bluuebunny/crossref_metadata_2025 huggingface dataset:
Soft Tissue Thickness Variations of the Nose: A Radiological Study
Authors: Çavuş Özkan Melekber , Yeşil Fatma , Bayramiçli İnci , Bayramiçli Mehmet
Published: January 2020

Background

Soft tissue thickness (STT) is a major factor affecting the outcome in rhinoplasty. However, limited information is found in the literature on the age- and gender-related variations of the nasal STT.

Objectives

The purpose of this study was to measure STT at various landmarks over the nasal framework and compare the age- and gender-related differences.

Methods

STT measurements were made at 11 landmarks in 325 patients by employing magnetic resonance imaging. Patients were divided into subgroups to compare the STT differences between female and male and between the age groups as young, middle age, and elderly.

Results

Soft tissue was thickest at the nasion and thinnest at the rhinion. The soft tissue coverage was significantly thicker in the male population at the supratip, tip, nasal bones, upper lateral cartilages, and alar lobules, whereas it is thicker in females at the rhinion. Average thickness of the soft tissues over the entire nasal framework increases with age except the rhinion.

Conclusions

The STT is variable over different parts of the osteocartilaginous framework. Gender and age influence the STT. The soft tissue is thicker at the distal half of the nose in male patients, and these areas become gradually thicker with age, whereas the soft tissue over the midvault becomes thinner. Increasing age presents a particular challenge to achieve predictable results in rhinoplasty, and an understanding of the soft tissue envelope allows for improved aesthetic outcome.

Level of Evidence 2
Evaluation of Selfies and Filtered Selfies and Effects on First Impressions
Authors: Cristel Robert T , Dayan Steven H , Akinosun Moriyike , Russell Parker T
Published: January 2020

Background

Selfies and filtered selfies are becoming more prevalent throughout society and in the facial plastic surgery clinic. The term “Snapchat dysmorphia” has been used to describe patients seeking procedures to look like their selfie or filtered selfie. This is particularly frequent in the Millennial population, aged 22 to 37 years.

Objectives

The authors sought to determine the effects on first impression from different photograph types: selfies, filtered selfies, a rear-facing smartphone camera, and a digital camera (DC). We hypothesize that the DC photographs will have the highest rated first impressions among evaluators despite the popularity of selfies and filtered selfies.

Methods

This study included 240 evaluators and 4 patients each completing the 4 different photograph types. The evaluators completed a survey rating first impression on various measures of success for each photograph type.

Results

A total of 960 first impressions were recorded for each of the 8 subscales, yielding 7680 individual assessments of first impression. The DC photograph was found to have the highest first impression scores among the 4 photograph types. There was no statistical difference between selfies and filtered selfies. The rear-facing smartphone camera received the lowest first impression scores.

Conclusions

Our findings indicate that the standard DC photograph taken during a preoperative consultation has higher first impressions than selfies or filtered selfies. Although “Snapchat dysmorphia” may continue to be a growing trend in the near future, our findings provide important information to discuss with patients in the preoperative visit to set realistic expectations.
Trapping starlight
Authors: Bowler Sue
Published: January 2020

Sue Bowler looks back at the interwoven early years of the RAS and photography.
A computational platform to identify origins of replication sites in eukaryotes
Authors: Dao Fu-Ying , Lv Hao , Zulfiqar Hasan , Yang Hui , Su Wei , Gao Hui , Ding Hui , Lin Hao
Published: January 2020

The locations of the initiation of genomic DNA replication are defined as origins of replication sites (ORIs), which regulate the onset of DNA replication and play significant roles in the DNA replication process. The study of ORIs is essential for understanding the cell-division cycle and gene expression regulation. Accurate identification of ORIs will provide important clues for DNA replication research and drug development by developing computational methods. In this paper, the first integrated predictor named iORI-Euk was built to identify ORIs in multiple eukaryotes and multiple cell types. In the predictor, seven eukaryotic (Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana, Pichia pastoris, Schizosaccharomyces pombe and Kluyveromyces lactis) ORI data was collected from public database to construct benchmark datasets. Subsequently, three feature extraction strategies which are k-mer, binary encoding and combination of k-mer and binary were used to formulate DNA sequence samples. We also compared the different classification algorithms’ performance. As a result, the best results were obtained by using support vector machine in 5-fold cross-validation test and independent dataset test. Based on the optimal model, an online web server called iORI-Euk (http://lin-group.cn/server/iORI-Euk/) was established for the novel ORI identification.
Natural and sexual selection shape the evolution of colour and conspicuousness in North American wood-warblers (Parulidae)
Authors: Simpson Richard K , Mistakidis Allison F , Doucet Stéphanie M
Published: January 2020

Natural and sexual selection drive colour evolution in animals. However, these different selective forces are often studied independently or without considering environmental variation. We evaluated the roles of natural and sexual selection together on colour evolution in 15 sympatric wood-warbler species, while considering the influence of variation in the light environment and visual background. We tested the influence of each selective pressure on male and female coloration and contrast against the background using avian visual models in phylogenetically controlled analyses. We found natural and sexual selection simultaneously driving cryptic and conspicuous plumage in males by acting on different body regions. For example, we found that ground-nesting species had males with conspicuous under-body plumage and cryptic upper-body plumage, showing how natural and sexual selection can drive colour evolution concordantly. We also found interesting relationships with female plumage, such as nest predation positively covarying with female contrast against the background, suggesting a cost to female conspicuousness. Our findings here showcase the complexity of selection on coloration and illustrate the importance of: (1) accounting for environmental variation when assessing how natural and sexual selection drive colour evolution; and (2) testing how multiple selection pressures are shaping colour diversity among species.
Decline in Hepatitis C Virus (HCV) Incidence in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Progress to HCV Microelimination in the United Kingdom?
Authors: Garvey Lucy J , Cooke Graham S , Smith Colette , Stingone Christoph , Ghosh Indrajit , Dakshina Subathira , Jain Lakshmi , Waters Laura J , Mahungu Tabitha , Ferro Filippo , Sood Chandni , Freeman Carolyn , Phillips Clare , Dhairyawan Rageshri , Burholt Ruth , Sharp Harriet , Ullah Sadna , Gilleece Yvonne , Brown Ashley , Orkin Chloe , Rodger Alison , Bhagani Sanjay
Published: January 2020

Background

Modeling of the London hepatitis C virus (HCV) epidemic in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV) suggested that early access to direct-acting antiviral (DAA) treatment may reduce incidence. With high rates of linkage to care, microelimination of HCV within MSM living with HIV may be realistic ahead of 2030 World Health Organization targets. We examined trends in HCV incidence in the pre- and post-DAA eras for MSM living with HIV in London and Brighton, United Kingdom.

Methods

A retrospective cohort study was conducted at 5 HIV clinics in London and Brighton between 2013 and 2018. Each site reported all acute HCV episodes during the study period. Treatment timing data were collected. Incidence rates and reinfection proportion were calculated.

Results

A total of

378 acute HCV infections were identified, comprising 292 first infections and 86 reinfections. Incidence rates of acute HCV in MSM living with HIV peaked at 14.57/1000 person-years of follow-up (PYFU; 95% confidence interval [CI], 10.95–18.20) in 2015. Rates fell to 4.63/1000 PYFU (95% CI, 2.60 to 6.67) by 2018. Time from diagnosis to starting treatment declined from 29.8 (2013) to 3.7 months (2018).

Conclusions

We observed a 78% reduction in the incidence of first HCV episode and a 68% reduction in overall HCV incidence since the epidemic peak in 2015, which coincides with wider access to DAAs in England. Further interventions to reduce transmission, including earlier access to treatment and for reinfection, are likely needed for microelimination to be achieved in this population.
Concurrent Initiation of Hepatitis C and Opioid Use Disorder Treatment in People Who Inject Drugs
Authors: Rosenthal Elana S , Silk Rachel , Mathur Poonam , Gross Chloe , Eyasu Rahwa , Nussdorf Laura , Hill Kristi , Brokus Christopher , D’Amore Aaron , Sidique Nadeera , Bijole Phyllis , Jones Miriam , Kier Randy , McCullough Dana , Sternberg David , Stafford Kristen , Sun Junfeng , Masur Henry , Kottilil Shyamasundaran , Kattakuzhy Sarah
Published: January 2020

Background

People who inject drugs have a high prevalence of hepatitis C virus (HCV) and significant disease associated with drug use; however, HCV treatment often occurs in absence of interventions to address opioid use disorder and drug use–related harms. The impact of concurrent initiation of opioid agonist therapy (OAT) on HCV treatment and drug use outcomes is unknown.

Methods

In this prospective, open-label, observational trial at a harm reduction organization’s drop-in center in Washington, DC, 100 patients with chronic HCV infection, opioid use disorder, and ongoing injection drug use were treated with sofosbuvir-velpatasvir for 12-weeks and offered buprenorphine initiation. The primary end point was sustained virologic response (SVR), and secondary end points included uptake of and retention in OAT, change in risk behavior, and determinants of SVR.

Results

Eighty-two patients (82%) achieved SVR, which was not associated with baseline OAT status (P = .33), on-treatment drug use (P >.99), or imperfect daily adherence (P = .35) but was significantly associated with completing 2 or more 28-pill bottles of sofosbuvir-velpatasvir (P < .001) and receiving OAT at week 24 (P = .01). Of 67 patients not already receiving OAT at baseline, 53 (79%) started OAT. At week 24, 68 (68%) patients were receiving OAT. Receipt of OAT was associated with fewer opiate-positive urine drug screens (P = .003), lower human immunodeficiency virus risk-taking behavior scores (P < .001), and lower rates of opioid overdose (P = .04).

Conclusions

The Novel Model of Hepatitis C Treatment as an Anchor to Prevent HIV, Initiate Opioid Agonist Therapy, and Reduce Risky Behavior study demonstrates high uptake of buprenorphine collocated with HCV treatment, and it shows that concurrent initiation of OAT with HCV treatment can result in high rates of SVR while reducing risks associated with drug use.

Clinical Trials Registration

NCT03221309.
Extensive Hospital In-Ward Clustering Revealed By Molecular Characterization of Influenza A Virus Infection
Authors: Sansone Martina , Andersson Maria , Gustavsson Lars , Andersson Lars-Magnus , Nordén Rickard , Westin Johan
Published: January 2020

Background

Nosocomial transmission of influenza A virus (InfA) infection is not fully recognized. The aim of this study was to describe the characteristics of hospitalized patients with InfA infections during an entire season and to investigate in-ward transmission at a large, acute-care hospital.

Methods

During the 2016–17 season, all hospitalized patients ≥18 years old with laboratory-verified (real-time polymerase chain reaction) InfA were identified. Cases were characterized according to age; sex; comorbidity; antiviral therapy; viral load, expressed as cycle threshold values; length of hospital stay; 30-day mortality; and whether the InfA infection met criteria for a health care–associated influenza A infection (HCAI). Respiratory samples positive for InfA that were collected at the same wards within 7 days were chosen for whole-genome sequencing (WGS) and a phylogenetic analysis was performed to detect clustering. For reference, concurrent InfA strains from patients with community-acquired infection were included.

Results

We identified a total of 435 InfA cases, of which 114 (26%) met the HCAI criteria. The overall 30-day mortality rate was higher among patients with HCAI (9.6% vs 4.6% among non-HCAI patients), although the difference was not statistically significant in a multivariable analysis, where age was the only independent risk factor for death (P < .05). We identified 8 closely related clusters (involving ≥3 cases) and another 10 pairs of strains, supporting in-ward transmission.

Conclusions

We found that the in-ward transmission of InfA occurs frequently and that HCAI may have severe outcomes. WGS may be used for outbreak investigations, as well as for evaluations of the effects of preventive measures.
Low first-year apparent survival of passerines in abandoned fields in northwestern Russia
Authors: Shitikov Dmitry , Grudinskaya Viktoria , Makarova Tatiana , Vaytina Tatiana , Fedotova Svetlana , Samsonov Stanislav , Grabovsky Alexander
Published: January 2020

First-year survival probability of migratory passerines during the period between fledging and first reproduction is a highly variable parameter that has a major effect on population dynamics. We used a long-term mark–recapture dataset (2002–2018) to examine first-year survival of 3 passerine species breeding in abandoned agricultural fields of northwestern Russia: Booted Warbler (Iduna caligata), Whinchat (Saxicola rubetra), and Western Yellow Wagtail (Motacilla flava). We banded 3,457 nestlings, including 1,363 Booted Warblers, 1,699 Whinchats, and 395 Western Yellow Wagtails, and resighted 12 Booted Warblers, 29 Whinchats, and 13 Western Yellow Wagtails in the year after fledging. We evaluated first-year apparent survival rates using Cormack-Jolly-Seber models in MARK program within the multispecies approach. We tested effect of fledge date on the first-year apparent survival. In all focal species, first-year apparent survival rates were low and reached the lower limits known for migratory passerines. We found no differences in first-year survival rates among the 3 species: the estimated average first-year apparent survival rate of all species was 0.05 ± 0.01. The fledge date had a considerable impact on first-year survival rate: later fledge dates negatively affected first-year survival. We suggest that first-year apparent survival rates in our study were low due to low natal philopatry and high mortality in the post-fledging period. Low apparent first-year survival may be a specific feature of open-nesting birds breeding in abandoned fields that are low-quality habitats because of high predation pressure.
Class A1 scavenger receptor prevents obesity-associated blood pressure elevation through suppressing overproduction of vascular endothelial growth factor B in macrophages
Authors: Zhu Xudong , Wang Yan , Zhu Liu , Zhu Ye , Zhang Kun , Wang Lei , Bai Hui , Yang Qing , Ben Jingjing , Zhang Hanwen , Li Xiaoyu , Xu Yong , Chen Qi
Published: January 2020

Aims

Dysfunctional innate immune function and inflammation contributes to the pathogenesis of obesity-associated hypertension, in which macrophage infiltration in the perivascular adipose tissue (PVAT) plays a key role. However, the mechanisms behind it are not well understood. Class A1 scavenger receptor (SR-A1) is one of the major pattern recognition receptors in modulating macrophage activity, and here, we aimed to investigate its role in obesity-associated hypertension.

Methods and results

Both diet-induced and genetic obesity were generated in mice. Deficiency in SR-A1 aggravated the obesity-induced blood pressure (BP) elevation and endothelial dysfunction in mice. The BP-elevating effect of SR-A1 deficiency was blocked by the down-regulation of vascular endothelial growth factor B (VEGF-B) in obese mice. Overexpression of VEGF-B raised BP in the obese mice but not in normal mice. Administration of fucoidan, a ligand of SR-A1, lowered BP, and VEGF-B levels in Sr-a1+/+ but not in Sr-a1−/− obese mice.

Conclusion

These results reveal a new link between PVAT and vascular biology in obesity orchestrated by the SR-A1/VEGF-B axis in macrophages. SR-A1 and VEGF-B may be promising therapeutic targets in the treatment of obesity-associated hypertension.
Is myocardial revascularization really necessary in patients with ≥50% but <70% coronary stenosis undergoing valvular surgery?
Authors: Del Forno Benedetto , Ascione Guido , Lapenna Elisabetta , Trumello Cinzia , Ruggeri Stefania , Belluschi Igor , Verzini Alessandro , Iaci Giuseppe , Ferrara David , Schiavi Davide , Meneghin Roberta , Castiglioni Alessandro , Alfieri Ottavio , De Bonis Michele
Published: January 2020

OBJECTIVES

The aim of this study is to evaluate the immediate and mid-term effects of omitting coronary artery bypass grafting in patients with moderate coronary artery stenosis who have a primary indication for valvular surgery.

METHODS

We included 77 consecutive patients admitted to our Institution for aortic or mitral valve surgery between June 2012 and June 2017 in whom a de novo diagnosis of ≥50%, but <70% coronary stenosis was made. In this cohort, the myocardial revascularization was omitted. All these patients were free from angina and ischaemia on echo and ECG.

RESULTS

There were no in-hospital deaths. In only 1 patient, acute myocardial infarction occurred postoperatively, which was immediately treated by percutaneous coronary intervention (PCI). The 6-year overall survival was 94.7 ± 2.59%. At 6 years, no cardiac deaths were recorded. At follow-up, 4 patients underwent elective PCI after a positive stress myocardial perfusion test. Only 1 patient underwent urgent PCI due to acute coronary syndrome. At 6 years, the cumulative incidence function of PCI, with death as competing risk, was 8 ± 3.9%.

CONCLUSIONS

In our experience, moderate coronary stenosis, occasionally discovered at the time of valvular heart surgery, can be safely overlooked and do not need any further treatment at follow-up in the majority of cases. Our results open up the opportunity to apply this ‘intentional omission strategy’ in different situations, such as minimally invasive heart surgery, percutaneous procedures and complex patients.
Timing of pulmonary valve replacement in patients with corrected Fallot to prevent QRS prolongation
Authors: Romeo Jamie L R , Takkenberg Johanna J M , Cuypers Judith A A E , de Groot Natasha M S , van de Woestijne Pieter , Bruining Nico , Bogers Ad J J C , Mokhles M Mostafa
Published: January 2020

OBJECTIVES

Timing of pulmonary valve replacement (PVR) remains one of the most heavily debated topics in congenital cardiac surgery. We aimed to analyse the temporal evolution of QRS duration before and after PVR.

METHODS

We included 158 consecutive patients who underwent PVR after previous correction with transannular patch. All 3549 available serial standard 12-lead surface QRS measurements of 158 (100%) patients were analysed with linear mixed-effect modelling.

RESULTS

PVR was performed at a mean age of 28.0 ± 10.7 years, 23.4 ± 8.4 years after correction. Hospital survival was 98.1%. A longer time interval between ToF correction and PVR (P < 0.001), and an older age at correction (P = 0.015) were predictive of progressive QRS prolongation after PVR. Women on average had a shorter QRS duration (P = 0.005) after PVR. The model predicted that in patients corrected early (model age 0.5 years), PVR within 17 years after correction leads to narrowing or stabilization of QRS width. PVR beyond 17 years was associated with prolongation of QRS duration. In a patient corrected late (model age 5 years), PVR has to be performed within 15 years after correction to prevent prolongation. Finally, a longer time period between correction and PVR was associated with an increased hazard of cardiac death (hazard ratio 1.097, 95% confidence interval 1.002–1.200).

CONCLUSIONS

Prolongation of QRS duration after PVR was associated with a longer time between correction and PVR, older age at correction and male sex. Prevention of progressive QRS prolongation by earlier PVR can potentially reduce the hazard of adverse events after PVR.
Experimental Insights for International Legal Theory
Authors: van Aaken Anne
Published: January 2020

Insights from experimental psychology and economics have rarely been applied to the study of international law and never to the study of international legal theory. This article applies them to socio-legal international theory that has grosso modo two important background paradigms with several variants: rationalist and constructivist. In both paradigms, the interest in understanding and explaining international law by uncovering causal mechanisms in international cooperation and compliance and in asking how cooperation is sustained in a system as decentralized as international law is paramount. In both, fundamental assumptions regarding the behaviour of actors are made. However, regardless of the theoretical standpoint, both fall short of experimental evidence about their behavioural assumptions. The article uses experimental evidence provided by public good games as a conceptualization of how social order is constructed and upheld in systems without central authority such as international law. It aims to illuminate the behavioural basis of important building blocks of international cooperation and law by discussing the preferences of states and strategic interaction, reciprocity, sanctions, communication and trust as well as consent and legitimacy, reflecting on what the experimental insights teach us on the assumptions of rationalist and constructivist approaches to international legal theory. These experiments are one means to test behavioural assumptions in international legal theory.
Total RNA sequencing reveals multilevel microbial community changes and functional responses to wood ash application in agricultural and forest soil
Authors: Bang-Andreasen Toke , Anwar Muhammad Zohaib , Lanzén Anders , Kjøller Rasmus , Rønn Regin , Ekelund Flemming , Jacobsen Carsten Suhr
Published: January 2020

Recycling of wood ash from energy production may counteract soil acidification and return essential nutrients to soils. However, wood ash amendment affects soil physicochemical parameters that control composition and functional expression of the soil microbial community. Here, we applied total RNA sequencing to simultaneously assess the impact of wood ash amendment on the active soil microbial communities and the expression of functional genes from all microbial taxa. Wood ash significantly affected the taxonomic (rRNA) as well as functional (mRNA) profiles of both agricultural and forest soil. Increase in pH, electrical conductivity, dissolved organic carbon and phosphate were the most important physicochemical drivers for the observed changes. Wood ash amendment increased the relative abundance of the copiotrophic groups Chitinonophagaceae (Bacteroidetes) and Rhizobiales (Alphaproteobacteria) and resulted in higher expression of genes involved in metabolism and cell growth. Finally, total RNA sequencing allowed us to show that some groups of bacterial feeding protozoa increased concomitantly to the enhanced bacterial growth, which shows their pivotal role in the regulation of bacterial abundance in soil.
Compilation of Escherichia coli K-12 outer membrane phage receptors – their function and some historical remarks
Authors: Hantke Klaus
Published: January 2020

Many Escherichia coli phages have been sequenced, but in most cases their sequences alone do not suffice to predict their host specificity. Analysis of phage resistant E. coli K-12 mutants have uncovered a certain set of outer membrane proteins and polysaccharides as receptors. In this review, a compilation of E. coli K12 phage receptors is provided and their functional characterization, often driven by studies on phage resistant mutants, is discussed in the historical context. While great progress has been made in this field thus far, several proteins in the outer membrane still await characterization as phage receptors.
Extracting novel hypotheses and findings from RNA-seq data
Authors: Doughty Tyler , Kerkhoven Eduard
Published: January 2020

Over the past decade, improvements in technology and methods have enabled rapid and relatively inexpensive generation of high-quality RNA-seq datasets. These datasets have been used to characterize gene expression for several yeast species and have provided systems-level insights for basic biology, biotechnology and medicine. Herein, we discuss new techniques that have emerged and existing techniques that enable analysts to extract information from multifactorial yeast RNA-seq datasets. Ultimately, this minireview seeks to inspire readers to query datasets, whether previously published or freshly obtained, with creative and diverse methods to discover and support novel hypotheses.
A new method of improving global geopotential models regionally using GNSS/levelling data
Authors: Liang Wei , Pail Roland , Xu Xinyu , Li Jiancheng
Published: January 2020

In this paper, a new method for regionally improving global geopotential models (GGMs) with global navigation satellite system (GNSS)/levelling data is proposed. In this method, the GNNS/levelling data are at first converted to disturbing potential data with inverse Bruns’ formula. Then the systematic errors in disturbing potential data are removed with a three-parameter correction surface. Afterwards, the disturbing potential data on the Earth's surface are downward continued to the surface of an inner sphere with inverse Poisson's integral equation. Global disturbing potential data on the whole sphere could be achieved with combination of the downward continued data and the GGM-derived data. At last, the final regionally improved geopotential model (RIGM) could be recovered from the disturbing potential data using least-squares method. Four RIGM models for Qingdao (QD) are determined based on four different sets of GNSS/levelling data points to validate the capability of the method. The standard deviation of height anomaly errors of RIGM-QDs are nearly 25 and 30 per cent on average smaller than Earth Gravity Model 2008 (EGM2008) on checkpoints and data points, respectively. This means that the RIGM-QDs fit better to the GNSS/levelling network in this area than EGM2008. The results show that the proposed method is successful at improving GGMs in regional area with regional GNSS/levelling data.
Mutation m.3395A > G in MT-ND1 leads to variable pathologic manifestations
Authors: Gutiérrez Cortés Nicolás , Pertuiset Claire , Dumon Elodie , Börlin Marine , Da Costa Barbara , Le Guédard Marina , Stojkovic Tanya , Loundon Natalie , Rouillon Isabelle , Nadjar Yann , Letellier Thierry , Jonard Laurence , Marlin Sandrine , Rocher Christophe
Published: January 2020

A non-synonymous mtDNA mutation, m.3395A > G, which changes tyrosine in position 30 to cysteine in p.MT-ND1, was found in several patients with a wide range of clinical phenotypes such as deafness, diabetes and cerebellar syndrome but no Leber’s hereditary optic neuropathy. Although this mutation has already been described, its pathogenicity has not been demonstrated. Here, it was found isolated for the first time, allowing a study to investigate its pathogenicity. To do so, we constructed cybrid cell lines and carried out a functional study to assess the possible consequences of the mutation on mitochondrial bioenergetics. Results obtained demonstrated that this mutation causes an important dysfunction of the mitochondrial respiratory chain with a decrease in both activity and quantity of complex I due to a diminution of p.MT-ND1 quantity. However, no subcomplexes were found in cybrids carrying the mutation, indicating that the quality of the complex I assembly is not affected. Moreover, based on the crystal structure of p.MT-ND1 and the data found in the literature, we propose a hypothesis for the mechanism of the degradation of p.MT-ND1. Our study provides new insights into the pathophysiology of mitochondrial diseases and in particular of MT-ND1 mutations.
Design, analysis and reporting of multi-arm trials and strategies to address multiple testing
Authors: Odutayo Ayodele , Gryaznov Dmitry , Copsey Bethan , Monk Paul , Speich Benjamin , Roberts Corran , Vadher Karan , Dutton Peter , Briel Matthias , Hopewell Sally , Altman Douglas G ,   and the ASPIRE study group
Published: January 2020

Background

It is unclear how multiple treatment comparisons are managed in the analysis of multi-arm trials, particularly related to reducing type I (false positive) and type II errors (false negative).

Methods

We conducted a cohort study of clinical-trial protocols that were approved by research ethics committees in the UK, Switzerland, Germany and Canada in 2012. We examined the use of multiple-testing procedures to control the overall type I error rate. We created a decision tool to determine the need for multiple-testing procedures. We compared the result of the decision tool to the analysis plan in the protocol. We also compared the pre-specified analysis plans in trial protocols to their publications.

Results

Sixty-four protocols for multi-arm trials were identified, of which 50 involved multiple testing. Nine of 50 trials (18%) used a single-step multiple-testing procedures such as a Bonferroni correction and 17 (38%) used an ordered sequence of primary comparisons to control the overall type I error. Based on our decision tool, 45 of 50 protocols (90%) required use of a multiple-testing procedure but only 28 of the 45 (62%) accounted for multiplicity in their analysis or provided a rationale if no multiple-testing procedure was used. We identified 32 protocol–publication pairs, of which 8 planned a global-comparison test and 20 planned a multiple-testing procedure in their trial protocol. However, four of these eight trials (50%) did not use the global-comparison test. Likewise, 3 of the 20 trials (15%) did not perform the multiple-testing procedure in the publication. The sample size of our study was small and we did not have access to statistical-analysis plans for the included trials in our study.

Conclusions

Strategies to reduce type I and type II errors are inconsistently employed in multi-arm trials. Important analytical differences exist between planned analyses in clinical-trial protocols and subsequent publications, which may suggest selective reporting of analyses.
Early experiences with combined fellowship training in clinical informatics
Authors: Palma Jonathan P , Hron Jonathan D , Luberti Anthony A
Published: January 2020

Given the ubiquitous nature of information systems in modern health care, interest in the pursuit of formal training in clinical informatics is increasing. This interest is not restricted to generalists—informatics training is increasingly being sought by future subspecialists. The traditional structure of Accreditation Council on Graduate Medical Education subspecialty training requires completion of both clinical and clinical informatics fellowship programs, and understandably lacks appeal due to the time commitment required. One approach to encourage clinical informatics training is to integrate it with clinical fellowships in order to confer dual-board eligibility. In this perspective, we describe 3 successful petitions for combined training in clinical informatics in order to support other programs and the American Board of Preventive Medicine in establishing pathways for training subspecialists in clinical informatics.
Policies and procedures governing patient portal use at an Academic Medical Center
Authors: Steitz Bryan D , Wong Joseph Isaac S , Cobb Jared G , Carlson Brian , Smith Gaye , Rosenbloom S Trent
Published: January 2020

Background and Objective

Patient portal use has increased over the last two decades in response to consumer demand and government regulation. Despite growing adoption, few guidelines exist to direct successful implementation and governance. We describe the policies and procedures that have governed over a decade of continuous My Health at Vanderbilt (MHAV) patient portal use.

Methods

We examined MHAV usage data between May 2007 and November 2017. We classified patient portal activity into eight functional categories: Appointment, Billing, Document Access, Genetics, Health Result, Immunization, Medication, and Messaging. We describe our operating policies and measure portal uptake, patient account activity, and function use over time.

Results

By the end of the study period, there were 375 517 registered accounts. Policies made MHAV available to competent adults and adolescents 13 and over. Patients signed up for a limited access account online, which could be upgraded to a full-access account after identity verification. Patients could assign proxy accounts to family and caregivers, which permitted nonpatient access to select MHAV functions. Laboratory and radiology results were accessible via MHAV. Results were classified into three groups based on sensitivity, which govern the length of delay before results appeared in MHAV.

Discussion and Conclusion

Patient portals offer significant opportunity to engage patients in their healthcare. However, there remains a need to understand how policies can promote uptake and use. We anticipate that other institutions can apply concepts from our policies to support meaningful patient portal engagement.
Bridging the Gap Between the Reality of Male Sexual Violence and Access to Justice and Accountability
Authors: Elliott Ingrid , Kivlahan Coleen , Rahhal Yahya
Published: January 2020

The limited accountability achieved to date for sexual violence in conflict has largely reflected one specific form: the rape of women and girls. Investigation, prosecution and convictions for other forms of sexual violence have lagged behind significantly. This is the case for sexual violence against men and boys. Using detailed data from over 130 expert medical reports of Syrian male former detainees, the article contrasts known typology of male sexual violence in conflict with penal codes and case law across a range of jurisdictions. It also considers the broader challenges for access to justice, reparation and recovery for such victims and survivors of these crimes. The article then turns to examine how these gaps might be bridged to provide better access and outcomes for justice to male survivors of conflict-related sexual violence. It explores a local Syrian interdisciplinary approach using medical expert documentation which has opened up investigation and awareness of male sexual violence. Lastly, it sets out concluding recommendations for approaching male sexual violence in national investigations and prosecutions.
The Many Harms of Forced Marriage
Authors: Denov Myriam S , Drumbl Mark A
Published: January 2020

Harnessing an interdisciplinary framework that merges elements of law and social science, this article aims to recast the crime of forced marriage, and thereby enhance accountability, in light of knowledge acquired through ethnographic fieldwork in northern Uganda. More specifically, we draw upon the perspectives and experiences of 20 men who were ‘bush husbands’ in the Lord’s Resistance Army (LRA). These men were abducted by the LRA between the ages of 10 and 38 and spent between 6 and 24 years in captivity. During their time in the LRA, these men became ‘bush husbands’ with each man fathering between 1 and 11 children. In-depth interviews explored men’s perspectives and experiences related to sexual violence, forced marriage, parenthood and post-war accountability. The data reveal the complexity of men’s self-identified positions not only as high-ranking members of the LRA, but also as captives of the LRA, as victims of forced marriage, as perpetrators, and as caring fathers and husbands. These findings nuance extant understandings and assumptions of men and masculinities in the context of forced marriage. Drawing from these findings, we articulate several key implications for law — notably, that law acknowledges the harms that the crime of forced marriage and sexual violence affects and imposes on all implicated parties, including boys, girls, men, and women. While noting the gendered component of the harms of forced marriage, as well as sexual violence, that disproportionately affects women and girls, the ethnographic data suggest detaching the criminalization of forced marriage from a largely gender-based analysis to a more gender-neutral one rooted in multiparty coercion. Senior commanders who order forced marriages should face criminal sanction that recognizes the totality of the harms caused, including to both husbands and wives and the children born of these compelled unions: this move would augment the retributive, deterrent and expressive value of criminal punishment. Finally, a granular and textured understanding of forced marriage would lay groundwork for more effective, tailored and targeted reintegrative and rehabilitative programmes for all afflicted parties.
In-House and Arm’s Length: Productivity Heterogeneity and Variation in Organizational Form
Authors: Lin Stephen F , Thomas Catherine , Kalnins Arturs
Published: January 2020

This paper analyzes firm boundaries in the US hotel industry. Hotel properties of a given brand are often managed either by a chain employee or by a franchisee. We document that brand properties with the lowest and the highest occupancy rates are more likely to be managed at arm’s length by franchisees. Variation in organizational form is consistent with a model in which the incentives embodied in management contracts vary with property-level productivity. We infer that most hotel chains franchise low-productivity relationships to keep property-level fixed costs low and franchise the most productive relationships to create high-powered incentives for franchisees. Franchisees of high-productivity properties face stronger incentives than the managers of both chain-managed properties and low-productivity franchises because the performance incentives in franchise contracts are proportional to hotel revenues and complement the incentives from franchisees’ property control rights. (JEL D23, F12, L23, D22)
Origen of Alexandria and the History of Racism as a Theological Problem
Authors: den Dulk Matthijs
Published: January 2020

Despite important work on the Greco-Roman antecedents of modern racism, very limited attention has been paid to early Christian literature in this connection. This is remarkable not least because modern Western racism took shape initially in a European context heavily influenced by Christianity. The present essay contributes to addressing this lacuna by analysing statements about ‘other’ ethnicities in the work of Origen of Alexandria, one of the most important thinkers of the first three centuries ce. It argues that Origen defends a number of positions that exhibit substantial similarities with later racist modes of thinking. Earlier scholarly accounts that portray Origen as a champion of human equality and as engaged in anti-racist efforts therefore cannot stand up to scrutiny. Origen disparages certain ethnic groups and develops arguments that connect ethnic identity and geographical location with various degrees of sinfulness. His work offers clear evidence that theories of ethnic inferiority have a long history within the Christian matrix that stretches considerably beyond the modern and medieval periods.
Constraining the origin of the planetary debris surrounding ZTF J0139+5245 through rotational fission of a triaxial asteroid
Authors: Veras Dimitri , McDonald Catriona H , Makarov Valeri V
Published: January 2020

White dwarfs containing orbiting planetesimals or their debris represent crucial benchmarks by which theoretical investigations of post-main-sequence planetary systems may be calibrated. The photometric transit signatures of likely planetary debris in the ZTF J0139+5245 white dwarf system have an orbital period of about 110 d. An asteroid which breaks up to produce this debris may spin itself to destruction through repeated close encounters with the star without entering its Roche radius and without influence from the white dwarf’s luminosity. Here, we place coupled constraints on the orbital pericentre (q) and the ratio (β) of the middle to longest semiaxes of a triaxial asteroid which disrupts outside of this white dwarf’s Roche radius (rRoche) soon after attaining its 110-d orbit. We find that disruption within tens of years is likely when β ≲ 0.6 and q ≈ 1.0–2.0rRoche, and when β ≲ 0.2 out to q ≈ 2.5rRoche. Analysing the longer time-scale disruption of triaxial asteroids around ZTF J0139+5245 is desirable but may require either an analytical approach relying on ergodic theory or novel numerical techniques.
On the aspect ratio of ’Oumuamua : less elongated shape for irregular surface properties
Authors: Vazan Allona , Sari Re’em
Published: January 2020

The large brightness variation in the observed light curve of ’Oumuamua is probably related to its shape, i.e. to the ratio between its longest axis and its shortest axis (aspect ratio). Several approaches found the aspect ratio of ’Oumuamua to be unusually elongated. Moreover, the spin axis orientation has to be almost perpendicular to the observer in order to obtain such an extreme light curve, a configuration which is unlikely. However, interstellar ’Oumuamua may have different surface properties than we know in our Solar system. Therefore, in this work we widen the parameter space for surface properties beyond the asteroid-like models and study its effect on ’Oumuamua’s light curve. We calculate reflection from a rotating ellipsoidal object for four models: Lambertian reflection, specular reflection, single scattering diffusive, and backscatter . We then calculate the probability to obtain a light-curve ratio larger than the observed, as a function of the object’s aspect ratio, assuming an isotopic spin orientation distribution. We find the elongation of ’Oumuamua to be less extreme for the Lambertian and specular reflection models. Consequently, the probability to observe the light-curve ratio of ’Oumuamua given its unknown spin axis orientation is larger for those models. We conclude that different surface reflection properties may suggest alternatives to the extreme shape of ’Oumuamua , relieving the need for complicated formation scenario, extreme albedo variation, or unnatural origin. Although the models suggested here are for ideal ellipsoidal shape and ideal reflection method, the results emphasize the importance of surface properties for the derived aspect ratio.
A phase I/II study of veliparib (ABT-888) with radiation and temozolomide in newly diagnosed diffuse pontine glioma: a Pediatric Brain Tumor Consortium study
Authors: Baxter Patricia A , Su Jack M , Onar-Thomas Arzu , Billups Catherine A , Li Xiao-Nan , Poussaint Tina Young , Smith Edward R , Thompson Patrick , Adesina Adekunle , Ansell Pete , Giranda Vincent , Paulino Arnold , Kilburn Lindsey , Quaddoumi Ibrahim , Broniscer Alberto , Blaney Susan M , Dunkel Ira J , Fouladi Maryam
Published: January 2020

Background

A Pediatric Brain Tumor Consortium (PBTC) phase I/II trial of veliparib and radiation followed by veliparib and temozolomide (TMZ) was conducted in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). The objectives were to: (i) estimate the recommended phase II dose (RP2D) of veliparib with concurrent radiation; (ii) evaluate the pharmacokinetic parameters of veliparib during radiation; (iii) evaluate feasibility of intrapatient TMZ dose escalation; (iv) describe toxicities of protocol therapy; and (v) estimate the overall survival distribution compared with historical series.

Methods

Veliparib was given Monday through Friday b.i.d. during radiation followed by a 4-week rest. Patients then received veliparib at 25 mg/m2 b.i.d. and TMZ 135 mg/m2 daily for 5 days every 28 days. Intrapatient dose escalation of TMZ was investigated for patients experiencing minimal toxicity.

Results

Sixty-six patients (65 eligible) were enrolled. The RP2D of veliparib was 65 mg/m2 b.i.d. with radiation. Dose-limiting toxicities during radiation with veliparib therapy included: grade 2 intratumoral hemorrhage (n = 1), grade 3 maculopapular rash (n = 2), and grade 3 nervous system disorder (generalized neurologic deterioration) (n = 1). Intrapatient TMZ dose escalation during maintenance was not tolerated. Following a planned interim analysis, it was concluded that this treatment did not show a survival benefit compared with PBTC historical controls, and accrual was stopped for futility. The 1- and 2-year overall survival rates were 37.2% (SE 7%) and 5.3% (SE 3%), respectively.

Conclusion

Addition of veliparib to radiation followed by TMZ and veliparib was tolerated but did not improve survival for patients with newly diagnosed DIPG.

Trial Registration

NCT01514201
The role of nutrition in asthma prevention and treatment
Authors: Alwarith Jihad , Kahleova Hana , Crosby Lee , Brooks Alexa , Brandon Lizoralia , Levin Susan M , Barnard Neal D
Published: January 2020

Asthma is a chronic respiratory condition characterized by airway inflammation and hyperreactivity. Prevalence has continued to rise in recent decades as Western dietary patterns have become more pervasive. Evidence suggests that diets emphasizing the consumption of plant-based foods might protect against asthma development and improve asthma symptoms through their effects on systemic inflammation, oxidation, and microbial composition. Additionally, increased fruit and vegetable intake, reduced animal product consumption, and weight management might mediate cytokine release, free radical damage, and immune responses involved in the development and course of asthma. The specific aim of this review paper is to examine the current literature on the associations between dietary factors and asthma risk and control in children and adults. Clinical trials examining the mechanism(s) by which dietary factors influence asthma outcomes are necessary to identify the potential use of nutritional therapy in the prevention and management of asthma.
Influence of the equation of state on a compact star made of hidden-sector nucleons
Authors: Maedan Shinji
Published: January 2020

We study a compact star made of degenerate hidden-sector nucleons which will be a candidate for cold dark matter. A hidden sector like quantum chromodynamics is considered, and as the low-energy effective theory we take the (hidden-sector) $ SU(2) $ chiral sigma model including a hidden-sector vector meson. With the mean field approximation, we find that one can treat the equation of state (EOS) of our model analytically by introducing a variable which depends on the Fermi momentum. The EOS is specified by the two parameters $ C'_{\sigma} $, $ C'_{\omega} $, and we discuss how these parameters affect the mass–radius relation for a compact star as well as the EOS. The dependence of the maximum stable mass of compact stars on the parameter $ C'_{\sigma} $ will also be discussed.