bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth and interaction of normal faults and fault network evolution in rifts: insights from three-dimensional discrete element modelling
Authors: Finch Emma , Gawthorpe Rob 
Published: August 2017

Abstract
The initiation, growth and interaction of faults within an extensional rift is an inherently four-dimensional process where connectivity with time and depth are difficult to constrain. A 3D discrete element model is employed that represents the crust as a two-layered brittle–ductile system in which faults nucleate, propagate and interact in response to local heterogeneities and resulting stresses. Faults nucleate in conjugate sets throughout the model brittle crust; they grow through a combination of tip propagation and interaction of co-linear segments to form larger normal faults. Segment linkage occurs by merging of adjacent fault segments located along strike, downdip or oblique to one another. Finally, deformation localizes onto the largest faults. Displacement distribution on faults is highly variable with marked along-strike and temporal variations in displacement rates. Displacement maxima continuously migrate as smaller fault segments interact and link to form the final fault plane. As a result, displacement maxima associated with fault nucleation sites are not coincident with the location of the maximum finite displacement on a fault where segment linkage overprints the record. The observed style of fault growth is consistent with the isolated growth model in the earliest stages which then gives way to a coherent (constant-length) fault growth model at greater strains.
Influence of nutrient ingestion on amino acid transporters and protein synthesis in human skeletal muscle after sprint exercise
Authors: Rundqvist Håkan C. , Esbjörnsson Mona , Rooyackers Olav , Österlund Ted , Moberg Marcus , Apro William , Blomstrand Eva , Jansson Eva 
Published: September 2017

Nutrient ingestion is known to increase the exercise-induced stimulation of muscle protein synthesis following resistance exercise. Less is known about the effect of nutrients on muscle protein synthesis following sprint exercise. At two occasions separated by 1 mo, 12 healthy subjects performed three 30-s sprints with 20-min rest between bouts. In randomized order, they consumed a drink with essential amino acids and maltodextrin (nutrient) or flavored water (placebo). Muscle biopsies were obtained 80 and 200 min after the last sprint, and blood samples were taken repeatedly during the experiment. Fractional synthetic rate (FSR) was measured by continuous infusion of l-[2H5]phenylalanine up to 200 min postexercise. The mRNA expression and protein expression of SNAT2 were both 1.4-fold higher ( P < 0.05) after nutrient intake compared with placebo at 200 min postexercise. Phosphorylated Akt, mammalian target of rapamycin (mTOR), and p70S6k were 1.7- to 3.6-fold higher ( P < 0.01) 80 min after the last sprint with nutrient ingestion as compared with placebo. In addition, FSR was higher ( P < 0.05) with nutrients when plasma phenylalanine (FSRplasma) was used as a precursor but not when intracellular phenylalanine (FSRmuscle) was used. Significant correlations were also found between FSRplasma on the one hand and plasma leucine and serum insulin on the other hand in the nutrient condition. The results show that nutrient ingestion induces the expression of the amino acid transporter SNAT2 stimulates Akt/mTOR signaling and most likely the rate of muscle protein synthesis following sprint exercise. NEW & NOTEWORTHY There is limited knowledge regarding the effect of nutrients on muscle protein synthesis following sprint as compared with resistance exercise. The results demonstrate that nutrient ingestion during repeated 30-s bouts of sprint exercise induces expression of the amino acid transporter SNAT2 and stimulates Akt/mTOR signaling and most likely the rate of muscle protein synthesis. Future studies to explore the chronic effects of nutritional ingestion during sprint exercise sessions on muscle mass accretion are warranted.
Immuno-oncology Trial Endpoints: Capturing Clinically Meaningful Activity
Authors: Anagnostou Valsamo , Yarchoan Mark , Hansen Aaron R. , Wang Hao , Verde Franco , Sharon Elad , Collyar Deborah , Chow Laura Q.M. , Forde Patrick M. 
Published: September 2017

Abstract
Immuno-oncology (I-O) has required a shift in the established paradigm of toxicity and response assessment in clinical research. The design and interpretation of cancer clinical trials has been primarily driven by conventional toxicity and efficacy patterns observed with chemotherapy and targeted agents, which are insufficient to fully inform clinical trial design and guide therapeutic decisions in I-O. Responses to immune-targeted agents follow nonlinear dose–response and dose–toxicity kinetics mandating the development of novel response evaluation criteria. Biomarker-driven surrogate endpoints may better capture the mechanism of action and biological response to I-O agents and could be incorporated prospectively in early-phase I-O clinical trials. While overall survival remains the gold standard for evaluation of clinical efficacy of I-O agents in late-phase clinical trials, exploration of potential novel surrogate endpoints such as objective response rate and milestone survival is to be encouraged. Patient-reported outcomes should also be assessed to help redefine endpoints for I-O clinical trials and drive more efficient drug development. This paper discusses endpoints used in I-O trials to date and potential optimal endpoints for future early- and late-phase clinical development of I-O therapies. Clin Cancer Res; 23(17); 4959–69. ©2017 AACR.
See all articles in this CCR Focus section, “Clinical Trial Design Considerations in the Immuno-oncology Era.”
Spotlight on Ibrutinib in PCNSL: Adding Another Feather to Its Cap
Authors: Lakshmanan Aparna , Byrd John C. 
Published: September 2017

Abstract
Summary: In this issue Grommes and colleagues elegantly show that the irreversible inhibitor of Bruton tyrosine kinase, ibrutinib, promotes a high proportion of durable responses in primary central nervous system lymphoma, a type of diffuse large B-cell lymphoma (DLBCL), and also in secondary DLBCL relapsing to the central nervous system. Mutations in the B-cell antigen receptor–associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing opportunity for further targeted therapy of this difficult-to-treat disease. Cancer Discov; 7(9); 940–2. ©2017 AACR.
See related article by Grommes et al., p. 1018.
As cartas de Osman Lins e Hermilo Borba Filho: uma amizade virtual, tocada pelo real
Authors: Barbosa Nelson Luís 
Published: September 2017

Os conterrâneos Osman Lins e Hermilo Borba Filho mantiveram constante e densa correspondência epistolar, entre 1965 e 1976, interrompida pela morte precoce de Hermilo. Tratavam com exclusividade de seus projetos de livros, romances, peças teatrais, e de dificuldades relacionadas com o mundo editorial, questões mais prementes em relação a literatura e escrita e a problemas do país de sua época, sob uma ditadura militar que duraria mais de 20 anos. Vivendo Hermilo no Recife e Osman em São Paulo, nas poucas vezes em que se encontravam pessoalmente, os assuntos de modo geral resvalavam para questões familiares, cotidianas etc. Assim, o espaço das cartas constituiu o universo virtual privilegiado para essa troca de experiências literárias e de escrita criativa, confirmando que as correspondências de escritores se constituem em verdadeiros arquivos de criação e canteiros de elaboração literária criativa.
Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study
Authors: Mehta Puja K. , Johnson B. Delia , Kenkre Tanya S. , Eteiba Wafia , Sharaf Barry , Pepine Carl J. , Reis Steven E. , Rogers William J. , Kelsey Sheryl F. , Thompson Diane V. , Bittner Vera , Sopko George , Shaw Leslee J. , Bairey Merz C. Noel 
Published: September 2017

Background

Sudden cardiac death (
SCD
) is often the first presentation of ischemic heart disease; however, there is limited information on
SCD
among women with and without obstructive coronary artery disease (
CAD
). We evaluated
SCD
incidence in the WISE (Women's Ischemia Syndrome Evaluation) study.

Methods and Results

Overall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as
SCD
or non‐
SCD
. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were
SCD
. Mortality per 1000 person‐hours increased linearly with
CAD
severity (no
CAD
: 5.8; minimal: 15.9; obstructive: 38.6;
P
<0.0001). However, the proportion of
SCD
was similar across
CAD
severity: 40%, 58%, and 38% for no, minimal, and obstructive
CAD
subgroups, respectively (
P
value not significant). In addition to traditional risk factors (age, diabetes mellitus, smoking), a history of depression (
P
=0.018) and longer corrected QT interval (
P
=0.023) were independent
SCD
predictors in the entire cohort. Corrected QT interval was an independent predictor of
SCD
in women without obstructive
CAD
(
P
=0.033).

Conclusions

SCD
contributes substantially to mortality in women with and without obstructive
CAD
. Corrected QT interval is the single independent
SCD
risk factor in women without obstructive
CAD
. In addition to management of traditional risk factors, these data indicate that further investigation should address mechanistic understanding and interventions targeting depression and corrected QT interval in women.
Alirocumab Treatment and Achievement of Non‐High‐Density Lipoprotein Cholesterol and Apolipoprotein B Goals in Patients With Hypercholesterolemia: Pooled Results From 10 Phase 3 ODYSSEY Trials
Authors: Bays Harold E. , Leiter Lawrence A. , Colhoun Helen M. , Thompson Desmond , Bessac Laurence , Pordy Robert , Toth Peter P. 
Published: September 2017

Background

Non‐high‐density lipoprotein cholesterol (non‐
HDL
‐C) and apolipoprotein (apo) B are better predictors of atherosclerotic cardiovascular disease risk than low‐density lipoprotein cholesterol alone.
US
and European lipid management guidelines support non‐
HDL
‐C and apoB as targets for lipid‐lowering therapy.

Methods and Results

This analysis evaluated the efficacy of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, on non‐
HDL
‐C and apoB. Data were derived from 4983 patients enrolled in 10 randomized, placebo‐ or ezetimibe‐controlled Phase 3
ODYSSEY
trials. Primary end point for this pooled analysis was percent reduction in non‐
HDL
‐C and apoB at Week 24; secondary end points included the percentage of patients achieving guideline‐directed treatment goals (National Lipid Association guidelines: non‐
HDL
‐C <100 or <130 mg/dL for patients at very high and high cardiovascular risk, respectively; European Society of Cardiology/European Atherosclerosis Society guidelines: apoB <80 mg/dL for patients at very‐high cardiovascular risk). Data were grouped according to comparator, alirocumab starting dose, and concomitant statin use. Compared with controls, alirocumab produced significantly greater reductions in non‐
HDL
‐C and apoB at Week 24 (
P
<0.0001), an effect extending up to 78 weeks. More alirocumab‐treated patients achieved levels of non‐
HDL
‐C <100 mg/dL and apoB <80 mg/dL (
P
≤0.0001 versus control). By Week 24, >70% of alirocumab‐treated patients on background statin achieved non‐
HDL
‐C <100 or <130 mg/dL, and apoB <80 mg/dL. Safety was comparable across pooled groups and in line with previous reports.

Conclusions

Alirocumab produced significant, sustained reductions in non‐
HDL
‐C and apoB, allowing more patients to achieve lipid goals compared with placebo or ezetimibe and irrespective of maximally tolerated statin use.
Physical Activity Frequency and the Risk of Stroke: A Nationwide Cohort Study in Korea
Authors: Jeong Han‐Gil , Kim Do Yeon , Kang Dong‐Wan , Kim Beom Joon , Kim Chi Kyung , Kim Yerim , Yang Wookjin , Park Eun‐Sun , Lee Seung‐Hoon 
Published: August 2017

Background

The current guideline recommends moderate‐ to vigorous‐intensity physical activity (
PA
) at least 40 min/day for 3 to 4 days/week. Although recent evidence has demonstrated that low‐dose
PA
could reduce cardiovascular mortality, the relationship between low‐dose
PA
and the risk of stroke remains uncertain.

Methods and Results

Using data from a nation‐wide sample cohort in Korea, we examined 336 326 individuals who received a general health examination between 2009 and 2010. Level of
PA
was assessed using a questionnaire for weekly
PA
frequencies regarding 3 intensity categories: light, moderate, and vigorous. Moderate‐ to vigorous‐intensity
PA
(
MVPA
) was classified into 4 frequency categories: none, 1 to 2, 3 to 4, or ≥5 times/week. Cox proportional hazard models were constructed to estimate the risk of stroke. During the average follow‐up of 3.6 years, 2213 stroke cases occurred.
MVPA
was none in 50%, 1 to 2 times/week in 20%, 3 to 4 times/week in 13%, and ≥5 times/week in 18% of the cohort. Individuals with
MVPA
1 to 2 times/week had a 16% reduced risk of stroke (adjusted hazard ratio, 0.84; 95% confidence interval, 0.73–0.96) compared with those with no
MVPA
. The population attributable fraction of no
MVPA
was 12%, which was the second most important risk factor for a stroke after hypertension.

Conclusions

Even 1 to 2 times a week of
MVPA
might be beneficial to prevent a first‐ever stroke in the general population, although a quantitative validation of the questionnaire is needed. From a public health perspective, we need to encourage inactive people to start exercising with more‐achievable goals.
Inspiratory Muscle Training Is Associated With Improved Inspiratory Muscle Strength, Resting Cardiac Output, and the Ventilatory Efficiency of Exercise in Patients With a Fontan Circulation
Authors: Laohachai Karina , Winlaw David , Selvadurai Hiran , Gnanappa Ganesh Kumar , d'Udekem Yves , Celermajer David , Ayer Julian 
Published: September 2017

Background

Patients with a Fontan circulation have reduced exercise capacity and respiratory muscle strength. Inspiratory muscle training (
IMT
) improves exercise capacity and quality of life in adults with heart failure. We assessed whether 6 weeks of a home‐based program of
IMT
improves inspiratory muscle strength and the ventilatory efficiency of exercise in adolescent patients with a Fontan circulation.

Methods and Results

Twenty‐three adolescent participants (aged 16±2 years) with a Fontan circulation underwent 6 weeks of
IMT
for 30 minutes daily. Respiratory muscle strength (maximal inspiratory pressure and expiratory pressure), lung function, and exercise capacity (cardiopulmonary exercise testing) were assessed. Fourteen of 23 participants also underwent exercise cardiac magnetic resonance imaging to examine the effects of
IMT
on cardiac output and systemic and pulmonary blood flow. Six weeks of
IMT
improved maximal inspiratory pressure by 36±24 cm H
2
O (61±46%) with no change in maximal expiratory pressure. Ventilatory efficiency of exercise improved after 6 weeks of
IMT
(from 34.2±7.8 to 32.2±5.6,
P
=0.04). In those who underwent exercise cardiac magnetic resonance imaging,
IMT
increased resting cardiac output (from 4.2±1.2 to 4.5±1.0 L/min,
P
=0.03) and ejection fraction (from 50.1±4.3 to 52.8±6.1%,
P
=0.03).

Conclusions

Six weeks of
IMT
is associated with improved inspiratory muscle strength, ventilatory efficiency of exercise, and resting cardiac output in young Fontan patients.
IMT
may be a simple beneficial addition to the current management of Fontan patients, potentially reducing exercise intolerance and long‐term morbidity and mortality.
Utilizing Probabilistic Downscaling Methods to Develop Streamflow Forecasts from Climate Forecasts
Authors: Mazrooei Amirhossein , Sankarasubramanian A. 
Published: September 2017

Abstract
Statistical information from ensembles of climate forecasts can be utilized in improving the streamflow predictions by using different downscaling methods. This study investigates the use of multinomial logistic regression (MLR) in downscaling large-scale ensemble climate forecasts into basin-scale probabilistic streamflow forecasts of categorical events over major river basins across the U.S. Sun Belt. The performance of MLR is then compared with the categorical forecasts estimated from the traditional approach, principal component regression (PCR). Results from both cross validation and split sampling reveal that in general, the probabilistic categorical forecasts from the MLR model have more accuracy and exhibit higher rank probability skill score (RPSS) compared to the PCR probabilistic forecasts. MLR forecasts are also more skillful than PCR forecasts during the winter season as well as for basins that exhibit high interannual variability in streamflows. The role of ensemble size of precipitation forecasts in developing MLR-based streamflow forecasts was also investigated. Because of its simplicity, MLR offers an alternate, reliable approach to developing categorical streamflow forecasts.
Satellite Precipitation Characterization, Error Modeling, and Error Correction Using Censored Shifted Gamma Distributions
Authors: Wright Daniel B. , Kirschbaum Dalia B. , Yatheendradas Soni 
Published: September 2017

Abstract
Satellite multisensor precipitation products (SMPPs) have a variety of potential uses but suffer from relatively poor accuracy due to systematic biases and random errors in precipitation occurrence and magnitude. The censored, shifted gamma distribution (CSGD) is used here to characterize the Tropical Rainfall Measurement Mission Multisatellite Precipitation Analysis (TMPA), a commonly used SMPP, and to compare it against the rain gauge–based North American Land Data Assimilation System phase 2 (NLDAS-2) reference precipitation dataset across the conterminous United States. The CSGD describes both the occurrence and the magnitude of precipitation. Climatological CSGD characterization reveals significant regional differences between TMPA and NLDAS-2 in terms of magnitude and probability of occurrence. A flexible CSGD-based error modeling framework is also used to quantify errors in TMPA relative to NLDAS-2. The framework can model conditional bias as either a linear or nonlinear function of satellite precipitation rate and can produce a “conditional CSGD” describing the distribution of “true” precipitation based on a satellite observation. The framework is also used to “merge” TMPA with atmospheric variables from version 2 of the Modern-Era Retrospective Analysis for Research and Applications (MERRA-2) to reduce SMPP errors. Despite the coarse resolution of MERRA-2, this merging offers robust reductions in random error due to the better performance of numerical models in resolving stratiform precipitation. Improvements in the near-real-time version of TMPA are relatively greater than for the higher-latency research version.
Arthroscopic Knot Removal for Failed Superior Labrum Anterior-Posterior Repair Secondary to Knot-Induced Pain
Authors: Park Jung Gwan , Cho Nam Su , Kim Jung Youn , Song Jong Hoon , Hong Se Jung , Rhee Yong Girl 
Published: September 2017

Background:Studies on failed superior labrum anterior-posterior (SLAP) repair are increasing. However, the number of reports on treatment options for failed SLAP repair remains quite low, and the clinical results vary between different study groups.Purpose:To describe the clinical presentation of failed SLAP repair due to knot-induced pain and evaluate the efficacy of arthroscopic knot removal.Study Design:Case series; Level of evidence, 4.Methods:The authors retrospectively reviewed records of 11 patients (mean age, 24.6 ± 8.6 years; range, 17-43 years) with stable, healed SLAP lesions with knot-induced pain after arthroscopic fixation of unstable type II SLAP lesions. All patients demonstrated a positive compression-rotation test before knot removal. The mean follow-up duration after knot removal was 48.0 ± 37.4 months (range, 24-156 months). The mean duration between primary fixation and knot removal was 21.2 ± 14.7 months (range, 8-56 months).Results:Sharp pain (100%) and clicking (64%) were the most common symptoms. The knot was positioned on the glenoid side in 5 patients and the labral side in 6 patients. The knots on the glenoid side had associated humeral head cartilage damage. The mean University of California at Los Angeles score significantly improved from 15.2 points to 31.7 points after knot removal ( P = .003) Additionally, the mean Constant score greatly improved from a mean of 56.5 points to 89.8 points ( P = .003). At a mean of 3 weeks after surgery, we observed dramatic pain relief. Six weeks after surgery, the compression-rotation test was negative in all patients.Conclusion:The most common symptom of knot-induced pain after SLAP repair was persistent sharp pain followed by clicking. The knot appears to be a cause of pain in failed SLAP repairs, and arthroscopic knot removal can provide dramatic pain relief and significant improvement of clinical outcomes.