bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep disorders and risk of dementia in patients with new‐onset type 2 diabetes: A nationwide population‐based cohort study
Authors: Jin Dallae , Choi Jae Woo
Published: July 2020

Background

This study examined the relationship between sleep disorders and the risk of dementia in patients with newly diagnosed type 2 diabetes.

Methods

This study used the Korean Health Screening Cohort data and included 39 135 subjects aged ≥40 years with new‐onset type 2 diabetes between 2004 and 2007, with follow‐up throughout 2013. Sleep disorders were measured by F51(sleep disorders not due to a substance or known physiological condition) or G47(sleep disorders) under International Classification of Diseases, Tenth Revision (ICD‐10) codes as a primary diagnosis, and the adjusted hazard ratio (AHR) and 95% CI of all‐cause dementia, Alzheimer disease, vascular dementia, and other dementia were estimated using multivariable Cox proportional hazards regression models.

Results

In the patients with type 2 diabetes with an age range between 42 and 84 years (M = 57.8, SD = 9.5), this study identified 2059 events of dementia during an average follow‐up time of 5.7 years. In patients with type 2 diabetes, subjects with sleep disorders were associated with an increased risk of all‐cause dementia (AHR, 1.46; 95% CI, 1.19‐1.80), Alzheimer disease (AHR, 1.39; 95% CI, 1.02‐1.88), and other dementia (AHR, 1.69; 95% CI, 1.23‐2.31) compared to those without sleep disorders. Men (AHR, 1.93; 95% CI, 1.42‐2.62) and older adults (AHR, 1.70; 95% CI, 1.35‐2.15) with sleep disorders were associated with an increased risk of dementia than their counterparts without sleep disorders among patients with type 2 diabetes.

Conclusions

These findings suggest that sleep disorders are significantly associated with an increased risk of dementia in patients with new‐onset type 2 diabetes.
A controversial topic in juvenile idiopathic arthritis: Association between biologic agents and malignancy
Authors: Koker Oya , Sahin Sezgin , Adrovic Amra , Yildiz Mehmet , Barut Kenan , Gulle Bugra , Eker Omeroglu Rukiye , Kasapcopur Ozgur
Published: July 2020

Objective

Over the last 2 decades, the usage of biological agents in the treatment of juvenile idiopathic arthritis (JIA) has been a successful and promising approach in controlling disease activity and preventing chronic sequelae. However, there are ongoing concerns about the long‐term safety data and side‐effect profile. We aimed to present preliminary data on the incidence of malignancy in patients with JIA treated with biological agents versus the general population rates in Turkey.

Method

A single‐center hospital‐based cohort study was performed to analyze cancer occurrence among JIA patients treated with biologic agents during the observation period between January 2004 and May 2019. As reference data for direct standardization, age, gender, and calendar year‐specific incidence rates from the Turkish cancer registry were used. The standardized incidence ratio (SIR, ratio of cancers observed to expected) was generated with 95% confidence intervals.

Results

The study sample consisted of 1023 JIA patients who had been treated with biologic or non‐biologic agents. In the biologic‐experienced group (n = 656), the mean age (at the study) was 16.7 ± 5.6 years. The mean length of follow‐up was 9.9 ± 5.0 years. One cancer was detected within the observation period (SIR: 1.3, 95% CI: 0.06‐6.3). The patient was an 18‐year‐old male who had previously received etanercept and tocilizumab until the diagnosis of the hematologic malignancy (SIR: 2.5, 95% CI: 0.1‐12.6).

Conclusion

Patients treated with biologic agents appeared to have an increased rate of incident hematologic malignancy versus the general population in Turkey. However, before mentioning a clear causal relationship, other potential contributing factors should be taken into consideration.
Semi‐portable solar power to facilitate continuous operation of technology in the field
Authors: Proppe Darren S. , Pandit Meelyn M. , Bridge Eli S. , Jasperse Philip , Holwerda Charles
Published: July 2020

The use of technology in field ecology is increasing rapidly and many applications require that equipment operates autonomously for weeks, months or even years. While reducing power requirements can extend the battery life of many field devices, research time frames are always limited without renewable power. However, commercially available units that provide autonomous solar power are either prohibitively expensive or too small to sustain continuous operation for many field devices.

We describe a semi‐portable, field deployable solar unit that can provide sustainable power for a wide variety of field devices, including passive acoustic recorders, motion‐activated cameras, speakers and microcomputers. Depending on power needs, these units can be built in‐house for only a few hundred dollars (USD) with minimal access to tools or shop facilities. Further, we provide information on how to calculate power requirements and modify the system design to accommodate user needs.

We have used these units effectively in the field for six research seasons, with continuous autonomous operation varying between 2 weeks and 8 months. Batteries and other parts are easily accessed and replaced if needed.

Our example system can be modified to provide different output voltage (e.g. 12, 5 V), or to power audio speakers. We also describe a switch that can be placed within the unit to regulate power production to certain times of the day or week. Our aim is to facilitate the use of electronics in the field for ecologists who may lack funding, time or the expertise to design a system independently.
Low‐dose hydrocortisone in patients with COVID‐19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan
Authors: Petersen Marie Warrer , Meyhoff Tine Sylvest , Helleberg Marie , Kjær Maj‐Brit Nørregaard , Granholm Anders , Hjortsø Carl Johan Steensen , Jensen Thomas Steen , Møller Morten Hylander , Hjortrup Peter Buhl , Wetterslev Mik , Vesterlund Gitte Kingo , Russell Lene , Jørgensen Vibeke Lind , Tjelle Klaus , Benfield Thomas , Ulrik Charlotte Suppli , Andreasen Anne Sofie , Mohr Thomas , Bestle Morten H. , Poulsen Lone Musaeus , Hitz Mette Friberg , Hildebrandt Thomas , Knudsen Lene Surland , Møller Anders , Sølling Christoffer Grant , Brøchner Anne Craveiro , Rasmussen Bodil Steen , Nielsen Henrik , Christensen Steffen , Strøm Thomas , Cronhjort Maria , Wahlin Rebecka Rubenson , Jakob Stephan , Cioccari Luca , Venkatesh Balasubramanian , Hammond Naomi , Jha Vivekanand , Myatra Sheila Nainan , Gluud Christian , Lange Theis , Perner Anders
Published: July 2020

Introduction

Severe acute respiratory syndrome coronavirus‐2 has caused a pandemic of coronavirus disease (COVID‐19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID‐19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID‐19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all‐cause mortality at day 28, day 90, and 1 year; and health‐related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID‐19 and severe hypoxia.
Disparities in Care: The Role of Race on the Utilization of Physical Restraints in the Emergency Setting
Authors: Schnitzer Kristina , Merideth Flannery , Macias‐Konstantopoulos Wendy , Hayden Douglas , Shtasel Derri , Bird Suzanne
Published: July 2020

Objective

Race‐based bias in health care occurs at organizational, structural, and clinical levels and impacts emergency medical care. Limited literature exists on the role of race on patient restraint in the emergency setting. This study sought to examine the role of race in physical restraint in an emergency department (ED) at a major academic medical center.

Methods

Retrospective chart analysis was performed, querying all adult ED visits over a 2‐year period (2016–2018) at Massachusetts General Hospital. The associations between race and restraint and selected covariates (sex, insurance, age, diagnosis, homelessness, violence) were analyzed.

Results

Of the 195,092 unique ED visits by 120,469 individuals over the selected period, 2,658 (1.4%) involved application of a physical restraint by health care providers. There was a significant effect of race on restraint (p < 0.0001). The risk ratio (RR) for Asian patients compared to white patients was 0.71 (95% confidence interval [CI] = 0.55 to 0.92, p = 0.009). The RR for Black patients compared to white patients was 1.22 (95% CI = 1.05 to 1.40, p = 0.007). Visits with patients having characteristics of male sex, public or no insurance, younger age, diagnoses pertaining to substance use, diagnoses pertaining to psychotic or bipolar disorders, current homelessness, and a history of violence were more likely to result in physical restraint.

Conclusions

There was a significant effect of race on restraint that remained when controlling for sex, insurance, age, diagnosis, homelessness, and history of violence, all of which additionally conferred independent effects on risk. These results warrant a careful examination of current practices and potential biases in utilization of restraint in emergency settings.
Context‐dependent behaviour and connectivity of recolonizing brown bear populations identify transboundary conservation challenges in Central Europe
Authors: Recio M. R. , Knauer F. , Molinari‐Jobin A. , Huber Đ. , Filacorda S. , Jerina K.
Published: July 2020

Following historical restrictions to isolated and patchy populations, large carnivores like the brown bear Ursus arctos are recolonizing areas of their historical range in Europe. This process is of particular interest in the Alps and the Dinaric Mountains in Central Europe, the largest mountain range in the continent and of transboundary conservation interest. To assist policies focused on the expansion of bears in this region, we conducted habitat selection analyses accounting for different behaviour between three populations (Trentino, pre‐Alps and Dinaric) where bears have adapted to different intensities of human persecution. We then identified the landscape connectivity between these fragmented populations that could provide viable habitat and stepping‐stone patches for recolonization. To handle individual and population differences in space‐use, we modelled habitat selection per population from an individual‐level and integrated results into a multi‐population model using scale‐integrated resource selection functions. We then calculated connectivity indices per patch and the contribution of various countries involved in bear management in the region to enhancing connectivity. Bears mostly selected forests across all populations while preferences for other variables differed among populations and across scales. Bears in the highly humanized habitats of the Trentino selected the most intricate topography, where they could more easily find refuge. Suitable but fragmented habitat patches were common all over the study area with the most suitable habitat in the pre‐Alpine and Dinaric populations. However, the Trentino and pre‐Alp included the patches of maximum/medium priority as stepping‐stones to connect these populations. Transboundary initiatives for the conservation of existing habitat and the facilitation of connectivity are required to promote current bear expansion and reduce conflicts with humans. Our framework provides insight into the adaptive behaviour of large carnivores in human‐dominated landscapes in a conservation context.
Adolescent cannabis and tobacco use are associated with opioid use in young adulthood—12‐year longitudinal study in an urban cohort
Authors: Thrul Johannes , Rabinowitz Jill A. , Reboussin Beth A. , Maher Brion S. , Ialongo Nicholas S.
Published: July 2020

Background and aims

Cannabis, tobacco and alcohol use are prevalent among youth in the United States and may be risk factors for opioid use. The current study aimed at investigating associations between developmental trajectories of cannabis, tobacco and alcohol use in adolescence and opioid use in young adulthood in an urban cohort over the span of 12 years.

Design

Cohort study of adolescents originally recruited for a randomized prevention trial with yearly assessments into young adulthood.

Setting

Nine urban elementary schools in Baltimore, MD in the United States.

Participants

Participants (n = 583, 86.8% African American, 54.7% male) were originally recruited as first grade students.

Measurements

Cannabis, tobacco and alcohol use were assessed annually from ages 14–18 years and opioid use from ages 19–26. Socio‐demographics were assessed at age 6. Intervention status was also randomly assigned at age 6. Gender, race, free/reduced‐priced lunch and intervention status were included as covariates in individual and sequential growth models.

Findings

There were significant positive associations between the cannabis use intercept at age 14 and the opioid use intercept at age 19 (beta = 1.43; P = 0.028), the tobacco use intercept at age 14 and the opioid use intercept at age 19 (beta = 0.82; P = 0.042). Specifically, more frequent use of cannabis or tobacco at age 14 was associated with more frequent use of opioids at age 19.

Conclusions

Cannabis and tobacco use in early adolescence may be risk factors for opioid use in young adulthood among African Americans living in urban areas.
Correlation of fecal metabolomics and gut microbiota in mice with endometriosis
Authors: Ni Zhexin , Sun Shuai , Bi Yanli , Ding Jie , Cheng Wen , Yu Jin , Zhou Ling , Li Mingqing , Yu Chaoqin
Published: July 2020

Problem

Endometriosis (EMS) is a chronic inflammatory disease with unclear pathogenesis. Three studies have uncovered the influence of gut microbiota on mice with EMS, but no study has investigated the characteristics of fecal metabolomics to determine some important clues on EMS. This research aims to uncover the interaction between fecal metabolomics and gut microbiota in EMS mice.

Method of study

Female C57BL/6J mice were used to construct the EMS model. Non‐target metabolomics was applied to detect the fecal metabolites of EMS mice. The 16s rRNA sequencing was used for clarifying the composition of the gut microbiota. The functional characteristics of gut microbiota were analyzed using the PICRUSt. The receiver operator characteristic curve (ROC) analysis was utilized for determining the potential important differential metabolites, and the Spearman correlation coefficient was applied for expressing the correlation between the important differential metabolites and gut microbiota.

Results

A total of 156 named differential metabolites were screened. The diversity and the abundance of gut microbiota in EMS mice decreased. Eleven pathways were involved in the differential metabolites and the functional prediction of gut microbiota, among which the second bile acid biosynthesis and alpha‐linolenic acid (ALA) metabolism were the significant enrichment pathways. The increased abundance of chenodeoxycholic and ursodeoxycholic acids and the decreased abundance of ALA and 12,13‐EOTrE were found in the feces of EMS mice.

Conclusion

The abnormal fecal metabolites, which are influenced by dysbacteriosis, may be the characteristics of EMS mice and can be the potential important indices to distinguish the disease.
Muheza approach: a sustainable mesh hernia service in a resource‐poor setting and developing a national methodology to hernia surgery in Tanzania
Authors: Hendra Louise , Kibaja John , Kibula Emanuel , Szymankiewicz Mark
Published: July 2020

Background

Hernias are amongst the most common general surgical problems worldwide. In 2019, an estimated 800 000 inguinal hernias remain untreated in Tanzania. Furthermore, only 5% of hernias in Africa are repaired with mesh due to costs, resulting in high recurrence rates. We describe the establishment of a safe, sustainable and affordable mesh hernia programme in Tanzania.

Methods

Hernia repairs were performed by a UK Consultant General Surgeon and two Tanzanian Surgical Assistant Medical Officers between November 2018 and April 2019. Tanzanian Assistant Medical Officers were taught in a modular fashion. Polyethylene ‘mosquito net’ mesh was sterilized using a steam autoclave on site. A standardized approach to intraoperative technique and perioperative care was adopted. Patients were followed up and a registry maintained.

Results

A total of 50 mesh hernia repairs were performed on all‐comers between November 2018 and April 2019. One additional hernia repair was carried out without mesh as the hernia contained perforated bowel with faecal contamination. Of the 50 patients, 47 were followed up. At 2 weeks, none were found to have recurrence, none had evidence of infection and none reported numbness. Of the 47 patients, nine reported low‐grade discomfort. On further follow‐up, the pain resolved in seven of the nine patients, and the remaining two reported persistent low‐grade discomfort (both recurrent hernias with the reported pain less than preoperatively).

Conclusion

Proposals have been accepted for a Tanzania National Hernia Project, which aims to establish mesh repair as the gold‐standard approach to inguinal hernia surgery across Tanzania. Through education and collaboration, this project hopes to address the major outstanding health issue of untreated hernias in Tanzania.
Retrorenal fat predicts grade C pancreatic fistula after pancreaticoduodenectomy
Authors: Kopljar Mario , Čoklo Miran , Krstačić Antonija , Krstačić Goran , Jeleč Vjekoslav , Zovak Mario , Pavić Roman , Kondža Goran
Published: July 2020

Background

Pancreatic fistula after pancreaticoduodenectomy is one of the most severe complications with mortality rates as high as 45%, and the prediction of most severe form of fistula (grade C) is crucial for successful management of patients who are to undergo cephalic pancreatoduodenectomy. It has been found that the amount of abdominal fat may predict grade C postoperative pancreatic fistula. In this study, we analysed the value of retrorenal fat thickness in the prediction of grade C pancreatic fistula.

Methods

A total of 140 patients who underwent pancreaticoduodenectomy were retrospectively analysed. Retrorenal fat thickness and intra‐abdominal fat, expressed as total fat area, visceral fat area and subcutaneous fat area, were determined from computed tomography slices using the known range of attenuation values (−190 to −30). Blood loss, operating time, pancreatic texture and main pancreatic duct diameter as well as body mass index were also analysed.

Results

Retrorenal fat thickness (P = 0.0004), duct diameter (P = 0.0008), subcutaneous fat area (P = 0.023) and total fat area (P = 0.014) were found to be significant predictors of grade C pancreatic fistula.

Conclusion

Although retrorenal fat tissue thickness may seem robust, it is a simple measure that can be used to predict the most severe grade of pancreatic fistula after pancreaticoduodenectomy.
Quantitative prediction of bone mineral density by using bone turnover markers in response to antiresorptive agents in postmenopausal osteoporosis: A model‐based meta‐analysis
Authors: Wu Junyi , Wang Chen , Li Guo‐Fu , Tang En‐Tzu , Zheng Qingshan
Published: July 2020

Aims

This study aimed to predict time course of bone mineral density (BMD) by using corresponding response of bone turnover markers (BTMs) in women with postmenopausal osteoporosis under antiresorptive treatments.

Methods

Data were extracted from literature searches in accessible public database. Time courses of percent change from baseline in serum C‐telopeptide of type 1 collagen (sCTX) and N‐telopeptide of type 1 collagen were described by complex exponential onset models. The relationship between BTM changes and BMD changes at lumbar spine and total hip was described using a multiscale indirect response model.

Results

The dataset included 41 eligible published trials of 5 US‐approved antiresorptive agents (alendronate, ibandronate, risedronate, zoledronic acid and denosumab), containing over 28 800 women with postmenopausal osteoporosis. The time courses of BTM changes for different drugs were differentiated by maximal effect and onset rate in developed model, while sCTX responses to zoledronic acid and denosumab were captured by another model formation. Furthermore, asynchronous relationship between BTMs and BMD was described by a bone remodelling‐based semimechanistic model, including zero‐order production and first‐order elimination induced by N‐telopeptide of type 1 collagen and sCTX, separately. After external and informative validations, the developed models were able to predict BMD increase using 1‐year data.

Conclusion

This exploratory analysis built a quantitative framework linking BTMs and BMD among antiresorptive agents, as well as a modelling approach to enhance comprehension of dynamic relationship between early and later endpoints among agents in a certain mechanism of action. Moreover, the developed models can offer predictions of BMD from BTMs supporting early drug development.
Temperature as a modulator of sexual selection
Authors: García‐Roa Roberto , Garcia‐Gonzalez Francisco , Noble Daniel W.A. , Carazo Pau
Published: July 2020

A central question in ecology and evolution is to understand why sexual selection varies so much in strength across taxa; it has long been known that ecological factors are crucial to this. Temperature is a particularly salient abiotic ecological factor that modulates a wide range of physiological, morphological and behavioural traits, impacting individuals and populations at a global taxonomic scale. Furthermore, temperature exhibits substantial temporal variation (e.g. daily, seasonally and inter‐seasonally), and hence for most species in the wild sexual selection will regularly unfold in a dynamic thermal environment. Unfortunately, studies have so far almost completely neglected the role of temperature as a modulator of sexual selection. Here, we outline the main pathways through which temperature can affect the intensity and form (i.e. mechanisms) of sexual selection, via: (i) direct effects on secondary sexual traits and preferences (i.e. trait variance, opportunity for selection and trait–fitness covariance), and (ii) indirect effects on key mating parameters, sex‐specific reproductive costs/benefits, trade‐offs, demography and correlated abiotic factors. Building upon this framework, we show that, by focusing exclusively on the first‐order effects that environmental temperature has on traits linked with individual fitness and population viability, current global warming studies may be ignoring eco‐evolutionary feedbacks mediated by sexual selection. Finally, we tested the general prediction that temperature modulates sexual selection by conducting a meta‐analysis of available studies experimentally manipulating temperature and reporting effects on the variance of male/female reproductive success and/or traits under sexual selection. Our results show a clear association between temperature and sexual selection measures in both sexes. In short, we suggest that studying the feedback between temperature and sexual selection processes may be vital to developing a better understanding of variation in the strength of sexual selection in nature, and its consequences for population viability in response to environmental change (e.g. global warming).
Questions Can Answer Questions About Mechanisms of Preschoolers’ Selective Word Learning
Authors: Luchkina Elena , Morgan James L. , Williams Deijah J. , Sobel David M.
Published: July 2020

This study examined how inferences about epistemic competence and generalized labeling errors influence children’s selective word learning. Three‐ to 4‐year‐olds (N = 128) learned words from informants who asked questions about objects, mentioning either correct or incorrect labels. Such questions do not convey stark differences in informants’ epistemic competence. Inaccurate labels, however, generate error signals that can lead to weaker encoding of novel information. Preschoolers retained novel labels from both informants but were slower to respond in the Inaccurate Labeler condition. When the test procedure was not sensitive to the strength of information encoding, children performed above chance in both conditions and their response times did not differ. These results suggest that epistemic‐level inferences and error generalizations influence preschoolers’ selective word learning concurrently.
MASP2 levels are elevated in thrombotic microangiopathies: association with microvascular endothelial cell injury and suppression by anti-MASP2 antibody narsoplimab
Authors: Elhadad S , Chapin J , Copertino D , Van Besien K , Ahamed J , Laurence J
Published: July 2020

Involvement of the alternative complement pathway (AP) in microvascular endothelial cell (MVEC) injury characteristic of a thrombotic microangiopathy (TMA) is well documented. However, the role of the lectin pathway (LP) of complement has not been explored. We examined mannose-binding lectin associated serine protease (MASP2), the effector enzyme of the LP, in thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome and post-allogeneic hematopoietic stem cell transplantation (alloHSCT) TMAs. Plasma MASP2 and terminal complement component sC5b-9 levels were assessed by enzyme-linked immunosorbent assay (ELISA). Human MVEC were exposed to patient plasmas, and the effect of the anti-MASP2 human monoclonal antibody narsoplimab on plasma-induced MVEC activation was assessed by caspase 8 activity. MASP2 levels were highly elevated in all TMA patients versus controls. The relatively lower MASP2 levels in alloHSCT patients with TMAs compared to levels in alloHSCT patients who did not develop a TMA, and a significant decrease in variance of MASP2 levels in the former, may reflect MASP2 consumption at sites of disease activity. Plasmas from 14 of the 22 TMA patients tested (64%) induced significant MVEC caspase 8 activation. This was suppressed by clinically relevant levels of narsoplimab (1·2 μg/ml) for all 14 patients, with a mean 65·7% inhibition (36.8–99.4%; P < 0·0001). In conclusion, the LP of complement is activated in TMAs of diverse etiology. Inhibition of MASP2 reduces TMA plasma-mediated MVEC injury in vitro. LP inhibition therefore may be of therapeutic benefit in these disorders.
The alternative complement pathway in ANCA-associated vasculitis: further evidence and a meta-analysis
Authors: Moiseev S , Lee J M , Zykova A , Bulanov N , Novikov P , Gitel E , Bulanova M , Safonova E , Shin J I , Kronbichler A , Jayne D R W
Published: July 2020

We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. The median concentrations of MAC, C5a, C3a and factor B were higher in active AAV patients (P < 0·001). Achievement of remission was associated with reductions in C3a (P = 0·005), C5a (P = 0·035) and factor B levels (P = 0·045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered into the meta-analysis. Plasma MAC, C5a and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.
Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1
Authors: Brownstein Zippora , Gulsuner Suleyman , Walsh Tom , Martins Fábio T.A. , Taiber Shahar , Isakov Ofer , Lee Ming K. , Bordeynik‐Cohen Mor , Birkan Maria , Chang Weise , Casadei Silvia , Danial‐Farran Nada , Abu‐Rayyan Amal , Carlson Ryan , Kamal Lara , Arnthórsson Asgeir Ö. , Sokolov Meirav , Gilony Dror , Lipschitz Noga , Frydman Moshe , Davidov Bella , Macarov Michal , Sagi Michal , Vinkler Chana , Poran Hana , Sharony Reuven , Samra Nadra , Zvi Na'ama , Baris‐Feldman Hagit , Singer Amihood , Handzel Ophir , Hertzano Ronna , Ali‐Naffaa Doaa , Ruhrman‐Shahar Noa , Madgar Ory , Sofrin‐Drucker Efrat , Peleg Amir , Khayat Morad , Shohat Mordechai , Basel‐Salmon Lina , Pras Elon , Lev Dorit , Wolf Michael , Steingrimsson Eirikur , Shomron Noam , Kelley Matthew W. , Kanaan Moien N. , Allon‐Shalev Stavit , King Mary‐Claire , Avraham Karen B.
Published: July 2020

Mutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness‐associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity. Genomic DNA samples from informative relatives of 88 multiplex families, all of self‐identified Jewish ancestry, with either non‐syndromic or syndromic hearing loss, were sequenced for known and candidate deafness genes using the HEar‐Seq gene panel. The genetic causes of hearing loss were identified for 60% of the families. One gene was encountered for the first time in human hearing loss: ATOH1 (Atonal), a basic helix‐loop‐helix transcription factor responsible for autosomal dominant progressive hearing loss in a five‐generation family. Our results show that genomic sequencing with a gene panel dedicated to hearing loss is effective for genetic diagnoses in a diverse population. Comprehensive sequencing enables well‐informed genetic counseling and clinical management by medical geneticists, otolaryngologists, audiologists, and speech therapists and can be integrated into newborn screening for deafness.
Knowledge‐Assisted Comparative Assessment of Breast Cancer using Dynamic Contrast‐Enhanced Magnetic Resonance Imaging
Authors: Nie K. , Baltzer P. , Preim B. , Mistelbauer G.
Published: July 2020

Breast perfusion data are dynamic medical image data that depict perfusion characteristics of the investigated tissue. These data consist of a series of static datasets that are acquired at different time points and aggregated into time intensity curves (TICs) for each voxel. The characteristics of these TICs provide important information about a lesion's composition, but their analysis is time‐consuming due to their large number. Subsequently, these TICs are used to classify a lesion as benign or malignant. This lesion scoring is commonly done manually by physicians and may therefore be subject to bias. We propose an approach that addresses both of these problems by combining an automated lesion classification with a visual confirmatory analysis, especially for uncertain cases. Firstly, we cluster the TICs of a lesion using ordering points to identify the clustering structure (OPTICS) and then visualize these clusters. Together with their relative size, they are added to a library. We then model fuzzy inference rules by using the lesion's TIC clusters as antecedents and its score as consequent. Using a fuzzy scoring system, we can suggest a score for a new lesion. Secondly, to allow physicians to confirm the suggestion in uncertain cases, we display the TIC clusters together with their spatial distribution and allow them to compare two lesions side by side. With our knowledge‐assisted comparative visual analysis, physicians can explore and classify breast lesions. The true positive prediction accuracy of our scoring system achieved 71.4 % in one‐fold cross‐validation using 14 lesions.
Hairy Slices II: Depth Cues for Visualizing 3D Streamlines Through Cutting Planes
Authors: Stevens Andrew H. , Ware Colin , Butkiewicz Thomas , Rogers David , Abram Greg
Published: July 2020

Visualizing 3D vector fields is challenging because of occlusion problems and the difficulty of providing depth cues that adequately support the perception of direction of flow lines in 3D space. One of the depth cues that has proven most valuable for the perception of other kinds of 3D data, notably 3D networks and 3D point clouds, is structure‐from‐motion (also called the Kinetic Depth Effect); another powerful depth cue is stereoscopic viewing. We carried out an experiment of the perception of direction for short streamlines passing through a cutting plane. The conditions included viewing with and without structure‐from‐motion and with and without stereoscopic depth. Conditions also include comparing streamtubes to lines. The results show that for this particular task, stereo provided an effective depth cue, but structure‐from‐motion did not. Ringed streamtubes and streamcones provided good 3D direction information, even without stereoscopic viewing. We conclude with guidelines for viewing slices through vector fields.
MotionGlyphs: Visual Abstraction of Spatio‐Temporal Networks in Collective Animal Behavior
Authors: Cakmak E. , Schäfer H. , Buchmüller J. , Fuchs J. , Schreck T. , Jordan A. , Keim D.
Published: July 2020

Domain experts for collective animal behavior analyze relationships between single animal movers and groups of animals over time and space to detect emergent group properties. A common way to interpret this type of data is to visualize it as a spatio‐temporal network. Collective behavior data sets are often large, and may hence result in dense and highly connected node‐link diagrams, resulting in issues of node‐overlap and edge clutter. In this design study, in an iterative design process, we developed glyphs as a design for seamlessly encoding relationships and movement characteristics of a single mover or clusters of movers. Based on these glyph designs, we developed a visual exploration prototype, MotionGlyphs, that supports domain experts in interactively filtering, clustering, and animating spatio‐temporal networks for collective animal behavior analysis. By means of an expert evaluation, we show how MotionGlyphs supports important tasks and analysis goals of our domain experts, and we give evidence of the usefulness for analyzing spatio‐temporal networks of collective animal behavior.
Classifier‐Guided Visual Correction of Noisy Labels for Image Classification Tasks
Authors: Bäuerle A. , Neumann H. , Ropinski T.
Published: July 2020

Training data plays an essential role in modern applications of machine learning. However, gathering labeled training data is time‐consuming. Therefore, labeling is often outsourced to less experienced users, or completely automated. This can introduce errors, which compromise valuable training data, and lead to suboptimal training results. We thus propose a novel approach that uses the power of pretrained classifiers to visually guide users to noisy labels, and let them interactively check error candidates, to iteratively improve the training data set. To systematically investigate training data, we propose a categorization of labeling errors into three different types, based on an analysis of potential pitfalls in label acquisition processes. For each of these types, we present approaches to detect, reason about, and resolve error candidates, as we propose measures and visual guidance techniques to support machine learning users. Our approach has been used to spot errors in well‐known machine learning benchmark data sets, and we tested its usability during a user evaluation. While initially developed for images, the techniques presented in this paper are independent of the classification algorithm, and can also be extended to many other types of training data.
Understanding the Design Space and Authoring Paradigms for Animated Data Graphics
Authors: Thompson J. , Liu Z. , Li W. , Stasko J.
Published: July 2020

Creating expressive animated data graphics often requires designers to possess highly specialized programming skills. Alternatively, the use of direct manipulation tools is popular among animation designers, but these tools have limited support for generating graphics driven by data. Our goal is to inform the design of next‐generation animated data graphic authoring tools. To understand the composition of animated data graphics, we survey real‐world examples and contribute a description of the design space. We characterize animated transitions based on object, graphic, data, and timing dimensions. We synthesize the primitives from the object, graphic, and data dimensions as a set of 10 transition types, and describe how timing primitives compose broader pacing techniques. We then conduct an ideation study that uncovers how people approach animation creation with three authoring paradigms: keyframe animation, procedural animation, and presets & templates. Our analysis shows that designers have an overall preference for keyframe animation. However, we find evidence that an authoring tool should combine these three paradigms as designers’ preferences depend on the characteristics of the animated transition design and the authoring task. Based on these findings, we contribute guidelines and design considerations for developing future animated data graphic authoring tools.
Visual Analysis of the Finite‐Time Lyapunov Exponent
Authors: Sagristà Antoni , Jordan Stefan , Sadlo Filip
Published: July 2020

In this paper, we present an integrated visual analytics approach to support the parametrization and exploration of flow visualization based on the finite‐time Lyapunov exponent. Such visualization of time‐dependent flow faces various challenges, including the choice of appropriate advection times, temporal regions of interest, and spatial resolution. Our approach eases these challenges by providing the user with context by means of parametric aggregations, with support and guidance for a more directed exploration, and with a set of derived measures for better qualitative assessment. We demonstrate the utility of our approach with examples from computation fluid dynamics and time‐dependent dynamical systems.
Augmenting Node‐Link Diagrams with Topographic Attribute Maps
Authors: Preiner R. , Schmidt J. , Krösl K. , Schreck T. , Mistelbauer G.
Published: July 2020

We propose a novel visualization technique for graphs that are attributed with scalar data. In many scenarios, these attributes (e.g., birth date in a family network) provide ambient context information for the graph structure, whose consideration is important for different visual graph analysis tasks. Graph attributes are usually conveyed using different visual representations (e.g., color, size, shape) or by reordering the graph structure according to the attribute domain (e.g., timelines). While visual encodings allow graphs to be arranged in a readable layout, assessingcontextualinformation such as the relative similarities of attributes across the graph is often cumbersome. In contrast, attribute‐based graph reordering serves the comparison task of attributes, but typically strongly impairs the readability of thestructuralinformation given by the graph's topology. In this work, we augment force‐directed node‐link diagrams with a continuous ambient representation of the attribute context. This way, we provide a consistent overview of the graph's topological structure as well as its attributes, supporting a wide range of graph‐related analysis tasks. We resort to an intuitive height field metaphor, illustrated by a topographic map rendering using contour lines and suitable color maps. Contour lines visually connect nodes of similar attribute values, and depict their relative arrangement within the global context. Moreover, our contextual representation supports visualizing attribute value ranges associated with graph nodes (e.g., lifespans in a family network) as trajectories routed through this height field. We discuss how user interaction with both the structural and the contextual information fosters exploratory graph analysis tasks. The effectiveness and versatility of our technique is confirmed in a user study and case studies from various application domains.
Quantitative Comparison of Time‐Dependent Treemaps
Authors: Vernier E. , Sondag M. , Comba J. , Speckmann B. , Telea A. , Verbeek K.
Published: July 2020

Rectangular treemaps are often the method of choice to visualize large hierarchical datasets. Nowadays such datasets are available over time, hence there is a need for (a) treemaps that can handle time‐dependent data, and (b) corresponding quality criteria that cover both a treemap's visual quality and its stability over time. In recent years a wide variety of (stable) treemapping algorithms has been proposed, with various advantages and limitations. We aim to provide insights to researchers and practitioners to allow them to make an informed choice when selecting a treemapping algorithm for specific applications and data. To this end, we perform an extensive quantitative evaluation of rectangular treemaps for time‐dependent data. As part of this evaluation we propose a novel classification scheme for time‐dependent datasets. Specifically, we observe that the performance of treemapping algorithms depends on the characteristics of the datasets used. We identify four potential representative features that characterize time‐dependent hierarchical datasets and classify all datasets used in our experiments accordingly. We experimentally test the validity of this classification on more than 2000 datasets, and analyze the relative performance of 14 state‐of‐the‐art rectangular treemapping algorithms across varying features. Finally, we visually summarize our results with respect to both visual quality and stability to aid users in making an informed choice among treemapping algorithms. All datasets, metrics, and algorithms are openly available to facilitate reuse and further comparative studies.
A Globally Conforming Lattice Structure for 2D Stress Tensor Visualization
Authors: Wang Junpeng , Wu Jun , Westermann Rüdiger
Published: July 2020

We present a visualization technique for 2D stress tensor fields based on the construction of a globally conforming lattice. Conformity ensures that the lattice edges follow the principal stress directions and the aspect ratio of lattice elements represents the stress anisotropy. Since such a lattice structure cannot be space‐filling in general, it is constructed from multiple intersecting lattice beams. Conformity at beam intersections is ensured via a constrained optimization problem, by computing the aspect ratio of elements at intersections so that their edges meet when continued along the principal stress lines. In combination with a coloring scheme that encodes relative stress magnitudes, a global visualization is achieved. By introducing additional constraints on the positional variation of the beam intersections, coherent visualizations are achieved when external loads or material parameters are changed. In a number of experiments using non‐trivial scenarios, we demonstrate the capability of the proposed visualization technique to show the global and local structure of a given stress field.
v‐plots: Designing Hybrid Charts for the Comparative Analysis of Data Distributions
Authors: Blumenschein Michael , Debbeler Luka J. , Lages Nadine C. , Renner Britta , Keim Daniel A. , El‐Assady Mennatallah
Published: July 2020

Comparing data distributions is a core focus in descriptive statistics, and part of most data analysis processes across disciplines. In particular, comparing distributions entails numerous tasks, ranging from identifying global distribution properties, comparing aggregated statistics (e.g., mean values), to the local inspection of single cases. While various specialized visualizations have been proposed (e.g., box plots, histograms, or violin plots), they are not usually designed to support more than a few tasks, unless they are combined. In this paper, we present the v‐plot designer; a technique for authoring custom hybrid charts, combining mirrored bar charts, difference encodings, and violin‐style plots. v‐plots are customizable and enable the simultaneous comparison of data distributions on global, local, and aggregation levels. Our system design is grounded in an expert survey that compares and evaluates 20 common visualization techniques to derive guidelines for the task‐driven selection of appropriate visualizations. This knowledge externalization step allowed us to develop a guiding wizard that can tailor v‐plots to individual tasks and particular distribution properties. Finally, we confirm the usefulness of our system design and the user‐guiding process by measuring the fitness for purpose and applicability in a second study with four domain and statistic experts.
Canis: A High‐Level Language for Data‐Driven Chart Animations
Authors: Ge T. , Zhao Y. , Lee B. , Ren D. , Chen B. , Wang Y.
Published: July 2020

In this paper, we introduce Canis, a high‐level domain‐specific language that enables declarative specifications of data‐driven chart animations. By leveraging data‐enriched SVG charts, its grammar of animations can be applied to the charts created by existing chart construction tools. With Canis, designers can select marks from the charts, partition the selected marks into mark units based on data attributes, and apply animation effects to the mark units, with the control of when the effects start. The Canis compiler automatically synthesizes the Lottie animation JSON files [Aira], which can be rendered natively across multiple platforms. To demonstrate Canis’ expressiveness, we present a wide range of chart animations. We also evaluate its scalability by showing the effectiveness of our compiler in reducing the output specification size and comparing its performance on different platforms against D3.