation is a widespread mechanism propelling the generation of the metazoan body plan. The posterior growth model predicts that a posterior growth zone generates sufficient tissue volume to elongate the posterior body. However, there are energy supply-related differences between vertebrates in the degree to which growth occurs concomitantly with embryogenesis. By applying a multi-scalar morphometric analysis in zebrafish embryos, we show that posterior body elongation is generated by an influx of cells from lateral regions, by convergence-extension of cells as they exit the tailbud, and finally by a late volumetric growth in the spinal cord and notochord. Importantly, the unsegmented region does not generate additional tissue volume. FGF inhibition blocks tissue convergence rather than volumetric growth, showing that a conserved molecular mechanism can control convergent morphogenesis through different cell behaviours. Finally, via a comparative morphometric analysis in lamprey, dogfish, zebrafish and mouse, we propose that elongation via posterior volumetric growth is linked to increased energy supply and is associated with an overall increase in volumetric growth and elongation.
DRACULA2, a dynamic nucleoporin with a role in the regulation of the shade avoidance syndrome in Arabidopsis
Authors: Gallemí Marçal , Galstyan Anahit , Paulišić Sandi , Then Christiane , Ferrández-Ayela Almudena , Lorenzo-Orts Laura , Roig-Villanova Irma , Wang Xuewen , Micol Jose Luis , Ponce Maria Rosa , Devlin Paul F. , Martínez-García Jaime F.
Published: March 2016

When plants grow in close proximity, basic resources such as light might become limiting. Under such conditions, plants respond to anticipate and/or adapt to the light shortage, a process known as the shade avoidance syndrome (SAS). After a genetic screening using a shade-responsive luciferase reporter line (PHYB:LUC), we identified DRACULA2 (DRA2) that encodes an Arabidopsis homolog to mammalian nucleoporin 98, a component of the nuclear pore complex (NPC). DRA2, together with other nucleoporines, positively participates in the control of the hypocotyl elongation response to plant proximity, a role that can be considered as dependent on the nucleocytoplasmic transport of macromolecules (i.e., transport-dependent). In addition, our results reveal a specific role for DRA2 in controlling shade-induced gene expression. We suggest that this novel regulatory role of DRA2 is transport-independent, and it might rely on its dynamic localization in and off the NPC. These results provide mechanistic insights on how SAS responses are rapidly established by light conditions. They also indicate that nucleoporins have an active role in plant signaling.