bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring unmet need for contraception as a point prevalence
Authors: Moreau Caroline , Shankar Mridula , Helleringer Stephane , Becker Stanley 
Published: August 2019

BackgroundThis study proposes a framework to address conceptual concerns with the standard indicator of unmet need for contraception. We define new point prevalence measures of current status (CS) unmet need and CS unmet demand, by linking contraceptive behaviours to pregnancy exposure and to women’s future contraceptive intentions. We explore the difference between standard and CS unmet need and estimate the proportion of women with CS unmet demand, who may be more likely to adopt contraception.MethodsWe use Demographic and Health Survey data from 46 low-income and middle-income countries released between 2010 and 2018. We assess differences in women’s classification between standard and CS unmet need indicators and estimate the percentage of women with CS unmet demand for contraception, defined as the percentage of women with CS unmet need who intend to use contraception in the future.FindingsWe find substantial country-level differences between standard and CS estimates of unmet need, ranging from −8.3% points in Niger to +11.1% points in Nepal. The average predictive value of the standard measure across the 46 countries for identifying prevalent cases of unmet need is 53%. Regardless of indicator (standard or CS), only half of women with unmet need intend to use contraception.InterpretationThe results of this study suggest that the standard measure of unmet need has low predictive value in identifying women with current unmet need. Thus, the standard indicator does not reflect a prevalence estimate of unmet need.
Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden
Authors: Brickley Elizabeth B , Connor Ruth I , Wieland-Alter Wendy F , Collett Marc S , Hartford Marianne , Van Der Avoort Harrie , Boesch Austin W , Weiner Joshua A , Ackerman Margaret E , McKinlay Mark A , Arita Minetaro , Bandyopadhyay Ananda S , Modlin John F , Wright Peter F 
Published: August 2019

BackgroundOur understanding of the acquisition of intestinal mucosal immunity and the control of poliovirus replication and transmission in later life is still emerging.MethodsAs part of a 2011 randomised, blinded, placebo-controlled clinical trial of the experimental antiviral agent pocapavir (EudraCT 2011-004804-38), Swedish adults, aged 18–50 years, who had previously received four doses of inactivated polio vaccine (IPV) in childhood were challenged with a single dose of monovalent oral polio vaccine type 1 (mOPV1). Using faecal samples collected before and serially, over the course of 45 days, after mOPV1 challenge from a subset of placebo-arm participants who did not receive pocapavir (N=12), we investigated the kinetics of the intestinal antibody response to challenge virus by measuring poliovirus type 1-specific neutralising activity and IgA concentrations.ResultsIn faecal samples collected prior to mOPV1 challenge, we found no evidence of pre-existing intestinal neutralising antibodies to any of the three poliovirus serotypes. Despite persistent high-titered vaccine virus shedding and rising serum neutralisation responses after mOPV1 challenge, intestinal poliovirus type 1-specific neutralisation remained low with a titer of ≤18.4 across all time points and individuals. Poliovirus types 1-specific, 2-specific and 3-specific IgA remained below the limit of detection for all specimens collected postchallenge.InterpretationIn contrast to recent studies demonstrating brisk intestinal antibody responses to oral polio vaccine challenge in young children previously vaccinated with IPV, this investigation finds that adults previously vaccinated with IPV have only modest intestinal poliovirus type 1-specific neutralisation and no IgA responses that are measurable in stool samples following documented mOPV1 infection.
Intervention development and treatment success in UK health technology assessment funded trials of physical rehabilitation: a mixed methods analysis
Authors: Goodwin Victoria A , Hill Jacqueline J , Fullam James A , Finning Katie , Pentecost Claire , Richards David A 
Published: August 2019

ObjectivesPhysical rehabilitation is a complex process, and trials of rehabilitation interventions are increasing in number but often report null results. This study aimed to establish treatment success rates in physical rehabilitation trials funded by the National Institute of Health Research Health Technology Assessment (NIHR HTA) programme and examine any relationship between treatment success and the quality of intervention development work undertaken.DesignThis is a mixed methods study.SettingThis study was conducted in the UK.MethodsThe NIHR HTA portfolio was searched for all completed definitive randomised controlled trials of physical rehabilitation interventions from inception to July 2016. Treatment success was categorised according to criteria developed by Djulbegovic and colleagues. Detailed textual data regarding any intervention development work were extracted from trial reports and supporting publications and informed the development of quality ratings. Mixed methods integrative analysis was undertaken to explore the relationship between quantitative and qualitative data using joint displays.ResultsFifteen trials were included in the review. Five reported a definitive finding, four of which were in favour of the ‘new’ intervention. Eight trials reported a true negative (no difference) outcome. Integrative analysis indicated those with lower quality intervention development work were less likely to report treatment success.ConclusionsDespite much effort and funding, most physical rehabilitation trials report equivocal findings. Greater focus on high quality intervention development may reduce the likelihood of a null result in the definitive trial, alongside high quality trial methods and conduct.
Longitudinal study of use and cost of subacromial decompression surgery: the need for effective evaluation of surgical procedures to prevent overtreatment and wasted resources
Authors: Jones Tim , Carr Andrew J , Beard David , Linton Myles-Jay , Rooshenas Leila , Donovan Jenny , Hollingworth William 
Published: August 2019

ObjectivesTo illustrate the need for better evaluation of surgical procedures, we investigated the use and cost of subacromial decompression in England over the last decade compared with other countries and explored how this related to the conduct and outcomes of randomised, placebo-controlled clinical trials.DesignLongitudinal observational study using Hospital Episode Statistics linked to Payment by Results tariffs in England, 2007/2008 to 2016/2017.SettingHospital care in England; Finland; New York State, USA; Florida State, USA and Western Australia.ParticipantsPatients with subacromial shoulder pain.InterventionsSubacromial decompression.Main outcome measuresNational procedure rates, costs and variation between clinical commissioning groups in England.ResultsWithout robust clinical evidence, the use of subacromial decompression in England increased by 91% from 15 112 procedures (30 per 100 000 population) in 2007/2008, to 28 802 procedures (52 per 100 000 population) in 2016/2017, costing over £125 million per year. Rates of use of subacromial decompression are even higher internationally: Finland (131 per 100 000 in 2011), Florida State (130 per 100 000 in 2007), Western Australia (115 per 100 000 in 2013) and New York State (102 per 100 000 in 2006). Two randomised placebo-controlled trials have recently (2018) shown the procedure to be no more effective than placebo or conservative approaches. Health systems appear unable to avoid the rapid widespread use of procedures of unknown effectiveness, and methods for ceasing ineffective treatments are under-developed.ConclusionsWithout good evidence, nearly 30 000 subacromial decompression procedures have been commissioned each year in England, costing over £1 billion since 2007/2008. Even higher rates of procedures are carried out in countries with less regulated health systems. High quality randomised trials need to be initiated before widespread adoption of promising operative procedures to avoid overtreatment and wasted resources, and methods to prevent or desist the use of ineffective procedures need to be expedited.
The prophylactic effects of long-acting granulocyte colony-stimulating factor for febrile neutropenia in newly diagnosed patients with epithelial ovarian cancer: a randomised controlled study
Authors: Li Lei , Ma Shuiqing , Wu Ming , Tan Xianjie , Zhong Sen , Lang Jinghe 
Published: August 2019

ObjectiveThis study explored the prophylactic effects of long-acting granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia (FN) in newly diagnosed patients with epithelial ovarian cancer (EOC).MethodsPatients were randomised into a study group (long-acting G-CSF for all chemotherapy cycles) and a control group (short-acting G-CSF for first cycle and treatment per physician discretion for subsequent cycles) at a ratio of 1:2. The incidences of FN and myelosuppression and the number of clinical visits, medication doses, complete blood count (CBC) tests and adverse events were compared between the two groups. A regression model was used to determine the risk factors for FN.ResultsFrom 30 November 2018 to 1 April 2019, 84 cases were included in the final analysis; there were 24 (28.6%) and 60 (71.4%) patients in the study and control groups, respectively, and 605 chemotherapy cycles. The study group or chemotherapy cycles utilising long-acting G-CSF had significantly fewer utilisations and doses of short-acting G-CSF; clinical visits; CBC tests; and incidences of FN and myelosuppression; and less G-CSF-associated pain. The utilisation of G-CSF was the only independent factor for FN in a binary regression model.ConclusionLong-acting G-CSF could effectively reduce the incidences of FN and myelosuppression and had mild adverse effects in newly diagnosed patients with EOC receiving chemotherapy.Trial registration numberNCT03740464.
Applied holography of the AdS5–Kerr space–time
Authors: McInnes Brett 
Published: August 2019

Asymptotically anti-de Sitter–Kerr black holes (we focus here on the five-dimensional case) are associated holographically with matter at conformal infinity which has a nonzero angular momentum density. It is natural to attempt to associate this angular momentum with the recently discovered vorticity of the plasmas produced in peripheral heavy-ion collisions. We assume that an AdS5–Kerr black hole with angular momentum to mass ratio [Formula: see text] is dual to boundary matter with an angular momentum density to energy density ratio also equal to [Formula: see text]. With this assumption, we find that, for collisions corresponding to a given value of [Formula: see text], there is a maximal possible angular velocity (well below the maximal value permitted by causality) for such matter at infinity, and that this value is in approximate agreement with the experimentally reported value of the average plasma vorticity produced in typical peripheral collisions of heavy ions.
Heart sound classification using machine learning and phonocardiogram
Authors: Arora Vinay , Leekha Rohan , Singh Raman , Chana Inderveer 
Published: August 2019

This research pertains to classification of the heart sound using digital Phonocardiogram (PCG) signals targeted to screen for heart ailments. In this study, an existing variant of the decision tree, i.e. XgBoost has been used with unsegmented heart sound signal. The dataset provided by PhysioNet Computing in Cardiology (CinC) Challenge 2016 has been used to validate the technique proposed in this research work. The said dataset comprises six databases (A–F) having 3240 heart sound recordings in all with the duration lasting from 5–120 s. The approach proposed in this paper has been compared with 18 existing methodologies. The proposed method is accurate with the mean score of 92.9, while sensitivity and specificity scores are 94.5 and 91.3, respectively. The timely prediction of heart health will support specialists to attain useful risk stratification of patients and also assist clinicians in effective decision-making. These predictive facts may serve as a guide to provide improved quality of care to the patients by way of effective treatment planning and monitoring.
Variation in Water Demand Responsiveness to Utility Policies and Weather: A Latent-Class Model
Authors: Stone Janine , Goemans Christopher , Costanigro Marco 
Published: August 2019

Water utilities use demand-side management (DSM) policies to incentivize conservation during shortages. However, because utilities often use DSM policies for the first time during drought, it may be difficult to determine the extent to which policy responsiveness relates to an overall conservation culture, and short-term policy responsiveness may not be generalizable to non-drought periods. This research evaluates the impact of drought and utility policies using 10 years of household-level panel data in the first known application of a fixed-effects, latent-class model [Deb, P and PK Trivedi (2013). Finite mixture for panels with fixed effects. Journal of Econometric Methods, 2(1), 35–51] to water demand data. This flexible estimation approach identifies heterogeneity in policy responsiveness over time as it relates to drought conditions and changes in the utility’s billing structure. Two classes of water demand are identified — one associated with responsiveness to weather and a second with responsiveness to policies. In the class of water demand associated with weather, households are less sensitive to policy changes but exhibit increased sensitivity to precipitation both when the utility is actively promoting conservation (during severe drought) and in post-drought years. Implications for long-term effectiveness of utility conservation policies are discussed.
TEA-sensitive K+ channels and human eccrine sweat gland output
Authors: Mack Gary W. , Smith Benjamin S. , Rowland Benjamin 
Published: August 2019

Cholinergic-activated sweating depends on an influx of Ca2+ from extracellular fluid. It is thought that the opening of K+ channels on secretory epithelial cells facilitates Ca2+ entry. We examined the hypothesis that tetraethylammonium (TEA)-sensitive K+ channels participate in sweat production. We used a pre-post experimental design and initiated cholinergic-mediated sweating with intradermal electrical stimulation, monitored local sweat rate (SR) with a small sweat capsule mounted on the skin, and delivered 50 mM TEA via intradermal microdialysis. Local SR was activated by intradermal stimulation frequencies of 0.2–64 Hz, and we generated a sigmoid-shaped stimulus-response curve by plotting the area under the SR-time curve versus log10 stimulus frequency. Peak local SR was reduced from 0.372 ± 0.331 to 0.226 ± 0.190 mg·min−1·cm−2 ( P = 0.0001) during application of 50 mM TEA, whereas the EC50 and Hill slopes were not altered. The global sigmoid-shaped stimulus-response curves for control and 50 mM TEA were significantly different ( P < 0.0001), and the plateau region was significantly reduced ( P = 0.0023) with the TEA treatment. The effect of TEA on peak local SR was similar in male and female subjects. However, we did note a small effect of sex on the shape of the stimulus-response curves during intradermal electrical stimulation. Overall, these data support the hypothesis that cholinergic control of sweat gland activity is modulated by the presence of TEA-sensitive K+ channels in human sweat gland epithelial cells. NEW & NOTEWORTHY The contribution of various potassium channels to the process of cholinergic-mediated human eccrine sweat production is unclear. Using a novel model for cholinergic-mediated sweating in humans, we provide evidence that tetraethylammonium-sensitive K+ channels (KCa1.1 and Kv channels) contribute to eccrine sweat production.
An investigation of p53 in skeletal muscle aging
Authors: Ebert Scott M. , Dierdorff Jason M. , Meyerholz David K. , Bullard Steven A. , Al-Zougbi Asma , DeLau Austin D. , Tomcheck Kristin C. , Skopec Zachary P. , Marcotte George R. , Bodine Sue C. , Adams Christopher M. 
Published: August 2019

Age-related skeletal muscle atrophy is a very common and serious condition that remains poorly understood at the molecular level. Several lines of evidence have suggested that the tumor suppressor p53 may play a central, causative role in skeletal muscle aging, whereas other, apparently contradictory lines of evidence have suggested that p53 may be critical for normal skeletal muscle function. To help address these issues, we performed an aging study in male muscle-specific p53-knockout mice (p53 mKO mice), which have a lifelong absence of p53 expression in skeletal muscle fibers. We found that the absence of p53 expression in skeletal muscle fibers had no apparent deleterious or beneficial effects on skeletal muscle mass or function under basal conditions up to 6 mo of age, when mice are fully grown and exhibit peak muscle mass and function. Furthermore, at 22 and 25 mo of age, when age-related muscle weakness and atrophy are clearly evident in mice, p53 mKO mice demonstrated no improvement or worsening of skeletal muscle mass or function relative to littermate control mice. At advanced ages, p53 mKO mice began to die prematurely and had an increased incidence of osteosarcoma, precluding analyses of muscle mass and function in very old p53 mKO mice. In light of these results, we conclude that p53 expression in skeletal muscle fibers has minimal if any direct, cell autonomous effect on basal or age-related changes in skeletal muscle mass and function up to at least 22 mo of age.NEW & NOTEWORTHY Previous studies implicated the transcriptional regulator p53 as a potential mediator of age-related skeletal muscle weakness and atrophy. We tested this hypothesis by investigating the effect of aging in muscle-specific p53-knockout mice. Our results strongly suggest that p53 activity within skeletal muscle fibers is not required for age-related skeletal muscle atrophy or weakness.
CDK7 Inhibition Suppresses Castration-Resistant Prostate Cancer through MED1 Inactivation
Authors: Rasool Reyaz ur , Natesan Ramakrishnan , Deng Qu , Aras Shweta , Lal Priti , Sander Effron Samuel , Mitchell-Velasquez Erick , Posimo Jessica M. , Carskadon Shannon , Baca Sylvan C. , Pomerantz Mark M. , Siddiqui Javed , Schwartz Lauren E. , Lee Daniel J. , Palanisamy Nallasivam , Narla Goutham , Den Robert B. , Freedman Matthew L. , Brady Donita C. , Asangani Irfan A. 
Published: August 2019

Abstract

Metastatic castration-resistant prostate cancer (CRPC) is a fatal disease, primarily resulting from the transcriptional addiction driven by androgen receptor (AR). First-line CRPC treatments typically target AR signaling, but are rapidly bypassed, resulting in only a modest survival benefit with antiandrogens. Therapeutic approaches that more effectively block the AR-transcriptional axis are urgently needed. Here, we investigated the molecular mechanism underlying the association between the transcriptional coactivator MED1 and AR as a vulnerability in AR-driven CRPC. MED1 undergoes CDK7-dependent phosphorylation at T1457 and physically engages AR at superenhancer sites, and is essential for AR-mediated transcription. In addition, a CDK7-specific inhibitor, THZ1, blunts AR-dependent neoplastic growth by blocking AR/MED1 corecruitment genome-wide, as well as reverses the hyperphosphorylated MED1-associated enzalutamide-resistant phenotype. In vivo, THZ1 induces tumor regression of AR-amplified human CRPC in a xenograft mouse model. Together, we demonstrate that CDK7 inhibition selectively targets MED1-mediated, AR-dependent oncogenic transcriptional amplification, thus representing a potential new approach for the treatment of CRPC.

Significance:
Potent inhibition of AR signaling is critical to treat CRPC. This study uncovers a driver role for CDK7 in regulating AR-mediated transcription through phosphorylation of MED1, thus revealing a therapeutically targetable potential vulnerability in AR-addicted CRPC.
See related commentary by Russo et al., p. 1490.
This article is highlighted in the In This Issue feature, p. 1469
ASSOCIATION OF TREE COMMUNITIES WITH SOIL PROPERTIES IN A SEMI DECIDUOUS FOREST OF PERLIS, PENINSULAR MALAYSIA
Authors: Zakaria Radhiah , Mohd Said Mohd Nizam , Ibrahim Faridah Hanum 
Published: August 2019

Plant community distribution is associated with environmental factors, particularly, the soil properties of habitats. This study was conducted to determine the effect of soil properties on the association of tree communities within three distinct habitats in a semi-deciduous forest in Perlis State Park (PSP), Perlis.Â Eighteen plots of 40 m Ã— 60 m (0.24 ha each) with sampling areas of 1.92 ha (8 plots) in Setul Formation, 0.96 ha (4 plots) in Granite and 1.44 ha (6 plots) in Kubang Pasu Formation (totalling 4.32 ha) were established at the PSP. All trees with 5.0 cm and above diameter at breast height (dbh) were enumerated, while the top soil samples were collected from each plot for soil analyses. A total of 412 tree species, 207 genera, and 68 families were recorded; 270 tree species from 152 genera and 57 families in the Setul forest; 204 tree species of 130 genera and 50 families in the Granite forest; and 109 tree species from 76 genera and 31 families in the Kubang Pasu forest. Euphorbiaceae was the most represented family at Setul, Granite and Kubang Pasu with 36, 19 and 12 species, respectively. Soil properties significantly varied among the study sites.Â Setul had loam, Kubang Pasu had clay-loam, and Granite had the sandy-loam texture.Â The soils were acidic, and had low to high concentrations of available nutrients. Ordinations using canonical correspondence analysis indicated that the soil factors play an important role in the distribution and diversity of plants in these forest habitats.
Derivation and Validation of a Novel Cardiac Intensive Care Unit Admission Risk Score for Mortality
Authors: Jentzer Jacob C. , Anavekar Nandan S. , Bennett Courtney , Murphree Dennis H. , Keegan Mark T. , Wiley Brandon , Morrow David A. , Murphy Joseph G. , Bell Malcolm R. , Barsness Gregory W. 
Published: August 2019

Background

There are no risk scores designed specifically for mortality risk prediction in unselected cardiac intensive care unit (
CICU
) patients. We sought to develop a novel
CICU
‐specific risk score for prediction of hospital mortality using variables available at the time of
CICU
admission.

Methods and Results

A database of
CICU
patients admitted from January 1, 2007 to April 30, 2018 was divided into derivation and validation cohorts. The top 7 predictors of hospital mortality were identified using stepwise backward regression, then used to develop the Mayo
CICU
Admission Risk Score (M‐
CARS
), with integer scores ranging from 0 to 10. Discrimination was assessed using area under the receiver‐operator curve analysis. Calibration was assessed using the Hosmer–Lemeshow statistic. The derivation cohort included 10 004 patients and the validation cohort included 2634 patients (mean age 67.6 years, 37.7% females). Hospital mortality was 9.2%. Predictor variables included in the M‐
CARS
were cardiac arrest, shock, respiratory failure, Braden skin score, blood urea nitrogen, anion gap and red blood cell distribution width at the time of
CICU
admission. The M‐
CARS
showed a graded relationship with hospital mortality (odds ratio 1.84 for each 1‐point increase in M‐
CARS
, 95%
CI
1.78–1.89). In the validation cohort, the M‐
CARS
had an area under the receiver‐operator curve of 0.86 for hospital mortality, with good calibration (
P
=0.21). The 47.1% of patients with M‐
CARS
<2 had hospital mortality of 0.8%, and the 5.2% of patients with M‐
CARS
>6 had hospital mortality of 51.6%.

Conclusions

Using 7 variables available at the time of
CICU
admission, the M‐
CARS
can predict hospital mortality in unselected
CICU
patients with excellent discrimination.