bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibodies to the Novel Human Pegivirus 2 Are Associated with Active and Resolved Infections
Authors: Coller Kelly E. , Berg Michael G. , Frankel Matthew , Forberg Kenn , Surani Rita , Chiu Charles Y. , Hackett John , Dawson George J.
Published: May 2016

A novel blood-borne human pegivirus (HPgV), HPgV-2, was recently identified in hepatitis C virus (HCV)-infected individuals and individuals who had received multiple transfusions. Robust serological assays capable of detecting antibodies in HPgV-2-infected individuals are needed to establish global seroprevalence rates and potential disease associations. The two objectives of this study were to determine the utility of mammalian cell-expressed HPgV-2 E2 glycoprotein or bacterium-expressed nonstructural protein 4AB (NS4AB) in detecting past or present infections and to compare the total prevalence (antibody and RNA positive) of HPgV-2 with that of the other human pegivirus, HPgV-1 (GB virus C [GBV-C]). HPgV-2 E2 antibodies were detected in 13 (92.86%) of 14 HPgV-2-viremic cases, and NS4AB antibodies were detected in 8 (57.14%) of 14 cases. The HPgV-2 seroprevalence was significantly higher (
P
< 0.0001) among HCV-infected individuals (3.31% [24 of 726 samples]) than among non-HCV-infected individuals (0.30% [4 of 1,348 samples]). Of 31 anti-E2-positive samples, 22 had supplemental supporting data; 12 samples were HPgV-2 RNA positive and 10 nonviremic samples were antibody positive for peptides or NS4AB. The total prevalence of HPgV-1 (35.00%) was significantly higher than that of HPgV-2 (1.33%) in all populations tested (
P
< 0.0001). For HPgV-1, codetection of antibodies to E2 and RNA was infrequent (5.88%). In contrast, antibodies to E2 were detected in most HPgV-2-viremic individuals (92.86%), as is observed among individuals chronically infected with HCV, most of whom are antibody positive for HCV E2. Our studies indicate that HPgV-2 circulates with HCV and displays a profile similar to the serological profile of HCV-infected persons, although the pathogenicity of this virus has yet to be established.
Use of a Rapid Test for Diagnosis of Dengue during Suspected Dengue Outbreaks in Resource-Limited Regions
Authors: Hunsperger Elizabeth A. , Sharp Tyler M. , Lalita Paul , Tikomaidraubuta Kini , Cardoso Yolanda Rebello , Naivalu Taina , Khan Aalisha Sahu , Marfel Maria , Hancock W. Thane , Tomashek Kay M. , Margolis Harold S.
Published: May 2016

Dengue is major public health problem, globally. Timely verification of suspected dengue outbreaks allows for public health response, leading to the initiation of appropriate clinical care. Because the clinical presentation of dengue is nonspecific, dengue diagnosis would benefit from a sensitive rapid diagnostic test (RDT). We evaluated the diagnostic performance of an RDT that detects dengue virus (DENV) nonstructural protein 1 (NS1) and anti-DENV IgM during suspected acute febrile illness (AFI) outbreaks in four countries. Real-time reverse transcription-PCR and anti-DENV IgM enzyme-linked immunosorbent assay were used to verify RDT results. Anti-DENV IgM RDT sensitivity and specificity ranged from 55.3 to 91.7% and 85.3 to 98.5%, respectively, and NS1 sensitivity and specificity ranged from 49.7 to 92.9% and 22.2 to 89.0%, respectively. Sensitivity varied by timing of specimen collection and DENV serotype. Combined test results moderately improved the sensitivity. The use of RDTs identified dengue as the cause of AFI outbreaks where reference diagnostic testing was limited or unavailable.
Comparison of Mycobacterial Growth Indicator Tube with Culture on RGM Selective Agar for Detection of Mycobacteria in Sputum Samples from Patients with Cystic Fibrosis
Authors: Eltringham Ian , Pickering Julie , Gough Helen , Preece Clair L. , Perry John D.
Published: May 2016

Nontuberculous mycobacteria (NTM) are an important cause of pulmonary disease in patients with cystic fibrosis (CF). A new culture medium (RGM medium) for the isolation of rapidly growing mycobacteria from the sputum of cystic fibrosis patients has recently been reported. The aim of this study was to compare culture of sputum samples on RGM medium with culture using a standard automated liquid culture method. Sputum samples were obtained from 187 distinct patients with CF attending King's College Hospital, London, United Kingdom. Each sample was decontaminated with 3% oxalic acid and inoculated into a mycobacterial growth indicator tube (MGIT) that was monitored for 42 days using the Bactec MGIT 960 instrument. Each sample was also cultured, without decontamination, onto RGM medium, which was incubated for 10 days at 30°C. Mycobacteria were isolated from 28 patients (prevalence, 15%). Mycobacteria were detected in 24 samples (86%) using the MGIT and in 23 samples (82%) using RGM medium (
P
= 1.00). In this setting, RGM medium showed sensitivity equivalent to that of the MGIT for isolation of NTM from the sputum of patients with CF. RGM medium offers a simple, convenient tool that can be embedded into routine culture methods, allowing the culture of all sputum samples that are submitted from patients with CF.
Serological and Molecular Detection of Senecavirus A Associated with an Outbreak of Swine Idiopathic Vesicular Disease and Neonatal Mortality
Authors: Gimenez-Lirola Luis Gabriel , Rademacher Chris , Linhares Daniel , Harmon Karen , Rotolo Marisa , Sun Yaxuan , Baum David H. , Zimmerman Jeffrey , Piñeyro Pablo
Published: May 2016

We performed a longitudinal field study in a swine breeding herd that presented with an outbreak of vesicular disease (VD) that was associated with an increase in neonatal mortality. Initially, a USDA Foreign Animal Disease (FAD) investigation confirmed the presence of Senecavirus A (SVA) and ruled out the presence of exotic agents that produce vesicular lesions, e.g., foot-and-mouth disease virus and others. Subsequently, serum samples, tonsil swabs, and feces were collected from sows (n =22) and their piglets (n =33) beginning 1 week after the onset of the clinical outbreak and weekly for 6 weeks. The presence of SVA RNA was evaluated in all specimens collected by reverse transcriptase quantitative PCR (RT-qPCR) targeting a conserved region of the 5′ untranslated region (5′-UTR). The serological response (IgG) to SVA was evaluated by the weekly testing of sow and piglet serum samples on a SVA VP1 recombinant protein (rVP1) indirect enzyme-linked immunosorbent assay (ELISA). The rVP1 ELISA detected seroconversion against SVA in clinically affected and non-clinically affected sows at early stages of the outbreak as well as maternal SVA antibodies in offspring. Overall, the absence of vesicles (gross lesions) in SVA-infected animals and the variability of RT-qPCR results among specimen type demonstrated that a diagnostic algorithm based on the combination of clinical observations, RT-qPCR in multiple diagnostic specimens, and serology are essential to ensure an accurate diagnosis of SVA.
Notwithstanding Circumstantial Alibis, Cytotoxic T Cells Can Be Major Killers of HIV-1-Infected Cells
Authors: Gadhamsetty Saikrishna , Coorens Tim , de Boer Rob J.
Published: May 2016

Several experiments suggest that in the chronic phase of human immunodeficiency virus type 1 (HIV-1) infection, CD8+cytotoxic T lymphocytes (CTL) contribute very little to the death of productively infected cells. First, the expected life span of productively infected cells is fairly long, i.e., about 1 day. Second, this life span is hardly affected by the depletion of CD8+T cells. Third, the rate at which mutants escaping a CTL response take over the viral population tends to be slow. Our main result is that all these observations are perfectly compatible with killing rates that are much faster than one per day once we invoke the fact that infected cells proceed through an eclipse phase of about 1 day before they start producing virus. Assuming that the major protective effect of CTL is cytolytic, we demonstrate that mathematical models with an eclipse phase account for the data when the killing is fast and when it varies over the life cycle of infected cells. Considering the steady state corresponding to the chronic phase of the infection, we find that the rate of immune escape and the rate at which the viral load increases following CD8+T cell depletion should reflect the viral replication rate, ρ. A meta-analysis of previous data shows that viral replication rates during chronic infection vary between 0.5 ≤ ρ ≤ 1 day−1. Balancing such fast viral replication requires killing rates that are several times larger than ρ, implying that most productively infected cells would die by cytolytic effects.

IMPORTANCEMost current data suggest that cytotoxic T cells (CTL) mediate their control of human immunodeficiency virus type 1 (HIV-1) infection by nonlytic mechanisms; i.e., the data suggest that CTL hardly kill. This interpretation of these data has been based upon the general mathematical model for HIV infection. Because this model ignores the eclipse phase between the infection of a target cell and the start of viral production by that cell, we reanalyze the same data sets with novel models that do account for the eclipse phase. We find that the data are perfectly consistent with lytic control by CTL and predict that most productively infected cells are killed by CTL. Because the killing rate should balance the viral replication rate, we estimate both parameters from a large set of published experiments in which CD8+T cells were depleted in simian immunodeficiency virus (SIV)-infected monkeys. This confirms that the killing rate can be much faster than is currently appreciated.
Deep Sequencing of the HIV-1
env
Gene Reveals Discrete X4 Lineages and Linkage Disequilibrium between X4 and R5 Viruses in the V1/V2 and V3 Variable Regions
Authors: Zhou Shuntai , Bednar Maria M. , Sturdevant Christa B. , Hauser Blake M. , Swanstrom Ronald
Published: May 2016

HIV-1 requires the CD4 receptor and a coreceptor (CCR5 [R5 phenotype] or CXCR4 [X4 phenotype]) to enter cells. Coreceptor tropism can be assessed by either phenotypic or genotypic analysis, the latter using bioinformatics algorithms to predict tropism based on the
env
V3 sequence. We used the Primer ID sequencing strategy with the MiSeq sequencing platform to reveal the structure of viral populations in the V1/V2 and C2/V3 regions of the HIV-1
env
gene in 30 late-stage and 6 early-stage subjects. We also used endpoint dilution PCR followed by cloning of
env
genes to create pseudotyped virus to explore the link between genotypic predictions and phenotypic assessment of coreceptor usage. We found out that the most stringently sequence-based calls of X4 variants (Geno2Pheno false-positive rate [FPR] of ≤2%) formed distinct lineages within the viral population, and these were detected in 24 of 30 late-stage samples (80%), which was significantly higher than what has been seen previously by using other approaches. Non-X4 lineages were not skewed toward lower FPR scores in X4-containing populations. Phenotypic assays showed that variants with an intermediate FPR (2 to 20%) could be either X4/dual-tropic or R5 variants, although the X4 variants made up only about 25% of the lineages with an FPR of <10%, and these variants carried a distinctive sequence change. Phylogenetic analysis of both the V1/V2 and C2/V3 regions showed evidence of recombination within but very little recombination between the X4 and R5 lineages, suggesting that these populations are genetically isolated.

IMPORTANCE
Primer ID sequencing provides a novel approach to study genetic structures of viral populations. X4 variants may be more prevalent than previously reported when assessed by using next-generation sequencing (NGS) and with a greater depth of sampling than single-genome amplification (SGA). Phylogenetic analysis to identify lineages of sequences with intermediate FPR values may provide additional information for accurately predicting X4 variants by using V3 sequences. Limited recombination occurs between X4 and R5 lineages, suggesting that X4 and R5 variants are genetically isolated and may be replicating in different cell types or that X4/R5 recombinants have reduced fitness.
Glutathione Depletion Is Linked with Th2 Polarization in Mice with a Retrovirus-Induced Immunodeficiency Syndrome, Murine AIDS: Role of Proglutathione Molecules as Immunotherapeutics
Authors: Brundu Serena , Palma Linda , Picceri Giusi Giada , Ligi Daniela , Orlandi Chiara , Galluzzi Luca , Chiarantini Laura , Casabianca Anna , Schiavano Giuditta Fiorella , Santi Martina , Mannello Ferdinando , Green Kathy , Smietana Michaël , Magnani Mauro , Fraternale Alessandra
Published: May 2016

Injection of the LP-BM5 murine leukemia virus into mice causes murine AIDS, a disease characterized by many dysfunctions of immunocompetent cells. To establish whether the disease is characterized by glutathione imbalance, reduced glutathione (GSH) and cysteine were quantified in different organs. A marked redox imbalance, consisting of GSH and/or cysteine depletion, was found in the lymphoid organs, such as the spleen and lymph nodes. Moreover, a significant decrease in cysteine and GSH levels in the pancreas and brain, respectively, was measured at 5 weeks postinfection. The Th2 immune response was predominant at all times investigated, as revealed by the expression of Th1/Th2 cytokines. Furthermore, investigation of the activation status of peritoneal macrophages showed that the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arginase1, was induced. Conversely, expression of inducible nitric oxide synthase, a marker of classical activation of macrophages, was detected only when Th1 cytokines were expressed at high levels.In vitrostudies revealed that during the very early phases of infection, GSH depletion and the downregulation of interleukin-12 (IL-12) p40 mRNA were correlated with the dose of LP-BM5 used to infect the macrophages. Treatment of LP-BM5-infected mice withN-(N-acetyl-l-cysteinyl)-S-acetylcysteamine (I-152), anN-acetyl-cysteine supplier, restored GSH/cysteine levels in the organs, reduced the expression of alternatively activated macrophage markers, and increased the level of gamma interferon production, while it decreased the levels of Th2 cytokines, such as IL-4 and IL-5. Our findings thus establish a link between GSH deficiency and Th1/Th2 disequilibrium in LP-BM5 infection and indicate that I-152 can be used to restore the GSH level and a balanced Th1/Th2 response in infected mice.

IMPORTANCEThe first report of an association between Th2 polarization and alteration of the redox state in LP-BM5 infection is presented. Moreover, it provides evidence that LP-BM5 infection causes a decrease in the thiol content of peritoneal macrophages, which can influence IL-12 production. The restoration of GSH levels by GSH-replenishing molecules can represent a new therapeutic avenue to fight this retroviral infection, as it reestablishes the Th1/Th2 balance. Immunotherapy based on the use of pro-GSH molecules would permit LP-BM5 infection and probably all those viral infections characterized by GSH deficiency and a Th1/Th2 imbalance to be more effectively combated.
MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis
Authors: Zhao Jincun , Vijay Rahul , Zhao Jingxian , Gale Michael , Diamond Michael S. , Perlman Stanley
Published: May 2016

West Nile virus (WNV) is the most important cause of epidemic encephalitis in North America. Innate immune responses, which are critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors, RIG-I and MDA5, and their downstream adaptor molecule, MAVS. Here, we show that a deficiency of MAVS in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In
Mavs
−/−
mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were polyfunctional and lysed peptide-pulsed target cells
in vitro
. However, virus-specific T cells in the brains of infected
Mavs
−/−
mice exhibited lower functional avidity than those in wild-type animals, and even virus-specific memory T cells generated by prior immunization could not protect
Mavs
−/−
mice from WNV-induced lethal disease. Concomitant with ineffective virus clearance, macrophage numbers were increased in the
Mavs
−/−
brain, and both macrophages and microglia exhibited an activated phenotype. Microarray analyses of leukocytes in the infected
Mavs
−/−
brain showed a preferential expression of genes associated with activation and inflammation. Together, these results demonstrate a critical role for MAVS in hematopoietic cells in augmenting the kinetics of WNV clearance and thereby preventing a dysregulated and pathogenic immune response.

IMPORTANCE
West Nile virus (WNV) is the most important cause of mosquito-transmitted encephalitis in the United States. The innate immune response is known to be critical for protection in infected mice. Here, we show that expression of MAVS, a key adaptor molecule in the RIG-I-like receptor RNA-sensing pathway, in hematopoietic cells is critical for protection from lethal WNV infection. In the absence of MAVS, there is a massive infiltration of myeloid cells and virus-specific T cells into the brain and overexuberant production of proinflammatory cytokines. These results demonstrate the important role that MAVS expression in hematopoietic cells has in regulating the inflammatory response in the WNV-infected brain.
Critical Role of the PA-X C-Terminal Domain of Influenza A Virus in Its Subcellular Localization and Shutoff Activity
Authors: Hayashi Tsuyoshi , Chaimayo Chutikarn , McGuinness James , Takimoto Toru
Published: May 2016

PA-X is a recently identified influenza virus protein that is composed of the PA N-terminal 191 amino acids and unique C-terminal 41 or 61 residues. We and others showed that PA-X has a strong ability to suppress host protein synthesis via host mRNA decay, which is mediated by endonuclease activity in its N-terminal domain (B. W. Jagger, H. M. Wise, J. C. Kash, K. A. Walters, N. M. Wills, Y. L. Xiao, R. L. Dunfee, L. M. Schwartzman, A. Ozinsky, G. L. Bell, R. M. Dalton, A. Lo, S. Efstathiou, J. F. Atkins, A. E. Firth, J. K. Taubenberger, and P. Digard, 2012, Science
337:
199–204,
http://dx.doi.org/10.1126/science.1222213
, and E. A. Desmet, K. A. Bussey, R. Stone, and T. Takimoto, 2013, J Virol
87:
3108–3118,
http://dx.doi.org/10.1128/JVI.02826-12
). However, the mechanism of host mRNA degradation, especially where and how PA-X targets mRNAs, has not been analyzed. In this study, we determined the localization of PA-X and the role of the C-terminal unique region in shutoff activity. Quantitative subcellular localization analysis revealed that PA-X was located equally in both cytoplasm and nucleus. By characterizing a series of PA-X C-terminal deletion mutants, we found that the first 9 amino acids were sufficient for nuclear localization, but an additional 6 residues were required to induce the maximum shutoff activity observed with intact PA-X. Importantly, forced nuclear localization of the PA-X C-terminal deletion mutant enhanced shutoff activity, highlighting the ability of nuclear PA-X to degrade host mRNAs more efficiently. However, PA-X also inhibited luciferase expression from transfected mRNAs synthesized
in vitro
, suggesting that PA-X also degrades mRNAs in the cytoplasm. Among the basic amino acids in the PA-X C-terminal region, 3 residues, 195K, 198K, and 199R, were identified as key residues for inducing host shutoff and nuclear localization. Overall, our data indicate a critical role for the 15 residues in the PA-X C-terminal domain in degrading mRNAs in both the cytoplasm and nucleus.

IMPORTANCE
Influenza A viruses express PA-X proteins to suppress global host gene expression, including host antiviral genes, to allow efficient viral replication in infected cells. However, little is known about how PA-X induces host shutoff. In this study, we showed that PA-X localized equally in both the cytoplasm and nucleus of the cells, but the nuclear localization of PA-X mediated by its C-terminal region has a significant impact on shutoff activity. Three basic residues at the C-terminal region play a critical role in nuclear localization, but additional basic residues were required for maximum shutoff activity. Our findings indicate that PA-X targets and degrades mRNAs in both the nucleus and cytoplasm, and that the first 15 residues of the PA-X unique C-terminal region play a critical role in shutoff activity.
Informed consent for paediatric clinical trials in Europe
Authors: Lepola Pirkko , Needham Allison , Mendum Jo , Sallabank Peter , Neubauer David , de Wildt Saskia
Published: May 2016

Objective

Paediatric clinical trials are often conducted as multinational trials. Informed consent or assent is part of the ethics committee approval for clinical trials. The consent requirements vary between countries due to national laws and regulations, which are not harmonised in Europe. These discrepancies can present challenges for paediatric clinical trials. The aim of this study was to assemble these consent and assent requirements across the European Economic Area. The collated national requirements have not been publicly available before, despite a real need for this data.

Methods

National consent and assent requirements for paediatric clinical trials were analysed and collated for 25 European Union Member States and 2 European Free Trade Association countries until the end of 2014. The data were retrieved from existing databases and through communication with the competent authorities and selected ethics committees. Results from a literature search for international or national guidelines, declarations and conventions and academic societies' publications served as comparison material.

Results

Consent and assent requirements are heterogeneous across these countries. We compiled our findings in ‘The Informed Consent and Assent Tool Kit’, a table including 27 national consent and assent requirements listed by individual country.

Conclusions

Wide variation in paediatric consents and assents presents challenges for multinational paediatric trials in Europe. The toolkit is available for all those involved in paediatric clinical trials and ethics committees, providing a new platform for proactive feedback on informed consent requirements, and may finally lead to a needed harmonisation process, including uniform standards accepted across Europe.
Postherpetic pseudohernia: delayed onset of paresis of abdominal muscles due to herpes zoster causing an ipsilateral abdominal bulge
Authors: Ohno Shunsuke , Togawa Yasuhiro , Chiku Tsuyoshi , Sano Wataru
Published: May 2016

Postherpetic pseudohernia causes an abdominal bulge as well as an abdominal wall herniation. This disease is one of the neurological complications of herpes zoster and essentially consists of paresis of ipsilateral abdominal muscles. Postherpetic pseudohernia may be mistaken for abdominal wall herniation because it is not well known. We describe two cases presenting an abdominal bulge. The ipsilateral abdominal bulge appeared after recovery from abdominal zoster. Abdominal CT showed no evidence of a herniation or mass. We diagnosed a postherpetic pseudohernia. One of the patients recovered spontaneously 4 months after the onset, and the other partially recovered after 2 months. This disease can be expected to disappear spontaneously, unlike abdominal herniation requiring surgery. It has been reported that 79.3% of patients eventually recovered spontaneously. For surgeons and general practitioners, it is beneficial to keep this disease in mind when examining a patient presenting an abdominal bulge.
Two similar cases of elderly women with moderate abdominal pain and pneumoperitoneum of unknown origin: a surgeon's successful conservative management
Authors: Vinzens Fabrizio , Zumstein Valentin , Bieg Christian , Ackermann Christoph
Published: May 2016

Patients presenting with abdominal pain and pneumoperitoneum in radiological examination usually require emergency explorative laparoscopy or laparotomy. Pneumoperitoneum mostly associates with gastrointestinal perforation. There are very few cases where surgery can be avoided. We present 2 cases of pneumoperitoneum with unknown origin and successful conservative treatment. Both patients were elderly women presenting to our emergency unit, with moderate abdominal pain. There was neither medical intervention nor trauma in their medical history. Physical examination revealed mild abdominal tenderness, but no clinical sign of peritonitis. Cardiopulmonary examination remained unremarkable. Blood studies showed only slight abnormalities, in particular, inflammation parameters were not significantly increased. Finally, obtained CTs showed free abdominal gas of unknown origin in both cases. We performed conservative management with nil per os, nasogastric tube, total parenteral nutrition and prophylactic antibiotics. After 2 weeks, both were discharged home.
Development of a brief assessment and algorithm for ascertaining dementia in low-income and middle-income countries: the 10/66 short dementia diagnostic schedule
Authors: Stewart Robert , Guerchet Maëlenn , Prince Martin
Published: May 2016

Objectives

To develop and evaluate a short version of the 10/66 dementia diagnostic schedule for use in low-income and middle-income countries.

Design

Split-half analysis for algorithm development and testing; cross-evaluation of short-schedule and standard-schedule algorithms in 12 community surveys.

Settings

(1) The 10/66 pilot sample data set of people aged 60 years and over in 25 international centres each recruiting the following samples: (a) dementia; (b) depression, no dementia; (c) no dementia, high education and (d) no dementia, low education. (2) Cross-sectional surveys of people aged 65 years or more from 12 urban and rural sites in 8 countries (Cuba, Dominican Republic, Peru, Mexico, Venezuela, India, China and Puerto Rico).

Participants

In the 10/66 pilot samples, the algorithm for the short schedule was developed in 1218 participants and tested in 1211 randomly selected participants; it was evaluated against the algorithm for the standard 10/66 schedule in 16 536 survey participants.

Outcome measures

The short diagnostic schedule was derived from the Community Screening Instrument for Dementia, the CERAD 10-word list recall task and the Euro-D depression screen; it was evaluated against clinically assigned groups in the pilot data and against the standard schedule (using the Geriatric Mental State (GMS) rather than Euro-D) in the surveys.

Results

In the pilot test sample, the short-schedule algorithm ascertained dementia with 94.2% sensitivity. Specificities were 80.2% in depression, 96.6% in the high-education group and 92.7% in the low-education group. In survey samples, it coincided with standard algorithm dementia classifications with over 95% accuracy in most sites. Estimated dementia prevalences in the survey samples were not consistently higher or lower using the short compared to standard schedule.

Conclusions

For epidemiological studies of dementia in low-income and middle-income settings where the GMS interview (and/or interviewer training required) is not feasible, the short 10/66 schedule and algorithm provide an alternative with acceptable levels of performance.
Examining the pathways for young people with drug and alcohol dependence: a mixed-method design to examine the role of a treatment programme
Authors: Nathan Sally , Rawstorne Patrick , Hayen Andrew , Bryant Joanne , Baldry Eileen , Ferry Mark , Williams Megan , Shanahan Marian , Jayasinha Ranmalie
Published: May 2016

Introduction

Young people with drug and alcohol problems are likely to have poorer health and other psychosocial outcomes than other young people. Residential treatment programmes have been shown to lead to improved health and related outcomes for young people in the short term. There is very little robust research showing longer term outcomes or benefits of such programmes. This paper describes an innovative protocol to examine the longer term outcomes and experiences of young people referred to a residential life management and treatment programme in Australia designed to address alcohol and drug issues in a holistic manner.

Methods and analysis

This is a mixed-methods study that will retrospectively and prospectively examine young people's pathways into and out of a residential life management programme. The study involves 3 components: (1) retrospective data linkage of programme data to health and criminal justice administrative data sets, (2) prospective cohort (using existing programme baseline data and a follow-up survey) and (3) qualitative in-depth interviews with a subsample of the prospective cohort. The study will compare findings among young people who are referred and (a) stay 30 days or more in the programme (including those who go on to continuing care and those who do not); (b) start, but stay fewer than 30 days in the programme; (c) are assessed, but do not start the programme.

Ethics and dissemination

Ethics approval has been sought from several ethics committees including a university ethics committee, state health departments and an Aboriginal-specific ethics committee. The results of the study will be published in peer-reviewed journals, presented at research conferences, disseminated via a report for the general public and through Facebook communications. The study will inform the field more broadly about the value of different methods in evaluating programmes and examining the pathways and trajectories of vulnerable young people.
Health and social predictors of applications to public housing: a population-based analysis
Authors: Hinds Aynslie M , Bechtel Brian , Distasio Jino , Roos Leslie L , Lix Lisa M
Published: May 2016

Background

Residents of public housing are often in poor health. However, it is unclear whether poor health precedes residency in public housing. We compared the health of people who applied to public housing to people who did not apply and had similar socioeconomic characteristics.

Methods

Population-based administrative databases from Manitoba, Canada, containing health, housing and income assistance information were used to identify a cohort of individuals who applied to public housing and a matched cohort from the general population. Conditional logistic regression was used to test the association between a public housing application and health status and health service use, after controlling for income.

Results

There were 10 324 individuals in each of the public housing applicant and matched cohorts; the majority were women, young, urban residents, and received income assistance. A higher per cent of the public housing cohort had physician-diagnosed physical and mental health conditions compared to the matched cohort. Physical health, mental health and health service use were significantly associated with applying to public housing, after controlling for individual and area-level income.

Conclusions

Applicants to public housing were in poorer health compared to people of the same income level who did not apply to public housing. These health issues may affect the long-term stability of their tenancy if appropriate services and supports are not provided. Additionally, preventing ill health, better management of mental health and additional supports may reduce the need for public housing, which, in turn, would alleviate the pressure on governments to provide this form of housing.
Stability analyses for deviated wellbores in unconsolidated cross-anisotropic formations
Authors: Akl Sherif A.Y. , Whittle Andrew J.
Published: May 2016

Production of oil from shallow reservoirs typically involves drilling highly deviated wells through unconsolidated (or poorly lithified) rocks or clays. This paper describes numerical analyses of the deformations and stability of deviated wellbores within a K0-consolidated clay. The analyses consider planar deformations in the plane orthogonal to the wellbore using a quasi three-dimensional (3D) finite element model that represents coupled flow and deformations within the soil mass. Cross-anisotropic mechanical properties of the clay are described by a generalized effective stress model, MIT-E3, with parameters previously calibrated from laboratory thick-walled cylinder tests. The analyses compute the relationship between the drilling mud pressure and wellbore stability associated with either the onset of localized failure mechanisms or large plastic deformations around the cavity. The results show that short-term, undrained stability requires mud pressures in excess of the in situ formation pore pressures for more highly deviated wellbores at inclinations greater than 45°. The analyses examine the mechanisms for further destabilization, due to consolidation within the formation, and how they are affected by drainage conditions at the wellbore wall. The results provide qualitative information for the design and control of drilling operations for deviated wellbores in unconsolidated formations.
The effect of marine closures on a feedback control management strategy used in a spatially aggregated stock assessment: a case study based on pink ling in Australia
Authors: Punt André E. , Haddon Malcolm , Little L. Richard , Tuck Geoffrey N.
Published: May 2016

Simulation is used to explore the effect of spatial heterogeneity and spatial closures on the ability of feedback-control management strategies to achieve goals relating to conservation and utilization of fishery resources. The operating model underlying the projections is based on pink ling, Genypterus blacodes, off southern Australia and assumes that animals are sedentary following settlement. The management strategies are able to move the resource towards the target level in the absence of spatial closures even though assessment results are biased. The probability of reducing the stock below its limit reference point is higher when growth rates vary spatially, but the effect is small. The probability of the stock being above its target reference point is lower when one of the smaller spatial areas is closed. However, performance is markedly different when a larger fraction of the total area is closed, with stock size being substantially larger than the target at the end of the projection period.
Germination of leafy spurge (Euphorbia esula L.) seeds under alternating temperatures: the effects of amplitude, midpoint, and imbibition in gibberellic acid
Authors: Foley Michael E.
Published: May 2016

Germinability of dormant seeds or the capacity to germinate under particular conditions is sometimes enhanced by a diurnal alternating temperature regime relative to a constant temperature. Alternating temperature regimes vary in amplitude (difference between the minimum and maximum) and midpoint (average). The aim of this research was to test the effects of amplitude and midpoint regimes on germination of dormant leafy spurge seed from a Fargo, ND population in water and gibberellic acid (GA3). The optimal regimes for germination in both water and GA3 were 20:30 °C (16 h:8 h) and 20:35 °C (19 h:5 h), which provided amplitudes of 10 °C and 15 °C, respectively, with both conditions having a midpoint temperature of 23.3 °C. However, midpoint temperature of 22 °C to 27 °C were equally effective for germination under the 20:30 °C and 20:35 °C alternating temperature regimes. Additional alternating temperature regimes with amplitudes of 15 °C (15:30 °C and 10:25 °C), 20 °C (10:30 °C), and 25 °C (10:35 °C) generally displayed reduced germination in both water and GA3, which is likely attributable to the low initial alternating temperature (≤15 °C) component of the regime relative to the higher initial temperature of 20 °C for the optimum regimes of 20:30 °C and 20:35 °C. Under the alternating temperature regimes tested, seeds germinated in GA3 generally displayed higher germination (≥80%) compared with seeds in water (30%–50%).
Possible origin of B chromosome in Dichotomius sericeus (Coleoptera)
Authors: Amorim Igor Costa , Milani Diogo , Cabral-de-Mello Diogo Cavalcanti , Rocha Marília França , Moura Rita Cássia
Published: May 2016

B chromosomes have so far been described in about 80 species of Coleoptera, mainly using conventional staining analysis. In this study, 152 individuals of the dung beetle Dichotomius sericeus (Coleoptera), collected from three isolated geographical areas in the State of Pernambuco, Brazil, were analyzed to determine the frequency, prevalence, distribution, meiotic behavior, and possible B chromosome origin. The cytogenetic analysis consisted of conventional staining, C-banding, triple fluorochrome staining (CMA3/DA/DAPI), and fluorescent in situ hybridization using ribosomal DNAs (rDNAs) and H3 histone gene as probes, as well as microdissection and chromosome painting of the B chromosome. The B chromosomes were detected in all populations analyzed. Analysis revealed the heterochromatic nature and the presence of G+C-rich blocks and 18S rDNA on the B chromosome. FISH with DNA from microdissected B chromosome painted the entire extension of the B chromosome for all populations, besides the pericentromeric regions of all the autosomes, as well as the X chromosome. Finally, cross-hybridization in nine related species of Dichotomius using the microdissected B chromosome as probe did not reveal any hybridization signal. The results suggest an intraspecific and monophyletic origin for B chromosomes in D. sericeus, probably from the second or third autosomal pair.
ANOTHER LOOK AT PRICE INSTABILITY AND CONSUMER WELL-BEING: NONDURABLE AND DURABLE (HOUSING) MARKETS
Authors: KAPUR BASANT K.
Published: May 2016

We explore the implications of future price uncertainty, although in a different setting from McKinnon (1967). We identify a further, hitherto-overlooked mechanism that can overturn the well-known ‘Waugh paradox’ that risk-averse consumers benefit from price instability, and show that it also has a particularly interesting application to the housing tenure choice issue.
CAPITAL ACCUMULATION, VINTAGE AND PRODUCTIVITY: THE JAPANESE EXPERIENCE
Authors: HAGIWARA TAIJI , MATSUBAYASHI YOICHI
Published: May 2016

We empirically examine the relationship between capital accumulation, vintage and productivity of industries in Japan using firm-level microdata. Our analyses confirm that vintage significantly influenced productivity during the period of economic expansion. The effect was particularly notable during the upturn that started in 2000, when most examined industries displayed strong vintage effects. The rejuvenation of capital equipment during this period clearly resulted from a strong productivity effect. During the economic bubble of the late 1980s, by contrast, vintage exerted no observable effects on productivity despite significant increase in investment. This finding shows that an increase in capital stock during this period was not necessarily productive and likely produced a merely temporary boom. We reconfirm that the relation between vintage and productivity changed in subtle ways in response to the phases of business cycles.
Research on the Vibration Control Algorithms for Large Space Truss Structure Based on Precise Integration Method
Authors: Cai Zhiqin , Zhang Yibei , Li Xuefu , Jin Bingbing
Published: May 2016

In this paper, vibration control algorithms for a large space truss structure are investigated. First, a precise integration method is used to solve the differential equation such that the validity and efficiency of the algorithm are guaranteed. Second, on the basis of the discrete algebraic equation combined with the decentralized control theory, the solving method of the control force based on the linear quadratic (LQ) optimal control theory is improved. Third, a new control method, the eigenvalue control method, is proposed in this paper, and its relationship with the LQ optimal control method is discussed. Finally, these two control methods are applied to the structure to analyze the effectiveness of vibration suppression. The simulation results show that the proposed algorithms can quickly suppress the vibration of a large space truss structure.
Early history of the Spanish Geological Survey: the Commission for the Geological Map of Spain (1849–1910)
Authors: Rábano Isabel
Published: May 2016

It was not until the mid-nineteenth century that geological investigation in Spain became institutionalized. This occurred in 1849 when a commission was formed to create a geological map of the province of Madrid, work on which was intended to culminate in the creation of a national geological map. Despite its name, the idea was not only to cover geological cartography, but also to create a geographical map and catalogues of the botanical and faunal resources. After the commission was dissolved in 1859, these objectives were lost and work on the geological map continued within the General Statistics Board. The project was once again modified in 1870, with the creation of a new organization, the Commission for the Geological Map of Spain, which fulfilled its objectives in 1889 with the publication of the first national geological map. The reason for the change in the Commission's aims was the change in circumstances produced by the loss of Spain's overseas colonies and the need to discover new sources of wealth and take advantage of the resources of the subsurface in Spain itself. The institution was modernized in 1910 and became the new Spanish Geological Institute; it was re-formed again in January 1927 as the Spanish Geological and Mining Institute.
Gene by environmental interactions affecting oxidative phosphorylation and thermal sensitivity
Authors: Baris Tara Z. , Blier Pierre U. , Pichaud Nicolas , Crawford Douglas L. , Oleksiak Marjorie F.
Published: May 2016

The oxidative phosphorylation (OxPhos) pathway is responsible for most aerobic ATP production and is the only metabolic pathway with proteins encoded by both nuclear and mitochondrial genomes. In studies examining mitonuclear interactions among distant populations within a species or across species, the interactions between these two genomes can affect metabolism, growth, and fitness, depending on the environment. However, there is little data on whether these interactions impact natural populations within a single species. In an admixed Fundulus heteroclitus population with northern and southern mitochondrial haplotypes, there are significant differences in allele frequencies associated with mitochondrial haplotype. In this study, we investigate how mitochondrial haplotype and any associated nuclear differences affect six OxPhos parameters within a population. The data demonstrate significant OxPhos functional differences between the two mitochondrial genotypes. These differences are most apparent when individuals are acclimated to high temperatures with the southern mitochondrial genotype having a large acute response and the northern mitochondrial genotype having little, if any acute response. Furthermore, acute temperature effects and the relative contribution of Complex I and II depend on acclimation temperature: when individuals are acclimated to 12°C, the relative contribution of Complex I increases with higher acute temperatures, whereas at 28°C acclimation, the relative contribution of Complex I is unaffected by acute temperature change. These data demonstrate a complex gene by environmental interaction affecting the OxPhos pathway.
Multiscale entropy analysis of heart rate variability in heart failure, hypertensive, and sinoaortic-denervated rats: classical and refined approaches
Authors: Silva Luiz Eduardo Virgilio , Lataro Renata Maria , Castania Jaci Airton , da Silva Carlos Alberto Aguiar , Valencia Jose Fernando , Murta Luiz Otavio , Salgado Helio Cesar , Fazan Rubens , Porta Alberto
Published: May 2016

The analysis of heart rate variability (HRV) by nonlinear methods has been gaining increasing interest due to their ability to quantify the complexity of cardiovascular regulation. In this study, multiscale entropy (MSE) and refined MSE (RMSE) were applied to track the complexity of HRV as a function of time scale in three pathological conscious animal models: rats with heart failure (HF), spontaneously hypertensive rats (SHR), and rats with sinoaortic denervation (SAD). Results showed that HF did not change HRV complexity, although there was a tendency to decrease the entropy in HF animals. On the other hand, SHR group was characterized by reduced complexity at long time scales, whereas SAD animals exhibited a smaller short- and long-term irregularity. We propose that short time scales (1 to 4), accounting for fast oscillations, are more related to vagal and respiratory control, whereas long time scales (5 to 20), accounting for slow oscillations, are more related to sympathetic control. The increased sympathetic modulation is probably the main reason for the lower entropy observed at high scales for both SHR and SAD groups, acting as a negative factor for the cardiovascular complexity. This study highlights the contribution of the multiscale complexity analysis of HRV for understanding the physiological mechanisms involved in cardiovascular regulation.
Seasonal changes in brown adipose tissue mitochondria in a mammalian hibernator: from gene expression to function
Authors: Ballinger Mallory A. , Hess Clair , Napolitano Max W. , Bjork James A. , Andrews Matthew T.
Published: May 2016

Brown adipose tissue (BAT) is a thermogenic organ that is vital for hibernation in mammals. Throughout the hibernation season, BAT mitochondrial uncoupling protein 1 (UCP1) enables rapid rewarming from hypothermic torpor to periodic interbout arousals (IBAs), as energy is dissipated as heat. However, BAT's unique ability to rewarm the body via nonshivering thermogenesis is not necessary outside the hibernation season, suggesting a potential seasonal change in the regulation of BAT function. Here, we examined the BAT mitochondrial proteome and mitochondrial bioenergetics in the thirteen-lined ground squirrel ( Ictidomys tridecemlineatus) across four time points: spring, fall, torpor, and IBA. Relative mitochondrial content of BAT was estimated by measuring BAT pad mass, UCP1 protein content, and mitochondrial DNA (mtDNA) copy number. BAT mtDNA content was significantly lower in spring compared with torpor and IBA ( P < 0.05). UCP1 mRNA and protein levels were highest during torpor and IBA. Respiration rates of isolated BAT mitochondria were interrogated at each complex of the electron transport chain. Respiration at complex II was significantly higher in torpor and IBA compared with spring ( P < 0.05), suggesting an enhancement in mitochondrial respiratory capacity during hibernation. Additionally, proteomic iTRAQ labeling identified 778 BAT mitochondrial proteins. Proteins required for mitochondrial lipid translocation and β-oxidation were upregulated during torpor and IBA and downregulated in spring. These data imply that BAT bioenergetics and mitochondrial content are not static across the year, despite the year-round presence of UCP1.