bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute kidney injury in severe sepsis: Pathophysiology, diagnosis, and treatment recommendations
Authors: Keir Iain , Kellum John A. 
Published: April 2015

AbstractObjectiveTo review the unique pathophysiology of sepsis‐induced acute kidney injury (AKI) and highlight the relevant aspects of the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury that may apply to veterinary patients.Data SourcesElectronic search of MEDLINE database.Human Data SynthesisSepsis‐induced AKI is diagnosed in up to 47% of human ICU patients and is seen as a major public health concern associated with increased mortality and increased progression to chronic kidney disease (CKD). Consensus criteria for the definition and classification of AKI has allowed for accurate description of the epidemiology of patients with AKI. AKI develops from a complex relationship between the initial insult and activation of inflammation and coagulation. In contrast to the traditional view, clinical and experimental data dispute the role of renal ischemia‐reperfusion in the development of sepsis‐induced AKI. Renal tubular dysfunction with activation of the tubuloglomerular feedback mechanism appears to be a crucial contributor to sepsis‐induced AKI. Furosemide and n‐acetylcysteine (NAC) do not appear to be helpful in the treatment of AKI. Hydroxyethyl starches (HES), dopamine, and supraphysiological concentrations of chloride are harmful in patients with AKI.Veterinary Data SynthesisCommunity and hospital‐acquired AKI is a significant factor affecting survival in critical ill patients. Sepsis‐induced AKI occurs in 12% of dogs with abdominal sepsis and is an important contributor to mortality. Early detection of AKI in hospitalized patients currently offers the best opportunity to improve patient outcome. The use of urinary biomarkers to diagnose early AKI should be evaluated in critical care patients.ConclusionVeterinary clinical trials comparing treatment choices with the development of AKI are needed to make evidence‐based recommendations for the prevention and treatment of AKI.
Do cognitive interventions improve general cognition in dementia? A meta-analysis and meta-regression
Authors: Huntley J D , Gould R L , Liu K , Smith M , Howard R J 
Published: April 2015

ObjectivesTo review the efficacy of cognitive interventions on improving general cognition in dementia.MethodOnline literature databases and trial registers, previous systematic reviews and leading journals were searched for relevant randomised controlled trials. A systematic review, random-effects meta-analyses and meta-regression were conducted. Cognitive interventions were categorised as: cognitive stimulation (CS), involving a range of social and cognitive activities to stimulate multiple cognitive domains; cognitive training (CT), involving repeated practice of standardised tasks targeting a specific cognitive function; cognitive rehabilitation (CR), which takes a person-centred approach to target impaired function; or mixed CT and stimulation (MCTS). Separate analyses were conducted for general cognitive outcome measures and for studies using ‘active’ (designed to control for non-specific therapeutic effects) and non-active (minimal or no intervention) control groups.Results33 studies were included. Significant positive effect sizes (Hedges’ g) were found for CS with the mini-mental state examination (MMSE) (g=0.51, 95% CI 0.29 to 0.69; p<0.001) compared to non-active controls and (g=0.35, 95% CI 0.06 to 0.65; p=0.019) compared to active controls. Significant benefit was also seen with the Alzheimer's disease Assessment Scale-Cognition (ADAS-Cog) (g=−0.26, 95% CI −0.445 to −0.08; p=0.005). There was no evidence that CT or MCTS produced significant improvements on general cognition outcomes and not enough CR studies for meta-analysis. The lowest accepted minimum clinically important difference was reached in 11/17 CS studies for the MMSE, but only 2/9 studies for the ADAS-Cog. Additionally, 95% prediction intervals suggested that although statistically significant, CS may not lead to benefits on the ADAS-Cog in all clinical settings.ConclusionsCS improves scores on MMSE and ADAS-Cog in dementia, but benefits on the ADAS-Cog are generally not clinically significant and difficulties with blinding of patients and use of adequate placebo controls make comparison with the results of dementia drug treatments problematic.
Lack of weight recording in patients being administered narrow therapeutic index antibiotics: a prospective cross-sectional study
Authors: Charani Esmita , Gharbi Myriam , Hickson Mary , Othman Shokri , Alfituri Aisha , Frost Gary , Holmes Alison 
Published: April 2015

ObjectivesPatient weight is a key measure for safe medication management and monitoring of patients. Here we report the recording of patient's body weight on admission in three hospitals in West London and its relationship with the prescription of antibiotic drugs where it is essential to have the body weight of the patient.MethodsA prospective cross-sectional study was conducted in three teaching hospitals in West London. Data were collected during March 2011–September 2011 and July 2012–August 2012, from adult admissions units, medical and surgical wards. Data from each ward were collected on a single day to provide a point prevalence data on weight recording. Patient medication charts, nursing and medical notes were reviewed for evidence of weight and height recording together with all the medication prescribed for the patients. An observational study collecting data on the weight recording process was conducted on two randomly selected wards to add context to the data.ResultsData were collected on 1012 patients. Weight was not recorded for 46% (474) of patients. Eighty-nine patients were prescribed a narrow therapeutic antibiotic, in 39% (35/89) of these weight was not recorded for the patient. Intravenous vancomycin was the most commonly prescribed antibiotic requiring therapeutic monitoring. In total 61 patients were receiving intravenous vancomycin and of these 44% (27/61) did not have their weight recorded. In the observational study, the most frequently identified barrier to weight not being recorded was interruptions to the admission process.ConclusionsDespite the clinical importance of body weight measurement it is poorly recorded in hospitalised patients, due to interruptions to the workflow and heavy staff workloads. In antibiotics a correct, recent patient weight is required for accurate dosing and to keep drugs within the narrow therapeutic index, to ensure efficacy of prescribing and reduce toxicity.
The association between obesity and severe disability among adults aged 50 or over in nine high-income, middle-income and low-income countries: a cross-sectional study
Authors: Koyanagi Ai , Moneta Maria Victoria , Garin Noe , Olaya Beatriz , Ayuso-Mateos Jose Luis , Chatterji Somnath , Leonardi Matilde , Sainio Päivi , Galas Aleksander , Haro Josep Maria 
Published: April 2015

ObjectiveThe association between obesity and disability may differ between high-income and low-income/middle-income countries but there are no studies comparing this association between these settings. The aim of the study was to assess this association in nine countries using nationally-representative data from the Collaborative Research on Ageing in Europe (COURAGE) study and the WHO's Study on global AGEing and Adult Health (SAGE).DesignPopulation-based cross-sectional studySettingThe survey was conducted in China, Finland, Ghana, India, Mexico, Poland, Russia, South Africa and Spain between 2007 and 2012.Participants42 116 individuals 50 years and older. The institutionalised and those with limited cognition were excluded.Primary outcome measureDisability was defined as severe or extreme difficulty in conducting at least one of six types of basic activities of daily living (ADL).ResultsThe mean body mass index (BMI) ranged from 20.4 kg/m2in India to 30.7 kg/m2in South Africa. Compared to normal BMI (18.5–24.9 kg/m2), BMI≥35 kg/m2was associated with significantly higher odds for ADL disability in Finland (OR 4.64), Poland (OR 2.77), South Africa (OR 2.19) and Spain (OR 2.42). Interaction analysis showed that obese individuals in high-income countries were more likely to have ADL limitations than those in low-income or middle-income countries.ConclusionsThe higher odds for disability among obese individuals in high-income countries may imply longer life lived with disability due to factors such as the decline in cardiovascular disease mortality. In South Africa, this may have been due to the exceptionally high prevalence of class III obesity. These findings underscore the importance of obesity prevention to reduce the disability burden among older adults.
Database improvements for motor vehicle/bicycle crash analysis
Authors: Lusk Anne C , Asgarzadeh Morteza , Farvid Maryam S 
Published: April 2015

BackgroundBicycling is healthy but needs to be safer for more to bike. Police crash templates are designed for reporting crashes between motor vehicles, but not between vehicles/bicycles. If written/drawn bicycle-crash-scene details exist, these are not entered into spreadsheets.ObjectiveTo assess which bicycle-crash-scene data might be added to spreadsheets for analysis.MethodsPolice crash templates from 50 states were analysed. Reports for 3350 motor vehicle/bicycle crashes (2011) were obtained for the New York City area and 300 cases selected (with drawings and on roads with sharrows, bike lanes, cycle tracks and no bike provisions). Crashes were redrawn and new bicycle-crash-scene details were coded and entered into the existing spreadsheet. The association between severity of injuries and bicycle-crash-scene codes was evaluated using multiple logistic regression.ResultsPolice templates only consistently include pedal-cyclist and helmet. Bicycle-crash-scene coded variables for templates could include: 4 bicycle environments, 18 vehicle impact-points (opened-doors and mirrors), 4 bicycle impact-points, motor vehicle/bicycle crash patterns, in/out of the bicycle environment and bike/relevant motor vehicle categories. A test of including these variables suggested that, with bicyclists who had minor injuries as the control group, bicyclists on roads with bike lanes riding outside the lane had lower likelihood of severe injuries (OR, 0.40, 95% CI 0.16 to 0.98) compared with bicyclists riding on roads without bicycle facilities.ConclusionsPolice templates should include additional bicycle-crash-scene codes for entry into spreadsheets. Crash analysis, including with big data, could then be conducted on bicycle environments, motor vehicle potential impact points/doors/mirrors, bicycle potential impact points, motor vehicle characteristics, location and injury.
Dynamic MIPS Rate Stabilization for Complex Processors
Authors: Suh Jinho , Huang Chieh-Ting , Dubois Michel 
Published: April 2015

Modern microprocessor cores reach their high performance levels with the help of high clock rates, parallel and speculative execution of a large number of instructions, and vast cache hierarchies. Modern cores also have adaptive features to regulate power and temperature and avoid thermal emergencies. All of these features contribute to highly unpredictable execution times. In this article, we demonstrate that the execution time of in-order (IO), out-of-order (OoO), and OoO simultaneous multithreaded processors can be stable and predictable by stabilizing their mega instructions executed per second (MIPS) rate via a proportional, integral, and differential (PID) gain feedback controller and dynamic voltage and frequency scaling (DVFS).
Processor cores in idle cycles are continuously consuming power, which is highly undesirable in systems, especially in real-time systems. In addition to meeting deadlines in real-time systems, our MIPS rate stabilization framework can be applied on top of it to reduce power and energy by avoiding idle cycles. If processors are equipped with MIPS rate stabilization, the execution time can be predicted. Because the MIPS rate remains steady, a stabilized processor meets deadlines on time in real-time systems or in systems with quality-of-service execution latency requirements at the lowest possible frequency.
To demonstrate and evaluate this capability, we have selected a subset of the MiBench benchmarks with the widest execution rate variations. We stabilize their MIPS rate on a 1GHz Pentium III--like OoO single-thread microarchitecture, a 1.32GHz StrongARM-like IO microarchitecture, and the 1GHz OoO processor augmented with two-way and four-way simultaneous multithreading. Both IO and OoO cores can take advantage of the stabilization framework, but the energy per instruction of the stabilized OoO core is less because it runs at a lower frequency to meet the same deadlines.
The MIPS rate stabilization of complex processors using a PID feedback control loop is a general technique applicable to environments in which lower power or energy coupled with steady, predictable performance are desirable, although we target more specifically real-time systems in this article.
Generalized Task Parallelism
Authors: Streit Kevin , Doerfert Johannes , Hammacher Clemens , Zeller Andreas , Hack Sebastian 
Published: April 2015

Existing approaches to automatic parallelization produce good results in specific domains. Yet, it is unclear how to integrate their individual strengths to match the demands and opportunities of complex software. This lack of integration has both practical reasons, as integrating those largely differing approaches into one compiler would impose an engineering hell, as well as theoretical reasons, as no joint cost model exists that would drive the choice between parallelization methods.
By reducing the problem of generating parallel code from a program dependence graph to integer linear programming, <i>generalized task parallelization</i> integrates central aspects of existing parallelization approaches into a single unified framework. Implemented on top of LLVM, the framework seamlessly integrates enabling technologies such as speculation, privatization, and the realization of reductions.
Evaluating our implementation on various C programs from different domains, we demonstrate the effectiveness and generality of generalized task parallelization. On a quad-core machine with hyperthreading we achieve speedups of up to 4.6 ×.
Inherited Genetic Variants Associated with Occurrence of Multiple Primary Melanoma
Authors: Gibbs David C. , Orlow Irene , Kanetsky Peter A. , Luo Li , Kricker Anne , Armstrong Bruce K. , Anton-Culver Hoda , Gruber Stephen B. , Marrett Loraine D. , Gallagher Richard P. , Zanetti Roberto , Rosso Stefano , Dwyer Terence , Sharma Ajay , La Pilla Emily , From Lynn , Busam Klaus J. , Cust Anne E. , Ollila David W. , Begg Colin B. , Berwick Marianne , Thomas Nancy E. 
Published: April 2015

Abstract
Recent studies, including genome-wide association studies, have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case–control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 SNPs from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% confidence intervals were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06). The GEM Study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma. Cancer Epidemiol Biomarkers Prev; 24(6); 992–7. ©2015 AACR.
Molecular Pathways: Targeting Cellular Energy Metabolism in Cancer via Inhibition of SLC2A1 and LDHA
Authors: Ooi Aik T. , Gomperts Brigitte N. 
Published: April 2015

Abstract
Reprogramming of cellular energy metabolism is widely accepted to be one of the main hallmarks of cancer. The aberrant expression pattern of key regulators in the glycolysis pathway in cancer cells corroborates with the hypothesis that most cancer cells utilize aerobic glycolysis as their main ATP production method instead of mitochondrial oxidative phosphorylation. Overexpression of SLC2A1 and LDHA, both important regulators of the glycolysis pathway, was detected in the premalignant lesions and tumors of lung cancer patients, suggesting the involvement of these proteins in early carcinogenesis and tumor progression in cancer. Preclinical studies demonstrated that inhibiting SLC2A1 or LDHA led to diminished tumor growth in vitro and in vivo. SLC2A1 and LDHA inhibitors, when administered in combination with other chemotherapeutic agents, showed synergistic antitumor effects by resensitizing chemoresistant cancer cells to the chemotherapies. These results indicate that disrupting SLC2A1, LDHA, or other regulators in cancer cell energetics is a very promising approach for new targeted therapies. Clin Cancer Res; 21(11); 2440–4. ©2015 AACR.
Pilot Study on the Bioactivity of Vitamin D in the Skin after Oral Supplementation
Authors: Curiel-Lewandrowski Clara , Tang Jean Y. , Einspahr Janine G. , Bermudez Yira , Hsu Chiu Hsieh , Rezaee Melika , Lee Alex H. , Tangrea Joseph , Parnes Howard L. , Alberts David S. , Chow H.-H. Sherry 
Published: April 2015

Abstract
Laboratory studies suggest that vitamin D (VD) supplementation inhibits skin carcinogenesis. However, epidemiologic studies report mixed findings in the association between circulating VD levels and skin cancer risk. We conducted a clinical study to determine whether oral cholecalciferol supplementation would exert direct bioactivity in human skin through modulation of the VD receptor (VDR). We enrolled 25 individuals with serum 25-hydroxyvitamin-D levels &lt;30 ng/mL and with skin photodamage to take 50,000 IU of cholecalciferol biweekly for 8 to 9 weeks. Then, we obtained baseline and end-of-study skin biopsies from photodamaged (PD) and photoprotected (PP) skin, and from benign nevi (BN) and tested for mRNA expression of VDR and cytochrome P450-24 (CYP24), and markers of keratinocytic differentiation. High-dose cholecalciferol supplementation significantly elevated circulating levels of 25-hydroxyvitamin-D (P &lt; 0.0001) and 1,25-dihydroxyvitamin-D (P &lt; 0.0001). VDR expression in PD- and PP-skin showed minimum changes after supplementation. CYP24 expression in PD- and PP-skin was increased after supplementation by 186%, P = 0.08, and 134%, P = 0.07, respectively. In BNs from 11 participants, a trend for higher VDR and CYP24 expression was observed (average of 20%, P = 0.08, and 544%, P = 0.09, respectively). Caspase-14 expression at the basal layer in PD skin samples was the only epidermal differentiation marker that was significantly increased (49%, P &lt; 0.0001). High-dose cholecalciferol supplementation raised serum VD metabolite levels concurrently with CYP24 mRNA and caspase-14 levels in the skin. Our findings of significant variability in the range of VDR and CYP24 expression across study samples represent an important consideration in studies evaluating the role of VD as a skin cancer chemopreventive agent. Cancer Prev Res; 8(6); 563–9. ©2015 AACR.
Longitudinal Association of Carotid Plaque Presence and Intima-Media Thickness With Depressive Symptoms in the Elderly
Authors: Prugger Christof , Godin Ophelia , Perier Marie-Cécile , Ritchie Karen , Helmer Catherine , Empana Jean-Philippe , Tzourio Christophe , Dufouil Carole 
Published: April 2015

Objective—
To investigate prospectively whether subclinical vascular disease is associated with future depressive symptoms in the elderly.

Approach and Results—

A multicenter cohort of community-dwelling individuals aged 65 to 85 years was examined for carotid plaque presence and common carotid artery intima-media thickness at baseline and followed up after 2, 4, 7, and 10 years. At baseline and follow-up examinations, depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). High level of depressive symptoms was defined as a CES-D score >16 in men and >22 in women. Among 4125 participants (58% women) at baseline, men more frequently showed carotid plaque presence and had higher mean common carotid artery intima-media thickness than women. After adjustment for major cardiovascular risk factors, carotid plaque presence was associated with a higher CES-D score at the 10-year follow-up in men (+1.46; 95% confidence interval, 0.71–2.20;
P
<0.001), but not in women. When restricting analyses to individuals without cardiovascular disease at baseline, carotid plaque presence increased the likelihood of high level of depressive symptoms at follow-up examinations in men (odds ratio, 1.47; 95% confidence interval, 1.06–2.05;
P
=0.022), but not in women. One SD increase in log-transformed common carotid artery intima-media thickness was associated with a higher CES-D score at the 10-year follow-up in women (+0.55; 95% confidence interval, 0.16–0.95;
P
=0.006) and men (+0.40; 95% confidence interval, 0.02–0.78;
P
=0.037). Common carotid artery intima-media thickness did not increase the likelihood of high level of depressive symptoms at follow-up in both sexes.

Conclusions—
Subclinical vascular disease is associated with the progression of depressive symptoms in elderly men and women and the occurrence of high level of depressive symptoms in elderly men.
High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease
Authors: Agarwala Anandita P. , Rodrigues Amrith , Risman Marjorie , McCoy Mary , Trindade Kevin , Qu Liming , Cuchel Marina , Billheimer Jeffrey , Rader Daniel J. 
Published: April 2015

Objective—
Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with reduced risk of CAD. Extremely high HDL-C with CAD is an unusual phenotype, and we hypothesized that the HDL in such individuals may have an altered composition and reduced function when compared with controls with similarly high HDL-C and no CAD.

Approach and Results—

Fifty-five subjects with very high HDL-C (mean, 86 mg/dL) and onset of CAD at the age of ≈60 years with no known risk factors for CAD (cases) were identified through systematic recruitment. A total of 120 control subjects without CAD, matched for race, sex, and HDL-C level (controls), were identified. In all subjects, HDL composition was analyzed and HDL cholesterol efflux capacity was assessed. HDL phospholipid composition was significantly lower in cases (92±37 mg/dL) than in controls (109±43 mg/dL;
P
=0.0095). HDL cholesterol efflux capacity was significantly lower in cases (1.96±0.39) than in controls (2.11±0.43;
P
=0.04).

Conclusions—
In people with very high HDL-C, reduced HDL phospholipid content and cholesterol efflux capacity are associated with the paradoxical development of CAD.