bluuebunny/crossref_metadata_2025 huggingface dataset:
Disentangling serology to elucidate henipa‐ and filovirus transmission in Madagascar fruit bats
Authors: Brook Cara E. , Ranaivoson Hafaliana C. , Broder Christopher C. , Cunningham Andrew A. , Héraud Jean‐Michel , Peel Alison J. , Gibson Louise , Wood James L. N. , Metcalf C. Jessica , Dobson Andrew P.
Published: March 2019

Bats are reservoirs for emerging human pathogens, including Hendra and Nipah henipaviruses and Ebola and Marburg filoviruses. These viruses demonstrate predictable patterns in seasonality and age structure across multiple systems; previous work suggests that they may circulate in Madagascar's endemic fruit bats, which are widely consumed as human food.

We aimed to (a) document the extent of henipa‐ and filovirus exposure among Malagasy fruit bats, (b) explore seasonality in seroprevalence and serostatus in these bat populations and (c) compare mechanistic hypotheses for possible transmission dynamics underlying these data.

To this end, we amassed and analysed a unique dataset documenting longitudinal serological henipa‐ and filovirus dynamics in three Madagascar fruit bat species.

We uncovered serological evidence of exposure to Hendra‐/Nipah‐related henipaviruses in Eidolon dupreanum, Pteropus rufus and Rousettus madagascariensis, to Cedar‐related henipaviruses in E. dupreanum and R. madagascariensis and to Ebola‐related filoviruses in P. rufus and R. madagascariensis. We demonstrated significant seasonality in population‐level seroprevalence and individual serostatus for multiple viruses across these species, linked to the female reproductive calendar. An age‐structured subset of the data highlighted evidence of waning maternal antibodies in neonates, increasing seroprevalence in young and decreasing seroprevalence late in life. Comparison of mechanistic epidemiological models fit to these data offered support for transmission hypotheses permitting waning antibodies but retained immunity in adult‐age bats.

Our findings suggest that bats may seasonally modulate mechanisms of pathogen control, with consequences for population‐level transmission. Additionally, we narrow the field of candidate transmission hypotheses by which bats are presumed to host and transmit potentially zoonotic viruses globally.
Non‐random loss of phylogenetically distinct rare species degrades phylogenetic diversity in semi‐natural grasslands
Authors: Uchida Kei , Hiraiwa Masayoshi K. , Cadotte Marc W.
Published: March 2019

Although biodiversity loss is a critically important topic, our understanding of how both land abandonment and land‐use intensification in semi‐natural grasslands alters the community diversity and assembly mechanisms is very limited. Large‐scale economic drivers of land‐use change might inadvertently result in the loss of vulnerable species and reduce ecosystem service provisioning.

In this study, we assessed non‐random community change by examining patterns of low‐abundance species loss, and community assembly in semi‐natural grasslands due to land abandonment and intensification in southwest Japan. We analysed relationships between evolutionary distinctiveness and abundance for each species. In addition, we used metrics of species and phylogenetic diversity and phylogenetic structure to assess patterns of non‐random biodiversity loss due to both abandoned and intensified land‐use.

We demonstrated that low‐abundance species were more evolutionarily distinct compared to high‐abundance (i.e. dominant) species. Furthermore, land‐use intensification resulted in further declines in low‐abundance species, whereas land abandonment resulted in declines in all species, regardless of their initial abundance.

We found that both forms of land‐use change (abandonment and intensification) resulted in non‐random patterns of community change, with traditional land‐use maintaining the highest biodiversity and land‐use change coinciding with decreased species and phylogenetic diversity measures. Intensified land‐use caused phylogenetic community structure to be more closely related than expected by chance, whereas the metrics of how distant species are from one another on average based on phylogenetic tree (i.e. mean pairwise phylogenetic distance) did not change from land abandonment.

Synthesis and applications. We show that the loss of phylogenetic diversity, and especially of low‐abundance species with high value of phylogenetic distinctiveness, resulted in non‐random community disassembly. Our results argue that in order to maintain biodiversity in these semi‐natural grasslands, traditional management practices should be encouraged over intensification and simple abandonment. Government agencies should adopt policies or provide incentives that encourage the maintenance of traditional practices in rural Japan, and elsewhere where the combination of land consolidation and abandonment are important conservation issues.
Different effects of Wnt/β‐catenin activation and parathyroid hormone on diaphyseal and metaphyseal in the early phase of femur bone healing of mice
Authors: Liu Daocheng , He Sihao , Chen Sixu , Yang Lei , Yang Jiazhi , Bao Quanwei , Qin Hao , Zhao Yufeng , Zong Zhaowen
Published: March 2019

Parathyroid hormone (PTH) and agents related to the manipulation of Wnt/β‐catenin signalling are two promising anabolic anti‐osteoporotic therapies that have been shown to promote the healing of bone fractures. Now, it is widely accepted that cortical bone and trabecular bone are two different compartments, and should be treated as separate compartments in pathological processes, such as fracture healing. It is currently unknown whether PTH and the activation of β‐catenin signalling would demonstrate different effects on cortical bone and trabecular bone healing. In the current study, single 0.6‐mm cortex holes were made in the femur metaphysis and diaphysis of mice, and then, PTH application and β‐catenin activation were used to observe the promoting effect on bone healing. The effects of β‐catenin and PTH signalling on fracture healing were observed by X‐ray and CT at 3, 6, and 14 days after fracture, and the levels of β‐catenin were detected by RT‐PCR assay, and the number of specific antigen‐positive cells of BRDU, OCN, RUNX2 was counted by immunohistochemical staining. While β‐catenin activation and PTH were found to demonstrate similar effects on accelerating metaphyseal bone healing, activation of β‐catenin showed a more striking effect than PTH on promoting diaphyseal bone healing. These findings might be helpful for selecting proper medication to accelerate fracture healing of different bone compartments.
Time, expertise and status: barriers faced by mainstream primary school SENCos in the pursuit of providing effective provision for children with SEND
Authors: Smith Mia D. , Broomhead Karen E.
Published: March 2019

The inclusion ‘ideal’ is one which has been both celebrated and maligned. It paved the way for equality; but also, out of its diversity sprang many misconceptions and concerns for children with Special Educational Needs and Disabilities (SEND). It is within this maelstrom of difficulty that the Special Educational Needs Co‐ordinator (SENCo) role is placed, so that those undertaking the position of SENCo face numerous barriers in the pursuit of providing effectively for children with SEND. Semi‐structured interviews were conducted with fifteen SENCos employed at mainstream primary schools within the North West of England. Findings revealed conflict between how SENCos viewed their role and responsibilities, and the expectations that they perceived to be placed on them by parents of children with SEND and mainstream colleagues. This study brings to the fore the complexities of the role of the SENCo, and the continuing demands placed on these practitioners.
CCTV surveillance for crime prevention
Authors: Piza Eric L. , Welsh Brandon C. , Farrington David P. , Thomas Amanda L.
Published: March 2019

Research Summary

We report on the findings of an updated systematic review and meta‐analysis of the effects of closed‐circuit television (CCTV) surveillance cameras on crime. The findings show that CCTV is associated with a significant and modest decrease in crime. The largest and most consistent effects of CCTV were observed in car parks. The results of the analysis also demonstrated evidence of significant crime reductions within other settings, particularly residential areas. CCTV schemes incorporating active monitoring generated larger effect sizes than did passive systems. Schemes deploying multiple interventions alongside CCTV generated larger effect sizes than did schemes deploying single or no other interventions alongside CCTV.

Policy Implications

The results of this systematic review—based on 40 years of evaluation research—lend support for the continued use of CCTV to prevent crime as well as reveal a greater understanding of some of the key mechanisms of effective use. Of particular salience is the continued need for CCTV to be narrowly targeted on vehicle crimes and property crime and not be deployed as a “stand‐alone” crime prevention measure. As CCTV surveillance continues to expand its reach in both public and private space and evolve with new technology, policy will benefit from high‐quality evaluations of outcomes and implementation.
Microwave‐Assisted Degradation of Polysaccharide from Polygonatum sibiricum and Antioxidant Activity
Authors: Zhang Hui , Cai Xiu‐ting , Tian Qing‐hua , Xiao Lin‐xia , Zeng Zhen , Cai Xin‐tong , Yan Ji‐zhong , Li Qing‐yong
Published: March 2019

Four polysaccharide fractions (P‐1: 71.40%, P‐2: 1.95%, P‐3: 1.14%, P‐4: 1.64%) were isolated from crude Polygonatum sibiricum polysaccharide (PSP), processed by water extraction, ethanol precipitation, and further separated with diethylaminoethyl cellulose‐52 anion‐exchange chromatography. Their molecular weights and monosaccharide compositions were characterized by high performance gel chromatography with evaporative light scattering detector and ultraviolet–visible detector. The antioxidant activity of four polysaccharides fractions were assessed by the electron transfer menchanism (DPPH, ferric reducing power, and ABST assays) and chelation of transition metals (Fe2+ and Cu2+ chelation ability). The highest content fraction P‐1 exhibited the lowest antioxidant activity, and the ranking of antioxidant capacity was P‐4 > P‐3 > P‐2 > PSP > P‐1. After processed by microwave‐assisted degradation, the molecular weight of P‐1 was decreased from 2.99 × 105 to 2.33 × 103 Da, while the antioxidant activity of degraded P‐1 was about eightfold higher than natural P‐1. These results indicated that the proposed microwave‐assisted degradation approach was an efficacious methodology to improve their bioactivity by lower the molecular weight of polysaccharides.

Practical Application

This study provided an environmentally friendly, convenient and efficient microwave‐assisted degradation technology to process the neutral polysaccharides from Polygonatum sibiricum. The results could be used for the development and utilization of various plant polysaccharides as a kind of food supplement in our daily life.
High dose rate brachytherapy boost for prostate cancer: Biochemical control and the impact of transurethral resection of the prostate and hydrogel spacer insertion on toxicity outcomes
Authors: Chao Michael , Bolton Damien , Lim Joon Daryl , Chan Yee , Lawrentschuk Nathan , Ho Huong , Spencer Sandra , Wasiak Jason , Guerrieri Mario , Ow Darren , Troy Andrew , Pham Trung , Sengupta Shomik , Tan Alwin , McMillan Kevin , Koufogiannis George , Foroudi Farshad , Ng Michael , Khoo Vincent
Published: March 2019

Introduction

To examine the long‐term outcomes of high dose rate brachytherapy boost (HDR‐BT) combined with external beam radiotherapy (EBRT) for intermediate and high‐risk prostate cancer patients.

Methods

Data from 95 patients who underwent combined EBRT (50.4 Gy) and HDR‐BT to the prostate between 2010 and 2017 were retrospectively analysed. Biochemical progression free survival (bPFS), local recurrence free survival (LRFS), metastatic free survival (MFS) and overall survival (OS) were estimated using Kaplan–Meier method. Regression analysis was conducted to identify important predictors of outcomes.

Results

A total of 24 patients received an initial HDR‐BT dose of 18 Gy in three fractions, with the remaining 71 patients receiving 16 Gy in two fractions as per departmental protocol changes. Most patients (88%) received androgen deprivation therapy. A transurethral resection of the prostate (TURP) was performed in 14 patients and hydrogel spacers (HS) were used in 30 patients. Median follow‐up was 58 months. The 5‐year bPFS, LRFS, MFS and OS were 92%, 100%, 92% and 88%. Univariate regression revealed no statistical association between patient characteristics and time to relapse (all P > 0.1). Late > grade 2 genitourinary (GU) toxicity was 6.3%. The use of HS or prior TURP had no impact on late GU toxicity. Late Grade 1 gastrointestinal (GI) toxicity was 5.3%.

Conclusion

The combined HDR‐BT with EBRT resulted in excellent bPFS. The cumulative risk of late GU and GI toxicity was low and can be further improved with preventative strategies such as a pre‐emptive TURP and/or HS insertion.
Targeting senescent cells alleviates obesity‐induced metabolic dysfunction
Authors: Palmer Allyson K. , Xu Ming , Zhu Yi , Pirtskhalava Tamar , Weivoda Megan M. , Hachfeld Christine M. , Prata Larissa G. , van Dijk Theo H. , Verkade Esther , Casaclang‐Verzosa Grace , Johnson Kurt O. , Cubro Hajrunisa , Doornebal Ewald J. , Ogrodnik Mikolaj , Jurk Diana , Jensen Michael D. , Chini Eduardo N. , Miller Jordan D. , Matveyenko Aleksey , Stout Michael B. , Schafer Marissa J. , White Thomas A. , Hickson LaTonya J. , Demaria Marco , Garovic Vesna , Grande Joseph , Arriaga Edgar A. , Kuipers Folkert , von Zglinicki Thomas , LeBrasseur Nathan K. , Campisi Judith , Tchkonia Tamar , Kirkland James L.
Published: March 2019

Adipose tissue inflammation and dysfunction are associated with obesity‐related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug‐inducible “suicide” genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra‐abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity‐related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity‐related metabolic dysfunction and its complications.
Intergenerational Effects of Alcohol: A Review of Paternal Preconception Ethanol Exposure Studies and Epigenetic Mechanisms in the Male Germline
Authors: Rompala Gregory R. , Homanics Gregg E.
Published: March 2019

While alcohol use disorder (AUD) is a highly heritable psychiatric disease, efforts to elucidate that heritability by examining genetic variation (e.g., single nucleotide polymorphisms) have been insufficient to fully account for familial AUD risk. Perhaps not coincidently, there has been a burgeoning interest in novel nongenomic mechanisms of inheritance (i.e., epigenetics) that are shaped in the male or female germ cells by significant lifetime experiences such as exposure to chronic stress, malnutrition, or drugs of abuse. While many epidemiological and preclinical studies have long pointed to a role for the parental preconception environment in offspring behavior, over the last decade many studies have implicated a causal relationship between the environmentally sensitive sperm epigenome and intergenerational phenotypes. This critical review will detail the heritable effects of alcohol and the potential role for epigenetics.
Combination of Clinically Utilized Kappa‐Opioid Receptor Agonist Nalfurafine With Low‐Dose Naltrexone Reduces Excessive Alcohol Drinking in Male and Female Mice
Authors: Zhou Yan , Kreek Mary Jeanne
Published: March 2019

Background

Nalfurafine is the first clinically approved kappa‐opioid receptor (KOP‐r) agonist as an antipruritus drug with few side effects in humans (e.g., sedation, depression, and dysphoria). No study, however, has been done using nalfurafine on alcohol drinking in rodents or humans.

Methods

We investigated whether nalfurafine alone or in combination with mu‐opioid receptor (MOP‐r) antagonist naltrexone changed excessive alcohol drinking in male and female C57BL/6J (B6) mice subjected to a chronic intermittent‐access drinking paradigm (2‐bottle choice, 24‐hour access every other day) for 3 weeks. Neuronal proopiomelanocortin enhancer (nPE) knockout mice with brain‐specific deficiency of beta‐endorphin (endogenous ligand of MOP‐r) were used as a genetic control for the naltrexone effects.

Results

Single administration of nalfurafine decreased alcohol intake and preference in both male and female B6 mice in a dose‐dependent manner. Pretreatment with nor‐BNI (a selective KOP‐r antagonist) blocked the nalfurafine effect on alcohol drinking, indicating a KOP‐r‐mediated mechanism. Pharmacological effects of a 5‐dosing nalfurafine regimen were further evaluated: The repeated nalfurafine administrations decreased alcohol consumption without showing any blunted effects, suggesting nalfurafine did not develop a tolerance after the multidosing regimen tested. Nalfurafine did not produce any sedation (spontaneous locomotor activity), anhedonia‐like (sucrose preference test), anxiety‐like (elevated plus maze test), or dysphoria‐like (conditioned place aversion test) behaviors, suggesting that nalfurafine had few side effects. Investigating synergistic effects between low‐dose naltrexone and nalfurafine, we found that single combinations of nalfurafine and naltrexone, at doses lower than individual effective dose, profoundly decreased excessive alcohol intake in both sexes. The effect of nalfurafine on decreasing alcohol consumption was confirmed in nPE−/− mice, suggesting independent mechanisms by which nalfurafine and naltrexone reduced alcohol drinking.

Conclusion

The clinically utilized KOP‐r agonist nalfurafine in combination with low‐dose naltrexone has potential in alcoholism treatment.
Protective Effects of Facilitated Removal of Blood Alcohol and Acetaldehyde Against Liver Injury in Animal Models Fed Alcohol and Anti‐HIV Drugs
Authors: Han Hui , He Yuxin , Johnson Heather , Mishra Pratibha , Lee Harrison , Ji Cheng
Published: March 2019

Background

We previously developed enzyme nanoparticles (ENP) of alcohol metabolism. This study was to evaluate protective effects of facilitated removal of blood alcohol and/or acetaldehyde on anti‐HIV drugs and alcohol‐induced liver injuries.

Methods

ENP were prepared for degrading alcohol completely (ENP1) or partially into acetaldehyde (ENP2), which were applied to mice of acute binge or chronic‐binge alcohol feeding in the presence of antivirals (ritonavir and lopinavir). Liver pathologies were examined to assess the protective effects of ENP.

Results

In the acute model, ENP1 and ENP2 reduced the blood alcohol concentration (BAC) by 41 and 32%, respectively, within 4 hr, whereas in control without ENP, BAC was reduced only by 15%. Blood acetaldehyde concentration (BADC) was increased by 39% in alcohol‐fed mice treated with ENP2 comparing to control. No significant effects of the anti‐HIV drugs on BAC or BADC were observed. Plasma alanine aminotransferase (ALT) and expression of liver TNF‐α were both significantly increased in the alcohol‐fed mice, which were normalized by ENP1. In the presence of the antivirals, ALT was partially reduced by ENP1 or ENP2. In the chronic model, inflammation, fatty liver, and ALT were increased, which were deteriorated by the antivirals. ENP1 partially reduced BAC, BADC, ALT, and expression of inflammation markers of TNF‐α, F4/80, and IL‐6 and lipogenic factors of ACC, LXRα, and SREBP1. ENP2 reduced BAC without significant effects on ALT, inflammation, or lipogenesis. Antivirals and alcohol synergistically increased expression of organelle stress markers of CHOP, sXBP‐1, ATF6, and GCP60. ENP1 reduced BAC, CHOP, and sXbp‐1. However, no effects of ENP1 were found on ATF6 or GCP60.

Conclusions

Removal of blood alcohol and acetaldehyde by the ENP protects the liver against alcoholic injuries, and the protection is less effective in chronic alcohol and antiviral feeding due to additional drug‐induced organelle stresses.
Incidence of medically treated depression in Denmark among individuals 15–44 years old: a comprehensive overview based on population registers
Authors: Musliner K. L. , Liu X. , Gasse C. , Christensen K. S. , Wimberley T. , Munk‐Olsen T.
Published: March 2019

Objective

Examine the overall incidence of medically treated depression in Denmark among individuals 15–44 years old, and estimate the 5‐year cumulative incidence of psychiatric hospital care among individuals treated first in non‐hospital‐based care.

Methods

We followed all individuals born in Denmark between 1969 and 1998 from age 15 or 2006 (whichever came first) until first depression treatment; death; emigration; or December 31, 2013. Incidence rates were estimated using Poisson regression. Cumulative incidence of hospital care following treatment in non‐hospital care was estimated using Kaplan–Meier curves.

Results

In this sample of 2 014 760 individuals, incidence rates of depression in non‐hospital and hospital‐based care in 2012–2013 were 6.6 (95% Confidence Interval: 6.5–6.7) per 1000 person‐years and 1.5 (95% CI: 1.5–1.6) per 1000 person‐years, respectively. Overall, 85–90% of first medical treatment for depression took place outside of psychiatric hospitals, but a quarter (26.3%) of individuals treated for depression received hospital care initially or within 5 years. Incidence of hospital care was higher in women and younger individuals.

Conclusions

Most medical treatment for depression in Denmark takes place in non‐hospital settings. Women and younger individuals are more likely to receive hospital care both initially and within 5 years after first antidepressant treatment.
A risk model for addictive behaviors in adolescents: interactions between personality and learning
Authors: D'Agostino Alexandra R. , Peterson Sarah J. , Smith Gregory T.
Published: March 2019

Background and Aims

To determine whether transdiagnostic risk, represented as elevations in one high‐risk personality trait, interacts with behavior‐specific risk, represented as elevated expectancies for reinforcement from either drinking or smoking, to account partly for early adolescent drinking and smoking behavior.

Design

Multiple regression analysis.

Setting

Twenty‐three public schools in two school systems in the United States.

Participants

A sample of 1897 adolescents tested in the spring of 5th, 6th, 7th, 8th and 9th grades.

Measurements

Transdiagnostic risk was measured as negative urgency, the tendency to act rashly when distressed, using the UPPS‐P child version. Drinking‐specific and smoking‐specific risk were measured as expectancies for reinforcement from drinking and smoking, using the Memory Model‐Based Expectancy Questionnaire (alcohol) and the Adolescent Smoking Consequences Questionnaire (smoking).

Findings

There was consistent concurrent prediction from the interactions of (a) negative urgency and alcohol reinforcement expectancies to early adolescent drinking and (b) negative urgency and smoking reinforcement expectancies to early adolescent smoking, above and beyond prediction from the main effects of those variables. In each case, expectancies were more predictive at higher levels of negative urgency. Incremental R2 values for main effects ranged from 0.07 to 0.26, and for interactions ranged from 0.01 to 0.03. Prospectively, the main effects predicted subsequent behavior but the interaction effects did not, except in one case.

Conclusions

Among elementary and high school students in the United States, the joint effects of negative urgency and behavior‐specific expectancies help to explain drinking and smoking behavior. Joint elevations on the trait and the learning variable account for drinking and smoking behavior beyond the main effects of each predictor. However, there is reason to doubt whether the joint effects predict subsequent increases in drinking and smoking beyond the main effects of those variables.
Clinical relevance of genome‐wide polygenic score may be less than claimed
Authors: Curtis David
Published: March 2019

Objectives

A recent study claimed that genome‐wide polygenic scores (GPSs) for five common diseases could identify individuals with risk equivalent to monogenic mutations. Receiver operator curve analyses were reported to have areas under the curve (AUCs) ranging from 0.63 for inflammatory bowel disease up to 0.81 for coronary artery disease (CAD), but these models also included age and sex, themselves strong predictors of risk. The GPS for CAD identified 8% of the population at threefold increased risk, which was claimed to be comparable to the excess risk from monogenic mutations.

Methods

In the present study, attempts were made to model the distribution of the GPS for CAD to match the information provided. These models were based on the reported distribution of prevalence by centile of GPS and on the distribution of GPS in controls and cases, and were fitted to the reported results using linear approximations to the distributions and using simulations of a liability‐threshold model.

Results

It was impossible to produce a compatible model in which the GPS produced an AUC as high as 0.81 and the most plausible estimate was that the true AUC was only 0.65. The reported distributions of the GPS in cases and controls overlap so much that they are not compatible with an AUC of 0.7 or higher.

Conclusions

The AUC of the GPS for these diseases is modest. Furthermore, the literature robustly demonstrates that the true CAD risk associated with monogenic mutations is much higher than the threefold increase that is predicted by the GPS. Together, these findings cast doubt on the clinical utility of the GPS.
Assessing edge effect on the spatial distribution of selected forest biochemical properties derived using the Worldview data in Dukuduku forests, South Africa
Authors: Mutanga Onisimo , Dube Timothy , Omer Galal
Published: March 2019

This work explores the potential of the high‐resolution WorldView‐2 sensor in quantifying edge effects on the spatial distribution of selected forest biochemical properties in fragmented Dukuduku forest in KwaZulu‐Natal, South Africa. Specifically, we sought to map fragmented patches within forested areas in Dukuduku area, using very high spatial resolution WorldView‐2 remotely sensed data and to statistically determine the effect of these fragmented patches on the spatial distribution of selected forest biochemical properties. Edge effects on carbon, LAI and foliar nitrogen were quantified based on the models derived by Omer et al. (IEEE Journal of Selected Topics in Applied Earth Observations and Remote Sensing, 2015, 8, 4825). Edge effect statistical results on the spatial distribution of carbon, LAI and nitrogen showed significant (α = 0.05) variations with change in distance from fragmented patches (>150 m2). Forest foliar carbon concentrations significantly (p‐value = 0.016) increased from 44.8% to 45.3% with increasing distance (25–375 m) from fragmented patches. A similar trend was observed for LAI. Nevertheless, for nitrogen the results show that its concentration significantly (p = 0.016) decreased with increase in distance from the fragmented patches. Overall, the findings of this work underscore the invaluable potential and strength of WorldView‐2 data set in assessing edge effect on the spatial distribution of selected forest biochemical properties.
Translated Justice? The Ixil Maya and the 2013 Trial of José Efraín Ríos Montt for Genocide in Guatemala
Authors: García María Luz
Published: March 2019

This article takes an ethnographically engaged, discourse‐centered approach to questions of representation and cultural difference in democratic process in postwar Guatemala. When José Efraín Ríos Montt became the first former head of state convicted of genocide within his own country, in 2013, Ixil Maya witnesses who testified against him became international human rights icons. However, the trial was marked by difficulties in communication between Ixil witnesses and non‐Ixil lawyers, judges, and observers. “Miscommunications” resulted from diverging forms of speech that are deeply connected to different identities and ways of experiencing and understanding history. Discursive expectations within the courtroom limited recognition of Ixil ways of speaking and, consequently, of Ixil subjects. These expectations also obscured Ixil contestations to systems of power both inside and outside the courtroom. This analysis calls attention to the central role of language in processes of justice and political activism in solidarity with marginalized populations. [discourse‐centered approach, genocide trial, Ixil, Maya, Guatemala]
Disruption of bovine sperm functions in the presence of aplastic midpiece defect
Authors: Díaz‐Miranda E. A. , Maitan P. P. , Machado T. P. , Camilo B. S. , Lima D. A. , Okano D. S. , Penitente‐Filho J. M. , Machado‐Neves M. , de Oliveira L. L. , Guimarães S. E. F. , da Costa E. P. , Guimarães J. D.
Published: March 2019

Background

Bulls are of great importance in the productive chain and for this reason they should have a good semen quality. There is no doubt that sperm morphology is very important to bull fertility, although little is known about how exactly the abnormal morphologies may affect sperm functions.

Objectives

To detail the morphological description of the aplastic midpiece defect (AMD), as well as to understand its consequences for male fertility based on membrane and acrosome status, mitochondrial membrane potential and DNA integrity parameters.

Materials and methods

The bulls were divided into two groups: control, consisting of satisfactory potential breeders (n = 3); and AMD, consisting of unsatisfactory potential breeders with a high percentage of AMD (n = 3). Bulls were evaluated by the breeding soundness evaluation; five ejaculates were collected from each animal and analyzed by flow cytometry.

Results

Spermatozoa from AMD group exhibited lower sperm motility and vigor (p < 0.05). In addition, it also exhibited lower mitochondrial membrane potential (p < 0.05), a higher percentage of spermatozoa with DNA fragmentation (p < 0.05), lower acrosome and plasma membrane integrity (p < 0.05), and higher lipid bilayer sperm membrane disorganization (p < 0.05) in comparison with control bulls.

Discussion

These findings may be due to oxidative stress and a reduction of the energy production capacity in addition to an alteration in the structural composition of the sperm cell. Moreover, semen with a high percentage of AMD may also be undergoing apoptosis.

Conclusion

Bulls with a high percentage of AMD in their semen are not suitable for reproduction. Furthermore, it suggests there is a putative genetic basis for this sperm defect.
ELECTIVE ANEURYSM REPAIR AND THE INCIDENCE OF AORTIC RUPTURE IN AN AGEING POPULATION
Authors: IVERS C. R. , BOURKE B. M.
Published: March 2019

During the period January 1984–July 1988, 191 abdominal aortic aneurysms were encountered at Gosford District Hospital, NSW, a hospital that services an ageing population. These aneurysms were either repaired or found as the cause of death at post‐mortem. During the study, the rate of elective repair rose from 0.25/month during the first 2 years to 3.67/month in the latter 2.5 years. The mortality for repair of non‐ruptured aneurysms was 0.9% compared with 55% for ruptured aneurysms. The 15‐fold increase in elective repair resulted in the 58% reduction in the incidence of abdominal aortic rupture from 1.87/month to 0.79/month. The mortality rate from known aneurysms fell from 46% to 14% in the final 2 years. Elective aneurysm repair reduces the incidence of and death from abdominal aortic rupture in an ageing population.
CHANGES IN BODY PROTEIN COMPOSITION FOLLOWING AORTIC RECONSTRUCTION
Authors: FLETCHER J. P. , ALLEN B. J. , BLAGOJEVIC N.
Published: March 2019

Major surgery initiates a stress response due to the body's neuroendocrine reaction which leads to a breakdown of muscle protein with an increased urinary nitrogen excretion and a negative nitrogen balance.

In vivo neutron activation analysis (IVNAA) is a technique which measures total body nitrogen. A total of 23 IVNNA studies were performed in six patients having aortic reconstruction to assess the effect of this major operation on body nitrogen and to determine the time required for a return to the pre‐operative state.

Aortic surgery caused a mean decrease of 2.9% in bodyweight (from a mean of 65.4 kg to 63.5 kg) but a much greater decrease of 9.9% in total body nitrogen (from a mean of 1778 g to 1602 g).

Only two of six patients had recovered to pre‐operative values by the end of the study period which extended for a mean of 92 days.
WEGLOWSKI AND WHAT MIGHT HAVE BEEN*
Authors: SHUMACKER HARRIS B
Published: March 2019

Ramuald Weglowski, whose work has remained practically unknown, made most significant contributions to vascular surgery during World War I and in the years that followed. These remarkably modern experiences and concepts are described. The possible influence upon the development of vascular surgery, an awareness of them and an understanding of their worth is discussed.
TOTAL EXCISION OF MUCINOUS BILIARY CYSTADENOMA
Authors: LAU W. Y. , CHOW C. H. , LEUNG M. L.
Published: March 2019

In the past year, total excision of mucinous biliary cystadenomas was carried out in three patients by shelling these lesions out from the liver substances. Formal hepatic resection was unnecessary. As any previous surgical procedure on the cyst will make subsequent excision technically more difficult, or even impossible, it is believed that excision should be carried out at the initial operation. Thus, a correct pre‐operative or intraoperative diagnosis is important. This requires a high index of clinical suspicion, an adequate pre‐operative work‐up and an appropriate use of intra‐operative ultrasound and frozen section to differentiate these lesions from other cystic lesions of the liver.
Semi‐automated quantification of geographic atrophy with blue‐light autofluorescence and spectral‐domain optical coherence tomography: a comparison between the region finder and the advanced retinal pigment epithelium tool in the clinical setting
Authors: Reumueller Adrian , Sacu Stefan , Karantonis Maria Georgia , Steiner Irene , Weigert Guenther , Schmidt‐Erfurth Ursula
Published: March 2019

Purpose

To compare inter‐ and intraobserver reliability and intermodality agreement on quantification of geographic atrophy, using two routinely available quantification tools, based on blue‐light fundus autofluorescence (BAF) and spectral‐domain optical coherence tomography (SD‐OCT).

Methods

Quantifications of atrophic lesions within the central 5 mm of 30 eyes from 30 patients (mean age: 76.1 years) were independently performed by two clinicians on BAF images using the region finder (RF; Heidelberg Engineering) and on SD‐OCT using the advanced retinal pigment epithelium tool (ARPET; Carl Zeiss Meditec) at baseline and follow‐up (mean interval: 336 days). Inter‐ and intraobserver reliability was determined by intraclass correlation coefficients (ICC) and Bland–Altmann plots. Additionally, graders rated the experienced difficulty of each measurement.

Results

Intraclass correlation coefficients (ICC) showed excellent inter‐ and intraobserver reliability with values between 0.994 and 0.998 for RF and slightly higher values for ARPET of 0.997 and 0.999. Bland–Altman plots showed smaller variability for ARPET. Mean interobserver differences (95% CI) for size measurements were −0.11 (−0.27; 0.05) (baseline) and −0.05 mm² (−0.18; 0.08) (follow‐up) for RF and −0.04 (−0.14; 0.06) and −0.06 mm² (−0.14; 0.02) for ARPET. Measurements of lesions were on average 0.57 mm² (0.35; 0.79) or 7.6% larger in ARPET. Lesion size between graders did not differ significantly. There was no statistically significant difference in relative enlargement rates between methods. There was poor to moderate agreement between graders when rating the experienced difficulty of each measurement.

Conclusion

Semi‐automated analysis of geographic atrophy with RF and ARPET is equally reliable and reproducible in clinical settings, despite both algorithms require frequent adjustment by users. The ARPET restricts size measurements to the central 5 mm, which limits its ability to fully track GA progression. Results of both tools are not interchangeable as measurements with ARPET result in larger lesion sizes.
Treatment access is only the first step to hepatitis C elimination: experience of universal anti‐viral treatment access in Australia
Authors: Doyle Joseph S. , Scott Nick , Sacks‐Davis Rachel , Pedrana Alisa E. , Thompson Alexander J. , Hellard Margaret E. ,   the Eliminate Hepatitis C Partnership
Published: March 2019

Background

Global targets to eliminate hepatitis C (HCV) might be met by sustained treatment uptake.

Aim

To describe factors facilitating HCV treatment uptake and potential challenges to sustaining treatment levels after universal access to direct‐acting anti‐virals (DAA) across Australia.

Methods

We analysed national Pharmaceutical Benefits Scheme data to determine the number of DAA prescriptions commenced before and after universal access from March 2016 to June 2017. We inferred facilitators and barriers to treatment uptake, and challenges that will prevent local and global jurisdictions reaching elimination targets.

Results

In 2016, 32 877 individuals (14% of people living with HCV in Australia) commenced HCV DAA treatment, and 34 952 (15%) individuals commenced treatment in the first year of universal access. Treatment uptake peaked at 13 109 DAA commencements per quarter immediately after universal access, but more than halved (to 5320 in 2017 Q2) within 12 months. General practitioners have written 24% of all prescriptions but with a significantly increased proportion over time (9% in 2016 Q1 to 37% in 2017 Q2). In contrast, hepatology or infectious diseases specialists have written a declining share from 74% to 38% during the same period. General practitioners provided a greater proportion (47%) of care in regional/remote areas than major cities.

Conclusions

Broad treatment access led to rapid initial increases in treatment uptake, but this uptake has not been sustained. Our results suggest achieving global elimination targets requires more than treatment availability: people with HCV need easy access to testing and linkage to care in community settings employing a diverse prescriber base.
Off‐label prescriptions of drugs used for the treatment of Crohn’s disease or ulcerative colitis
Authors: Simsek Melek , Lissenberg‐Witte Birgit I. , van Riswijk Milou L. M. , Verschuren Sander , Hoentjen Frank , Oldenburg Bas , Ponsioen Cyriel Y. , van der Woude C. Janneke , van der Meulen Andrea E. , Pierik Marieke , Dijkstra Gerard , de Boer Nanne K. H. ,   the Parelsnoer Institute (PSI), the Dutch Initiative on Crohn's and Colitis (ICC)
Published: March 2019

Background

Off‐label prescribing is encountered across various fields of medicine and creates alternative treatment options, but is associated with unknown safety risks. The use of off‐label drugs for the treatment of patients with inflammatory bowel diseases (IBD) has not been characterised before.

Aim

To assess the proportion and characteristics of off‐label prescribing for IBD in tertiary care centres in the Netherlands.

Methods

A prospective database of IBD patients from all Dutch university hospitals was used to collect data on drug prescriptions for IBD and demographics. Drugs were classified as off‐label if they were unlicensed for Crohn's disease and/or ulcerative colitis by the Medicines Evaluation Board. Uni‐ and multivariable analyses were used to identify patient‐specific characteristics predictive of increased off‐label use.

Results

For the induction and/or maintenance treatment of 4583 IBD patients, 12 651 historical and current drug records were available in the database. Of these, 2374 (19%) were considered off‐label prescriptions. Out of 4583 IBD patients, 1477 (32%) were exposed to off‐label drugs. Commonly prescribed off‐label IBD drugs were mercaptopurine (18%), beclomethasone (12%), thioguanine (4%) and allopurinol (3%). Non‐thiopurine/methotrexate off‐label drugs were prescribed in 243 patients (6%), including biological agents or tofacitinib in 47 IBD patients (1%). Off‐label prescriptions were more common in ulcerative colitis than Crohn's disease (37% vs 29%, P < 0.001). Smokers and patients that received ≥5 drug types during their disease course were more likely to be exposed to off‐label drugs (smoking 33% vs 27% and multiple drug use 66% vs 22%, both P < 0.001).

Conclusion

About one‐fifth of prescriptions for IBD were off‐label and one‐third of IBD patients, especially ulcerative colitis patients, were exposed to off‐label drugs.
Day Labor Agencies, “Backdoor” Hires, and the Spread of Unfree Labor
Authors: Purser Gretchen
Published: March 2019

This article focuses upon a previously overlooked aspect of the “flesh‐peddling” day labor business, widely recognized as the epitome of the precarious regime of employment. By physically stockpiling surplus labor to meet their clients’ immediate and unpredictable demands, day labor agencies inadvertently give rise to informal day labor markets outside their doors. Drawing upon ethnographic research carried out in the day labor agencies of Baltimore and Oakland, I examine how day laborers and agency dispatchers negotiate and navigate the practice of what I call “backdoor” hiring, wherein employers hire workers from, but not through, the agency. The struggles surrounding backdoor hiring not only challenge and complicate the binary division in the literature between formal and informal day labor, but reveal the dogged efforts of dispatchers to cultivate workers’ dependency, restrict their mobility, and curtail their labor‐market freedom. This article thus contributes to the growing debate within anthropology and related disciplines about the conditions exacerbating unfreedom at the bottom of the labor market.
A task‐ and role‐based perspective on super‐recognizers: Commentary on ‘Super‐recognizers: From the lab to the world and back again’
Authors: Moreton Reuben , Pike Graham , Havard Catriona
Published: March 2019

This article provides a commentary on recent work by Ramon et al. (2019, British Journal of Psychology) on super‐recognizers. The commentary advocates a task‐ and role‐based approach to SR research and greater collaboration between researchers and the applied community.
Antitumor activity of Raddeanin A is mediated by Jun amino‐terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma
Authors: Wang Zhuoying , Shen Jiakang , Sun Wei , Zhang Tao , Zuo Dongqing , Wang Hongsheng , Wang Gangyang , Xu Jing , Yin Fei , Mao Min , Zhou Zifei , Hua Yingqi , Cai Zhengdong
Published: March 2019

Osteosarcoma is the most common primary malignant bone tumor. Raddeanin A (RA) is an active oleanane‐type triterpenoid saponin extracted from the traditional Chinese herb Anemone raddeana Regel that exerts antitumor activity against several cancer types. However, the effect of RA on osteosarcoma remains unclear. In the present study, we showed that RA inhibited proliferation and induced apoptosis of osteosarcoma cells in a dose‐ and time‐dependent way in vitro and in vivo. RA treatment resulted in excessive reactive oxygen species (ROS) generation and JNK and ERK1/2 activation. Apoptosis induction was evaluated by the activation of caspase‐3, caspase‐8, and caspase‐9 and poly‐ADP ribose polymerase (PARP) cleavage. RA‐induced cell death was significantly restored by the ROS scavenger glutathione (GSH), the pharmacological inhibitor of JNK SP600125, or specific JNK knockdown by shRNA. Additionally, signal transducer and activator of transcription 3 (STAT3) activation was suppressed by RA in human osteosarcoma, and this suppression was restored by GSH, SP600125, and JNK‐shRNA. Further investigation showed that STAT3 phosphorylation was increased after JNK knockdown. In a tibial xenograft tumor model, RA induced osteosarcoma apoptosis and notably inhibited tumor growth. Taken together, our results show that RA suppresses proliferation and induces apoptosis by modulating the JNK/c‐Jun and STAT3 signaling pathways in human osteosarcoma. Therefore, RA may be a promising candidate antitumor drug for osteosarcoma intervention.
Area‐level social development and indicators of public dental services in Southern Brazil
Authors: Godoi Heloisa , Singh Ankur , de Mello Ana Lúcia S. Ferreira , Brennan David S. , Peres Marco A.
Published: March 2019

Objectives

This study aimed to test associations between a municipal social development indicator and indicators of public dental services; examine differences in the achievement of public dental services goals between fluoridated and nonfluoridated municipalities; and, quantify contribution of a municipal social development indicator in estimated mean differences in the public dental services indicators between fluoridated and nonfluoridated municipalities.

Methods

A secondary analysis of data from 293 municipal dental health services records from Southern Brazil between 2010 and 2015 was conducted. Multivariable log‐binomial regression models were fitted to test the associations between municipal Human Development Index (HDI) and multiple public dental services indicators (proportion of public dental health service coverage, the proportion of tooth extraction among all clinical procedures, and monthly participation in supervised tooth brushing). Cut‐off points for outcomes were based on state goals for public dental services. Blinder‐Oaxaca decomposition analyses were performed to quantify the relative contribution of HDI in the differences in outcomes according to the municipal water fluoridation status.

Results

Municipalities within the lowest tertile of HDI had 66% lower prevalence of having insufficient public dental health service coverage (less than state goals)than those in the highest tertile of HDI (PR: 0.44; 95% CI: 0.24, 0.50). Municipalities with lowest HDI had nearly 30% higher prevalence of failing the state goals regarding the proportion of extraction and supervised tooth brushing (PR: 1.30; 95% CI: 1.20, 1.40 and PR: 1.34; 95% CI: 1.23, 1.45, respectively). Mean public dental health service coverage was higher in nonfluoridated municipalities than fluoridated municipalities, and municipal HDI explained 36% of the total estimated mean difference.

Conclusions

This study found associations between municipal social development and public dental services indicators in Southern Brazil. However, higher HDI was associated with lower public dental health service coverage, lower proportion of extraction and higher coverage of supervised tooth brushing [Correction added on 2 April 2019, after first online publication: In the preceding sentence, the text “but with a higher proportion of extraction and supervised tooth brushing” was changed to “lower proportion of extraction and higher coverage of supervised tooth brushing”]. Municipal HDI contributed significantly towards the gap in public dental coverage between fluoridated and nonfluoridated municipalities, favoring nonfluoridated municipalities. These findings have important policy implications for reducing oral health inequalities as it highlights the interplay between key oral health policies and their distribution according to municipal social development.