bluuebunny/crossref_metadata_2025_split huggingface dataset:
The reduced cost of providing a nationally recognised service for familial hypercholesterolaemia
Authors: Pears Robert , Griffin Michael , Watson Melanie , Wheeler Rebecca , Hilder Debbie , Meeson Beverley , Bacon Sallie , Byrne Christopher D 
Published: August 2014

ObjectiveFamilial hypercholesterolaemia (FH) affects 1 in 500 people in the UK population and is associated with premature morbidity and mortality from coronary heart disease. In 2008, National Institute for Health and Care Excellence (NICE) recommended genetic testing of potential FH index cases and cascade testing of their relatives. Commissioners have been slow to respond although there is strong evidence of cost and clinical effectiveness. Our study quantifies the recent reduced cost of providing a FH service using generic atorvastatin and compares NICE costing estimates with three suggested alternative models of care (a specialist-led service, a dual model service where general practitioners (GPs) can access specialist advice, and a GP-led service).MethodsRevision of existing 3 year costing template provided by NICE for FH services, and prediction of costs for running a programme over 10 years. Costs were modelled for the first population-based FH service in England which covers Southampton, Hampshire, Isle of Wight and Portsmouth (SHIP). Population 1.95 million.ResultsWith expiry of the Lipitor (Pfizer atorvastatin) patent the cost of providing a 10-year FH service in SHIP reduces by 42.5% (£4.88 million on patent vs £2.80 million off patent). Further cost reductions are possible as a result of the reduced cost of DNA testing, more management in general practice, and lower referral rates to specialists. For instance a dual-care model with GP management of patients supported by specialist advice when required, costs £1.89 million.ConclusionsThe three alternative models of care are now <50% of the cost of the original estimates undertaken by NICE.
Design and Prototype of a Solid-State Cache
Authors: Saxena Mohit , Swift Michael M. 
Published: August 2014

The availability of high-speed solid-state storage has introduced a new tier into the storage hierarchy. Low-latency and high-IOPS solid-state drives (SSDs) cache data in front of high-capacity disks. However, most existing SSDs are designed to be a drop-in disk replacement, and hence are mismatched for use as a cache.

This article describes
FlashTier
, a system architecture built upon a
solid-state cache
(SSC), which is a flash device with an interface designed for caching. Management software at the operating system block layer directs caching. The FlashTier design addresses three limitations of using traditional SSDs for caching. First, FlashTier provides a unified logical address space to reduce the cost of cache block management within both the OS and the SSD. Second, FlashTier provides a new SSC block interface to enable a warm cache with consistent data after a crash. Finally, FlashTier leverages cache behavior to silently evict data blocks during garbage collection to improve performance of the SSC.

We first implement an SSC simulator and a cache manager in Linux to perform an in-depth evaluation and analysis of FlashTier's design techniques. Next, we develop a prototype of SSC on the OpenSSD Jasmine hardware platform to investigate the benefits and practicality of FlashTier design. Our prototyping experiences provide insights applicable to managing modern flash hardware, implementing other SSD prototypes and new OS storage stack interface extensions.
Overall, we find that FlashTier improves cache performance by up to 168% over consumer-grade SSDs and up to 52% over high-end SSDs. It also improves flash lifetime for write-intensive workloads by up to 60% compared to SSD caches with a traditional flash interface.
GBV-C Infection and Risk of NHL among U.S. Adults
Authors: Chang Cindy M. , Stapleton Jack T. , Klinzman Donna , McLinden James H. , Purdue Mark P. , Katki Hormuzd A. , Engels Eric A. 
Published: August 2014

AbstractSome retrospective studies suggest an association between infection with GB virus-C (GBV-C) and non-Hodgkin lymphoma (NHL). We evaluated this association prospectively in a nested case–control study within the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Cases (N = 658) and controls (N = 1,316) were individually matched by age, sex, race/ethnicity, timing of study entry, and sample selection. Prediagnostic PLCO serum samples were tested for GBV-C RNA (as a measure of active infection) and E2 antibody (active or resolved infection). Logistic regression was used to estimate odds ratios (OR) for the association between GBV-C and NHL overall and NHL subtypes. Twelve cases (1.8%) and seven controls (0.5%) were GBV-C RNA-positive. GBV-C RNA positivity was associated with NHL overall [OR, 3.43; 95% confidence interval (CI), 1.35–8.71] and, based on small numbers, diffuse large B-cell lymphoma (OR, 5.31; 95% CI, 1.54–18.36). The association with NHL persisted when the interval between testing and selection was greater than 4 years (OR, 6.00; 95% CI, 1.21–29.73). In contrast, E2 antibody positivity was not associated with NHL risk (OR, 1.08; 95% CI, 0.74–1.58). Our study demonstrates that GBV-C infection precedes development of NHL. GBV-C infection may play an etiologic role in a small proportion of NHL cases, perhaps by causing chronic immune stimulation or impaired immunosurveillance. Cancer Res; 74(19); 5553–60. ©2014 AACR.
Combined Inhibition of Wee1 and PARP1/2 for Radiosensitization in Pancreatic Cancer
Authors: Karnak David , Engelke Carl G. , Parsels Leslie A. , Kausar Tasneem , Wei Dongping , Robertson Jordan R. , Marsh Katherine B. , Davis Mary A. , Zhao Lili , Maybaum Jonathan , Lawrence Theodore S. , Morgan Meredith A. 
Published: August 2014

Abstract
Purpose: While the addition of radiation to chemotherapy improves survival in patients with locally advanced pancreatic cancer, more effective therapies are urgently needed. Thus, we investigated the radiosensitizing efficacy of the novel drug combination of Wee1 and PARP1/2 inhibitors (AZD1775 and olaparib, respectively) in pancreatic cancer.
Experimental Design: Radiosensitization of AsPC-1 or MiaPaCa-2 human pancreatic cancer cells was assessed by clonogenic survival and tumor growth assays. Mechanistically, the effects of AZD1775, olaparib, and radiation on cell cycle, DNA damage (γH2AX), and homologous recombination repair (HRR) were determined.
Results: Treatment of AsPC-1 and MiaPaCa-2 cells with either AZD1775 or olaparib caused modest radiosensitization, whereas treatment with the combination significantly increased radiosensitization. Radiosensitization by the combination of AZD1775 and olaparib was associated with G2 checkpoint abrogation and persistent DNA damage. In addition, AZD1775 inhibited HRR activity and prevented radiation-induced Rad51 focus formation. Finally, in vivo, in MiaPaCa-2–derived xenografts, olaparib did not radiosensitize, whereas AZD1775 produced moderate, yet significant, radiosensitization (P &lt; 0.05). Importantly, the combination of AZD1775 and olaparib produced highly significant radiosensitization (P &lt; 0.0001) evidenced by a 13-day delay in tumor volume doubling (vs. radiation alone) and complete eradication of 20% of tumors.
Conclusions: Taken together, these results demonstrate the efficacy of combined inhibition of Wee1 and PARP inhibitors for radiosensitizing pancreatic cancers and support the model that Wee1 inhibition sensitizes cells to PARP inhibitor–mediated radiosensitization through inhibition of HRR and abrogation of the G2 checkpoint, ultimately resulting in unrepaired, lethal DNA damage and radiosensitization. Clin Cancer Res; 20(19); 5085–96. ©2014 AACR.
Comparison of Trends and Outcomes of Carotid Artery Stenting and Endarterectomy in the United States, 2001 to 2010
Authors: Kim Luke K , Yang David C. , Swaminathan Rajesh V. , Minutello Robert M. , Okin Peter M. , Lee Min Kyeong , Sun Xuming , Wong S. Chiu , McCormick Daniel J. , Bergman Geoffrey , Allareddy Veerasathpurush , Singh Harsimran , Feldman Dmitriy N. 
Published: August 2014

Background—
Given the controversy regarding whether carotid endarterectomy (CEA) or carotid artery stenting (CAS) may be superior for stroke prevention, it is uncertain how recent clinical evidence, guidelines, and reimbursement policies have influenced the volume and outcomes after these procedures.

Methods and Results—

We conducted a serial, cross-sectional study with time trends of patients undergoing CAS (n=124 265) and CEA (n=1 260 647) between 2001 and 2010 from the Nationwide Inpatient Sample database. During the 10-year period, the frequency of CEA declined, whereas CAS use slowly increased. After multivariate propensity score–matched analysis, CAS was associated with an increased risk of death (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.40–2.04), stroke (OR, 1.43; 95% CI, 1.23–1.66), and major adverse events including death, stroke, and myocardial infarction (OR, 1.25; 95% CI, 1.13–1.39). In asymptomatic patients, there was no significant difference in major adverse events (OR, 1.08; 95% CI, 0.92–1.20;
P
=0.16 [
P
<0.001 for interaction between procedure type and symptom status]) between CAS and CEA. Importantly, there was a significant improvement in CAS outcomes during the course of 10 years (reduction in death [OR, 0.51; 95% CI, 0.49–0.67;
P
for trend=0.03] and major adverse events [OR, 0.75; 95% CI, 0.66–0.84;
P
for trend=0.05] comparing years 2010 versus 2001).

Conclusions—
In US hospitals between 2001 and 2010, CAS was associated with worse in-hospital outcomes, partly attributable to selection and ascertainment bias. Asymptomatic patients undergoing CAS versus CEA had similar adjusted rates of major adverse events. CAS outcomes improved significantly during the course of the decade likely attributable to improvements in patient selection, operator skills, and technological advancements.
White Matter Perivascular Spaces Are Related to Cortical Superficial Siderosis in Cerebral Amyloid Angiopathy
Authors: Charidimou Andreas , Jäger Rolf H. , Peeters Andre , Vandermeeren Yves , Laloux Patrice , Baron Jean-Claude , Werring David J. 
Published: August 2014

Background and Purpose—
We set out to investigate whether MRI-visible centrum semiovale perivascular spaces (CSO-PVS), a potential biomarker of impaired interstitial fluid drainage in sporadic cerebral amyloid angiopathy, is associated with cortical superficial siderosis (cSS), reflecting recurrent hemorrhage from severe leptomeningeal and superficial cortical vascular amyloid.

Methods—
Retrospective multicenter cohort study of possible/probable cerebral amyloid angiopathy according to the Boston criteria. PVS were rated in basal ganglia and CSO (CSO-PVS) on axial T2-weighted sequences, using a validated 4-point visual rating scale and were classified as high (score >2) or low degree (score ≤2) for prespecified analyses. Independent risk factors for high CSO-PVS degree were investigated in logistic regression.

Results—

The final cohort consisted of 138 cerebral amyloid angiopathy patients (mean age, 71.8 years; 95% confidence interval, 70.2–73.4 years; 52.2% men). High CSO-PVS degree was present in 61.2% of cases. The prevalence of any cSS, and disseminated cSS (involving >3 sulci), was higher in patients with high versus low CSO-PVS degree (for any cSS 45.9% versus 13.5%;
P
<0.00005; for disseminated cSS 31.8% versus 0%;
P
<0.00005). In multivariable logistic regression analysis, cSS presence (odds ratio, 4.78; 95% confidence interval, 1.64–13.87;
P
=0.004) was an independent predictors of high CSO-PVS degree. We found no associations between basal ganglia PVS and cSS.

Conclusions—
High degree of CSO-PVS is highly prevalent in sporadic cerebral amyloid angiopathy and is related to cSS. Our findings suggest that severe leptomeningeal and cortical vascular amyloid (causing cSS) is related to impaired interstitial fluid drainage from cerebral white matter, although determining the causal direction of this relationship requires prospective studies.
Coronary Artery Calcification, Intima-Media Thickness, and Ankle-Brachial Index Are Complementary Stroke Predictors
Authors: Gronewold Janine , Bauer Marcus , Lehmann Nils , Mahabadi Amir A. , Kälsch Hagen , Weimar Christian , Berger Klaus , Moebus Susanne , Jöckel Karl-Heinz , Erbel Raimund , Hermann Dirk M. 
Published: August 2014

Background and Purpose—
Coronary artery calcification (CAC), a marker of coronary atherosclerosis, predicts stroke in addition to established risk factors. Whether CAC’s predictive value can be improved by peripheral atherosclerosis markers, namely carotid intima-media thickness (CIMT) and ankle-brachial index (ABI), was unknown.

Methods—
A total of 3289 participants of the population-based Heinz Nixdorf Recall study (45–75 years; 48.8% men) without previous stroke or coronary heart disease were evaluated for incident stroke for 9.0±1.9 years. CAC, CIMT, and ABI were examined as stroke predictors.

Results—

Eighty-four strokes occurred during follow-up. In multivariable Cox proportional hazard regressions, CAC (hazard ratio, 1.45 [95% confidence interval, 1.11–1.88] per SD increase in ln(CAC+1); SD, 2.40), CIMT (1.34 [1.08–1.66] per SD increase; SD, 0.127 mm), and ABI (1.55 [1.32–1.82] per SD decrease; SD, 0.148) were associated with stroke in addition to established risk factors. When combined with each other, ln(CAC+1)’s hazard ratio remained similar when CIMT (1.41 [1.09–1.83]) was inserted into the multivariable model, but slightly decreased when ABI (1.31 [1.01–1.72]) or CIMT and ABI (1.29 [0.99–1.68]) were included. Although CAC alone did not significantly elevate the area under the curve in Harrell’s c-statistics (by 0.009;
P
=0.379) in addition to established risk factors, the combination of CAC and ABI increased area under the curve (by 0.029;
P
=0.047), as did ABI (by 0.025;
P
=0.038) but not CIMT (by 0.002;
P
=0.795) alone. The combination of CAC and ABI also resulted in significant category-free net reclassification and integrated discrimination improvement.

Conclusions—
CAC, CIMT, and ABI provide complementary information about stroke risk. ABI, which is distinctive in a small subpopulation, had the highest and CIMT, which is distributed across a larger range of values, had the lowest predictive value.
<span lang="EN-GB">Phanerosorus</span><span lang="EN-GB"> (Matoniaceae), a new fern genus record for the Philippines</span>
Authors: BARCELONA JULIE F. , PELSER PIETER B. 
Published: August 2014

The fern family Matoniaceae C. Presl (1847: 32) is a small group composed of only two genera, Matonia R. Brown in Wallich (1829: 16) and Phanerosorus Copeland (1909: 344) with three or four species characterized by rhizomes with polycyclic solenosteles covered with thick uniseriate hairs, anastomosing veins in fertile parts of the lamina, peltate and fugacious indusia, relatively large sporangia and gametangia, and tetrahedral, trilete spores (Kramer 1990, Kato & Setoguchi 1998). The two genera differ from each other in leaf architecture (pedate in Matonia and pinnate in Phanerosorus), habit, and habitat preferences (Phanerosorus pendent and obligately calcicolous and Matonia erect and preferring exposed, sometimes mineralized ridges of high mountains; Kato & Iwatsuki 1985, Barcelona et al. 1996).
<p class="Default">Rhynchosia ravii (Leguminosae-Papilionoideae), a new species from Andhra Pradesh, India
Authors: PRASAD K. , SWAMY A. NARAYANA 
Published: August 2014

Rhynchosia ravii, a new species from Andhra Pradesh, India is described and illustrated. Full description, distribution details and conservation status are presented, and the new species is compared with its most closely related species, Rhynchosia beddomei.
Gastrointestinal Nematodes of Laudakia nupta nupta (Sauria: Agamidae) from Iran with Descriptions of Two New Species (Oxyuridea: Pharyngodonidae) and comments on the diagnostic features of Parapharyngodon and Thelandros
Authors: RAHIMIAN HASSAN , PAZOKI SAMANEH , HABASHI SIMA ABBASI 
Published: August 2014

Seventeen specimens of Laudakia nupta nupta (De Filippi, 1843), from several locations in central plain of Iran were examined for gastrointestinal parasitic helminths. Nematodes of different families and genera were the only worms found. The nematodes included one Parapharyngodon sp., three Thelandros spp., and one Thubunea sp. All species found in this study are new geographical records and two of the species are new to science. Parapharyngodon thulini sp. nov. and Thelandros karkasensis sp. nov. are, hereby, described and illustrated. To identify some of the fine morphological characteristics, Scanning Electron Microscopy (SEM) was carried out for selected specimens. Furthermore, the most important discriminating characteristics for species of Parapharyngodon and Thelandros are described. This study represents the first parasitological study on L. nupta nupta.
Evolving an Information Diffusion Model Using a Genetic Algorithm for Monthly River Discharge Time Series Interpolation and Forecasting
Authors: Bai Chengzu , Hong Mei , Wang Dong , Zhang Ren , Qian Longxia 
Published: August 2014

Abstract
The identification of the rainfall–runoff relationship is a significant precondition for surface–atmosphere process research and operational flood forecasting, especially in inadequately monitored basins. Based on an information diffusion model (IDM) improved by a genetic algorithm, a new algorithm (GIDM) is established for interpolating and forecasting monthly discharge time series; the input variables are the rainfall and runoff values observed during the previous time period. The genetic operators are carefully designed to avoid premature convergence and “local optima” problems while searching for the optimal window width (a parameter of the IDM). In combination with fuzzy inference, the effectiveness of the GIDM is validated using long-term observations. Conventional IDMs are also included for comparison. On the Yellow River or Yangtze River, twelve gauging stations are discussed, and the results show that the new method can simulate the observations more accurately than traditional IDMs, using only 50% or 33.33% of the total data for training. The low density of observations and the difficulties in information extraction are key problems for hydrometeorological research. Therefore, the GIDM may be a valuable tool for improving water management and providing the acceptable input data for hydrological models when available measurements are insufficient.
Snowpack Changes in the Hindu Kush–Karakoram–Himalaya from CMIP5 Global Climate Models
Authors: Terzago Silvia , von Hardenberg Jost , Palazzi Elisa , Provenzale Antonello 
Published: August 2014

AbstractThe Hindu Kush, Karakoram, and Himalaya (HKKH) mountain ranges feed the most important Asian river systems, providing water to about 1.5 billion people. As a consequence, changes in snow dynamics in this area could severely impact water availability for downstream populations. Despite their importance, the amount, spatial distribution, and seasonality of snow in the HKKH region are still poorly known, owing to the limited availability of surface observations in this remote and high-elevation area. This work considers global climate models (GCM) participating in phase 5 of the Coupled Model Intercomparison Project (CMIP5) and analyzes how they represent current and future snowpack in the HKKH region in terms of snow depth and snow water equivalent. It is found that models with high spatial resolution (up to 1.25°) simulate a spatial pattern of the winter snowpack in greater agreement with each other, with observations, with reanalysis datasets, and with the orographic features of the region, compared to most lower-resolution models. The seasonal cycle of snow depth displays a unimodal regime, with a maximum in February–March and almost complete melting in summer. The models generally indicate thicker [in Hindu Kush–Karakoram (HKK)] or comparable (in the Himalayas) snow depth and higher snow water equivalent compared to the reanalyses for the control period 1980–2005. Future projections, evaluated in terms of the ensemble mean of GCM simulations, indicate a significant reduction in the spatial average of snow depth over the HKK and an even stronger decrease in the Himalayas, where a reduction between 25% and 50% is expected by the end of the twenty-first century.
Modeling of 137Cs as a Tracer in a Regional Model for the Western Pacific, after the Fukushima–Daiichi Nuclear Power Plant Accident of March 2011
Authors: Garraffo Zulema D. , Kim Hae-Cheol , Mehra Avichal , Spindler Todd , Rivin Ilya , Tolman Hendrik L. 
Published: August 2014

Abstract
In this study, results are presented from the first operational ocean tracer dispersion model operated by the National Oceanic and Atmospheric Administration/National Weather Service/National Centers for Environmental Prediction (NOAA/NWS/NCEP). This study addresses the dispersion of radionuclide contaminants after the Fukushima–Daiichi nuclear accident that was triggered by the 11 March 2011 earthquake and tsunami. The tracer capabilities of the Hybrid Coordinate Ocean Model (HYCOM) were used in a regional domain for the northwestern Pacific, with nesting lateral boundary conditions using daily nowcast–forecast fields from the global operational Real-Time Ocean Forecast System (RTOFS-Global), a ° HYCOM global forecast from NCEP, based on data-assimilative ° HYCOM Global Ocean Forecast System (GOFS) analyses from the Naval Research Laboratory/Naval Oceanographic Office (NRL/NAVOCEANO). This regional model, RTOFS Episodic Tracers for a region of the North West Pacific (RTOFS-ET_WPA), was in operation until the beginning of 2014, when the simulated 137Cs concentration was very close to the background level in the Pacific before the accident, which was about 2 Becquerel m−3 [Bq; 1 Becquerel = 1 (nuclear decay) s−1].
Biocompatibility and Efficacy of Collagen/Gelatin Sponge Scaffold With Sustained Release of Basic Fibroblast Growth Factor on Vocal Fold Fibroblasts in 3-Dimensional Culture
Authors: Hiwatashi Nao , Hirano Shigeru , Mizuta Masanobu , Tateya Ichiro , Kanemaru Shin-ichi , Nakamura Tatsuo , Ito Juichi , Kawai Katsuya , Suzuki Shigehiko 
Published: August 2014

Objective: Treatment of vocal fold scarring remains challenging. We have previously reported the therapeutic effects of local injection of basic fibroblast growth factor (bFGF) in animal models and humans. A novel collagen/gelatin sponge (CGS) is capable of sustained release of bFGF, which compensates for its quick absorption in vivo, avoiding multiple injections. This study aimed to evaluate the biocompatibility and efficacy of the CGS in rat vocal fold fibroblasts prior to human trials. Methods: Fibroblasts extracted from Sprague-Dawley rat vocal folds were seeded onto a CGS and then cultivated with bFGF at concentrations of 0, 10, and 100 ng/mL. Vocal fold fibroblast morphology, adhesion, proliferation, and gene expression were measured under these 3-dimensional conditions. Results: Cells adhered to the CGS from day 1. Although no significant differences in cell morphology were detected, cell proliferation was accelerated by bFGF administration. Expression of endogenous bFGF and hepatocyte growth factor was significantly up-regulated at 10 ng/mL bFGF. The expression of procollagen I and procollagen III was significantly suppressed, whereas HAS-1 and HAS-2 were up-regulated at 10 and 100 ng/mL bFGF. Conclusion: The collagen/gelatin sponge is biocompatible with vocal fold fibroblasts and may be useful as a bFGF drug delivery system for the treatment of scarred vocal folds.