bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a context-specific nutrient profiling system for food policy in Samoa
Authors: Reeve Erica , Naseri Take , Martyn Tim , Bollars Caroline , Thow Anne-Marie
Published: October 2018

The objective of this study was to develop a transparent system for defining ‘less healthy’ foods to underpin effective policy to reduce noncommunicable diseases in Samoa, replacing a fatty-meat ban lifted for accession to the WTO. In the absence of nutrition survey data, we calculated nutrient availability using food acquisition data from Samoa's Household Income and Expenditure Surveys. Together with published literature and local food composition data, we identified foods and nutrients (i) consumed in amounts greater than those recommended for good health and (ii) with a demonstrated causal link to health conditions of concern. Nutrient thresholds were developed based on desired level of decrease per nutrient per person necessary to reduce population intake in line with specific targets. We found average energy and sodium consumption to be higher than recommended, and foods high in sugar and saturated fat being consumed in large amounts. We selected a threshold-based, category-specific model to provide straightforward policy administration and incentivise healthy production and import, and then applied and tested nutrient thresholds across 7 threshold groups. The validation process indicated that the development of a nutrient profiling system to identify less healthy food items in Samoa provided a stronger basis for local policymaking. This study contributes to global understanding of approaches to developing a robust and transparent basis for policies to improve diets in lower income countries, and is relevant to other settings with high rates of noncommunicable diseases and similar resource and data constraints.
The whole and inclusive university: a critical review of health promoting universities from Aotearoa New Zealand
Authors: Came Heather A , Tudor Keith
Published: October 2018

As well as serving as a critic and conscience for societies, universities are elite sites of privilege which, at a surface level, are unlikely locations for health promotion interventions. This paper provides a critical review of the existing health promoting universities (HPU) approaches which is informed by health promotion values. It explores the silence in the global literature around issues of structural discrimination such as the sexism, homophobia and institutional racism that can thrive within university settings. The existing literature also reveals a very limited engagement about positive mental health or indigeneity. In response, this paper brings together these three factors—structural discrimination, mental health, and indigeneity—all of which the authors consider are criterial to health and its promotion. The authors introduce the New Zealand university landscape, in which there are eight Western universities and three whare wānanga (Māori universities), and, drawing on a survey of their Charters and other official statements, offer a moemoeā (vision or dream) of an HPU that addresses structural discrimination, is based on holistic conceptions of health, and is centred on indigenous worldviews and concerns.
Exploring causality of the association between smoking and Parkinson’s disease
Authors: Gallo Valentina , Vineis Paolo , Cancellieri Mariagrazia , Chiodini Paolo , Barker Roger A , Brayne Carol , Pearce Neil , Vermeulen Roel , Panico Salvatore , Bueno-de-Mesquita Bas , Vanacore Nicola , Forsgren Lars , Ramat Silvia , Ardanaz Eva , Arriola Larraitz , Peterson Jesper , Hansson Oskar , Gavrila Diana , Sacerdote Carlotta , Sieri Sabina , Kühn Tilman , Katzke Verena A , van der Schouw Yvonne T , Kyrozis Andreas , Masala Giovanna , Mattiello Amalia , Perneczky Robert , Middleton Lefkos , Saracci Rodolfo , Riboli Elio
Published: October 2018

Background

The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson’s disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait.

Methods

A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset.

Results

Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose–response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67–1.07], 20–29 years 0.73 (95% CI 0.56–0.96) and >30 years 0.54 (95% CI 0.43–0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose–response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49–0.99) ruled out the effect of unmeasured confounding.

Conclusions

These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.
European Asylum Policies and the Stranded Asylum Seekers in Southeastern Europe
Authors: Valenta Marko , Lønning Moa Nyamwathi , Jakobsen Jo , Župarić-Iljić Drago
Published: October 2018

This article focuses on the restrictive European asylum policies and on their humanitarian consequences in Southeastern Europe. We discuss two interrelated topics: (i) the dynamic of the migration of asylum seekers to Europe and (ii) the specific position of Southeastern European countries and the situation of stranded migrants in the region. We identify central elements in the European asylum system and suggest that different parts of the system may be seen as a set of interacting lines of deterrence used to curb asylum migrations. It is argued herein that Greece and the other countries at the southern borders of the European Union have an idiosyncratic position within the European system of deterrence. Furthermore, we discuss how European deterrence policies and local responses influence the migration patterns of asylum seekers in Southeastern Europe. It is maintained that the deterrence measures have contributed to increasing the number of stranded asylum seekers in the region, especially in Greece with clear and regrettable humanitarian consequences.
Positive Luminex and negative flow cytometry in kidney transplantation: a systematic review and meta-analysis
Authors: Buttigieg Jesmar , Ali Hatem , Sharma Ajay , Halawa Ahmed
Published: October 2018

The presence of pre-formed donor-specific antibodies (DSAs) in kidney transplantation is associated with worse overall outcomes compared with DSA-negative transplantation. A positive complement-dependant cytotoxic crossmatch presents a high immunological risk, while a negative flow cytometry crossmatch is at the lower end of the risk spectrum. Yet, the presence of low-level DSA detected by Luminex alone, that is, positive Luminex and negative flow (PLNF) cytometry crossmatch lacks robust scientific exploration. In this systematic review and pooled analysis, we investigate the glomerular filtration rate, acute rejection (AR), graft survival and patient survival of PLNF transplants compared with DSA-negative transplants. Our analysis identified seven retrospective studies consisting of 429 PLNF transplants and 10 677 DSA-negative transplants. Pooled analysis identified no significant difference in the incidence of AR at 1 year [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.90–2.02, Z = 1.46, P = 0.14, I2 = 0%], graft failure at 1 year (RR = 1.66, 95% CI 0.94–2.94, Z = 1.75, P = 0.08, I2 = 23%), graft failure at 5 years (RR = 1.29, 95% CI 0.90–1.87, Z = 1.38, P = 0.17, I2 = 0%), patient mortality at 1 year (RR = 0.89, 95% CI 0.31–2.56, Z = 0.22, P = 0.82, I2 = 0%) and patient mortality at 5 years (RR = 1.76, 95% CI 0.48–6.48, Z = 0.85, P = 0.39, I2 = 61%). Pooled analysis of graft function was not possible due to insufficient data. Current evidence suggests that low-level DSA detected by Luminex alone does not pose significant risk at least in the short–medium term. Considering the shortage of kidney transplants and the ever-increasing waiting time, the avoidance of PLNF transplants may be unwarranted especially in patients who have been enlisted for a long time.
Knowledge and Awareness of Added Sugar in Cigarettes
Authors: Seidenberg Andrew B , Jo Catherine L , Ribisl Kurt M
Published: October 2018

Introduction

Sugars naturally occur in tobacco leaf but are also commonly added to cigarettes by tobacco companies. Added sugar increases levels of toxic chemicals in cigarette smoke. Little is known about smokers’ knowledge of added sugar in cigarettes and awareness of its effects.

Methods

Adult cigarette smokers were recruited through Amazon Mechanical Turk to participate in an online experiment on electronic cigarette advertising. After completing the experiment, participants (N = 4351) answered two items assessing knowledge and awareness of added sugar in cigarettes. Participants had the option of providing open-ended comments about the overall study, and two reviewers read and independently coded comments pertaining to the sugar items.

Results

Only 5.5% of participants responded “yes” to the question: “Is sugar added to cigarettes?”, and only 3.8% of participants indicated being aware that added sugar increases toxins in cigarette smoke. Forty-eight participants mentioned the sugar items when asked to comment about the overall questionnaire. Fifty-two percent of these comments expressed an interest in obtaining more information about added sugar, and 23% described the sugar items as interesting or informative. Three participants commented that learning about added sugar motivated them to quit or cut down on smoking.

Conclusions

Among a large sample of smokers, few reported knowledge of added sugar in cigarettes and awareness of its effects. Further, several smokers expressed an interest in learning more about added sugar. Messages about added sugar in cigarettes may be a promising new angle for campaigns to discourage smoking.

Implications

Few American smokers are aware that sugar is added to cigarettes, and some participants expressed a desire to learn more about this additive. Given such low awareness, the interest among smokers, and increased popular concerns about added sugar in foods and beverages, messaging about added sugar in cigarettes should be developed and tested for inclusion in public health media campaigns.
Prevalence of hepatitis B virus infection and uptake of hepatitis B vaccine among healthcare workers, Makueni County, Kenya 2017
Authors: Kisangau E N , Awour A , Juma B , Odhiambo D , Muasya T , Kiio S N , Too R , Lowther S A
Published: October 2018

Background

Hepatitis B virus (HBV) is a vaccine-preventable infection that can spread in healthcare setting. Data on HBV infections and vaccine in African healthcare workers (HCWs) are limited. We estimated HBV infection prevalence, hepatitis B vaccination status and identified factors associated with vaccination in one Kenyan county.

Methods

Randomly selected HCWs completed a questionnaire about HBV exposure and self-reported immunization histories, and provided blood for testing of selected HBV biomarkers to assess HBV infection and vaccination status: HBV core antibodies (anti-HBc), HBV surface antigen (HBsAg) and HBV surface antibodies (anti-HBs). Prevalence odds ratios (OR) with 95% confidence intervals (95% CI) were calculated to identify factors associated with vaccination.

Results

Among 312 HCWs surveyed, median age was 31 years (range: 19–67 years). Of 295 blood samples tested, 13 (4%) were anti-HBc and HBsAg-positive evidencing chronic HBV infection; 139 (47%) had protective anti-HBs levels. Although 249 (80%) HCWs received ≥1 HBV vaccine dose, only 119 (48%) received all three recommended doses. Complete vaccination was more likely among those working in hospitals compared to those working in primary healthcare facilities (OR = 2.5; 95% CI: 1.4–4.3).

Conclusion

We recommend strengthening county HCW vaccination, and collecting similar data nationally to guide HBV prevention and control.
The New Keynesian Transmission Mechanism: A Heterogeneous-Agent Perspective
Authors: Broer Tobias , Harbo Hansen Niels-Jakob , Krusell Per , Öberg Erik
Published: October 2018

We present a tractable heterogeneous-agent version of the New Keynesian model that allows us to study the interaction between inequality and monetary policy. Though formulated as a precautionary-saving model à la Huggett–Aiyagari, its reduced form is a two-agent model with a highly concentrated wealth distribution. When prices are sticky and wages flexible, as in the textbook representative-agent model, monetary policy affects the distribution of consumption, but has no effect on output as workers choose not to change their hours worked in response to wage movements. This highlights a transmission mechanism of the textbook model that we find implausible: in response to a monetary stimulus, the representative worker’s labor supply is greatly affected by the profits she receives. First, the lower profits induced by higher wages raise labor supply through a wealth effect and, secondly, the mere presence of profits reduces the negative income effect of a wage rise. When wages are rigid, in contrast, our model exhibits plausible responses of output and hours worked to monetary policy shocks.
Paracingulate Sulcus Morphology and Hallucinations in Clinical and Nonclinical Groups
Authors: Garrison Jane R , Fernyhough Charles , McCarthy-Jones Simon , Simons Jon S , Sommer Iris E C
Published: October 2018

Hallucinations are a characteristic symptom of psychotic mental health conditions that are also experienced by many individuals without a clinical diagnosis. Hallucinations in schizophrenia have been linked to differences in the length of the paracingulate sulcus (PCS), a structure in the medial prefrontal cortex which has previously been associated with the ability to differentiate perceived and imagined information. We investigated whether this putative morphological basis for hallucinations extends to individuals without a clinical diagnosis, by examining whether nonclinical individuals with hallucinations have shorter PCS than nonclinical individuals without hallucinations. Structural MRI scans were examined from 3 demographically matched groups of individuals: 50 patients with psychotic diagnoses who experienced auditory verbal hallucinations (AVHs), 50 nonclinical individuals with AVHs, and 50 healthy control subjects with no life-time history of hallucinations. Results were verified using automated data-driven gyrification analyses. Patients with hallucinations had shorter PCS than both healthy controls and nonclinical individuals with hallucinations, with no difference between nonclinical individuals with hallucinations and healthy controls. These findings suggest that the association of shorter PCS length with hallucinations is specific to patients with a psychotic disorder. This presents challenges for full-continuum models of psychosis and suggests possible differences in the mechanisms underlying hallucinations in clinical and nonclinical groups.
Testing for Human Papillomavirus Strains 16 and 18 Helps Predict the Presence of Anal High-Grade Squamous Intraepithelial Lesions
Authors: Sambursky Jacob A. , Terlizzi Joseph P. , Goldstone Stephen E.
Published: October 2018

BACKGROUND:

More than 90% of anal cancers are caused by human papillomavirus, and human papillomavirus strains 16 and 18 are the most oncogenic. Anal high-grade squamous intraepithelial lesions are cancer precursors. Treating these high-grade intraepithelial lesions likely reduces the risk of cancer, but cytology is an imperfect screening test.

OBJECTIVE:

The purpose of this study was to determine whether human papillomavirus 16 and/or 18 testing better predicts the presence of high-grade squamous intraepithelial lesions.

DESIGN:

In this retrospective study, 894 consecutive patients underwent anal dysplasia screening with digital anorectal examination, anal cytology, high-risk human papillomavirus testing, and high-resolution anoscopy with biopsy. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of each test and for a novel screening protocol. The absolute and relative risk of high-grade squamous intraepithelial lesions for all of the cytology/human papillomavirus combinations were also calculated.

SETTINGS:

The study was conducted at a single practice specializing in anal dysplasia.

PATIENTS:

Ninety-two percent of participants were men who have sex with men. Forty-four percent were HIV-positive individuals who were well controlled on antiretroviral therapy. The median age was 50 years.

MAIN OUTCOME MEASURES:

The presence of high-grade squamous intraepithelial lesions as a function of human papillomavirus and the cytology results were measured.

RESULTS:

High-risk human papillomavirus testing alone demonstrated better sensitivity (96% vs 89%; p = 0.03) and negative predictive value (99% vs 96%; p = 0.008) over cytology. Human papillomavirus 16/18 testing increased specificity (48% to 71%; p < 0.0001) and positive predictive value (24% to 37%; p = 0.003) over testing for all of the high-risk strains. For each cytology category, high-grade squamous intraepithelial lesions were more prevalent when human papillomavirus 16/18 was detected. Benign cytology with 16/18 had a 31-fold increased risk of high-grade squamous intraepithelial lesions.

LIMITATIONS:

This study was conducted in a single private practice specializing in anal dysplasia screening with a mostly male population, and results might not be generalizable.

CONCLUSIONS:

Testing of high-risk human papillomavirus strains 16/18 improves specificity and positive predictive value over cytology for anal dysplasia screening. Patients testing positive for strains 16/18 are at a high risk for high-grade squamous intraepithelial lesions and should undergo high-resolution anoscopy regardless of the cytology result. See Video Abstract at http://links.lww.com/DCR/A654.
Glaucoma Gel Implant Learning Curve in a Teaching Tertiary Hospital
Authors: Marques Raquel Esteves , Ferreira Nuno Pinto , Sousa David Cordeiro , Pinto Joana , Barata André , Sens Paula , Abegão Pinto Luís
Published: October 2018

Purpose:

The XEN gel stent is a minimally invasive surgical device aimed at creating a subconjunctival drainage of aqueous humor, thereby reducing intraocular pressure (IOP). Being a novel device, doubts remain with regard to the efficacy and safety of its implantation in the early stage of new users. This paper illustrates the XEN implantation learning curve, assessed through several surgeons of different expertise.

Methods:

This was a retrospective study on the first 6 XEN implants performed by each of the 10 certified ophthalmic surgeons. Simultaneous cataract surgery was allowed (phaco-XEN). Primary outcomes were as follows: surgical time; intraoperative and postoperative surgical complications. Secondary outcomes were as follows: IOP; the number of topical drugs in use; the need for needling procedures. Outcome data were collected preoperatively and at postoperative days 1, 7, 15, 30, 60, and 90. Statistical analysis was performed with STATA 14.1 and SPSS.

Results:

Sixty patients were included (56.7% female patients). Mean age was 73 years (45 to 89). Mean preoperative IOP was 23.8±8.95 mm Hg. From the included patients, 29 (48.3%) were submitted to simple XEN implant and 31 (51.7%) to phaco-XEN. In both groups, mean surgical time decreased by 9 minutes throughout the 6-implant learning curve. Final IOP was 15±7.27 mm Hg in the stent group (−43% than baseline), and 14.92±3.32 mm Hg in the phaco-XEN group (−16% than baseline). On average, patients decreased 2 topical IOP-lowering drugs. Needling procedures were performed in 17 patients (28.3%).

Conclusions:

XEN gel stent was associated with a fast learning curve, by both experienced surgeons and novice residents. By the sixth implant, both groups had considerably decreased mean surgical time and complication rates.
Impact of Deep Learning Assistance on the Histopathologic Review of Lymph Nodes for Metastatic Breast Cancer
Authors: Steiner David F. , MacDonald Robert , Liu Yun , Truszkowski Peter , Hipp Jason D. , Gammage Christopher , Thng Florence , Peng Lily , Stumpe Martin C.
Published: October 2018

Advances in the quality of whole-slide images have set the stage for the clinical use of digital images in anatomic pathology. Along with advances in computer image analysis, this raises the possibility for computer-assisted diagnostics in pathology to improve histopathologic interpretation and clinical care. To evaluate the potential impact of digital assistance on interpretation of digitized slides, we conducted a multireader multicase study utilizing our deep learning algorithm for the detection of breast cancer metastasis in lymph nodes. Six pathologists reviewed 70 digitized slides from lymph node sections in 2 reader modes, unassisted and assisted, with a wash-out period between sessions. In the assisted mode, the deep learning algorithm was used to identify and outline regions with high likelihood of containing tumor. Algorithm-assisted pathologists demonstrated higher accuracy than either the algorithm or the pathologist alone. In particular, algorithm assistance significantly increased the sensitivity of detection for micrometastases (91% vs. 83%, P=0.02). In addition, average review time per image was significantly shorter with assistance than without assistance for both micrometastases (61 vs. 116 s, P=0.002) and negative images (111 vs. 137 s, P=0.018). Lastly, pathologists were asked to provide a numeric score regarding the difficulty of each image classification. On the basis of this score, pathologists considered the image review of micrometastases to be significantly easier when interpreted with assistance (P=0.0005). Utilizing a proof of concept assistant tool, this study demonstrates the potential of a deep learning algorithm to improve pathologist accuracy and efficiency in a digital pathology workflow.
Prognostic Nutritional Index, Tumor-infiltrating Lymphocytes, and Prognosis in Patients with Esophageal Cancer
Authors: Okadome Kazuo , Baba Yoshifumi , Yagi Taisuke , Kiyozumi Yuki , Ishimoto Takatsugu , Iwatsuki Masaaki , Miyamoto Yuji , Yoshida Naoya , Watanabe Masayuki , Baba Hideo
Published: October 2018

Objective:

To determine whether prognostic nutritional index (PNI) affects clinical outcome through local immunity in esophageal cancers.

Background:

PNI is an indicator of nutritional status and systemic immune competence, and has attracted attention as a prognostic biomarker. Tumor-infiltrating lymphocytes (TILs) are a specific histological feature of human cancers, reflecting an individual's immunological tumor response.

Methods:

Using a nonbiased database of 337 curatively resected esophageal cancers, we evaluated the relationship between PNI, TILs status, CD8 expression by immunohistochemical staining, and clinical outcome.

Results:

Compared with PNI-high cases (n = 220), PNI-low cases (n = 117) showed significantly worse overall survival (log-rank P < 0.001; hazard ratio: 2.23; 95% confidence interval: 1.56–3.18; P < 0.001; multivariate hazard ratio: 1.67; 95% confidence interval: 1.14–2.44; P = 0.008). The TILs status was also significantly correlated with overall survival (P < 0.001). In addition, PNI was significantly associated with TILs status (P < 0.001) and the CD8-positive cell count (P = 0.041). A significant relationship between the peripheral blood lymphocyte count and TILs status was also observed (P < 0.001).

Conclusions:

PNI and TILs score expression were associated with clinical outcome in esophageal cancer, supporting their roles as prognostic biomarkers. Considering the relationship between PNI and TILs, nutritional status and systemic immune competence may influence patient prognosis through local immune response.
Electrophysiological Assessment and Classification of Motor Pathway Function in Patients With Spinal Dural Arteriovenous Fistula
Authors: Nakanishi Kazuyoshi , Tanaka Nobuhiro , Fujimoto Yoshinori , Nishikawa Koichiro , Kamei Naosuke , Nakamae Toshio , Kotaka Shinji , Adachi Nobuo
Published: October 2018

Purpose:

The diagnosis of spinal dural arteriovenous fistula (SDAVF) is difficult and often delayed because clinical features are often nonspecific. We assessed the motor function electrophysiologically in patients with SDAVF.

Methods:

Motor-evoked potentials after transcranial magnetic stimulation and compound muscle action potentials and F-waves after electrical stimulation in the ulnar and tibial nerves were measured from the abductor hallucis (AH) muscles in 14 patients with SDAVF (SDAVF group), 12 patients with compressive thoracic myelopathy (CTM group), and 16 normal subjects (control group). The peripheral conduction time determined from abductor hallucis muscles (PCT-AH) and the central motor conduction time determined from abductor hallucis muscles (CMCT-AH) were calculated. According to the neurological findings, patients in the SDAVF group were classified to upper motor neuron (UMN) sign and lower motor neuron (LMN) sign categories.

Results:

CMCT-AH in the SDAVF and CMT groups were significantly longer than those in the control group. PCT-AH in the SDAVF group was significantly longer than that in the control and CMT groups. Twelve patients in the SDAVF group showed abnormal CMCT-AH and/or PCT-AH. Abnormal CMCT-AH and PCT-AH were detected in five cases that exhibited UMN sign and/or LMN sign. Three cases with abnormal CMCT-AH and normal PCT-AH exhibited UMN sign. LMN sign without UMN sign was observed in four cases with abnormal PCT-AH and normal CMCT-AH.

Conclusions:

Our study revealed abnormalities in the corticospinal tract and/or lower motor neurons, and classified the patients with SDAVF into three types: the UMN type, LMN type, and mixed type.
Adaptive walks on high-dimensional fitness landscapes and seascapes with distance-dependent statistics
Authors: Agarwala Atish , Fisher Daniel S.
Published: October 2018

The dynamics of evolution is intimately shaped by epistasis — interactions between genetic elements which cause the fitness-effect of combinations of mutations to be non-additive. Analyzing evolutionary dynamics that involves large numbers of epistatic mutations is intrinsically difficult. A crucial feature is that the fitness landscape in the vicinity of the current genome depends on the evolutionary history. A key step is thus developing models that enable study of the effects of past evolution on future evolution. In this work, we introduce a broad class of high-dimensional random fitness landscapes for which the correlations between fitnesses of genomes are a general function of genetic distance. Their Gaussian character allows for tractable computational as well as analytic understanding. We study the properties of these landscapes focusing on the simplest evolutionary process: random adaptive (uphill) walks. Conventional measures of “ruggedness” are shown to not much affect such adaptive walks. Instead, the long-distance statistics of epistasis cause all properties to be highly conditional on past evolution, determining the statistics of the local landscape (the distribution of fitness-effects of available mutations and combinations of these), as well as the global geometry of evolutionary trajectories. In order to further explore the effects of conditioning on past evolution, we model the effects of slowly changing environments. At long times, such fitness “seascapes” cause a statistical steady state with highly intermittent evolutionary dynamics: populations undergo bursts of rapid adaptation, interspersed with periods in which adaptive mutations are rare and the population waits for more new directions to be opened up by changes in the environment. Finally, we discuss prospects for studying more complex evolutionary dynamics and on broader classes of high-dimensional landscapes and seascapes.
What drives mortality among HIV patients in a conflict setting? A prospective cohort study in the Central African Republic
Authors: Crellen Thomas , Ssonko Charles , Piening Turid , Simaleko Marcel Mbeko , St. Calvaire Diemer Henri , Gieger Karen , Siddiqui M. Ruby
Published: October 2018

Background

Provision of antiretroviral therapy (ART) during conflict settings is rarely attempted and little is known about the expected patterns of mortality. The Central African Republic (CAR) continues to have a low coverage of ART despite an estimated 120,000 people living with HIV and 11,000 AIDS-related deaths in 2013. We present results from a cohort in Zemio, Haut-Mboumou prefecture. This region had the highest prevalence of HIV nationally (14.8% in 2010) and was subject to repeated attacks by armed groups on civilians during the observed period.

Methods

Conflict from armed groups can impact cohort mortality rates i) directly if HIV patients are victims of armed conflict, or ii) indirectly if population displacement or fear of movement reduces access to ART. Using monthly counts of civilian deaths, injuries and abductions, we estimated the impact of the conflict on patient mortality. We also determine patient-level risk factors for mortality and how this varies with time spent in the cohort. Model-fitting was performed in a Bayesian framework, using generalised-linear models with terms accounting for temporal autocorrelation.

Results

Patients were recruited and observed from October 2011 to May 2017. Overall 1631 patients were enrolled, giving 4107 person-years and 148 deaths. Our first model shows that patient mortality did not increase during periods of heightened conflict. The monthly risk (probability) of mortality was markedly higher at the beginning of the program (0.047 in November 2011 [95% credible interval; CrI 0.0078, 0.21]) and had declined greater than ten-fold by the end of the observed period (0.0016 in June 2017 [95% CrI 0.00042, 0.0036]). Our second model shows the risk of mortality for individual patients was highest in the first five months spent in the cohort. Male sex was associated with a higher mortality (odds ratio; OR 1.7 [95% CrI 1.2, 2.8]) along with the severity of opportunistic infections at baseline.

Conclusions

Our results show that chronic conflict did not appear to adversely affect rates of mortality in this cohort, and that mortality was driven predominantly by patient specific risk factors. In areas initiating ART for the first time, particular attention should be focussed on stabilising patients with advanced symptoms.

Funding

Médecins Sans Frontières
Fast, volumetric live-cell imaging using high-resolution light-field microscopy
Authors: Li Haoyu , Guo Changliang , Kim-Holzapfel Deborah , Li Weiyi , Altshuller Yelena , Schroeder Bryce , Liu Wenhao , Meng Yizhi , French Jarrod B. , Takamaru Ken-Ichi , Frohman Michael A. , Jia Shu
Published: October 2018

Visualizing diverse anatomical and functional traits that span many spatial scales with high spatio-temporal resolution provides insights into the fundamentals of living organisms. Light-field microscopy (LFM) has recently emerged as a scanning-free, scalable method that allows for high-speed, volumetric functional brain imaging. Given those promising applications at the tissue level, at its other extreme, this highly-scalable approach holds great potential for observing structures and dynamics in single-cell specimens. However, the challenge remains for current LFM to achieve subcellular level, near-diffraction-limited 3D spatial resolution. Here, we report high-resolution LFM (HR-LFM) for live-cell imaging with a resolution of 300-700 nm in all three dimensions, an imaging depth of several micrometers, and a volume acquisition time of milliseconds. We demonstrate the technique by imaging various cellular dynamics and structures and tracking single particles. The method may advance LFM as a particularly useful tool for understanding biological systems at multiple spatio-temporal levels.
Bioorthogonal antigens allow the unbiased study of antigen processing and presentation
Authors: Araman Can , Pieper-Pournara Linda , van Leeuwen Tyrza , Kampstra Arieke S. B. , Bakkum Thomas , Marqvorsen Mikkel H. S. , Nascimento Clarissa R. , Mirjam Groenewold G. J. , van der Wulp Willemijn , Camps Marcel G. M. , Overkleeft Herman S. , Ossendorp Ferry A. , Toes René E. M. , van Kasteren Sander I.
Published: October 2018

Proteolysis is fundamental to many biological processes. In the immune system, it underpins the activation of the adaptive immune response: degradation of antigenic material into short peptides and presentation thereof on major histocompatibility complexes, leads to activation of T-cells. This initiates the adaptive immune response against many pathogens.
An inexpensive air stream temperature controller and its use to facilitate temperature controlled behavior in livingDrosophila
Authors: Sangston Ryan , Hirsh Jay
Published: October 2018

Controlling the environment of an organism has many biologically relevant applications. Temperature-dependent inducible biological reagents have proven invaluable for elucidating signaling cascades and dissection of neural circuits. Here we develop a simple and affordable system for rapidly changing temperature in a chamber housing adultDrosophilamelanogaster. Utilizing flies expressing the temperature inducible channel dTrpA1 in dopaminergic neurons, we show rapid and reproducible changes in locomotor behavior. This device should have wide application to temperature modulated biological reagents.

Method Summary

We develop widely applicable and affordable solution to rapidly changing temperature within an enclosed chamber using commercially available components.
The influence of molecular reach and diffusivity on the efficacy of membrane-confined reactions
Authors: Zhang Ying , Clemens Lara , Goyette Jesse , Allard Jun , Dushek Omer , Isaacson Samuel. A.
Published: October 2018

Signalling by surface receptors often relies on tethered reactions whereby an enzyme bound to the cytoplasmic tail of a receptor catalyses reactions on substrates within reach. The overall length and stiffness of the receptor tail, the enzyme, and the substrate determine a biophysical parameter termed the molecular reach of the reaction. This parameter determines the probability that the receptor-tethered-enzyme will contact the substrate, in the volume proximal to the membrane, when separated by different distances within the membrane plane. In this work we develop particle-based stochastic reaction-diffusion models to study the interplay between molecular reach and diffusion. We find that increasing the molecular reach can increase reaction efficacy for slowly diffusing receptors, while for rapidly diffusing receptors increasing molecular reach reduces reaction efficacy. In contrast, if reactions are forced to take place within the 2D plasma membrane instead of the 3D volume proximal to it, or if molecules diffuse in 3D, increasing molecular reach increases reaction efficacy for all diffusivities. We show results in the context of immune checkpoint receptors (PD-1 dephosphorylating CD28), a standard opposing kinase-phosphatase reaction, and a minimal two-particle model. The work highlights the importance of the 3D nature of many 2D membrane-confined interactions, illustrating a role for molecular reach in controlling biochemical reactions.
Multi-allele species reconstruction using ASTRAL
Authors: Rabiee Maryam , Sayyari Erfan , Mirarab Siavash
Published: October 2018

Genome-wide phylogeny reconstruction is becoming increasingly common, and one driving factor behind these phylogenomic studies is the promise that the potential discordance between gene trees and the species tree can be modeled. Incomplete lineage sorting is one cause of discordance that bridges population genetic and phylogenetic processes. ASTRAL is a species tree reconstruction method that seeks to find the tree with minimum quartet distance to an input set of inferred gene trees. However, the published ASTRAL algorithm only works with one sample per species. To account for polymorphisms in present-day species, one can sample multiple individuals per species to create multi-allele datasets. Here, we introduce how ASTRAL can handle multi-allele datasets. We show that the quartet-based optimization problem extends naturally, and we introduce heuristic methods for building the search space specifically for the case of multi-individual datasets. We study the accuracy and scalability of the multi-individual version of ASTRAL-III using extensive simulation studies and compare it to NJst, the only other scalable method that can handle these datasets. We do not find strong evidence that using multiple individuals dramatically improves accuracy. When we study the trade-off between sampling more genes versus more individuals, we find that sampling more genes is more effective than sampling more individuals, even under conditions that we study where trees are shallow (median length: ≈ 1Ne) and ILS is extremely high.
A phylum-wide survey reveals multiple independent gains of head regeneration ability in Nemertea
Authors: Zattara Eduardo E. , Fernández-Álvarez Fernando A. , Hiebert Terra C. , Bely Alexandra E. , Norenburg Jon L.
Published: October 2018

Animals vary widely in their ability to regenerate, suggesting that regenerative abilities have a rich evolutionary history. However, our understanding of this history remains limited because regeneration ability has only been evaluated in a tiny fraction of species. Available comparative regeneration studies have identified losses of regenerative ability, yet clear documentation of gains is lacking. We surveyed regenerative ability in 34 species spanning the phylum Nemertea, assessing the ability to regenerate heads and tails either through our own experiments or from literature reports. Our sampling included representatives of the 10 most diverse families and all three orders comprising this phylum. We generated a phylogenetic framework using sequence data to reconstruct the evolutionary history of head and tail regeneration ability across the phylum and found that while all evaluated species can remake a posterior end, surprisingly few could regenerate a complete head. Our analysis reconstructs a nemertean ancestor unable to regenerate a head and indicates at least four separate lineages have independently gained head regeneration ability, one such gains reconstructed as taking place within the last 10-15 mya. Our study highlights nemerteans as a valuable group for studying evolution of regeneration and identifying mechanisms associated with repeated gains of regenerative ability.
Crop Information Engine and Research Assistant (CIERA) for managing genealogy, phenotypic and genotypic data for breeding programs
Authors: Yates Shawn , Lagüe Martin , Knox Ron , Cuthbert Richard , Clarke Fran , Clarke John , Ruan Yuefeng , Sangha Jatinder , Bhadauria Vijai
Published: October 2018

Background

With the advent of next-generation marker platforms and phenomics in crop breeding programs, the volume of both the genotypic and phenotypic data produced has increased exponentially. Often the data remain underutilized if not properly collated, managed and accessed. Effective management of the data is paramount to making sound and timely decision on cross planning in order to accelerate genetic gain (ΔG) in crops for disease resistance, agronomic and end-use quality traits.

Results

To address the challenges in managing and efficient utilization of the sheer volume of data generated in a crop breeding program, we developed an electronic information system called the Crop Information Engine and Research Assistant (CIERA). The CIERA, written in Visual Basic, runs on the Microsoft Windows operating system and requires the .Net Framework 4.7 as well as the MySQL Community Server 5.7. The highly intuitive graphical user interface of CIERA includes user-friendly query tools to facilitate the collation of data across relevant phenotypic environments from its phenotypic data management database and can combine that information with the genealogy and genetic data from its genealogy management and genetic data management databases, respectively.

Conclusions

Using CIERA, breeders can build a comprehensive profile of germplasm, within a few minutes, to assist them in planning crosses for enhancing genetic gain by selecting superior lines for crosses.
Differential Metabolic and Multi-tissue Transcriptomic Responses to Fructose Consumption among Genetically Diverse Mice
Authors: Zhang Guanglin , Byun Hyae Ran , Ying Zhe , Blencowe Montgomery , Zhao Yuqi , Hong Jason , Shu Le , Krishnan Karthick Chella , Gomez-Pinilla Fernando , Yang Xia
Published: October 2018

High fructose intake is a major risk for metabolic syndrome; however, its effects seem to vary across individuals. To determine main factors involved in the inter-individual responses to fructose, we fed inbred mouse strains C57BL/6J (B6), DBA/2J (DBA) and FVB/NJ (FVB) with fructose. DBA mice showed the highest susceptibility to gain adiposity and glucose intolerance. Elevated insulin was found in DBA and FVB mice, and cholesterol levels were uniquely elevated in B6 mice. The transcriptional profiles of liver, hypothalamus, and adipose tissues showed strain- and tissue-specific pathways altered by fructose, such as fatty acid and cholesterol pathways for B6 and PPAR signaling for DBA in liver, and oxidative phosphorylation for B6 and protein processing for DBA in hypothalamus. Using network modeling, we predicted potential strain-specific key regulators of fructose response such as Fgf21 (DBA) and Lss (B6) in liver, and validated strain-biased responses as well as the regulatory actions of Fgf21 and Lss in primary hepatocytes. Our findings support that fructose perturbs individualized tissue networks and pathways and associates with distinct features of metabolic dysfunctions across genetically diverse mice. Our results elucidate the molecular pathways and gene regulatory mechanisms underlying inter-individual variability in response to high fructose diet.
Microbial contamination screening and interpretation for biological laboratory environments
Authors: Li Xi , Zhu Xue , Wang Wenjie , Ning Kang
Published: October 2018

Advances in microbiome researches have led us to the realization that the composition of microbial communities of indoor environment is profoundly affected by the function of buildings, and in turn may bring detrimental effects to the indoor environment and the occupants. Thus investigation is warranted for a deeper understanding of the potential impact of the indoor microbial communities. Among these environments, the biological laboratories stand out because they are relatively clean and yet are highly susceptible to microbial contaminants. In this study, we assessed the microbial compositions of samples from the surfaces of various sites across different types of biological laboratories. We have qualitatively and quantitatively assessed these possible microbial contaminants, and found distinct differences in their microbial community composition. We also found that the type of laboratories has a larger influence than the sampling site in shaping the microbial community, in terms of both structure and richness. On the other hand, the public areas of the different types of laboratories share very similar sets of microbes. Tracing the main sources of these microbes, we identified both environmental and human factors that are important factors in shaping the diversity and dynamics of these possible microbial contaminations in biological laboratories. These possible microbial contaminants that we have identified will be helpful for people who aim to eliminate them from samples.

Importance

Microbial communities from biological laboratories might hamper the conduction of molecular biology experiments, yet these possible contaminations are not yet carefully investigated. In this work, a metagenomic approach has been applied to identify the possible microbial contaminants and their sources, from the surfaces of various sites across different types of biological laboratories. We have found distinct differences in their microbial community compositions. We have also identified the main sources of these microbes, as well as important factors in shaping the diversity and dynamics of these possible microbial contaminations. The identification and interpretation of these possible microbial contaminants in biological laboratories would be helpful for alleviate their potential detrimental effects.
Comparative whole-genome analysis reveals genetic adaptation of the invasive pinewood nematode
Authors: Li Jiarui , Cheng Xinyue , Lin Runmao , Xiao Shijun , Yi Xinxin , Mao Zhenchuan , Zhang Xi , Ling Jian , Kou Xiaojun , Yan Xia , Luo Ji , Cheng Feixue , Li Yilong , Wang Laifa , Chen Nansheng , Xie Bingyan
Published: October 2018

Genetic adaptation to new environments is essential for invasive species. To explore the genetic underpinnings of invasiveness of a dangerous invasive species, the pinewood nematode (PWN)Bursaphelenchus xylophilus, we analysed the genome-wide variations of a large cohort of 55 strains isolated from both the native and introduced regions. Comparative analysis showed abundant genetic diversity existing in the nematode, especially in the native populations. Phylogenetic relationships and principal component analysis indicate a dominant invasive population/group (DIG) existing in China and expansion beyond, with few genomic variations. Putative origin and migration paths at a global scale were traced by targeted analysis of rDNA sequences. A progressive loss of genetic diversity was observed along spread routes. We focused on variations with a low frequency allele (<50%) in the native USA population but fixation in DIG, and a total of 25,992 single nuclear polymorphisms (SNPs) were screened out. We found that a clear majority of these fixation alleles originated from standing variation. Functional annotation of these SNP-harboured genes showed that adaptation-related genes are abundant, such as genes that encode for chemoreceptors, proteases, detoxification enzymes, and proteins involved in signal transduction and in response to stresses and stimuli. Some genes under positive selection were predicted. Our results suggest that adaptability to new environments plays essentially roles in PWN invasiveness. Genetic drift, mutation and strong selection drive the nematode to rapidly evolve in adaptation to new environments, which including local pine hosts, vector beetles, commensal microflora and other new environmental factors, during invasion process.