bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidestination Pedestrian Flows in Equilibrium: A Cellular Automaton‐Based Approach
Authors: Crociani Luca , Lämmel Gregor 
Published: April 2016

AbstractThis article presents a new simulation approach for multidestination pedestrian crowds in complex environments. The work covers two major topics. In the first part, a novel cellular automaton (CA) model is proposed. The model describes the pedestrian movement by a set of simple rules and produces fundamental diagrams similar to those derived from laboratory experiments. The second topic of this work describes how the CA can be integrated into an iterative learning cycle where the individual pedestrian can adapt travel plans based on experiences from previous iterations. Depending on the setup, the overall travel behavior moves either toward a Nash equilibrium or the system optimum. The functional interaction of the CA with the iterative learning approach is demonstrated on a set of transport paradoxes. Furthermore, time series of speed and density observed in a small‐scale experiment show a general agreement between the CA simulation and laboratory experiments. The scalability of the proposed approach is demonstrated on a large‐scale scenario.
The effectiveness of sedentary behaviour interventions for reducing body mass index in children and adolescents: systematic review and meta‐analysis
Authors: Azevedo Liane B. , Ling Jonathan , Soos Istvan , Robalino Shannon , Ells Louisa 
Published: April 2016

SummaryIntervention studies have been undertaken to reduce sedentary behaviour (SB) and thereby potentially ameliorate unhealthy weight gain in children and adolescents. We synthesised evidence and quantified the effects of SB interventions (single or multiple components) on body mass index (BMI) or BMI z‐score in this population. Publications up to March 2015 were located through electronic searches. Inclusion criteria were interventions targeting SB in children that had a control group and objective measures of weight and height. Mean change in BMI or BMI z‐score from baseline to post‐intervention were quantified for intervention and control groups and meta‐analyzed using a random effects model. The pooled mean reduction in BMI and BMI z‐score was significant but very small (standardized mean difference = −0.060, 95% confidence interval: −0.098 to −0.022). However, the pooled estimate was substantially greater for an overweight or obese population (standardized mean difference = −0.255, 95% confidence interval: −0.400 to −0.109). Multicomponent interventions (SB and other behaviours) delivered to children from 5 to 12 years old in a non‐educational setting appear to favour BMI reduction. In summary, SB interventions are associated with very small improvement in BMI in mixed‐weight populations. However, SB interventions should be part of multicomponent interventions for treating obese children. © 2016 World Obesity
Mortal and Immortal Souls, Ghosts and the (Restless) Dead in Ancient Mesopotamia
Authors: Scurlock JoAnn 
Published: April 2016

AbstractEver since their original creation from mortal clay mixed with the flesh and blood of an immortal god, Ancient Mesopotamians had a part of themselves that survived death. We call this death‐surviving part the soul. Ancient Mesopotamians, however, like ancient Greeks, understood this surviving bit as a complex of elements with differing possibilities of survival or, if you will, multiple souls of differing levels of immortality. Of these spiritual essences, one is what we would call a ghost. Unfortunately this was not, like our own ghosts, limited to haunting houses, but fully capable of doing serious harm to the living. Partly this was because the dead, although no longer living, continued to feel hunger and thirst without being able to provide food and drink for themselves, and partly it was because certain bad deaths produced very unhappy ghosts. Ancient Mesopotamians dealt with this problem using a multiplex strategy. Former members of the family received a continual round of offerings as long as the family survived to supply them. If afflicted with spectral attack, there were healing rituals designed to deal with the troublemaker. Finally, special entertainment was provided at festivals of the dead (similar to our Halloween) when ghosts were released from the Netherworld prison to which they were confined for the rest of the year. These festivals also provided an opportunity for last visits with dead family members, consultation with the dead for advice (necromancy) and even witchcraft to revenge oneself on personal enemies. In what follows, I will give a brief overview of the current state of knowledge, with suggestions for further reading.
Effect of CPAP Withdrawal on myocardial perfusion in OSA: A randomized controlled trial
Authors: Schwarz Esther I. , Schlatzer Christian , Stehli Julia , Kaufmann Philipp A. , Bloch Konrad E. , Stradling John R. , Kohler Malcolm 
Published: April 2016

AbstractBackground and objectiveObstructive sleep apnoea (OSA) is highly prevalent and associated with an increased incidence of cardiovascular events. Endothelial dysfunction is the proposed causative mechanism. Continuous positive airway pressure (CPAP) is presumed to improve cardiovascular outcome in OSA. CPAP withdrawal was recently shown to lead to peripheral endothelial dysfunction. However, it is not known whether short‐term CPAP withdrawal reduces myocardial perfusion in OSA.MethodsIn this double‐blind randomized controlled study, 45 patients with moderate to severe OSA previously adherent to CPAP were assigned to either subtherapeutic or continuing therapeutic CPAP for 2 weeks. The primary outcome was adenosine‐induced myocardial blood flow (MBF) as a measure of endothelial function, assessed by 13N‐ammonia positron emission tomography. Secondary outcomes were measures of dermal and renal microvascular function, morning blood pressure (BP) and heart rate.ResultsDespite return of OSA associated with significant increases in BP (+9.1 mm Hg, 95% CI +4.9 to +13.4 mm Hg, P < 0.001) and heart rate (+9.6 bpm, 95% confidence interval (CI) +4.6 to +14.6 bpm, P < 0.001), CPAP withdrawal had no significant effect on maximal myocardial perfusion capacity (hyperaemic MBF −0.01 ml/min/g, 95% CI −0.33 to +0.24 ml/min/g, P = 0.91), nor renal and dermal microvascular function.ConclusionIn patients with OSA, a short‐term CPAP withdrawal does not lead to detectable impairment of coronary endothelial function, as has been demonstrated in the brachial artery, despite a clinically relevant increase in BP of nearly 10 mm Hg. There was also no evidence of an impairment of renal or dermal microvascular function.
Does Ideology Matter?*
Authors: Gries Peter Hays 
Published: April 2016

ObjectiveThis study revisits the idea that the American public is moderate or nonideological. In this longstanding view, only informed elites maintain consistent ideologies that constrain their political attitudes and behaviors; the mass public is driven instead by partisan identities that they are socialized into. The study explores whether the public's liberal‐to‐conservative self‐placement is temporally stable, and whether it is predictive of political attitudes when pit against partisanship.MethodsThe study examines data from the 2010 American National Election Survey and the 2008–2012 General Social Survey longitudinal panel.ResultsThe American public today maintains coherent and consistent ideologies that systematically divide them in their sociopolitical attitudes and policy preferences.ConclusionWhile partisanship is a powerful top‐down driver of the American public's attitudes and policy preferences toward overtly partisan issues and behaviors like Obamacare and voting, on broader sociopolitical issues like abortion, ideology is a powerful bottom‐up driver of attitudes.
Field evaluation of a novel preservation medium to transport sputum specimens for molecular detection of Mycobacterium tuberculosis in a rural African setting
Authors: Omar Shaheed V. , Peters Remco P. H. , Ismail Nazir A. , Jonkman Kelly , Dreyer Andries W. , Said Halima M. , Gwala Thabisile , Ismail Nabila , Fourie P. Bernard 
Published: April 2016

AbstractObjectivesTo assess the performance of an innovative method of transporting sputum to centralised facilities for molecular detection of Mycobacterium tuberculosis: using a swab to inoculate sputum in a transport medium, PrimeStore® Molecular Transport Medium (PS‐MTM).MethodsTwo sputum specimens were obtained from suspected patients with tuberculosis (TB) at rural healthcare facilities in South Africa. A swab was taken from each specimen and placed into PS‐MTM, prior to it being processed by either liquid culture or Xpert MTB/RIF assay (Xpert).ResultsA total of 141 patients (including 47 with laboratory‐confirmed TB) were included in this analysis. M. tuberculosis was detected at 29% by culture and 29% by Xpert, whereas 31% tested positive by IS6110 real‐time PCR of PS‐MTM from the culture and 36% from the Xpert‐paired specimen. Concordance between the method under evaluation with culture was 82% (McNemar, P = 0.55) and 84% (McNemar, P = 0.05) for Xpert. Stratified by culture result, the detection rate by IS6110 real‐time PCR of PS‐MTM was similar to Xpert for patients with positive culture (P = 0.32), but significantly higher if culture was negative (P = 0.008).ConclusionsThese results suggest that swab collection of sputum into PS‐MTM for transport is a promising method for diagnosis of TB in rural healthcare settings, thereby potentially improving the options available for molecular diagnosis of TB in countries incapable of applying decentralised high‐tech molecular testing.
Supervised oral HIV self‐testing is accurate in rural KwaZulu‐Natal, South Africa
Authors: Martínez Pérez Guillermo , Steele Sarah J. , Govender Indira , Arellano Gemma , Mkwamba Alec , Hadebe Menzi , van Cutsem Gilles 
Published: April 2016

AbstractObjectivesTo achieve UNAIDS 90‐90‐90 targets, alternatives to conventional HIV testing models are necessary in South Africa to increase population awareness of their HIV status. One of the alternatives is oral mucosal transudates‐based HIV self‐testing (OralST). This study describes implementation of counsellor‐introduced supervised OralST in a high HIV prevalent rural area.MethodsCross‐sectional study conducted in two government‐run primary healthcare clinics and three Médecins Sans Frontières‐run fixed‐testing sites in uMlalazi municipality, KwaZulu‐Natal. Lay counsellors sampled and recruited eligible participants, sought informed consent and demonstrated the use of the OraQuick™ OralST. The participants used the OraQuick™ in front of the counsellor and underwent a blood‐based Determine™ and a Unigold™ rapid diagnostic test as gold standard for comparison. Primary outcomes were user error rates, inter‐rater agreement, sensitivity, specificity and predictive values.ResultsA total of 2198 participants used the OraQuick™, of which 1005 were recruited at the primary healthcare clinics. Of the total, 1457 (66.3%) were women. Only two participants had to repeat their OraQuick™. Inter‐rater agreement was 99.8% (Kappa 0.9925). Sensitivity for the OralST was 98.7% (95% CI 96.8–99.6), and specificity was 100% (95% CI 99.8–100).ConclusionThis study demonstrates high inter‐rater agreement, and high accuracy of supervised OralST. OralST has the potential to increase uptake of HIV testing and could be offered at clinics and community testing sites in rural South Africa. Further research is necessary on the potential of unsupervised OralST to increase HIV status awareness and linkage to care.
Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap
Authors: Gray Glenda E. , Mayer Kenneth H. , Elizaga Marnie L. , Bekker Linda-Gail , Allen Mary , Morris Lynn , Montefiori David , De Rosa Stephen C. , Sato Alicia , Gu Niya , Tomaras Georgia D. , Tucker Timothy , Barnett Susan W. , Mkhize Nonhlanhla N. , Shen Xiaoying , Downing Katrina , Williamson Carolyn , Pensiero Michael , Corey Lawrence , Williamson Anna-Lise 
Published: April 2016

ABSTRACT

A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 10
9
PFU (months 4 and 5) (
n
= 40) or of a placebo (
n
= 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 μg or placebo, as 2 i.m. injections, 3 months apart. The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen, CD4
+
T-cell and CD8
+
T-cell responses occurred in 74% and 32% of the participants, respectively. The protein boost increased CD4
+
T-cell responses to 87% of the subjects. All participants developed tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4
+
T-cell responses to HIV-1 envelope. (This study has been registered at ClinicalTrials.gov under registration no. NCT00574600 and NCT01423825.)
Application of Whole-Genome Sequencing Data for O-Specific Antigen Analysis and
In Silico
Serotyping of Pseudomonas aeruginosa Isolates
Authors: Thrane Sandra Wingaard , Taylor Véronique L. , Lund Ole , Lam Joseph S. , Jelsbak Lars 
Published: April 2016

ABSTRACT

Accurate typing methods are required for efficient infection control. The emergence of whole-genome sequencing (WGS) technologies has enabled the development of genome-based methods applicable for routine typing and surveillance of bacterial pathogens. In this study, we developed the
Pseudomonas aeruginosa
serotyper (PAst) program, which enabled
in silico
serotyping of
P. aeruginosa
isolates using WGS data. PAst has been made publically available as a web service and aptly facilitates high-throughput serotyping analysis. The program overcomes critical issues such as the loss of
in vitro
typeability often associated with
P. aeruginosa
isolates from chronic infections and quickly determines the serogroup of an isolate based on the sequence of the O-specific antigen (OSA) gene cluster. Here, PAst analysis of 1,649 genomes resulted in successful serogroup assignments in 99.27% of the cases. This frequency is rarely achievable by conventional serotyping methods. The limited number of nontypeable isolates found using PAst was the result of either a complete absence of OSA genes in the genomes or the artifact of genomic misassembly. With PAst,
P. aeruginosa
serotype data can be obtained from WGS information alone. PAst is a highly efficient alternative to conventional serotyping methods in relation to outbreak surveillance of serotype O12 and other high-risk clones, while maintaining backward compatibility to historical serotype data.
Characterization of Epitope-Specific Anti-Respiratory Syncytial Virus (Anti-RSV) Antibody Responses after Natural Infection and after Vaccination with Formalin-Inactivated RSV
Authors: Widjaja Ivy , Wicht Oliver , Luytjes Willem , Leenhouts Kees , Rottier Peter J. M. , van Kuppeveld Frank J. M. , Haijema Bert Jan , de Haan Cornelis A. M. 
Published: April 2016

ABSTRACTAntibodies against the fusion (F) protein of respiratory syncytial virus (RSV) play an important role in the protective immune response to this important respiratory virus. Little is known, however, about antibody levels against multiple F-specific epitopes induced by infection or after vaccination against RSV, while this is important to guide the evaluation of (novel) vaccines. In this study, we analyzed antibody levels against RSV proteins and F-specific epitopes in human sera and in sera of vaccinated and experimentally infected cotton rats and the correlation thereof with virus neutralization. Analysis of human sera revealed substantial diversity in antibody levels against F-, G (attachment)-, and F-specific epitopes between individuals. The highest correlation with virus neutralization was observed for antibodies recognizing prefusion-specific antigenic site Ø. Nevertheless, our results indicate that high levels of antibodies targeting other parts of the F protein can also mediate a potent antiviral antibody response. In agreement, sera of experimentally infected cotton rats contained high neutralizing activity despite lacking antigenic site Ø-specific antibodies. Strikingly, vaccination with formalin-inactivated RSV (FI-RSV) exclusively resulted in the induction of poorly neutralizing antibodies against postfusion-specific antigenic site I, although antigenic sites I, II, and IV were efficiently displayed in FI-RSV. The apparent immunodominance of antigenic site I in FI-RSV likely explains the low levels of neutralizing antibodies upon vaccination and challenge and may play a role in the vaccination-induced enhancement of disease observed with such preparations.IMPORTANCERSV is an importance cause of hospitalization of infants. The development of a vaccine against RSV has been hampered by the disastrous results obtained with FI-RSV vaccine preparations in the 1960s that resulted in vaccination-induced enhancement of disease. To get a better understanding of the antibody repertoire induced after infection or after vaccination against RSV, we investigated antibody levels against fusion (F) protein, attachment (G) protein, and F-specific epitopes in human and animal sera. The results indicate the importance of prefusion-specific antigenic site Ø antibodies as well as of antibodies targeting other epitopes in virus neutralization. However, vaccination of cotton rats with FI-RSV specifically resulted in the induction of weakly neutralizing, antigenic site I-specific antibodies, which may play a role in the enhancement of disease observed after vaccination with such preparations.
SUMO Ligase Protein Inhibitor of Activated STAT1 (PIAS1) Is a Constituent Promyelocytic Leukemia Nuclear Body Protein That Contributes to the Intrinsic Antiviral Immune Response to Herpes Simplex Virus 1
Authors: Brown James R. , Conn Kristen L. , Wasson Peter , Charman Matthew , Tong Lily , Grant Kyle , McFarlane Steven , Boutell Chris 
Published: April 2016

ABSTRACT

Aspects of intrinsic antiviral immunity are mediated by
p
ro
m
yelocytic
l
eukemia
n
uclear
b
ody (PML-NB) constituent proteins. During herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. Central to the execution of this particular antiviral response is the
s
mall
u
biquitin-like
mo
difier (SUMO) signaling pathway. However, the participating SUMOylation enzymes are not fully characterized. We identify the SUMO ligase
p
rotein
i
nhibitor of
a
ctivated
S
TAT1 (PIAS1) as a constituent PML-NB protein. We show that PIAS1 localizes at PML-NBs in a
S
UMO
i
nteraction
m
otif (SIM)-dependent manner that requires SUMOylated or SUMOylation-competent PML. Following infection with herpes simplex virus 1 (HSV-1), PIAS1 is recruited to nuclear sites associated with viral genome entry in a SIM-dependent manner, consistent with the SIM-dependent recruitment mechanisms of other well-characterized PML-NB proteins. In contrast to that of Daxx and Sp100, however, the recruitment of PIAS1 is enhanced by PML. PIAS1 promotes the stable accumulation of SUMO1 at nuclear sites associated with HSV-1 genome entry, whereas the accumulation of other evaluated PML-NB proteins occurs independently of PIAS1. We show that PIAS1 cooperatively contributes to HSV-1 restriction through mechanisms that are additive to those of PML and cooperative with those of PIAS4. The antiviral mechanisms of PIAS1 are counteracted by ICP0, the HSV-1 SUMO-targeted ubiquitin ligase, which disrupts the recruitment of PIAS1 to nuclear domains that contain infecting HSV-1 genomes through mechanisms that do not directly result in PIAS1 degradation.

IMPORTANCE
Adaptive, innate, and intrinsic immunity cooperatively and efficiently restrict the propagation of viral pathogens. Intrinsic immunity mediated by constitutively expressed cellular proteins represents the first line of intracellular defense against infection. PML-NB constituent proteins mediate aspects of intrinsic immunity to restrict herpes simplex virus 1 (HSV-1) as well as other viruses. These proteins repress viral replication through mechanisms that rely on SUMO signaling. However, the participating SUMOylation enzymes are not known. We identify the SUMO ligase PIAS1 as a constituent PML-NB antiviral protein. This finding distinguishes a SUMO ligase that may mediate signaling events important in PML-NB-mediated intrinsic immunity. Moreover, this research complements the recent identification of PIAS4 as an intrinsic antiviral factor, supporting a role for PIAS proteins as both positive and negative regulators of host immunity to virus infection.