bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in attrition at subnational level: review of the Botswana National HIV/AIDS Treatment (Masa) programme data (2002–2013)
Authors: Farahani Mansour , Price Natalie , El‐Halabi Shenaaz , Mlaudzi Naledi , Keapoletswe Koona , Lebelonyane Refeletswe , Fetogang Ernest Benny , Chebani Tony , Kebaabetswe Poloko , Masupe Tiny , Gabaake Keba , Auld Andrew , Nkomazana Oathokwa , Marlink Richard 
Published: October 2015

AbstractObjectiveTo evaluate the variation in all‐cause attrition [mortality and loss to follow‐up (LTFU)] among HIV‐infected individuals in Botswana by health district during the rapid and massive scale‐up of the National Treatment Program.MethodsAnalysis of routinely collected longitudinal data from 226 030 patients who received ART through the Botswana National HIV/AIDS Treatment Program across all 24 health districts from 2002 to 2013. A time‐to‐event analysis was used to measure crude mortality and loss to follow‐up rates (LTFU). A marginal structural model was used to evaluate mortality and LTFU rates by district over time, adjusted for individual‐level risk factors (e.g. age, gender, baseline CD4, year of treatment initiation and antiretroviral regimen).ResultsMortality rates in the districts ranged from the lowest 1.0 (95% CI 0.9–1.1) in Selibe‐Phikwe, to the highest 5.0 (95% CI 4.0–6.1), in Mabutsane. There was a wide range of overall LTFU across districts, including rates as low as 4.6 (95% CI 4.4–4.9) losses per 100 person‐years in Ngamiland, and 5.9 (95% CI 5.6–6.2) losses per 100 person‐years in South East district, to rates as high as 25.4 (95% CI 23.08–27.89) losses per 100 person‐years in Mabutsane and 46.3 (95% CI 43.48–49.23) losses per 100 person‐years in Okavango. Even when known risk factors for mortality and LTFU were adjusted for, district was a significant predictor of both mortality and LTFU rates.ConclusionWe found statistically significant variation in attrition (mortality and LTFU) and data quality among districts. These findings suggest that district‐level contextual factors affect retention in treatment. Further research needs to investigate factors that can potentially cause this variation.
A refined genome‐scale reconstruction of Chlamydomonas metabolism provides a platform for systems‐level analyses
Authors: Imam Saheed , Schäuble Sascha , Valenzuela Jacob , López García de Lomana Adrián , Carter Warren , Price Nathan D. , Baliga Nitin S. 
Published: October 2015

SummaryMicroalgae have reemerged as organisms of prime biotechnological interest due to their ability to synthesize a suite of valuable chemicals. To harness the capabilities of these organisms, we need a comprehensive systems‐level understanding of their metabolism, which can be fundamentally achieved through large‐scale mechanistic models of metabolism. In this study, we present a revised and significantly improved genome‐scale metabolic model for the widely‐studied microalga, Chlamydomonas reinhardtii. The model, iCre1355, represents a major advance over previous models, both in content and predictive power. iCre1355 encompasses a broad range of metabolic functions encoded across the nuclear, chloroplast and mitochondrial genomes accounting for 1355 genes (1460 transcripts), 2394 and 1133 metabolites. We found improved performance over the previous metabolic model based on comparisons of predictive accuracy across 306 phenotypes (from 81 mutants), lipid yield analysis and growth rates derived from chemostat‐grown cells (under three conditions). Measurement of macronutrient uptake revealed carbon and phosphate to be good predictors of growth rate, while nitrogen consumption appeared to be in excess. We analyzed high‐resolution time series transcriptomics data using iCre1355 to uncover dynamic pathway‐level changes that occur in response to nitrogen starvation and changes in light intensity. This approach enabled accurate prediction of growth rates, the cessation of growth and accumulation of triacylglycerols during nitrogen starvation, and the temporal response of different growth‐associated pathways to increased light intensity. Thus, iCre1355 represents an experimentally validated genome‐scale reconstruction of C. reinhardtii metabolism that should serve as a useful resource for studying the metabolic processes of this and related microalgae.
Technical Note: MR‐visualization of interventional devices using transient field alterations and balanced steady‐state free precession imaging
Authors: Eibofner Frank , Martirosian Petros , Würslin Christian , Graf Hansjörg , Syha Roland , Clasen Stephan 
Published: October 2015

Purpose:In interventional magnetic resonance imaging, instruments can be equipped with conducting wires for visualization by current application. The potential of sequence triggered application of transient direct currents in balanced steady‐state free precession (bSSFP) imaging is demonstrated.Methods:A conductor and a modified catheter were examined in water phantoms and in an ex vivo porcine liver. The current was switched by a trigger pulse in the bSSFP sequence in an interval between radiofrequency pulse and signal acquisition. Magnitude and phase images were recorded. Regions with transient field alterations were evaluated by a postprocessing algorithm. A phase mask was computed and overlaid with the magnitude image.Results:Transient field alterations caused continuous phase shifts, which were separated by the postprocessing algorithm from phase jumps due to persistent field alterations. The overlaid images revealed the position of the conductor. The modified catheter generated visible phase offset in all orientations toward the static magnetic field and could be unambiguously localized in the ex vivo porcine liver.Conclusions:The application of a sequence triggered, direct current in combination with phase imaging allows conspicuous localization of interventional devices with a bSSFP sequence.
Effect of
SLCO1B1
Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis
Authors: Hennig Stefanie , Naiker Suhashni , Reddy Tarylee , Egan Deirdre , Kellerman Tracy , Wiesner Lubbe , Owen Andrew , McIlleron Helen , Pym Alexander 
Published: October 2015

ABSTRACT

Rifabutin, used to treat HIV-infected tuberculosis, shows highly variable drug exposure, complicating dosing. Effects of
SLCO1B1
polymorphisms on rifabutin pharmacokinetics were investigated in 35 African HIV-infected tuberculosis patients after multiple doses. Nonlinear mixed-effects modeling found that influential covariates for the pharmacokinetics were weight, sex, and a 30% increased bioavailability among heterozygous carriers of
SLCO1B1
rs1104581 (previously associated with low rifampin concentrations). Larger studies are needed to understand the complex interactions of host genetics in HIV-infected tuberculosis patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00640887.)
Multidrug-Resistant Neisseria gonorrhoeae Isolates from Nanjing, China, Are Sensitive to Killing by a Novel DNA Gyrase Inhibitor, ETX0914 (AZD0914)
Authors: Su Xiao-Hong , Wang Bao-Xi , Le Wen-Jing , Liu Yu-Rong , Wan Chuan , Li Sai , Alm Richard A. , Mueller John P. , Rice Peter A. 
Published: October 2015

ABSTRACT

We tested the activity of ETX0914 against 187
Neisseria gonorrhoeae
isolates from men with urethritis in Nanjing, China, in 2013. The MIC
50
, MIC
90
, and MIC range for ETX0914 were 0.03 μg/ml, 0.06 μg/ml, and ≤0.002 to 0.125 μg/ml, respectively. All isolates were resistant to ciprofloxacin, and 36.9% (69/187) were resistant to azithromycin. Of the isolates, 46.5% were penicillinase-producing
N. gonorrhoeae
(PPNG), 36% were tetracycline-resistant
N. gonorrhoeae
(TRNG), and 13% (24 isolates) had an MIC of 0.125 μg/ml for ceftriaxone. ETX0914 may be an effective treatment option for gonorrhea.
Pharmacokinetics/Pharmacodynamics of Peptide Deformylase Inhibitor GSK1322322 against Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in Rodent Models of Infection
Authors: Hoover Jennifer , Lewandowski Thomas , Straub Robert J. , Novick Steven J. , DeMarsh Peter , Aubart Kelly , Rittenhouse Stephen , Zalacain Magdalena 
Published: October 2015

ABSTRACTGSK1322322 is a novel inhibitor of peptide deformylase (PDF) with goodin vitroactivity against bacteria associated with community-acquired pneumonia and skin infections. We have characterized thein vivopharmacodynamics (PD) of GSK1322322 in immunocompetent animal models of infection withStreptococcus pneumoniaeandHaemophilus influenzae(mouse lung model) and withStaphylococcus aureus(rat abscess model) and determined the pharmacokinetic (PK)/PD index that best correlates with efficacy and its magnitude. Oral PK studies with both models showed slightly higher-than-dose-proportional exposure, with 3-fold increases in area under the concentration-time curve (AUC) with doubling doses. GSK1322322 exhibited dose-dependentin vivoefficacy against multiple isolates ofS. pneumoniae,H. influenzae, andS. aureus. Dose fractionation studies with twoS. pneumoniaeandS. aureusisolates showed that therapeutic outcome correlated best with the free AUC/MIC (fAUC/MIC) index inS. pneumoniae(R2, 0.83), whereasfAUC/MIC and free maximum drug concentration (fCmax)/MIC were the best efficacy predictors forS. aureus(R2, 0.9 and 0.91, respectively). Median dailyfAUC/MIC values required for stasis and for a 1-log10reduction in bacterial burden were 8.1 and 14.4 for 11S. pneumoniaeisolates (R2, 0.62) and 7.2 and 13.0 for fiveH. influenzaeisolates (R2, 0.93). The data showed that for eightS. aureusisolates,fAUC correlated better with efficacy thanfAUC/MIC (R2, 0.91 and 0.76, respectively), as efficacious AUCs were similar for all isolates, independent of their GSK1322322 MIC (range, 0.5 to 4 μg/ml). MedianfAUCs of 2.1 and 6.3 μg · h/ml were associated with stasis and 1-log10reductions, respectively, forS. aureus.
In Vitro
Pharmacodynamics of Human Simulated Exposures of Telavancin against Methicillin-Susceptible and -Resistant Staphylococcus aureus with and without Prior Vancomycin Exposure
Authors: Thabit Abrar K. , Nicolau David P. , Kuti Joseph L. 
Published: October 2015

ABSTRACT

Telavancin is a lipoglycopeptide with potent activity against methicillin-resistant
Staphylococcus aureus
(MRSA) and methicillin-susceptible
S. aureus
(MSSA). The activity of telavancin against MRSA and MSSA after prior vancomycin exposure was studied in an
in vitro
pharmacodynamic model. Two clinical MRSA and two MSSA isolates, all with vancomycin MICs of 2 μg/ml, were subjected to humanized free drug exposures of vancomycin at 1 g every 12 h (q12h) for 96 h, telavancin at 750 mg q24h for 96 h, and vancomycin at 1 g q12h for 72 h followed by telavancin at 750 mg q24h for 48 h (120 h total). The microbiological responses were measured by changes from 0 h in log
10
CFU/ml at the end of experiments and area under the bacterial killing and regrowth curves over 96 h (AUBC
0−96
). The control isolates grew to 8.8 ± 0.3 log
10
CFU/ml. Initially, all regimens caused −4.5 ± 0.9 reductions in log
10
CFU/ml by 48 h followed by slight regrowth over the following 48 to 72 h. After 96 h, vancomycin and telavancin achieved −3.7 ± 0.9 and −3.8 ± 0.8 log
10
CFU/ml changes from baseline, respectively (
P
= 0.74). Sequential exposure to telavancin after vancomycin did not result in additional CFU reductions or increases, with ultimate log
10
CFU/ml reductions of −4.3 ± 1.1 at 96 h and −4.2 ± 1.3 at 120 h (
P
> 0.05 for all comparisons at 96 h). The AUBC
0–96
was significantly smaller for the regimen of telavancin for 96 h than for the regimens of vancomycin for 96 h and vancomycin followed by telavancin (
P
≤ 0.04). No resistance was observed throughout the experiment. Against these MRSA and MSSA isolates with vancomycin MICs of 2 μg/ml, telavancin was comparable with vancomycin and its activity was unaffected by prior vancomycin exposure.
Bovine Immunoinhibitory Receptors Contribute to Suppression of Mycobacterium avium subsp. paratuberculosis-Specific T-Cell Responses
Authors: Okagawa Tomohiro , Konnai Satoru , Nishimori Asami , Ikebuchi Ryoyo , Mizorogi Seiko , Nagata Reiko , Kawaji Satoko , Tanaka Shogo , Kagawa Yumiko , Murata Shiro , Mori Yasuyuki , Ohashi Kazuhiko 
Published: October 2015

ABSTRACT

Johne's disease (paratuberculosis) is a chronic enteritis in cattle that is caused by intracellular infection with
Mycobacterium avium
subsp.
paratuberculosis
. This infection is characterized by the functional exhaustion of T-cell responses to
M. avium
subsp.
paratuberculosis
antigens during late subclinical and clinical stages, presumably facilitating the persistence of this bacterium and the formation of clinical lesions. However, the mechanisms underlying T-cell exhaustion in Johne's disease are poorly understood. Thus, we performed expression and functional analyses of the immunoinhibitory molecules programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) and lymphocyte activation gene 3 (LAG-3)/major histocompatibility complex class II (MHC-II) in
M. avium
subsp.
paratuberculosis
-infected cattle during the late subclinical stage. Flow cytometric analyses revealed the upregulation of PD-1 and LAG-3 in T cells in infected animals, which suffered progressive suppression of interferon gamma (IFN-γ) responses to the
M. avium
subsp.
paratuberculosis
antigen. In addition, PD-L1 and MHC-II were expressed on macrophages from infected animals, consistent with PD-1 and LAG-3 pathways contributing to the suppression of IFN-γ responses during the subclinical stages of
M. avium
subsp.
paratuberculosis
infection. Furthermore, dual blockade of PD-L1 and LAG-3 enhanced
M. avium
subsp.
paratuberculosis
-specific IFN-γ responses in blood from infected animals, and
in vitro
LAG-3 blockade enhanced IFN-γ production from
M. avium
subsp.
paratuberculosis
-specific CD4
+
and CD8
+
T cells. Taken together, the present data indicate that
M. avium
subsp.
paratuberculosis
-specific T-cell exhaustion is in part mediated by PD-1/PD-L1 and LAG-3/MHC-II interactions and that LAG-3 is a molecular target for the control of
M. avium
subsp.
paratuberculosis
-specific T-cell responses.
The mental health of US Black women: the roles of social context and severe intimate partner violence
Authors: Lacey Krim K , Parnell Regina , Mouzon Dawne M , Matusko Niki , Head Doreen , Abelson Jamie M , Jackson James S 
Published: October 2015

ObjectiveBlack women continue to have rates of mental health conditions that can be negative for their well-being. This study examined the contribution of social and contextual factors and severe physical intimate partner violence on the mental health of US Black women (African-American and Caribbean Black).SettingData were largely collected via in-person community interviews at participants’ homes.ParticipantsWe studied 3277 African-American and Black Caribbean women from the 2001–2003 National Survey of American Life (NSAL), the largest and most complete sample of Blacks residing in the USA.Primary and secondary outcomesKey outcomes included an array of psychiatric disorders based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).ResultsBivariate results revealed noticeably high rates of any anxiety disorder, post-traumatic stress disorder, any substance disorder, alcohol abuse disorder, suicide ideation and attempts, and any overall mental disorder among African-American women relative to Caribbean Black women. Multiple social and contextual factors were associated with various mental disorders among both sets of Black women in multivariate models, with the most consistent associations found for severe physical intimate partner violence. Everyday discrimination was associated with anxiety disorders (95% AOR=2.08 CI 1.23 to 3.51), eating disorders (95% AOR=2.69 CI 1.38 to 5.22), and any disorder (95% AOR=2.18 CI 1.40 to 3.40), while neighbourhood drug problems contributed to mood (95% AOR=1.19 CI 1.04 to 1.36), substance disorders (95% AOR=1.37 CI 1.11 to 1.69) and any disorder (95% AOR=1.18 CI 1.03 to 1.34).ConclusionsSevere physical intimate partner violence, discrimination, and to a lesser extent, neighbourhood problems are important predictors of Black women's health, findings that inform intervention and clinical services tailored to meet the needs of Black women from diverse ethnic and cultural backgrounds.
Prevalence and severity of asthmatic symptoms in Grenadian school children: the Grenada National Asthma Survey
Authors: Thongkham D , Tran J , Clunes M T , Brahim F 
Published: October 2015

ObjectiveThe goal of this study was to determine the prevalence of asthma in school children in the tri-island Caribbean nation of Grenada.Setting, participants and outcomesThis was a self-report study provided to the guardians of all primary school children between ages 6 and 7 throughout Grenada, Carriacou and Petite Martinique in 2013. Of the 2362 surveys provided, 1374 were returned, resulting in a response rate of 58.2%. Only responders listing birthdays between 1 January 2006 and 31 December 2007 were included in the analysis, resulting in 1165 qualifying responders. Asthma diagnosis was based on previous physician diagnosed asthma and/or self-reported presence of wheeze in the past 12 months (current wheeze). Severity of asthma, medication usage, environmental exposures, physician and emergency department visits were compared among respondents.ResultsThe prevalence of wheezing in the past year was 30.5±1.8%, and of these 68.4% were previously diagnosed with asthma. Of the current wheeze participants, 39.9±9.2% reported moderate to severe asthma symptoms and increased exposure to cigarette smoke, excessive dust, burning brush and landfills. Carriacou and Petite Martinique, the two smaller islands, had a lower incidence of current wheeze (14.1±7.7%) and exposure rates to cigarette smoke and burning brush as compared to the larger, denser island of Grenada. Although 65.7% of respondents diagnosed with asthma reported taking medication, the number of annual doctor and emergency department visits were high (2.82 and 0.86, respectively). Respondents with the most severe asthma symptoms reported the most emergency department visits with an average of 1.05 visits annually, whereas respondents with moderate asthma symptoms had the most doctor visits with an average of 3.33 visits annually.ConclusionsThis study indicates that the prevalence of childhood asthma in Grenada is very high and warrants policy consideration in public health and education to decrease its morbidity.
Beliefs underlying pain-related fear and how they evolve: a qualitative investigation in people with chronic back pain and high pain-related fear
Authors: Bunzli Samantha , Smith Anne , Schütze Robert , O'Sullivan Peter 
Published: October 2015

ObjectivesThe fear-avoidance model describes how the belief that pain is a sign of damage leads to pain-related fear and avoidance. But other beliefs may also trigger the fear and avoidance responses described by the model. Experts have called for the next generation of fear avoidance research to explore what beliefs underlie pain-related fear and how they evolve. We have previously described damage beliefs and suffering/functional loss beliefs underlying high pain-related fear in a sample of individuals with chronic back pain. The aim of this study is to identify common and differential factors associated with the beliefs in this sample.DesignA qualitative study employing semistructured interviews.SettingMusculoskeletal clinics in Western Australia.Participants36 individuals with chronic back pain and high scores on the Tampa Scale (mean 47/68).ResultsThe overarching theme was a pain experience that did not make sense to the participants. The experience of pain as unpredictable, uncontrollable and intense made it threatening. Attempting to make sense of the threatening pain, participants with damage beliefs drew on past personal experiences of pain, societal beliefs, and sought diagnostic certainty. Met with diagnostic uncertainty, or diagnoses of an underlying pathology that could not be fixed, they were left fearful of damage and confused about how to ‘fix’ it. Participants with suffering/functional loss beliefs drew on past personal experiences of pain and sought help from healthcare professionals to control their pain. Failed treatments and the repeated failure to achieve functional goals left them unable to make ‘sensible’ decisions of what to do about their pain.ConclusionsThe findings raise the suggestion that sense-making processes may be implicated in the fear-avoidance model. Future research is needed to explore whether fear reduction may be enhanced by considering beliefs underlying fear and providing targeted intervention to help individuals make sense of their pain.
A Phase I/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed/Refractory Lymphoma
Authors: Evens Andrew M. , Balasubramanian Sriram , Vose Julie M. , Harb Wael , Gordon Leo I. , Langdon Robert , Sprague Julian , Sirisawad Mint , Mani Chitra , Yue Jeanne , Luan Ying , Horton Sharon , Graef Thorsten , Bartlett Nancy L. 
Published: October 2015

Abstract
Purpose: Additional targeted therapeutics are needed for the treatment of lymphoma. Abexinostat is an oral pan-histone deacetylase inhibitor (HDACi) displaying potent activity in preclinical models. We conducted a multicenter phase I/II study (N = 55) with single-agent abexinostat in relapsed/refractory lymphoma.
Experimental Design: In phase I, 25 heavily pretreated patients with any lymphoma subtype received oral abexinostat ranging from 30 to 60 mg/m2 twice daily 5 days/week for 3 weeks or 7 days/week given every other week. Phase II evaluated abexinostat at the maximum tolerated dose in 30 patients with relapsed/refractory follicular lymphoma or mantle cell lymphoma.
Results: The recommended phase II dose was 45 mg/m2 twice daily (90 mg/m2 total), 7 days/week given every other week. Of the 30 follicular lymphoma and mantle cell lymphoma patients enrolled in phase II, 25 (14 follicular lymphoma, 11 mantle cell lymphoma) were response-evaluable. Tumor size was reduced in 86% of follicular lymphoma patients with an investigator-assessed ORR of 64.3% for evaluable patients [intent-to-treat (ITT) ORR 56.3%]. Median duration of response was not reached, and median progression-free survival (PFS) was 20.5 months (1.2–22.3+). Of responding follicular lymphoma patients, 89% were on study/drug &gt;8 months. In mantle cell lymphoma, the ORR was 27.3% for evaluable patients (ITT ORR 21.4%), and median PFS was 3.9 months (range, 0.1–11.5). Grade 3–4 treatment-related adverse events (phase II) with ≥10% incidence were thrombocytopenia (20%), fatigue (16.7%), and neutropenia (13.3%) with rare QTc prolongation and no deaths.
Conclusions: The pan-HDACi, abexinostat, was overall well tolerated and had significant clinical activity in follicular lymphoma, including highly durable responses in this multiply relapsed patient population. Clin Cancer Res; 22(5); 1059–66. ©2015 AACR.