bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproductive Health and Bodily Integrity in Tanzania
Authors: Westeneng Judith , D'Exelle Ben 
Published: August 2017

AbstractSeveral policy initiatives support the empowerment of women to improve their reproductive health. Little is known, however, about the inverse effect that reproductive health might have on women's empowerment. Women are pressured to conform to their reproductive role, and an inability to do so might affect their empowerment, including control over their own body. Using a panel dataset of 504 married women in Northern Tanzania, we find that women who experienced a pregnancy loss show more tolerant views of partner violence and that child mortality lowers their perceived control over the sexual relationship with their spouse. The number of living children did not affect bodily integrity. These results confirm that women's bodily integrity is partly dependent on the ability to fulfill their reproductive role. They strengthen the case for policies and programs that improve women's reproductive health and underline the importance of counselling after pregnancy or child loss.
Muscle length effect on corticospinal excitability during maximal concentric, isometric and eccentric contractions of the knee extensors
Authors: Doguet Valentin , Nosaka Kazunori , Guével Arnaud , Thickbroom Gary , Ishimura Kazuhiro , Jubeau Marc 
Published: August 2017

New Findings
What is the central question of this study?
Does sensory input from peripheral mechanoreceptors determine the specific neural control of eccentric contractions? How corticospinal excitability (i.e. muscle responses to motor cortex stimulation) is affected by muscle length has never been investigated during eccentric contractions.

What is the main finding and its importance?
Muscle length does not influence corticospinal excitability during concentric and isometric maximal contractions, but does during eccentric maximal contractions. This indicates that neural control in eccentric contractions differs from that in concentric and isometric contractions.

Neural control of eccentric contractions differs from that of concentric and isometric contractions, but no previous study has compared responses to motor cortex stimulations at long muscle lengths during such contraction types. In this study, we compared the effect of muscle length on corticospinal excitability between maximal concentric, isometric and eccentric contractions of the knee extensors. Twelve men performed 12 maximal concentric, isometric and eccentric voluntary contractions (36 contractions in total), separated by a 5 min rest between contraction types. The 12 contractions for the same contraction type were performed every 10 s, and transcranial magnetic stimulations (first eight contractions) and electrical femoral nerve stimulations (last four contractions) were superimposed alternately at 75 and 100 deg of knee flexion. Average motor evoked potential amplitude, normalized to the maximal M wave amplitude (MEP/M) and cortical silent period duration were calculated for each angle and compared among the contraction types. The MEP/M was lower (−23 and −28%, respectively) during eccentric than both concentric and isometric contractions at 75 deg, but similar between contraction types at 100 deg (P < 0.05). The cortical silent period duration was shorter (−12 and −10%, respectively) during eccentric than both concentric and isometric contractions at 75 deg, but longer (+11 and +9%, respectively) during eccentric contractions at 100 deg (P < 0.05). These results show that corticospinal excitability during eccentric contractions is angle dependent such that cortical inhibitory processes are greater with no alteration of corticospinal excitability at 100 deg, whereas this control is reversed at 75 deg.
Determination of Disk Diffusion and MIC Quality Control Guidelines for High-Dose Cefepime-Tazobactam (WCK 4282), a Novel Antibacterial Combination Consisting of a β-Lactamase Inhibitor and a Fourth-Generation Cephalosporin
Authors: Riedel Stefan , Huband Michael D. , Sader Helio S. , Flamm Robert K. , Jones Ronald N. 
Published: August 2017

ABSTRACT

High-dose cefepime-tazobactam (1:1; WCK 4282), a novel antibacterial combination consisting of the β-lactamase inhibitor tazobactam and a fourth-generation cephalosporin, is under clinical development for the treatment of serious Gram-negative infections. A quality control (QC) study was performed to establish disk diffusion and MIC ranges for cefepime-tazobactam for multiple QC reference strains. The cefepime-tazobactam QC ranges for a fixed tazobactam MIC of 8 μg/ml and disk diffusion (30/20-μg disk) test methods were approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing in January 2015 and January 2016. These QC ranges will be important for accurate
in vitro
activity evaluations of cefepime-tazobactam when tested against clinical Gram-negative bacteria during clinical studies and routine patient care.
No Substantial Evidence for Sexual Transmission of Minority HIV Drug Resistance Mutations in Men Who Have Sex with Men
Authors: Chaillon Antoine , Nakazawa Masato , Wertheim Joel O. , Little Susan J. , Smith Davey M. , Mehta Sanjay R. , Gianella Sara 
Published: August 2017

ABSTRACT

During primary HIV infection, the presence of minority drug resistance mutations (DRM) may be a consequence of sexual transmission,
de novo
mutations, or technical errors in identification. Baseline blood samples were collected from 24 HIV-infected antiretroviral-naive, genetically and epidemiologically linked source and recipient partners shortly after the recipient's estimated date of infection. An additional 32 longitudinal samples were available from 11 recipients. Deep sequencing of HIV reverse transcriptase (RT) was performed (Roche/454), and the sequences were screened for nucleoside and nonnucleoside RT inhibitor DRM. The likelihood of sexual transmission and persistence of DRM was assessed using Bayesian-based statistical modeling. While the majority of DRM (>20%) were consistently transmitted from source to recipient, the probability of detecting a minority DRM in the recipient was not increased when the same minority DRM was detected in the source (Bayes factor [BF] = 6.37). Longitudinal analyses revealed an exponential decay of DRM (BF = 0.05) while genetic diversity increased. Our analysis revealed no substantial evidence for sexual transmission of minority DRM (BF = 0.02). The presence of minority DRM during early infection, followed by a rapid decay, is consistent with the “mutation-selection balance” hypothesis, in which deleterious mutations are more efficiently purged later during HIV infection when the larger effective population size allows more efficient selection. Future studies using more recent sequencing technologies that are less prone to single-base errors should confirm these results by applying a similar Bayesian framework in other clinical settings.

IMPORTANCE
The advent of sensitive sequencing platforms has led to an increased identification of minority drug resistance mutations (DRM), including among antiretroviral therapy-naive HIV-infected individuals. While transmission of DRM may impact future therapy options for newly infected individuals, the clinical significance of the detection of minority DRM remains controversial. In the present study, we applied deep-sequencing techniques within a Bayesian hierarchical framework to a cohort of 24 transmission pairs to investigate whether minority DRM detected shortly after transmission were the consequence of (i) sexual transmission from the source, (ii)
de novo
emergence shortly after infection followed by viral selection and evolution, or (iii) technical errors/limitations of deep-sequencing methods. We found no clear evidence to support the sexual transmission of minority resistant variants, and our results suggested that minor resistant variants may emerge
de novo
shortly after transmission, when the small effective population size limits efficient purge by natural selection.
Pseudorabies Virus dUTPase UL50 Induces Lysosomal Degradation of Type I Interferon Receptor 1 and Antagonizes the Alpha Interferon Response
Authors: Zhang Rui , Xu Aotian , Qin Chao , Zhang Qiong , Chen Shifan , Lang Yue , Wang Mengdong , Li Chuang , Feng Wenhai , Zhang Rui , Jiang Zhengfan , Tang Jun 
Published: August 2017

ABSTRACT
Alphaherpesviruses that establish persistent infections rely partly on their ability to evade host antiviral responses, notably the type I interferon (IFN) response. However, the mechanisms employed by alphaherpesviruses to avoid this response are not well understood. Pseudorabies virus (PRV) is an economically important pathogen and a useful model system for studying alphaherpesvirus biology. To identify PRV proteins that antagonize type I IFN signaling, we performed a screen by using an IFN-stimulated response element reporter in the swine cell line CRL. Unexpectedly, we identified the dUTPase UL50 as a strong inhibitor. We confirmed that UL50 has the ability to inhibit type I IFN signaling by performing ectopic expression of UL50 in cells and deletion of UL50 in PRV. Mechanistically, UL50 impeded type I IFN-induced STAT1 phosphorylation, likely by accelerating lysosomal degradation of IFN receptor 1 (IFNAR1). In addition, this UL50 activity was independent of its dUTPase activity and required amino acids 225 to 253 in the C-terminal region. The UL50 encoded by herpes simplex virus 1 (HSV-1) also possessed similar activity. Moreover, UL50-deleted PRV was more susceptible to IFN than UL50-proficient PRV. Our results suggest that in addition to its dUTPase activity, the UL50 protein of alphaherpesviruses possesses the ability to suppress type I IFN signaling by promoting lysosomal degradation of IFNAR1, thereby contributing to immune evasion. This finding reveals UL50 as a potential antiviral target.

IMPORTANCE
Alphaherpesviruses can establish lifelong infections and cause many diseases in humans and animals. Pseudorabies virus (PRV) is a swine alphaherpesvirus that threatens pig production. Using PRV as a model, we found that this alphaherpesvirus could utilize its encoded dUTPase UL50 to induce IFNAR1 degradation and inhibit type I IFN signaling in an enzymatic activity-independent manner. Our finding reveals a mechanism employed by an alphaherpesvirus to evade the immune response and indicates that UL50 is an important viral protein in pathogenesis and is a potential target for antiviral drug development.
Ancient Evolution and Dispersion of Human Papillomavirus 58 Variants
Authors: Chen Zigui , Ho Wendy C. S. , Boon Siaw Shi , Law Priscilla T. Y. , Chan Martin C. W. , DeSalle Rob , Burk Robert D. , Chan Paul K. S. 
Published: August 2017

ABSTRACT

Human papillomavirus 58 (HPV58) is found in 10 to 18% of cervical cancers in East Asia but is rather uncommon elsewhere. The distribution and oncogenic potential of HPV58 variants appear to be heterogeneous, since the E7 T20I/G63S variant is more prevalent in East Asia and confers a 7- to 9-fold-higher risk of cervical precancer and cancer. However, the underlying genomic mechanisms that explain the geographic and carcinogenic diversity of HPV58 variants are still poorly understood. In this study, we used a combination of phylogenetic analyses and bioinformatics to investigate the deep evolutionary history of HPV58 complete genome variants. The initial splitting of HPV58 variants was estimated to occur 478,600 years ago (95% highest posterior density [HPD], 391,000 to 569,600 years ago). This divergence time is well within the era of speciation between
Homo sapiens
and Neanderthals/Denisovans and around three times longer than the modern
Homo sapiens
divergence times. The expansion of present-day variants in Eurasia could be the consequence of viral transmission from Neanderthals/Denisovans to non-African modern human populations through gene flow. A whole-genome sequence signature analysis identified 3 amino acid changes, 16 synonymous nucleotide changes, and a 12-bp insertion strongly associated with the E7 T20I/G63S variant that represents the A3 sublineage and carries higher carcinogenetic potential. Compared with the capsid proteins, the oncogenes E7 and E6 had increased substitution rates indicative of higher selection pressure. These data provide a comprehensive evolutionary history and genomic basis of HPV58 variants to assist further investigation of carcinogenic association and the development of diagnostic and therapeutic strategies.

IMPORTANCE
Papillomaviruses (PVs) are an ancient and heterogeneous group of double-stranded DNA viruses that preferentially infect the cutaneous and mucocutaneous epithelia of vertebrates. Persistent infection by specific oncogenic human papillomaviruses (HPVs), including HPV58, has been established as the primary cause of cervical cancer. In this work, we reveal the complex evolutionary history of HPV58 variants that explains the heterogeneity of oncogenic potential and geographic distribution. Our data suggest that HPV58 variants may have coevolved with archaic hominins and dispersed across the planet through host interbreeding and gene flow. Certain genes and codons of HPV58 variants representing higher carcinogenic potential and/or that are under positive selection may have important implications for viral host specificity, pathogenesis, and disease prevention.
Restructuring hospitalist work schedules to improve care timeliness and efficiency
Authors: Wells Monika , Coates Evan , Williams Barbara , Blackmore Craig 
Published: August 2017

BackgroundIn 2014, we recognised that the pace of admissions frequently exceeded our ability to assign a hospitalist. Long patient wait times occurred at admission, especially for patients arriving in the late afternoon when hospitalist day shifts were ending. Our purpose was to redesign hospitalist schedules, duties and method of distributing admissions to match demand.DesignWe used administrative data to tabulate Hospital Medicine admission requests by time of day and identified mismatch between volume and capacity with the current staffing model. We determined that we needed to accommodate 29 admits per day with peak admission volume in the late afternoon and early evening. The current staffing model failed after 22 admits. To realign staffing around patient admissions, we organised a series of Lean quality improvements, starting with a 2-day event in July 2014, and followed by a series of Plan-Do-Study-Act (PDSA) cycles. The improvement team included hospitalists, residents and administrators, and each PDSA cycle involved collection of feedback from all affected providers.StrategyAt baseline, our hospitalist group had six daytime and two nighttime services, including teaching services and attending-only services. Four of eight services were available for admissions, while four were rounding-only. Admitting capacity (patients per day) was 22. Through three PDSA cycles, we successively adapted our staffing and admitting model until the final staffing model aligned with patient admissions. The final model included different shift start times, use of all 10 shifts for admissions and addition of an Advanced Registered Nurse Practitioner (ARNP) service.ResultsAdmitting capacity increased to 30. We confirmed success with follow-up data on patient wait times. Emergency department mean patient wait times for admission decreased 36% from 66 to 43 min (p<0.001).ConclusionQuantifying admission demand by time of day, then designing work schedules and duties around meeting this demand was an effective approach to reduce patient wait times.
Neutrophil gelatinase-associated lipocalin prior to cardiac surgery predicts acute kidney injury and mortality
Authors: Bulluck Heerajnarain , Maiti Raju , Chakraborty Bibhas , Candilio Luciano , Clayton Tim , Evans Richard , Jenkins David P , Kolvekar Shyam , Kunst Gudrun , Laing Christopher , Nicholas Jennifer , Pepper John , Yellon Derek M , Hausenloy Derek J 
Published: August 2017

ObjectiveWe aimed to investigate whether preoperative serum neutrophil gelatinase-associated lipocalin (sNGALpre-op) predicted postoperative acute kidney injury (AKI) during hospitalisation and 1-year cardiovascular and all-cause mortality following adult cardiac surgery.MethodsThis study was a post hoc analysis of the Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patient Undergoing Coronary Artery Bypass Graft Surgery trial involving adult patients undergoing coronary artery bypass graft. Postoperative AKI within 72 hours was defined using the International Kidney Disease: Improving Global Outcomes classification.Results1371 out of 1612 patients had data on sNGALpre-op. The overall 1-year cardiovascular and all-cause mortality was 5.2% (71/1371) and 7.7% (105/1371), respectively. There was an observed increase in the incidence of AKI from the first to the third tertile of sNGALpre-op(30.5%, 41.5% and 45.9%, respectively, p<0.001). There was also an increase in both cardiovascular and all-cause mortality from the first to the third tertile of sNGALpre-op, linear trend test with adjusted p=0.018 and p=0.013, respectively. The adjusted HRs for those in the second and third tertiles of sNGALpre-opcompared with the first tertile were 1.60 (95% CI 0.78 to 3.25) and 2.22 (95% CI 1.13 to 4.35) for cardiovascular mortality, and 1.25 (95% CI 0.71 to 2.22) and 1.91 (95% CI 1.13 to 3.25) for all-cause mortality at 1 year.ConclusionIn a cohort of high-risk adult patients undergoing cardiac surgery, there was an increase in postoperative AKI and 1-year mortality from the first to the third tertile of preoperative serum NGAL. Those in the last tertile (>220 ng/L) had an estimated twofold increase risk of cardiovascular and all-cause mortality at 1 year.Clinical trial registrationNCT101247545; Post-results.
Assessing the association between thinking dispositions and clinical error
Authors: Kinnear John , Wilson Nick 
Published: August 2017

AbstractBackgroundDual-process theory suggests that type 1 thinking results in a propensity to make ‘intuitive’ decisions based on limited information. Type 2 processes, on the other hand, are able to analyse these initial responses and replace them with rationalised decisions. Individuals may have a preference for different modes of rationalisation, on a continuum from careful to cursory. These ‘dispositions’ of thinking reside in type 2 processes and may result in error when the preference is for ‘quick and casual’ decision-making.MethodsWe asked clinicians to answer a cognitive puzzle to which there was an obvious, but incorrect, answer, to measure their propensity for ‘quick and casual’ decision-making. The same clinicians were also asked to report the number of clinical errors they had committed in the previous two weeks. We hypothesised an association between committing error and settling for an incorrect answer, and that the cognitive puzzle would have predictive capability.Results90 of 153 (59%) clinicians reported that they had committed error, while 103 (67%) gave the incorrect ‘intuitive’ answer to the cognitive puzzle. There was no statistically significant difference between clinicians who committed error and answered incorrectly, and those who did not and answered correctly (χ2(1, n=1153)=0.021, p=0.885).ConclusionsThe prevalence of clinical error in our study was higher than previously reported in the literature, and the propensity for accepting intuitive solutions was high. Although the cognitive puzzle was unable to predict who was more likely to commit error, the study offers insights into developing other predictive models for error.
Immature platelets as a novel biomarker for adverse cardiovascular events in patients after non-cardiac surgery
Authors: Anetsberger Aida , Blobner Manfred , Haller Bernhard , Schmid Sebastian , Umgelter Katrin , Hager Theresa , Langgartner Clemens , Kochs Eberhard , Laugwitz Karl-Ludwig , Jungwirth Bettina , Bernlochner Isabell 
Published: August 2017

SummaryThis study evaluates whether immature platelets (IPF) determined in the post anesthesia care unit (PACU) can predict major adverse cardiovascular events (MACE) or other thromboembolic events after intermediate and high-risk surgery. IPF are increased in patients with acute coronary syndrome and recently gained interest as novel biomarker for risk stratification. In this prospective observational trial 732 patients undergoing intermediate or high-risk non-cardiac surgery were enrolled (NCT02097602). IPF was measured preoperatively and postoperatively in the PACU. Primary outcome was a composite endpoint defined as MACE, deep vein thrombosis or pulmonary embolism during hospital stay (modMACE). A cut off for IPF identifying a threshold between a low and high risk for modMACE was calculated by logrank optimization. A multivariate Cox regression was calculated in a forward stepwise manner to assess the relation between this IPF cut off and modMACE as well as other established risk factors (inclusion if p<0.05). Preoperatively, there were no differences in IPF between patients with and without modMACE (3.1% [2.2% – 4.7%](median [interquartile range]) vs. 2.8% [1.9% – 4.3%]. Patients with modMACE (28 of 730 patients; 3.8%) had higher IPF values in the PACU compared to patients without modMACE (3.6% [2.6–6%] vs. 2.9% [2–4.4%]; p=0.011). The optimal cut off of IPF > 5.4% was associated with an increased risk for modMACE after adjustment for covariates (hazard ratio: 2.528; 95% confidence interval: 1.156 to 5.528, p=0.02). In conclusion, IPF is an independent predictor of modMACE after surgery and might improve risk stratification of surgical patients.Institution where the work was performed and funded: Klinikum rechts der Isar der Technischen Universität München, Ismaningerstr. 22, 81675 Munich, Germany.
Idiopathic Ventricular Arrhythmias Originating From the Parietal Band
Authors: Yamada Takumi , Yoshida Naoki , Itoh Taihei , Litovsky Silvio H. , Doppalapudi Harish , McElderry H. Thomas , Kay G. Neal 
Published: August 2017

Backgrounds—
The parietal band is one of the muscle bands in the right ventricle. This study investigated the electrocardiographic and electrophysiological characteristics and ablation outcome of idiopathic ventricular arrhythmias (VAs) originating from the parietal band.

Methods and Results—
We studied 14 patients with idiopathic VA origins in the parietal band among 294 consecutive patients with VA origins in the right ventricle. The QRS morphologies of the parietal band VAs were characterized by a left bundle branch block and left inferior (n=12) or superior (n=2) axis pattern with the presence of a notch in the middle of the QRS in all cases, precordial transition at ≤lead V3 in 7 patients, and a slow QRS onset in 4 patients. During parietal band VAs, a far-field ventricular electrogram with an early activation was always recorded in the His bundle region, regardless of the location of the VA origins. During the catheter ablation, a mean number of 10.4±7.4 radiofrequency applications with a duration of 1099±1034 seconds were delivered. Catheter ablation was successful in 10 patients, and VAs recurred in 4 during a mean follow-up period of 41±24 months. A change in the QRS morphology was observed spontaneously in 4 patients, immediately after the ablation in 4, and at the time of a VA recurrence in 2.

Conclusions—
Idiopathic VAs rarely originated from the parietal band. The catheter ablation of the parietal band VAs was always challenging, requiring a large amount of the radiofrequency energy delivery for a successful ablation with a relatively high recurrence rate.