bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substandard and falsified medicines in the UK: a retrospective review of drug alerts (2001–2011)
Authors: Almuzaini Tariq , Sammons Helen , Choonara Imti 
Published: July 2013

ObjectiveTo determine the extent of substandard and falsified medicines in the UK.DesignA retrospective review of drug alerts and company-led recalls.SettingThe Medicines and Healthcare Products Regulatory Agency (MHRA) website search for drug alerts issued between 2001 and 2011.Eligibility criteriaDrug alerts related to quality defect in medicinal products.Main outcome measureRelevant data about defective medicines reported in drug alerts and company-led recalls, including description of the defect, type of formulation, year of the alert and category of the alert.ResultsThere were 280 substandard medicines of which 222 were recalled. The two most frequent problems were contamination (74 incidents) and issues related to packaging (98 incidents). Formulations for parenteral administration (117 incidents) were the formulation most frequently affected. There were 11 falsified medicines, as defined by the MHRA, reported over the 11-year period. The number of defective medicines reported by the MHRA increased 10-fold from 5 in 2001 to 50 in 2011.ConclusionsSubstandard medicines are a significant problem in the UK. It is uncertain whether the increasing number of reports relates to improved detection or an increase in the number of substandard medicines.
Opportunities and challenges for enhancing preconception health in primary care: qualitative study with women from ethnically diverse communities
Authors: Tuomainen Helena , Cross-Bardell Laura , Bhoday Mandeep , Qureshi Nadeem , Kai Joe 
Published: July 2013

Objective There is a growing interest in developing and offering more systematic preconception healthcare. However, it is unclear how this might be regarded by ethnically diverse communities at higher risk of poor maternal and child health outcomes. We sought to explore perceptions about preconception health and care among women from these communities to identify opportunities and challenges for intervention development in primary care.DesignQualitative study using focus groups and semistructured interviews.SettingEthnically diverse and socially disadvantaged community settings of the UK.Participants41 women aged 18–45 years, of Pakistani, Indian, Caribbean, African, White and mixed ethnic origin, participating in nine focus groups, half of whom (n=19) had one-to-one follow-up telephone interviews.ResultsWomen had modest or poor awareness of preconception health issues. They perceived these could be addressed in primary care, particularly if raised within a range of clinically ‘relevant’ consultations, such as for contraception, or when opportune for individuals in their social context. However, challenges for engaging women in preconception care more routinely were underlined. These included little prevailing culture of preparing for pregnancy and the realities of their pregnancies often being unplanned; and, for those planning pregnancy, sensitivity and maintaining secrecy when trying to conceive. A preference for female professionals, engaging men, and enhancing access for younger people or women less disposed to general practice, in educational and other settings were highlighted.ConclusionsRaising preconception health when this has heightened clinical or social resonance for women may hold promise for initiating more systematic intervention. In primary care this could offer greater potential to directly engage those with low awareness or not considering pregnancy, while enlarging opportunity for others who may be seeking to conceive. Promoting ‘preparation for pregnancy’ more widely might form part of healthcare and education over the life course. Further intervention development research exploring these possibilities, including their feasibility and acceptability is needed.
Thread-based multi-engine model checking for multicore platforms
Authors: Cabodi Gianpiero , Nocco Sergio , Quer Stefano 
Published: July 2013

This article describes a multithreaded, portfolio-based approach to model checking, where multiple cores are exploited as the underlying computing framework to support concurrent execution of cooperative engines.

We introduce a portfolio-based approach to model checking. Our portfolio is first driven by an approximate runtime predictor that provides a heuristic approximation to a
perfect oracle
and suggests which engines are more suitable for each verification instance. Scalability and robustness of the overall model-checking effort highly rely on a concurrent, multithreaded model of execution.

Following similar approaches in related application fields, we dovetail data partitioning, focused on proving several properties in parallel, and engine partitioning, based on concurrent runs of different model-checking engines competing for completion of the same problem.
We investigate concurrency not only to effectively exploit several available engines, which operate independently, but also to show that a cooperative effort is possible. In this case, we adopt a straightforward, light-weight, model of inter-engine communication and data sharing.
We provide a detailed description of the ideas, algorithms, and experimental results obtained on the benchmarks from the Hardware Model Checking Competition suites (HWMCC'10 and HWMCC'11).
Multi-core systems modeling for formal verification of parallel algorithms
Authors: Desnoyers Mathieu , McKenney Paul E. , Dagenais Michel R. 
Published: July 2013

Modeling parallel algorithms at the architecture level enables exploring side-effects of the weakly ordered nature of modern processors. Formal verification of such models with model-checking can ensure that algorithm guarantees will hold even in the presence of the most aggressive compiler and processor optimizations.
This paper proposes a virtual architecture to model the effects of such optimizations. It first presents the OoOmem framework to model out-of-order memory accesses. It then presents the OoOisched framework to model the effects of out-of-order instruction scheduling.
These two frameworks are explained and tested using weaklyordered memory interaction scenarios known to be affected by weak ordering. Then, modeling of user-level RCU (Read- Copy Update) synchronization algorithms is presented. It uses the virtual architecture proposed to verify that the RCU guarantees are indeed respected.
Glycolysis Inhibition Sensitizes Non–Small Cell Lung Cancer with T790M Mutation to Irreversible EGFR Inhibitors via Translational Suppression of Mcl-1 by AMPK Activation
Authors: Kim Sun Mi , Yun Mi Ran , Hong Yun Kyoung , Solca Flavio , Kim Joo-Hang , Kim Hyun-Jung , Cho Byoung Chul 
Published: July 2013

Abstract
The secondary EGF receptor (EGFR) T790M is the most common mechanism of resistance to reversible EGFR-tyrosine kinase inhibitors (TKI) in patients with non–small cell lung cancer (NSCLC) with activating EGFR mutations. Although afatinib (BIBW2992), a second-generation irreversible EGFR-TKI, was expected to overcome the acquired resistance, it showed limited efficacy in a recent phase III clinical study. In this study, we found that the inhibition of glycolysis using 2-deoxy-d-glucose (2DG) improves the efficacy of afatinib in H1975 and PC9-GR NSCLC cells with EGFR T790M. Treatment with the combination of 2DG and afatinib induced intracellular ATP depletion in both H1975 and PC9-GR cells, resulting in activation of AMP-activated protein kinase (AMPK). AMPK activation played a central role in the cytotoxicity of the combined treatment with 2DG and afatinib through the inhibition of mTOR. The alteration of the AMPK/mTOR signaling pathway by the inhibition of glucose metabolism induced specific downregulation of Mcl-1, a member of the antiapoptotic Bcl-2 family, through translational control. The enhancement of afatinib sensitivity by 2DG was confirmed in the in vivo PC9-GR xenograft model. In conclusion, this study examined whether the inhibition of glucose metabolism using 2DG enhances sensitivity to afatinib in NSCLC cells with EGFR T790M through the regulation of the AMPK/mTOR/Mcl-1 signaling pathway. These data suggest that the combined use of an inhibitor of glucose metabolism and afatinib is a potential therapeutic strategy for the treatment of patients with acquired resistance to reversible EGFR-TKIs due to secondary EGFR T790M. Mol Cancer Ther; 12(10); 2145–56. ©2013 AACR.
Regional Climate Projections of Extreme Heat Events in Nine Pilot Canadian Communities for Public Health Planning
Authors: Casati Barbara , Yagouti Abderrahmane , Chaumont Diane 
Published: July 2013

AbstractPublic health planning needs the support of evidence-based information on current and future climate, which could be used by health professionals and decision makers to better understand and respond to the health impacts of extreme heat. Climate models provide information regarding the expected increase in temperatures and extreme heat events with climate change and can help predict the severity of future health impacts, which can be used in the public health sector for the development of adaptation strategies to reduce heat-related morbidity and mortality. This study analyzes the evolution of extreme temperature indices specifically defined to characterize heat events associated with health risks, in the context of a changing climate. The analysis is performed by using temperature projections from the Canadian Regional Climate Model. A quantile-based statistical correction is applied to the projected temperatures, in order to reduce model biases and account for the representativeness error. Moreover, generalized Pareto distributions are used to extend the temperature distribution upper tails and extrapolate the statistical correction to extremes that are not observed in the present but that might occur in the future. The largest increase in extreme daytime temperatures occurs in southern Manitoba, Canada, where the already overly dry climate and lack of soil moisture can lead to an uncontrolled enhancement of hot extremes. The occurrence of warm nights and heat waves, on the other hand, is already large and will increase substantially in the communities of the Great Lakes region, characterized by a humid climate. Impact and adaptation studies need to account for the temperature variability due to local effects, since it can be considerably larger than the model natural variability.
An Evaluation of the Software System Dependency of a Global Atmospheric Model
Authors: Hong Song-You , Koo Myung-Seo , Jang Jihyeon , Esther Kim Jung-Eun , Park Hoon , Joh Min-Su , Kang Ji-Hoon , Oh Tae-Jin 
Published: July 2013

Abstract
This study presents the dependency of the simulation results from a global atmospheric numerical model on machines with different hardware and software systems. The global model program (GMP) of the Global/Regional Integrated Model system (GRIMs) is tested on 10 different computer systems having different central processing unit (CPU) architectures or compilers. There exist differences in the results for different compilers, parallel libraries, and optimization levels, primarily a result of the treatment of rounding errors by the different software systems. The system dependency, which is the standard deviation of the 500-hPa geopotential height averaged over the globe, increases with time. However, its fractional tendency, which is the change of the standard deviation relative to the value itself, remains nearly zero with time. In a seasonal prediction framework, the ensemble spread due to the differences in software system is comparable to the ensemble spread due to the differences in initial conditions that is used for the traditional ensemble forecasting.
Value of Magnetic Resonance Diffusion‐Weighted Imaging for the Prediction of Radiosensitivity in Nasopharyngeal Carcinoma
Authors: Hong Jinsheng , Yao Yiqi , Zhang Yu , Tang Tianlan , Zhang Hao , Bao Daoliang , Chen Yunbin , Pan Jianji 
Published: July 2013

ObjectiveThe effectiveness of radiotherapy in nasopharyngeal carcinoma (NPC) is closely related to the radiosensitivity of the carcinoma; however, there is currently no effective method to predict radiosensitivity in NPC. We explored the predictive value of magnetic resonance diffusion‐weighted imaging (MR‐DWI) for radiosensitivity in NPC.Study DesignProspective cohort study.SettingSingle hospital.Subjects and MethodsPatients with NPC who received intensity‐modulated radiotherapy (IMRT) with or without chemotherapy were enrolled from April 2010 through November 2011. Primary tumor apparent diffusion coefficient (ADC) was measured before treatment (ADC0) and 2 weeks after the start of IMRT (ADC1). ADC change (ΔADC) was calculated as (ADC1 – ADC0)/ADC0 * 100%. Three months after the end of radiotherapy, the short‐term effect of radiotherapy was assessed using the World Health Organization's response evaluation criteria in solid tumors.ResultsOf 134 eligible NPC patients, 121 received combination chemotherapy. Three months after radiotherapy, residual local tumors were detected in 23 (17.2%) cases, and no residual tumors were detected in 111 (82.8%) cases. There was no significant difference in the residual tumor rates of patients receiving combination chemotherapy vs those who did not (P = 1.000). There were no significant differences in the ADC0 or ADC1 values of patients with and without residual tumors (P =. 083 and. 262). The ΔADC values of patients with (49.77% ± 31.02%) and without (68.35% ± 34.22%) residual tumors were significantly different (t = −2.406, P =. 017). Logistic regression analysis indicated that ΔADC was an independent prognostic factor for the short‐term effect of IMRT in NPC.ConclusionMagnetic resonance diffusion‐weighted imaging may potentially have value for predicting radiosensitivity in NPC.
After-hours physician care for patients with do-not-resuscitate orders: An observational cohort study
Authors: Hsu Nin-Chieh , Chang Ray-E , Tsai Hung-Bin , Lin Yu-Feng , Shu Chin-Chung , Ko Wen-Je , Yu Chong-Jen 
Published: July 2013

Background: Medical care at night for patients with do-not-resuscitate orders and the practice patterns of the on-call residents have rarely been reported. Aim: To evaluate the after-hours physician care for patients with do-not-resuscitate orders in the general medicine ward. Design: Observational study. Setting/participants: This study was conducted at an urban, university-affiliated academic medical center in Taiwan. The night shift nurses consecutively recorded every event that required calling the duty residents. Patients with and without a do-not-resuscitate order were compared in demographics, reasons for calling, residents’ response, and nurses’ satisfaction. A standard report form was established for the nurses to record events. Results: From October 2009 to September 2010, 1379 inpatients contributed to 456 after-hours calls. do-not-resuscitate patients accounted for 256 (18.7%) of all inpatients, and 160 (35.1%) of all after-hours calls. The leading reason for calls was abnormal vital signs, which was significantly higher for patients with do-not-resuscitate orders compared to patients without a do-not-resuscitate order (64.4% vs 36.1%, p < 0.001). The pattern of residents’ responses showed a significant difference with more bedside visits for patients with do-not-resuscitate orders ( p < 0.001). The nurses were usually satisfied with the residents’ management of both groups. Conclusion: Abnormal vital sign, rather than symptom, was the leading reason for after-hours calls. The existence of do-not-resuscitate order produced different medical needs and physician workload. Patients with do-not-resuscitate orders accounted for one-third of night calls and nearly half of bedside visits by on-call residents and may require a different care approach.
MRI-guided stereotactic aspiration of brain abscesses by use of an optical tracking navigation system
Authors: Lü Yubo , Li Chengli , Liu Ming , Fritz Jan , Carrino John A , Wu Lebin , Zhao Bin 
Published: July 2013

Background Owing to the high risk of abscess drainage by craniotomy, imaging-guided stereotactic aspiration is considered an ideal choice in the management of brain abscesses. Interventional magnetic resonance imaging (MRI) represents a valuable technique for the treatment of brain abscess as a guiding modality. Purpose To evaluate the safety and efficacy of an interventional MRI system in performing the procedure. Material and Methods Thirteen brain abscesses in 11 patients were treated with percutaneous aspiration. All procedures were performed solely under the guidance of a 0.23-T open-configuration MRI scanner with optical tracking. Clinical and imaging follow-up was at 1 week, 1 month, 3 months, and 6 months. The changes of abscess, MRI features, and clinical symptoms were recorded. Procedure efficacy and safety were evaluated by success rate, procedure time, decrease of abscess, recovery rate, and complication. Descriptive statistical analysis was performed. Results MRI-guided stereotactic aspirations were performed successfully in 13/13 (100%) abscesses. The mean operating time was 70 min (range, 45–100 min). Follow-up MRI at 1 week after the procedure showed average reduction of abscesses by 60% (2.1/3.5). And the abscesses continued to get smaller by up to 89.7% (3.14/3.5) at 1-month follow-up. All cavities resolved at the end of the 6-month follow-up period. The recovery rate was 100% for fever, headache, vomiting, papilledema, meningismus, altered sensorium, 75% (3/4) for hemiparesis, and 83.3% (5/6) for epilepsy. There were no complications. Conclusion Punctures of brain abscesses with subsequent aspiration can be performed safely and efficiently by monitoring the procedure using an open interventional MRI system.
Interference of silica nanoparticles with the traditional Limulus amebocyte lysate gel clot assay
Authors: Kucki Melanie , Cavelius Christian , Kraegeloh Annette 
Published: July 2013

Endotoxin contaminations of engineered nanomaterials can be responsible for observed biological responses, especially for misleading results in in vitro test systems, as well as in vivo studies. Therefore, endotoxin testing of nanomaterials is necessary to benchmark their influence on cells. Here, we tested the traditional Limulus amebocyte lysate gel clot assay for the detection of endotoxins in nanoparticle suspensions with a focus on possible interference of the particles with the test system. We systematically investigated the effects of nanomaterials made of, or covered by, the same material. Different types of bare or PEGylated silica nanoparticles, as well as iron oxide–silica core shell nanoparticles, were tested. Detailed inhibition/enhancement controls revealed enhanced activity in the Limulus coagulation cascade for all particles with bare silica surface. In comparison, PEGylation led to a lower degree of enhancement. These results indicate that the protein–particle interactions are the basis for the observed inhibition and enhancement effects. The enhancement activity of a particle type was positively related to the calculated particle surface area. For most silica particles tested, a dilution of the sample within the maximum valid dilution was sufficient to overcome non-valid enhancement, enabling semi-quantification of the endotoxin contamination.
Pathways of volcanic glass alteration in laboratory experiments through inorganic and microbially-mediated processes
Authors: Cuadros J. , Afsin B. , Jadubansa P. , Ardakani M. , Ascaso C. , Wierzchos J. 
Published: July 2013

AbstractRhyolitic obsidian was reacted with natural waters to study the effect of water chemistry and biological activity on the composition and formation mechanisms of clay. Two sets of experiments (18 months, 6 years) used fresh, hypersaline water (Mg-Na-SO4-Cl- and NaCl-rich) and seawater. The 6-year experiments produced the transformation of obsidian into quartz, apparently by in situ re-crystallization (Cuadros et al., 2012). The most abundant neoformed clay was dioctahedral (typically montmorillonite), indicating chemical control by the glass (where Al > Mg). Altered glass morphology and chemistry in the 18-months experiments indicated in situ transformation to clay. Magnesium-rich (saponite) clay formed under water-chemistry control in the bulk and within biofilms with elevated Mg concentration (Cuadros et al., 2013). The contact between microbial structures and glass was very intimate. Glass transformation into quartz may be due to some characteristic of the obsidian and/or alteration conditions. Such combination needs not to be uncommon in nature and opens new possibilities of quartz origin.
Smectite contents of road aggregates derived from crushed volcanic rocks and their impact on the durability of road pavements
Authors: Stanjek H. , Glasmann R. , Hellmann A. 
Published: July 2013

AbstractBasalts and other mafic rocks are frequently used for road construction. The aggregates have to provide intrinsic mechanical strength and skid resistance. However, smectite contents stemming from alteration processes may deteriorate these mechanical properties considerably because of the resulting contrast in hardness. Quantitative relationships between smectite content, kind of distribution, and aggregate stability are rare except for a recent study by Kaufhold et al. (2012). In this work thirteen basalt and andesite samples from German quarries were analysed by X-ray diffraction (XRD) for their mineral contents (including clay minerals), their cation exchange capacities (CEC) and their resistance against disaggregation in dimethyl sulfoxide. Smectite contents from XRD exceeded those calculated from the CEC regardless of the kind of occurrence of smectite observed in thin sections. The hypothesis that rocks with smectites occurring mostly in patches should differ in terms of CEC and mechanical properties from those rocks where smectites are more disseminated could not be confirmed. However, the amounts of smectite accessible to cation exchange correlated with the DMSO losses. Therefore, the fast CEC determination with Cu-Trien exchange can be substituted for the time-consuming DMSO test.