bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interventions to combat or prevent drug counterfeiting: a systematic review
Authors: El-Jardali Fadi , Akl Elie A , Fadlallah Racha , Oliver Sandy , Saleh Nadine , El-Bawab Lamya , Rizk Rana , Farha Aida , Hamra Rasha 
Published: March 2015

ObjectiveDrug counterfeiting has serious public health and safety implications. The objective of this study was to systematically review the evidence on the effectiveness of interventions to combat or prevent drug counterfeiting.Data sourcesWe searched multiple electronic databases and the grey literature up to March 2014. Two reviewers completed, in duplicate and independently, the study selection, data abstraction and risk of bias assessment.Study eligibility criteria, participants and interventionsWe included randomised trials, non-randomised studies, and case studies examining any intervention at the health system-level to combat or prevent drug counterfeiting. Outcomes of interest included changes in failure rates of tested drugs and changes in prevalence of counterfeit medicines. We excluded studies that focused exclusively on substandard, degraded or expired drugs, or that focused on medication errors.Appraisal and synthesisWe assessed the risk of bias in each included study. We reported the results narratively and, where applicable, we conducted meta-analyses.ResultsWe included 21 studies representing 25 units of analysis. Overall, we found low quality evidence suggesting positive effects of drug registration (OR=0.23; 95% CI 0.08 to 0.67), and WHO-prequalification of drugs (OR=0.06; 95% CI 0.01 to 0.35) in reducing the prevalence of counterfeit and substandard drugs. Low quality evidence suggests that licensing of drug outlets is probably ineffective (OR=0.66; 95% CI 0.41 to 1.05). For multifaceted interventions (including a mix of regulations, training of inspectors, public-private collaborations and legal actions), low quality evidence suggest they may be effective. The single RCT provided moderate quality evidence of no effect of ‘two extra inspections’ in improving drug quality.ConclusionsPolicymakers and stakeholders would benefit from registration and WHO-prequalification of drugs and may also consider multifaceted interventions. Future effectiveness studies should address the methodological limitations of the available evidence.Trial registration numberPROSPERO CRD42014009269.
Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial
Authors: Collins Carmel T , Gibson Robert A , Anderson Peter J , McPhee Andrew J , Sullivan Thomas R , Gould Jacqueline F , Ryan Philip , Doyle Lex W , Davis Peter G , McMichael Judy E , French Noel P , Colditz Paul B , Simmer Karen , Morris Scott A , Makrides Maria 
Published: March 2015

ObjectiveTo determine if improvements in cognitive outcome detected at 18 months’ corrected age (CA) in infants born <33 weeks’ gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood.DesignFollow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital.SettingFive Australian tertiary hospitals from 2008 to 2013.Participants626 of the 657 participants randomised between 2001 and 2005 were eligible to participate.InterventionsHigh-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2–4 days until term CA.Primary outcomeFull Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted.Results604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital −0.3, 95% CI −2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet.ConclusionsSupplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years’ CA.Trial registration numberAustralian New Zealand Clinical Trials Registry: ACTRN12606000327583.
PMMA Third-Body Wear after Unicondylar Knee Arthroplasty Decuples the UHMWPE Wear Particle GenerationIn Vitro
Authors: Paulus Alexander Christoph , Franke Manja , Kraxenberger Michael , Schröder Christian , Jansson Volkmar , Utzschneider Sandra 
Published: March 2015

Introduction. Overlooked polymethylmethacrylate after unicondylar knee arthroplasty can be a potential problem, since this might influence the generated wear particle size and morphology. The aim of this study was the analysis of polyethylene wear in a knee wear simulator for changes in size, morphology, and particle number after the addition of third-bodies.Material and Methods. Fixed bearing unicondylar knee prostheses (UKA) were tested in a knee simulator for 5.0 million cycles. Following bone particles were added for 1.5 million cycles, followed by 1.5 million cycles with PMMA particles. A particle analysis by scanning electron microscopy of the lubricant after the cycles was performed. Size and morphology of the generated wear were characterized. Further, the number of particles per 1 million cycles was calculated for each group.Results. The particles of all groups were similar in size and shape. The number of particles in the PMMA group showed 10-fold higher values than in the bone and control group (PMMA:10.251×1012; bone:1.145×1012; control:1.804 × 1012).Conclusion. The addition of bone or PMMA particles in terms of a third-body wear results in no change of particle size and morphology. PMMA third-bodies generated tenfold elevated particle numbers. This could favor an early aseptic loosening.
Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites
Authors: Kluger Harriet M. , Zito Christopher R. , Barr Meaghan L. , Baine Marina K. , Chiang Veronica L.S. , Sznol Mario , Rimm David L. , Chen Lieping , Jilaveanu Lucia B. 
Published: March 2015

Abstract
Purpose: Programmed death ligand-1 (PD-L1) tumor expression represents a mechanism of immune escape for melanoma cells. Drugs blocking PD-L1 or its receptor have shown unprecedented activity in melanoma, and our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in metastatic melanomas.
Experimental Design: We used a tissue microarray (TMA) consisting of two cores from 95 metastatic melanomas characterized for clinical stage, outcome, and anatomic site of disease. We assessed PD-L1 expression and tumor-infiltrating lymphocyte (TIL) content (total T cells and CD4/CD8 subsets) by quantitative immunofluorescence.
Results: High PD-L1 expression was associated with improved survival (P = 0.02) and higher T-cell content (P = 0.0005). Higher T-cell content (total and CD8 cells) was independently associated with improved overall survival; PD-L1 expression was not independently prognostic. High TIL content in extracerebral metastases was associated with increased time to developing brain metastases (P = 0.03). Cerebral and dermal metastases had slightly lower PD-L1 expression than other sites, not statistically significant. Cerebral metastases had less T cells (P = 0.01).
Conclusions: T-cell–infiltrated melanomas, particularly those with high CD8 T-cell content, are more likely to be associated with PD-L1 expression in tumor cells, an improved prognosis, and increased time to development of brain metastases. Studies of T-cell content and subsets should be incorporated into trials of PD-1/PD-L1 inhibitors to determine their predictive value. Furthermore, additional studies of anatomic sites with less PD-L1 expression and T-cell infiltrate are needed to determine if discordant responses to PD-1/PD-L1 inhibitors are seen at those sites. Clin Cancer Res; 21(13); 3052–60. ©2015 AACR.
Acute phase treatment of venous thromboembolism: advanced therapy
Authors: Wärntges Simone , Konstantinides Stavros V. 
Published: March 2015

SummaryVenous thromboembolism, which encompasses deep-vein thrombosis and acute pulmonary embolism (PE), represents a major contributor to global disease burden worldwide. For patients who present with cardiogenic shock or persistent hypotension (acute high-risk PE), there is consensus that immediate reperfusion treatment applying systemic fibrinolysis or, in the case of a high bleeding risk, surgical or catheterdirected techniques, is indicated. On the other hand, for the large, heterogeneous group of patients presenting without overt haemodynamic instability, the indications for advanced therapy are less clear. The recently updated guidelines of the European Society of Cardiology emphasise the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for distinguishing between an intermediate and a low risk for an adverse early outcome. In intermediate-high-risk PE defined by the presence of both right ventricular dysfunction on echocardiography (or computed tomography) and a positive troponin (or natriuretic peptide) test, the bleeding risks of full-dose fibrinolytic treatment have been shown to outweigh its potential clinical benefits unless clinical signs of haemodynamic decompensation appear (rescue fibrinolysis). Recently published trials suggest that catheter-directed, ultrasoundassisted, low-dose local fibrinolysis may provide an effective and particularly safe treatment option for some of these patients.
A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran
Authors: Moschetti Viktoria , Norris Stephen , Stangier Joachim , Schmohl Michael , Ryn Joanne van , Lang Benjamin , Ramael Steven , Reilly Paul , Glund Stephan 
Published: March 2015

SummaryIdarucizumab, a monoclonal antibody fragment that binds dabigatran with high affinity, is in development as a specific antidote for dabigatran. In this first-in-human, single-rising-dose study, we investigated the pharmacokinetics, safety and tolerability of idarucizumab. Healthy male volunteers aged 18–45 years received between 20 mg and 8 g idarucizumab as a 1-hour intravenous infusion in 10 sequential dose groups, or 1, 2 or 4 g idarucizumab as a 5-minute infusion. Subjects within each dose group were randomised 3:1 to idarucizumab or placebo. A total of 110 randomised subjects received study drug (27 placebo, 83 idarucizumab). Peak and total exposure to idarucizumab increased proportionally with dose. Maximum plasma concentrations were achieved near the end of infusion, followed by a rapid decline, with an initial idarucizumab half-life of ∼45 minutes. For the 5-minute infusions, this resulted in a reduction of plasma concentrations to less than 5 % of peak within 4 hours. Idarucizumab (in the absence of dabigatran) had no effect on coagulation parameters or endogenous thrombin potential. Overall adverse event (AE) frequency was similar for idarucizumab and placebo, and no relationship with idarucizumab dose was observed. Drug-related AEs (primary endpoint) were rare (occurring in 2 placebo and 3 idarucizumab subjects) and were mostly of mild intensity; none of them resulted in study discontinuation. In conclusion, the pharmacokinetic profile of idarucizumab meets the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. Idarucizumab was safe and well tolerated in healthy males.Clinical trial registration: http://clinicaltrials.gov/ct2/show/NCT01688830?term=NCT01688830&rank=1 (NCT01688830).
Variability and Trends in U.S. Cloud Cover: ISCCP, PATMOS-x, and CLARA-A1 Compared to Homogeneity-Adjusted Weather Observations
Authors: Sun Bomin , Free Melissa , Yoo Hye Lim , Foster Michael J. , Heidinger Andrew , Karlsson Karl-Göran 
Published: March 2015

Abstract
Variability and trends in total cloud cover for 1982–2009 across the contiguous United States from the International Satellite Cloud Climatology Project (ISCCP), AVHRR Pathfinder Atmospheres–Extended (PATMOS-x), and EUMETSAT Satellite Application Facility on Climate Monitoring Clouds, Albedo and Radiation from AVHRR Data Edition 1 (CLARA-A1) satellite datasets are assessed using homogeneity-adjusted weather station data. The station data, considered as “ground truth” in the evaluation, are generally well correlated with the ISCCP and PATMOS-x data and with the physically related variables diurnal temperature range, precipitation, and surface solar radiation. Among the satellite products, overall, the PATMOS-x data have the highest interannual correlations with the weather station cloud data and those other physically related variables. The CLARA-A1 daytime dataset generally shows the lowest correlations, even after trends are removed. For the U.S. mean, the station dataset shows a negative but not statistically significant trend of −0.40% decade−1, and satellite products show larger downward trends ranging from −0.55% to −5.00% decade−1 for 1984–2007. PATMOS-x 1330 local time trends for U.S. mean cloud cover are closest to those in the station data, followed by the PATMOS-x diurnally corrected dataset and ISCCP, with CLARA-A1 having a large negative trend contrasting strongly with the station data. These results tend to validate the usefulness of weather station cloud data for monitoring changes in cloud cover, and they show that the long-term stability of satellite cloud datasets can be assessed by comparison to homogeneity-adjusted station data and other physically related variables.
Realizing Surface-Driven Flows in the Primitive Equations
Authors: Bembenek Eric , Poulin Francis J. , Waite Michael L. 
Published: March 2015

AbstractThe surface quasigeostrophic (SQG) model describes flows with surface buoyancy perturbations with no interior quasigeostrophic potential vorticity at small Rossby number Ro and O(1) Burger number, where quasigeostrophic dynamics are expected to hold. Numerical simulations of SQG dynamics have shown that vortices are frequently generated at small scales, which may have O(1) Rossby numbers and therefore may be beyond the limits of SQG. This paper examines the dynamics of an initially geostrophically balanced elliptical surface buoyancy perturbation in both the SQG model and the nonhydrostatic Boussinesq primitive equations (PE). In the case of very small Rossby number, it is confirmed that both models agree, as expected. For larger Ro, non-SQG effects emerge and as a result the solution of the PE deviates significantly from that of SQG. In particular, an increase in the Rossby number has the following effects: (i) the buoyancy filaments at the surface are stabilized in that they generate fewer secondary vortices; (ii) the core of the vortex experiences inertial instability, which results in a uniform buoyancy profile in its interior; (iii) the divergent part of the energy spectrum increases in magnitude; (iv) the PE model has significantly more gravity waves that are radiated from the vortex; (v) the magnitude of the vertical velocity increases; and (vi) in the mature stages of evolution, there are gravitational instabilities that develop because of the complicated dynamics inside the vortex. It is demonstrated that significant non-SQG effects are evident when the large-scale Rossby number of the initial flow is about 0.05 and the local Rossby number is O(1).
The Role of Observed Environmental Conditions and Precipitation Evolution in the Rapid Intensification of Hurricane Earl (2010)
Authors: Susca-Lopata Gabriel , Zawislak Jonathan , Zipser Edward J. , Rogers Robert F. 
Published: March 2015

Abstract
An investigation into the possible causes of the rapid intensification (RI) of Hurricane Earl (2010) is carried out using a combination of global analyses, aircraft Doppler radar data, and observations from passive microwave satellites and a long-range lightning network. Results point to an important series of events leading to, and just after, the onset of RI, all of which occur despite moderate (7–12 m s−1) vertical wind shear present. Beginning with an initially vertically misaligned vortex, observations indicate that asymmetric deep convection, initially left of shear but not distinctly up- or downshear, rotates into more decisively upshear regions. Following this convective rotation, the vortex becomes aligned and precipitation symmetry increases. The potential contributions to intensification from each of these structural changes are discussed.
The radial distribution of intense convection relative to the radius of maximum wind (RMW; determined from Doppler wind retrievals) is estimated from microwave and lightning data. Results indicate that intense convection is preferentially located within the upper-level (8 km) RMW during RI, lending further support to the notion that intense convection within the RMW promotes tropical cyclone intensification. The distribution relative to the low-level RMW is more ambiguous, with intense convection preferentially located just outside of the low-level RMW at times when the upper-level RMW is much greater than the low-level RMW.
Novel Mutations in LRTOMT Associated With Moderate Progressive Hearing Loss in Autosomal Recessive Inheritance
Authors: Ichinose Aya , Moteki Hideaki , Hattori Mitsuru , Nishio Shin-ya , Usami Shin-ichi 
Published: March 2015

Objective: We present a patient who was identified with novel mutations in the LRTOMT gene and describe the clinical features of the phenotype including serial audiological findings. Methods: One hundred six Japanese patients with mild to moderate sensorineural hearing loss from unrelated and nonconsanguineous families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were performed to identify the genetic cause of hearing loss. Results: Compound heterozygotes with a novel frame-shift mutation and a missense mutation were identified in the LRTOMT gene. The mutated residues were segregated in both alleles of LRTOMT, present within the LRTOMT2 protein coding region. The patient had moderate sloping hearing loss at high frequencies, which progressed at 1000 Hz and higher frequencies over a period of 6 years. Conclusion: Hearing loss caused by mutations in the LRTOMT gene is extremely rare. This is the first case report of a compound heterozygous mutation in a nonconsanguineous family.
Decreased regional activity and network homogeneity of the fronto-limbic network at rest in drug-naive major depressive disorder
Authors: Guo Wenbin , Liu Feng , Yu Miaoyu , Zhang Jian , Zhang Zhikun , Liu Jianrong , Xiao Changqing , Zhao Jingping 
Published: March 2015

Objective: The fronto-limbic network is implicated in the neurobiology of major depressive disorder. However, no studies are designed to assess directly the abnormalities of regional activity and network homogeneity of this network in major depressive disorder. Methods: A total of 44 drug-naive major depressive disorder patients and 44 healthy controls participated in the study, and resting-state functional magnetic resonance imaging data were obtained. The fractional amplitude of low-frequency fluctuations and network homogeneity methods were employed to analyze the data. Results: Compared with the controls, the patients exhibited reduced fractional amplitude of low-frequency fluctuations in the right middle frontal gyrus (orbital part) and decreased network homogeneity in the left middle frontal gyrus. There was no correlation between abnormal fractional amplitude of low-frequency fluctuations/network homogeneity and clinical variables. Conclusions: Our findings suggest that decreased regional activity and network homogeneity in the frontal cortex may be the key impairment of the fronto-limbic network in major depressive disorder, and thus highlight the importance of the fronto-limbic network in the neurobiology of major depressive disorder.
Når mor ikke vil spise – Etiske dilemmaer i møte med underernærte mennesker med demens i sykehjem
Authors: Kuven Britt Moene , Giske Tove 
Published: March 2015

Aim This article explores the ethical dilemmas nurses in nursing homes experience when caring for malnourished patents with dementia. The background for the study is the increasing number of patients with dementia in nursing homes in Norway, and the growing awareness of malnutrition amongst these patients. Method The study has a qualitative, descriptive design. Data came from four focus group interviews with 15 nurses working with patients with dementia from six different nursing homes. The transcribed interviews were analysed and five ethical dilemmas were identified. Findings The ethical dilemmas were: ‘Guilty conscience or abuse against patient’, ‘To take account of patient or relatives’, ‘Professional judgment or national guidelines’, ‘Busy times lead to weight loss for patients’ and ‘Reflection with colleagues or professional uncertainty’. Conclusion By understanding and articulating ethical dilemmas nurses experience in caring for undernourished patients with dementia, these challenges can be better dealt with. By reflecting upon the various forms of pressure nurses face in every day practice, they can be better prepared to act for the benefit of malnourished patients with dementia.