bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of land use change on soil aggregate dynamics in the dry tropics
Authors: Singh Mahesh Kumar , Singh Sunil , Ghoshal Nandita 
Published: April 2017

AbstractA 2‐year study was conducted to elucidate land use change (LUC) impact on the distribution of aggregate size fractions and associated carbon (C) concentration involving natural forest (NF), degraded forest (DF), cropland (CL), and biofuel plantation (JP, Jatropha plantation) in the dry tropical region of India across the soil profile (0–10, 10–20, and 20–30 cm). Across the seasons and the land uses, the proportion of macro‐ and microaggregates was maximum at upper and minimum at lower layer whereas mesoaggregates increase with depth. The trend of macro‐ and microaggregate fractions through the soil profile was NF > JP > DF > CL whereas that of mesoaggregates was CL > DF < JP > NF. Dry mean weight diameter was highest at upper layer and decreased down the depth in all the land uses and followed the trend NF > JP > DF > CL. Aggregate associated organic carbon (OC) concentration in all the fractions decreased from NF to DF, CL, or JP indicates that macroaggregate associated OC concentration was more susceptible to loss than that of meso‐ and microaggregate associated OC concentration. LUC induced decline in macroaggregate associated OC stock and increase in meso‐ and microaggregate associated OC stock; indicated redistribution of OC stock among aggregate fractions. It may be concluded that JP in dry tropics can be an efficient strategy for rehabilitation of degraded land as it improves aggregate structure and stability in the whole profile and aggregate associated OC stock in upper layer of soil.
Assessing PTSD in the military: Validation of a scale distributed to Danish soldiers after deployment since 1998
Authors: Karstoft Karen‐Inge , Andersen Søren B. , Nielsen Anni B. S. 
Published: April 2017

Since 1998, soldiers deployed to war zones with the Danish Defense (≈31,000) have been invited to fill out a questionnaire on post‐mission reactions. This provides a unique data source for studying the psychological toll of war. Here, we validate a measure of PTSD‐symptoms from the questionnaire. Soldiers from two cohorts deployed to Afghanistan with the International Security Assistance Force (ISAF) in 2009 (ISAF7, N = 334) and 2013 (ISAF15, N = 278) filled out a standard questionnaire (Psychological Reactions following International Missions, PRIM) concerning a range of post‐deployment reactions including symptoms of PTSD (PRIM‐PTSD). They also filled out a validated measure of PTSD‐symptoms in DSM‐IV, the PTSD‐checklist (PCL). We tested reliability of PRIM‐PTSD by estimating Cronbach's alpha, and tested validity by correlating items, clusters, and overall scale with corresponding items in the PCL. Furthermore, we conducted two confirmatory factor analytic models to test the factor structure of PRIM‐PTSD, and tested measurement invariance of the selected model. Finally, we established a screening and a clinical cutoff score by application of ROC analysis. We found high internal consistency of the PRIM‐PTSD (Cronbach's alpha = 0.88; both cohorts), strong item‐item (0.48–0.83), item‐cluster (0.43–0.72), cluster‐cluster (0.71–0.82) and full‐scale (0.86–0.88) correlations between PRIM‐PTSD and PCL. The factor analyses showed adequate fit of a one‐factor model, which was also found to display strong measurement invariance across cohorts. ROC curve analysis established cutoff scores for screening (sensitivity = 1, specificity = 0.93) and clinical use (sensitivity = 0.71, specificity = 0.98). In conclusion, we find that PRIM‐PTSD is a valid measure for assessing PTSD‐symptoms in Danish soldiers following deployment.
Comparative Pharmacodynamics of Telavancin and Vancomycin in the Neutropenic Murine Thigh and Lung Infection Models against Staphylococcus aureus
Authors: Lepak Alexander J. , Zhao Miao , Andes David R. 
Published: April 2017

ABSTRACT

The pharmacodynamics of telavancin and vancomycin were compared using neutropenic murine thigh and lung infection models. Four
Staphylococcus aureus
strains were included. The telavancin MIC ranged from 0.06 to 0.25 mg/liter, and the vancomycin MIC ranged from 1 to 4 mg/liter. The plasma pharmacokinetics of escalating doses (1.25, 5, 20, and 80 mg/kg of body weight) of telavancin and vancomycin were linear over the dose range. Epithelial lining fluid (ELF) pharmacokinetics for each drug revealed that penetration into the ELF mirrored the percentage of the free fraction (the fraction not protein bound) in plasma for each drug. Telavancin (0.3125 to 80 mg/kg/6 h) and vancomycin (0.3125 to 1,280 mg/kg/6 h) were administered by the subcutaneous route in treatment studies. Dose-dependent bactericidal activity against all four strains was observed in both models. A sigmoid maximum-effect model was used to determine the area under the concentration-time curve (AUC)/MIC exposure associated with net stasis and 1-log
10
kill relative to the burden at the start of therapy. The 24-h plasma free drug AUC (
f
AUC)/MIC values associated with stasis and 1-log kill were remarkably congruent. Net stasis for telavancin was noted at
f
AUC/MIC values of 83 and 40.4 in the thigh and lung, respectively, and 1-log kill was noted at
f
AUC/MIC values of 215 and 76.4, respectively. For vancomycin, the
f
AUC/MIC values for stasis were 77.9 and 45.3, respectively, and those for 1-log kill were 282 and 113, respectively. The 24-h ELF total drug AUC/MIC targets in the lung model were very similar to the 24-h plasma free drug AUC/MIC targets for each drug. Integration of human pharmacokinetic data for telavancin, the results of the MIC distribution studies, and the pharmacodynamic targets identified in this study suggests that the current dosing regimen of telavancin is optimized to obtain drug exposures sufficient to treat
S. aureus
infections.
Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons
Authors: Asante-Appiah Ernest , Curry Stephanie , McMonagle Patricia , Ingravallo Paul , Chase Robert , Nickle David , Qiu Ping , Howe Anita , Lahser Frederick C. 
Published: April 2017

ABSTRACT

Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents—grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor—in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC
50
) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC
50
for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM;
n
= 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from
de novo
resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC
50
against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC
50
for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM;
n
= 14).
De novo
resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir. The activity profiles of grazoprevir and elbasvir supported the testing of the direct-acting antivirals in clinical studies.
Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model
Authors: Zhao Chunxia , Gunawardana Manjula , Villinger Francois , Baum Marc M. , Remedios-Chan Mariana , Moench Thomas R. , Zeitlin Larry , Whaley Kevin J. , Bohorov Ognian , Smith Thomas J. , Anderson Deborah J. , Moss John A. 
Published: April 2017

ABSTRACT

The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known human immunodeficiency virus type 1 (HIV-1) isolates
in vitro
, is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other underdeveloped regions may be limited by the high cost of conventionally produced antibodies and the limited capacity to manufacture such antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering
Nicotiana
-manufactured VRC01 (VRC01-N) over a range of release rates have been developed. The pharmacokinetics and preliminary safety of VRC01-N pod-IVRs were evaluated in a rhesus macaque model. The devices sustained VRC01-N release for up to 21 days at controlled rates, with mean steady-state VRC01-N levels in vaginal fluids in the range of 10
2
to 10
3
μg g
−1
being correlated with
in vitro
release rates. No adverse safety indications were observed. These findings indicate that pod-IVRs are promising devices for the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection and merit further preclinical evaluation.
Relationship between oxygen concentration and temperature in an exothermic warming device
Authors: Brooks Ben , Deakin Charles D 
Published: April 2017

IntroductionActively warming hypothermic patients or preventing hypothermia is critical in optimising outcomes in patients with traumatic injuries. Our aim was to investigate the effect of ambient oxygen concentration on the rate and change in temperature of the TechTrade Ready-Heat II exothermic (oxygen-activated) warming blanket, to evaluate safety and ascertain the risk of thermal injury.MethodsA mannequin covered with an exothermic blanket was placed in a sealed oxygen tent. An ambulance blanket was placed between the TechTrade Ready-Heat II exothermic blanket and the mannequin. Two temperature probes were placed directly on the surface of the mannequin; one on the torso away from the heating packs and the other directly beneath the exothermic heating pack. The mannequin was exposed to increasing oxygen concentrations at 10% increments, starting at 21%. The experiment was conducted nine times, each time using a new blanket. Maximum temperature of the mannequin ‘skin’ and rate of rise were recorded from both temperature sensors.ResultsIn room air (21% oxygen), the mannequin surface reached 52°C after 60 min, matching manufacturer specifications. At 30% oxygen concentration, the temperature directly beneath the exothermic heating pack exceeded the 65°C threshold at which rapid thermal burns occur, reaching 72.5°C, with minimal change in overall torso temperature.ConclusionThe supplemental use of oxygen in patients with traumatic injuries that increases ambient oxygen levels in the presence of exothermic warming devices may represent a significant risk to the patient. We suggest that prehospital care providers remain highly vigilant of heat when using high-flow oxygen and the subsequent fire risk, while manufacturers of exothermic blankets should consider ways to improve safety.
Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies
Authors: Bui Mai H. , Lin Xiaoyu , Albert Daniel H. , Li Leiming , Lam Lloyd T. , Faivre Emily J. , Warder Scott E. , Huang Xiaoli , Wilcox Denise , Donawho Cherrie K. , Sheppard George S. , Wang Le , Fidanze Steve , Pratt John K. , Liu Dachun , Hasvold Lisa , Uziel Tamar , Lu Xin , Kohlhapp Fred , Fang Guowei , Elmore Steven W. , Rosenberg Saul H. , McDaniel Keith F. , Kati Warren M. , Shen Yu 
Published: April 2017

Abstract
ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models, representing a variety of hematologic malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell-cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo combination studies uncovered surprising benefits of low doses of ABBV-075 coupled with bortezomib and azacitidine treatment, despite the lack of in vitro synergy between ABBV-075 and these agents. The in vitro/in vivo activities of ABBV-075 described here may serve as a useful reference to guide the development of ABBV-075 and other BET family inhibitors for cancer therapy. Cancer Res; 77(11); 2976–89. ©2017 AACR.
Internal Intraseasonal Variability of the West African Monsoon in WRF
Authors: Alaka Ghassan J. , Maloney Eric D. 
Published: April 2017

AbstractThe West African monsoon (WAM) and its landmark features, which include African easterly waves (AEWs) and the African easterly jet (AEJ), exhibit significant intraseasonal variability in boreal summer. However, the degree to which this variability is modulated by external large-scale phenomena, such as the Madden–Julian oscillation (MJO), remains unclear. The Weather Research and Forecasting (WRF) Model is employed to diagnose the importance of the MJO and other external influences for the intraseasonal variability of the WAM and associated AEW energetics by removing 30–90-day signals from initial and lateral boundary conditions in sensitivity tests. The WAM produces similar intraseasonal variability in the absence of external influences, indicating that the MJO is not critical to produce WAM variability. In control and sensitivity experiments, AEW precursor signals are similar near the AEJ entrance in East Africa. For example, an eastward extension of the AEJ increases barotropic and baroclinic energy conversions in East Africa prior to a 30–90-day maximum of perturbation kinetic energy in West Africa. The WAM appears to prefer a faster oscillation when MJO forcing is removed, suggesting that the MJO may serve as a pacemaker for intraseasonal oscillations in the WAM. WRF results show that eastward propagating intraseasonal signals (e.g., Kelvin wave fronts) are responsible for this pacing, while the role of westward propagating intraseasonal signals (e.g., MJO-induced Rossby waves) appears to be limited. Mean state biases across the simulations complicate the interpretation of results.
Longitudinal changes in the antecedent and early manifest course of bipolar disorder—A narrative review of prospective studies
Authors: Pfennig Andrea , Leopold Karolina , Ritter Philipp , Böhme Anne , Severus Emanuel , Bauer Michael 
Published: April 2017

Objective: Prospective study designs ideally allow patients to be followed from the first manifestations of the illness or even from an at-risk stage. It can thus provide data on the predictive value of changes in clinical symptomatology, cognition or further biological markers to broaden our understanding of the etiopathology and symptomatic trajectory of bipolar disorders. The scope of this narrative review is to summarize evidence from prospectively collected data on psychopathological and other clinical and biological changes in the early developmental course of bipolar disorders. Methods: The narrative review was based on a literature search conducted in February 2016 within the PubMed library for prospective study data of persons in antecedent and early manifest stages of manifest bipolar disorder published within the last 15 years. Results: A total of 19 prospective studies were included. Regarding psychopathological features; personality, temperament and character traits as well as changes in sleep and circadian rhythm, the evidence suggests that risk factors for the development of bipolar disorder can already be described and should be studied further to understand their interaction, mediation with other factors and timing in the developmental process of bipolar disorder. Apart from the positive family history, childhood anxiety, sleep problems, subthreshold (hypo)manic symptoms and certain character traits/emotionality should be identified and monitored already in clinical practice as their presence likely increases risk of bipolar disorder. Up to date no substantiated evidence was found from prospective studies addressing cognitive features, life events, immunological parameters and morphological central nervous system changes as potential risk factors for bipolar disorder. Conclusion: For an improved understanding of episodic disorders, longitudinal data collection is essential. Since the etiology of bipolar disorders is complex, a number of potential risk factors have been proposed. Prospective studies addressing this spectrum and resilience factors are critical and will be best conducted within multi-site research networks or initiatives.
Tracheostomy for Severe Pediatric Obstructive Sleep Apnea: Indications and Outcomes
Authors: Rizzi Christopher J. , Amin Julian D. , Isaiah Amal , Valdez Tulio A. , Jeyakumar Anita , Smart Suzanne E. , Pereira Kevin D. 
Published: April 2017

Objectives(1) To describe characteristics of pediatric patients undergoing tracheostomy for obstructive sleep apnea (OSA). (2) To highlight perioperative events and outcomes of the procedure.Study DesignCase series with chart review.SettingFour tertiary care academic children’s hospitals.Subjects and MethodsTwenty‐nine children aged <18 years from January 1, 2010, to December 31, 2015, who underwent tracheostomy for severe OSA, defined as an apnea‐hypopnea index (AHI) >10, were included in the study. Data on patient characteristics, polysomnographic findings, comorbidities, and perioperative events and outcomes were collected and analyzed.ResultsTwenty‐nine patients were included. Mean age at tracheostomy was 2.0 years (95% CI, −2.2 to 6.2). Mean body mass index z score was −1.2 (95% CI, −4.9 to −2.5). Mean preoperative AHI was 60.2 (95% CI, −15.7 to 136.1). Mean postoperative intensive care unit stay was 23.2 days (95% CI, 1.44‐45.0). One procedure was complicated by bronchospasm. Thirteen patients had craniofacial abnormalities; 10 had a neurologic disorder resulting in hypotonia; and 5 had a diagnosis of laryngomalacia. Mean follow‐up was 30.6 months (95% CI, −10.4 to 71.6). Six patients were decannulated, with a mean time to decannulation of 40.8 months (95% CI, 7.9‐73.7). Five patients underwent capped sleep study prior to decannulation with a mean AHI of 6.6 (95% CI, −9.9 to 23.1) and a mean oxygen nadir of 90.0% (95% CI, 80%‐100%).ConclusionOSA is an uncommon indication for tracheostomy in children. Patients who require the procedure usually have an associated syndromic diagnosis resulting in upper airway obstruction. The majority of children who undergo tracheostomy for OSA will remain dependent at 24 months.
Otolaryngology Residency Program Research Resources and Scholarly Productivity
Authors: Villwock Jennifer A. , Hamill Chelsea S. , Nicholas Brian D. , Ryan Jesse T. 
Published: April 2017

ObjectiveTo delineate research resources available to otolaryngology residents and their impact on scholarly productivity.Study DesignSurvey of current otolaryngology program directors.SettingOtolaryngology residency programs.Subjects and MethodsAn anonymous web‐based survey was sent to 98 allopathic otolaryngology training program directors. Fisher exact tests and nonparametric correlations were used to determine statistically significant differences among various strata of programs.ResultsThirty‐nine percent (n = 38) of queried programs responded. Fourteen (37%) programs had 11 to 15 full‐time, academic faculty associated with the residency program. Twenty (53%) programs have a dedicated research coordinator. Basic science lab space and financial resources for statistical work were present at 22 programs (58%). Funding is uniformly provided for presentation of research at conferences; a minority of programs (13%) only funded podium presentations. Twenty‐four (63%) have resident research requirements beyond the Accreditation Council for Graduate Medical Education (ACGME) mandate of preparing a “manuscript suitable for publication” prior to graduation. Twenty‐five (67%) programs have residents with 2 to 3 active research projects at any given time. None of the investigated resources were significantly associated with increased scholarly output. There was no uniformity to research curricula.ConclusionsOtolaryngology residency programs value research, evidenced by financial support provided and requirements beyond the ACGME minimum. Additional resources were not statistically related to an increase in resident research productivity, although they may contribute positively to the overall research experience during training. Potential future areas to examine include research curricula best practices, how to develop meaningful mentorship and resource allocation that inspires continued research interest, and intellectual stimulation.
The Relationship of Static Tibial Tubercle–Trochlear Groove Measurement and Dynamic Patellar Tracking
Authors: Carlson Victor R. , Sheehan Frances T. , Shen Aricia , Yao Lawrence , Jackson Jennifer N. , Boden Barry P. 
Published: April 2017

Background: The tibial tubercle to trochlear groove (TT-TG) distance is used for screening patients with a variety of patellofemoral joint disorders to determine who may benefit from patellar medialization using a tibial tubercle osteotomy. Clinically, the TT-TG distance is predominately based on static imaging with the knee in full extension; however, the predictive ability of this measure for dynamic patellar tracking patterns is unknown. Purpose: To determine whether the static TT-TG distance can predict dynamic lateral displacement of the patella. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: The static TT-TG distance was measured at full extension for 70 skeletally mature subjects with (n = 32) and without (n = 38) patellofemoral pain. The dynamic patellar tracking patterns were assessed from approximately 45° to 0° of knee flexion by use of dynamic cine-phase contrast magnetic resonance imaging. For each subject, the value of dynamic lateral tracking corresponding to the exact knee angle measured in the static images for that subject was identified. Linear regression analysis determined the predictive ability of static TT-TG distance for dynamic patellar lateral displacement for each cohort. Results: The static TT-TG distance measured with the knee in full extension cannot accurately predict dynamic lateral displacement of the patella. There was weak predictive ability among subjects with patellofemoral pain ( r2 = 0.18, P = .02) and no predictive capability among controls. Among subjects with patellofemoral pain and static TT-TG distances 15 mm or more, 8 of 13 subjects (62%) demonstrated neutral or medial patellar tracking patterns. Conclusion: The static TT-TG distance cannot accurately predict dynamic lateral displacement of the patella. A large percentage of patients with patellofemoral pain and pathologically large TT-TG distances may have neutral to medial maltracking patterns.