bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Clinically Relevant Androgen Receptor Mutation Confers Resistance to Second-Generation Antiandrogens Enzalutamide and ARN-509
Authors: Joseph James D. , Lu Nhin , Qian Jing , Sensintaffar John , Shao Gang , Brigham Dan , Moon Michael , Maneval Edna Chow , Chen Isan , Darimont Beatrice , Hager Jeffrey H. 
Published: June 2013

Abstract
Despite the impressive clinical activity of the second-generation antiandrogens enzalutamide and ARN-509 in patients with prostate cancer, acquired resistance invariably emerges. To identify the molecular mechanisms underlying acquired resistance, we developed and characterized cell lines resistant to ARN-509 and enzalutamide. In a subset of cell lines, ARN-509 and enzalutamide exhibit agonist activity due to a missense mutation (F876L) in the ligand-binding domain of the androgen receptor (AR). AR F876L is sufficient to confer resistance to ARN-509 and enzalutamide in in vitro and in vivo models of castration-resistant prostate cancer (CRPC). Importantly, the AR F876L mutant is detected in plasma DNA from ARN-509–treated patients with progressive CRPC. Thus, selective outgrowth of AR F876L is a clinically relevant mechanism of second-generation antiandrogen resistance that can potentially be targeted with next-generation antiandrogens.
Significance: A missense mutation in the ligand-binding domain of the androgen receptor F876L confers resistance to the second-generation antiandrogens enzalutamide and ARN-509 in preclinical models of AR function and prostate cancer and is detected in plasma DNA from ARN-509–treated patients with progressive disease. These results chart a new path for the discovery and development of next-generation antiandrogens that could be coupled with a blood-based companion diagnostic to guide treatment decisions. Cancer Discov; 3(9); 1020–9. ©2013 AACR.
See related commentary by Nelson and Yegnasubramanian, p. 971
This article is highlighted in the In This Issue feature, p. 953
Chinese Medicine Neuroaid Efficacy on Stroke Recovery
Authors: Chen Christopher L.H. , Young Sherry H.Y. , Gan Herminigildo H. , Singh Rajinder , Lao Annabelle Y. , Baroque Alejandro C. , Chang Hui Meng , Hiyadan John Harold B. , Chua Carlos L. , Advincula Joel M. , Muengtaweepongsa Sombat , Chan Bernard P.L. , de Silva H. Asita , Towanabut Somchai , Suwanwela Nijasri C. , Poungvarin Niphon , Chankrachang Siwaporn , Wong K.S. Lawrence , Eow Gaik Bee , Navarro Jose C. , Venketasubramanian Narayanaswamy , Lee Chun Fan , Bousser Marie-Germaine 
Published: June 2013

Background and Purpose—
Previous clinical studies suggested benefit for poststroke recovery when MLC601 was administered between 2 weeks and 6 months of stroke onset. The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study tested the hypothesis that MLC601 is superior to placebo in acute, moderately severe ischemic stroke within a 72-hour time window.

Methods—

This multicenter, double-blind, placebo-controlled trial randomized 1100 patients with a National Institutes of Health
Stroke
Scale score 6 to 14, within 72 hours of onset, to trial medications for 3 months. The primary outcome was a shift in the modified Rankin Scale. Secondary outcomes were modified Rankin Scale dichotomy, National Institutes of Health
Stroke
Scale improvement, difference in National Institutes of Health
Stroke
Scale total and motor scores, Barthel index, and mini-mental state examination. Planned subgroup analyses were performed according to age, sex, time to first dose, baseline National Institutes of Health
Stroke
Scale, presence of cortical signs, and antiplatelet use.

Results—
The modified Rankin Scale shift analysis–adjusted odds ratio was 1.09 (95% confidence interval, 0.86–1.32). Statistical difference was not detected between the treatment groups for any of the secondary outcomes. Subgroup analyses showed no statistical heterogeneity for the primary outcome; however, a trend toward benefit in the subgroup receiving treatment beyond 48 hours from stroke onset was noted. Serious and nonserious adverse events rates were similar between the 2 groups.

Conclusions—
MLC601 is statistically no better than placebo in improving outcomes at 3 months when used among patients with acute ischemic stroke of intermediate severity. Longer treatment duration and follow-up of participants with treatment initiated after 48 hours may be considered in future studies.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00554723.
Sovereign Wealth Funds and Socially Responsible Investing: An Emerging Public Fiduciary
Authors: Richardson Benjamin J. 
Published: June 2013

The dramatic growth of sovereign wealth funds (SWFs) in recent decades has made them a significant phenomenon in global financial markets and raised the prospect of more enlightened investing that respects the environmental underpinnings of economic prosperity. Until the Global Financial Crisis of 2008, the movement for socially responsible investing (SRI) had been the only noteworthy dissenting voice to the traditional complacency about the financial economy’s wider impacts. That financial calamity not only unveiled a systemic malaise in the financial alchemy of the global economy but also highlighted its social and environmental sequelae. The rise of SWFs, several of which are legally mandated to practice SRI, gives hope that states may reclaim some public oversight over finance capitalism.
The purpose of this article is to investigate the governance of some SWFs with a view to assessing their capacity to contribute to environmental sustainability. As public financial institutions empowered by a broader conception of investment that takes account of social and environmental factors, SWFs have the incipient markings of ‘public fiduciaries’. SWFs could provide a novel way to interpolate the public trust environmental responsibilities of the state into the governance of the financial economy. This article focuses on the French and Norwegian SWFs, which arguably have the most comprehensive SRI practices of all SWFs. Both, however, have struggled to reconcile their ethical and financial mandates into a coherent investment philosophy. But their putative fiduciary responsibilities to society through an increasingly long-term investing perspective suggest a new normative direction to reconcile these tensions and to thereby help institutionalize the principles of intergenerational equity and sustainable development in the context of financial markets.
Evaluation of Turbulent Surface Flux Parameterizations over Tall Grass in a Beijing Suburb
Authors: Wang Linlin , Gao Zhiqiu , Pan Zaitao , Guo Xiaofeng , Bou-Zeid Elie 
Published: June 2013

Abstract
Numerical weather and climate prediction systems necessitate accurate land surface–atmosphere fluxes, whose determination typically replies on a suite of parameterization schemes. The authors present a field investigation over tall grass in a Beijing suburb, where the aerodynamic roughness length (z0) and zero-plane displacement height (d) are found to be 0.02 and 0.44 m, respectively (the value of d is close to two-thirds the average grass height during this field experiment). Both z0 and d values are then used as input parameters of an analytic model of flux footprint; the footprint model reveals that eddy-covariance flux measurements are mainly representative of the tall grass surface concerned herein, potential influences from anthropogenic sources in this suburban area notwithstanding. Based on the “fair weather” data (with an energy balance ratio of 0.89), the authors evaluate four parameterizations of turbulent surface fluxes, namely, a total of three traditional “iterative” schemes and one “noniterative” scheme developed recently to reduce computational time. Their performances are intercompared in terms of the estimations of the sensible heat flux and two turbulence components (the friction velocity and temperature scale). In weakly stable to unstable conditions, two schemes are recommended here for their good performance overall; the first scheme stems jointly from the work of Högström and Beljaars and Holtslag, and the second stems from that of Li et al.. For this tall grass surface, the choice of z0/z0h = 100 (z0h is the thermal roughness length) is more appropriate than another choice of 10, because the former produces comparatively accurate sensible heat flux estimations.
A Global Model for the Diapycnal Diffusivity Induced by Internal Gravity Waves
Authors: Olbers Dirk , Eden Carsten 
Published: June 2013

AbstractAn energetically consistent model for the diapycnal diffusivity induced by breaking of internal gravity waves is proposed and tested in local and global settings. The model [Internal Wave Dissipation, Energy and Mixing (IDEMIX)] is based on the spectral radiation balance of the wave field, reduced by integration over the wavenumber space, which yields a set of balances for energy density variables in physical space. A further simplification results in a single partial differential equation for the total energy density of the wave field. The flux of energy to high vertical wavenumbers is parameterized by a functional derived from the wave–wave scattering integral of resonant wave triad interactions, which also forms the basis for estimates of dissipation rates and related diffusivities of ADCP and hydrography fine-structure data. In the current version of IDEMIX, the wave energy is forced by wind-driven near-inertial motions and baroclinic tides, radiating waves from the respective boundary layers at the surface and the bottom into the ocean interior. The model predicts plausible magnitudes and three-dimensional structures of internal wave energy, dissipation rates, and diapycnal diffusivities in rough agreement to observational estimates. IDEMIX is ready for use as a mixing module in ocean circulation models and can be extended with more spectral components.
Predicting Spring Tornado Activity in the Central Great Plains by 1 March
Authors: Elsner James B. , Widen Holly M. 
Published: June 2013

Abstract
The authors illustrate a statistical model for predicting tornado activity in the central Great Plains by 1 March. The model predicts the number of tornado reports during April–June using February sea surface temperature (SST) data from the Gulf of Alaska (GAK) and the western Caribbean Sea (WCA). The model uses a Bayesian formulation where the likelihood on the counts is a negative binomial distribution and where the nonstationarity in tornado reporting is included as a trend term plus first-order autocorrelation. Posterior densities for the model parameters are generated using the method of integrated nested Laplacian approximation (INLA). The model yields a 51% increase in the number of tornado reports per degree Celsius increase in SST over the WCA and a 15% decrease in the number of reports per degree Celsius increase in SST over the GAK. These significant relationships are broadly consistent with a physical understanding of large-scale atmospheric patterns conducive to severe convective storms across the Great Plains. The SST covariates explain 11% of the out-of-sample variability in observed F1–F5 tornado reports. The paper demonstrates the utility of INLA for fitting Bayesian models to tornado climate data.
Facts about FEMA Household Disaster Aid: Examining the 2008 Floods and Tornadoes in Missouri
Authors: Kousky Carolyn 
Published: June 2013

AbstractVery little empirical work has been done on disaster aid in the United States. This paper examines postdisaster grants to households from the Federal Emergency Management Agency in the state of Missouri in 2008, when the state experienced flooding, storms, and tornadoes. The paper answers the following questions: What was the aid for? How much was given? How many people applied for aid? How many households received aid and how many were denied? Why were some applicants denied aid? Is there any relationship between aid received and socioeconomic or demographic characteristics of communities? The paper finds that the majority of aid grants are for very small amounts of money, on the order of a few thousand dollars. Over half of aid applications are denied, often because of ineligible or insufficient damage. The paper provides some important basic information on the nature of disaster grants to households and also generates several hypotheses for future research.
Challenges to using evidence from systematic reviews to stop ineffective practice: an interview study
Authors: Shepperd Sasha , Adams Richard , Hill Alison , Garner Sarah , Dopson Sue 
Published: June 2013

Objectives To examine the challenges to using systematic review evidence to develop guidance for decommissioning ineffective health services, and the problems experienced by clinicians and commissioners when they attempt to implement the evidence from this guidance. Methods Interviews with 23 clinicians and 15 commissioners from nine commissioning organizations (Primary Care Trusts) in the south of England. Results Participants identified generic and intervention-specific barriers to using systematic review evidence to develop and implement decommissioning. Generic barriers included: contradictions within the health care system arising from policy; managing a high volume of evidence; difficulty in applying the evidence to the local context; and patient or parent expectations. Intervention-specific factors included: the influence of industry; an absence of systems for monitoring local implementation of guidance; and the availability of different codes for the same procedure which made monitoring some practices unreliable. Conclusions The micro practices of commissioners are shaped by the wider system of health policy, the knowledge producing and delivery agencies associated with health care, and power dynamics within the health care system. If decommissioning is to be guided by evidence, then adequate resources to support the process are necessary. This includes long-term engagement of clinicians, providing alternatives to the decommissioned activity and tackling perverse incentives. An important precursor to decommissioning is obtaining data on the nature and extent of current clinical practice and using these data to monitor variation in the implementation of guidance.
The effect of psychosocial interventions delivered by telephone and videophone on quality of life in early-stage breast cancer survivors and their supportive partners
Authors: Badger Terry , Segrin Chris , Pasvogel Alice , Lopez Ana Maria 
Published: June 2013

Summary We examined the effectiveness of two psychosocial interventions for improving QOL in recently diagnosed breast cancer survivors and their partners. The interventions were telephone health education (THE) and interpersonal counselling. The latter was delivered by telephone (TC) or by videophone (VC) in 8 weekly one-to-one sessions. Fifty two dyads composed of a woman with breast cancer and her supportive partner were randomly assigned to THE, TC or VC. The average age of the survivors was 53 years (range 40–66), and they were mainly white, married, with a college education, and employed. Approximately half of the supportive partners were spouses. Surveys of quality of life (QOL) were made at three points in the study, each separated by 8 weeks. There was significantly higher attrition in the THE group compared to the videophone or telephone counselling groups among both survivors (44% vs. 10% and 8%) and partners (44% vs. 10% and 15%). Regardless of group, participants showed increased QOL over time. Survivors’ and partners’ social well-being improved in the telephone and videophone interpersonal counselling treatment groups, but not in the health education group. Telephone-delivered psychosocial interventions can be effective for managing QOL in breast cancer survivors and their supportive partners. There was no evidence of superior outcomes associated with using videophones over the conventional telephone.
A 9-year evaluation of temporal trends in alosetron postmarketing safety under the risk management program
Authors: Tong Kenneth , Nicandro Jean Paul , Shringarpure Reshma , Chuang Emil , Chang Lin 
Published: June 2013

Objectives: Adverse events (AEs) of ischemic colitis (IC) and complications of constipation (CoC) associated with alosetron are rare and have been adjudicated during the first 5.5 years of the risk management program (RMP); however, changes in incidence rates relative to reductions in AE reports and increases in alosetron prescriptions over the 9-year RMP have not been evaluated. The authors aim to evaluate temporal trends in alosetron postmarketing safety over the 9-year RMP. Methods: The alosetron safety database was searched to identify cases of IC, CoC, and related AEs from 20 November 2002 to 31 December 2011. Adjudication of IC and CoC cases were based on US Food and Drug Administration-defined criteria. Incidence rates were calculated using the number of AEs and alosetron prescriptions (expressed as cases/1000 patient-years exposure). Results: A total of 29 cases were adjudicated as probable/possible IC and 7 cases were adjudicated as CoC. Cumulative adjudicated incidence rate of IC (1.03 cases/1000 patient-years) is low and stable, while that of CoC (0.25 cases/1000 patient-years) is low, declining progressively over time. Decreases in the incidence rates of potential symptoms of IC (abdominal pain with bloody diarrhea/hematochezia) and CoC (constipation) were also observed. Conclusions: Over the 9-year RMP period, incidence rates of IC and CoC remain rare. Substantial reductions over time were observed in the incidence of CoC and in symptoms suggestive of IC or CoC, while IC incidence has been stable at approximately 1.0 case/1000 patient-years. Decreases in AEs and serious outcomes associated with IC and CoC since the reintroduction of alosetron are likely attributable to the RMP.
Improving PMTCT Uptake in Rural South Africa
Authors: Weiss Stephen M. , Karl Peltzer , Olga Villar-Loubet , Shikwane Molatelo E. , Ryan Cook , Jones Deborah L. 
Published: June 2013

Introduction: Despite the widespread availability of prevention of mother-to-child transmission (PMTCT) programs, many women in sub-Saharan Africa do not participate in PMTCT. This pilot study aimed to utilize partner participation in an intervention to support PMTCT uptake. Methods: Couples (n = 239) were randomized to receive either a comprehensive couples-based PMTCT intervention or the standard of care. Results: Compared to the standard of care, participants receiving the intervention increased HIV- and PMTCT-related knowledge ( F1,474 = 13.94, p = .004) and uptake of PMTCT, as defined by infant medication dosing (74% vs. 46%, χ2 = 4.69, p = .03). Discussion: Results indicate that increasing male attendance at antenatal clinic visits may be “necessary but not sufficient” to increase PMTCT uptake. Increasing HIV knowledge of both partners and encouraging active male participation in the PMTCT process through psychoeducational interventions may be a strategy to increase the uptake of PMTCT in South Africa.
Autosomal and uniparental portraits of the native populations of Sakha (Yakutia): implications for the peopling of Northeast Eurasia
Authors: Fedorova Sardana A , Reidla Maere , Metspalu Ene , Metspalu Mait , Rootsi Siiri , Tambets Kristiina , Trofimova Natalya , Zhadanov Sergey I , Kashani Baharak Hooshiar , Olivieri Anna , Voevoda Mikhail I , Osipova Ludmila P , Platonov Fedor A , Tomsky Mikhail I , Khusnutdinova Elza K , Torroni Antonio , Villems Richard 
Published: June 2013

AbstractBackgroundSakha – an area connecting South and Northeast Siberia – is significant for understanding the history of peopling of Northeast Eurasia and the Americas. Previous studies have shown a genetic contiguity between Siberia and East Asia and the key role of South Siberia in the colonization of Siberia.ResultsWe report the results of a high-resolution phylogenetic analysis of 701 mtDNAs and 318 Y chromosomes from five native populations of Sakha (Yakuts, Evenks, Evens, Yukaghirs and Dolgans) and of the analysis of more than 500,000 autosomal SNPs of 758 individuals from 55 populations, including 40 previously unpublished samples from Siberia. Phylogenetically terminal clades of East Asian mtDNA haplogroups C and D and Y-chromosome haplogroups N1c, N1b and C3, constituting the core of the gene pool of the native populations from Sakha, connect Sakha and South Siberia. Analysis of autosomal SNP data confirms the genetic continuity between Sakha and South Siberia. Maternal lineages D5a2a2, C4a1c, C4a2, C5b1b and the Yakut-specific STR sub-clade of Y-chromosome haplogroup N1c can be linked to a migration of Yakut ancestors, while the paternal lineage C3c was most likely carried to Sakha by the expansion of the Tungusic people. MtDNA haplogroups Z1a1b and Z1a3, present in Yukaghirs, Evens and Dolgans, show traces of different and probably more ancient migration(s). Analysis of both haploid loci and autosomal SNP data revealed only minor genetic components shared between Sakha and the extreme Northeast Siberia. Although the major part of West Eurasian maternal and paternal lineages in Sakha could originate from recent admixture with East Europeans, mtDNA haplogroups H8, H20a and HV1a1a, as well as Y-chromosome haplogroup J, more probably reflect an ancient gene flow from West Eurasia through Central Asia and South Siberia.ConclusionsOur high-resolution phylogenetic dissection of mtDNA and Y-chromosome haplogroups as well as analysis of autosomal SNP data suggests that Sakha was colonized by repeated expansions from South Siberia with minor gene flow from the Lower Amur/Southern Okhotsk region and/or Kamchatka. The minor West Eurasian component in Sakha attests to both recent and ongoing admixture with East Europeans and an ancient gene flow from West Eurasia.