bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loop Current Variability as Trigger of Coherent Gulf Stream Transport Anomalies
Authors: Hirschi Joël J.-M. , Frajka-Williams Eleanor , Blaker Adam T. , Sinha Bablu , Coward Andrew , Hyder Pat , Biastoch Arne , Böning Claus , Barnier Bernard , Penduff Thierry , Garcia Ixetl , Fransner Filippa , Madec Gurvan 
Published: May 2019

AbstractSatellite observations and output from a high-resolution ocean model are used to investigate how the Loop Current in the Gulf of Mexico affects the Gulf Stream transport through the Florida Straits. We find that the expansion (contraction) of the Loop Current leads to lower (higher) transports through the Straits of Florida. The associated surface velocity anomalies are coherent from the southwestern tip of Florida to Cape Hatteras. A simple continuity-based argument can be used to explain the link between the Loop Current and the downstream Gulf Stream transport: as the Loop Current lengthens (shortens) its path in the Gulf of Mexico, the flow out of the Gulf decreases (increases). Anomalies in the surface velocity field are first seen to the southwest of Florida and within 4 weeks propagate through the Florida Straits up to Cape Hatteras and into the Gulf Stream Extension. In both the observations and the model this propagation can be seen as pulses in the surface velocities. We estimate that the Loop Current variability can be linked to a variability of several Sverdrups (1Sv = 106 m3 s−1) through the Florida Straits. The exact timing of the Loop Current variability is largely unpredictable beyond a few weeks and its variability is therefore likely a major contributor to the chaotic/intrinsic variability of the Gulf Stream. However, the time lag between the Loop Current and the flow downstream of the Gulf of Mexico means that if a lengthening/shortening of the Loop Current is observed this introduces some predictability in the downstream flow for a few weeks.
Catheter-directed foam sclerotherapy with tumescence of the great saphenous vein versus ultrasound-guided foam sclerotherapy: A randomized controlled trial
Authors: dos Santos Jorgete B , Júnior Walter Campos , Porta Rina MP , Puggina Juliana , da Silva Daniela FT , Puech-Leão Pedro , de Luccia Nelson , da Silva Erasmo S 
Published: May 2019

Objectives To compare the effectiveness of two foam sclerotherapy techniques of the great saphenous vein. Methods Fifty subjects with varicose veins, edema, and great saphenous vein incompetence (diameter 6–10 mm) were randomly categorized into two equal groups and were treated with different foam sclerotherapy techniques: A (usual ultrasound-guided) and B (catheter-directed with tumescence). Concomitant phlebectomy was performed in all patients. Patients were seen on days 7 and 28, and at six and 12 months. The primary outcomes were the full success rate of the treated great saphenous vein and the number of patients who required retreatment sessions performed at 28-day follow-up. The secondary-assisted outcomes were the full success rates of the treated great saphenous vein after the retreatment sessions at six- and 12-month follow-up. Secondary outcomes were changes in quality of life and side effects and complications of the intervention. In case of reflux, retreatment sessions were performed at 28 days and six months in both groups. Results Full success rate of the treated great saphenous vein was 36% in group A vs. 80% in group B ( p = 0.012) and the number of patients who required retreatment sessions were n = 14 in group A vs. n = 3 in group B at 28-day follow-up ( p = 0.002). Both were statistically significant. At six and 12 months, the success rates were not statistically significant between the groups. Complication rates were similar between the groups. Quality of life improved in both groups with statistical difference ( p < 0.001). Conclusions Catheter-directed foam sclerotherapy with tumescence was better than usual ultrasound-guided foam sclerotherapy as it reached higher full success rate of the treated great saphenous vein and as a lower number of patients required retreatment sessions in the short-term. Both methods proved to be safe and improved the quality of life.
Persistent Sunk Cost Fallacy in a Real Effort Experiment
Authors: Banerjee Priyodorshi , Chandrasekhar S. , Srikant P. 
Published: May 2019

Subjects chose whether to leave with an endowment or stay to perform some simple tasks in a real effort experiment. In addition to performance pay, staying subjects received their endowment in the control condition, but had to sacrifice it in the treatment condition. We found average performance of staying subjects, after controlling for selection effects, was higher in the treatment condition. Further, the sunk cost effect persisted well after the decision as to whether to stay or leave had been made. JEL Classification: D24, D83, J24
HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting
Authors: Khan Nawaid Hussain , Kohli Mikashmi , Gupta Kartik , Das Bimal Kumar , Pandey Ravindra Mohan , Sinha Sanjeev 
Published: May 2019

Introduction: The present study aimed to report the prevalent HIV-1 drug-resistant mutations in patients with HIV-1 alone and tuberculosis (TB) coinfection alone to improve our understanding of the mutation patterns and aid treatment decisions. Methods: Patients with HIV-1 and HIV-TB on treatment for more than 1 year with suspected failure were recruited. Sequencing of protease and two-thirds of the region of reverse transcriptase gene was done for drug-resistant mutations. Results: In the HIV-TB group (n = 25), 88%, 92%, and 12% had mutations to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs), respectively. In the HIV-alone group (n = 25), 84%, 100%, and 4% had mutations to NRTIs, NNRTIs, and PIs, respectively. M184V, M41L, D67N, G190A, A98G, and K103N were the most common mutations seen. Conclusion: There is a high prevalence of drug-resistant mutations in HIV and HIV-TB coinfected patients.
Computed Tomography Features of Glenoid Osteophytes in Traumatic Anterior Shoulder Instability: Comparison Between Younger and Older Patients
Authors: Hirose Takehito , Nakagawa Shigeto , Sato Seira , Tachibana Yuta , Mae Tatsuo 
Published: May 2019

Background: Osteoarthritis that develops after traumatic anterior shoulder instability is known as dislocation arthropathy, but its frequency and characteristics are still unclear. Purpose: To evaluate glenoid osteophytes in shoulders with traumatic anterior instability by using computed tomography (CT) and to elucidate the influence of instability on the progression of dislocation arthropathy in different age groups. Study Design: Cross-sectional study; Level of evidence, 3. Methods: This study involved 214 unoperated patients with unilateral instability who underwent CT of both shoulders. The patients were divided into 2 groups according to age at the time of CT: ≤30 years (younger group; n = 172) and ≥31 years (older group; n = 42). Patient demographics as well as the presence, size, and location of glenoid osteophytes were compared between the 2 groups and also between patients with and without osteophytes. Furthermore, patients with osteophytes in the older group were divided into 2 subgroups according to age at the time of the initial injury: as a teenager (early-onset subgroup; n = 9) or at ≥31 years (late-onset subgroup; n = 14), and the same assessments were conducted. Results: Osteophytes were significantly more frequent on the affected side of the older group compared with the younger group (71.4% vs 13.9%, respectively; P < .001). In the younger group, patients with osteophytes had more multiple-instability events ( P = .002) and a longer interval from injury to CT ( P < .001) than those without osteophytes. Although there was no difference in osteophyte size between the 2 groups, most osteophytes were located at the anteroinferior part of the glenoid in the younger group, while osteophytes were usually circumferential around the glenoid in the older group. A comparison between the early- and late-onset subgroups in older patients with osteophytes revealed that the osteophytes were more frequently located at the anteroinferior glenoid region in the early-onset subgroup. Conclusion: CT allowed a detailed evaluation of glenoid osteophytes, revealing that osteophytes were not uncommon in younger patients. Instability itself might influence the progression of osteoarthritic changes in younger patients, while aging seems to have a greater effect in older patients.
Navigating Organisation in Times of VUCA: Implications for the HR and OD Profession
Authors: Alasingachar Vasudevan 
Published: May 2019

This article addresses two vectors of VUCA interwoven in the narratives, a summary of personal theories about VUCA. Such theories are anchored and arise from experiential learning in my practice as HR/L&D and OD consultants over the past four decades. The implication for HR and OD profession is to consider their relevance when organisations navigate VUCA. Next is the culling out of the specific learning about HR and OD interphases that has worked in my experience, supported by examples and metaphors. The premise I put forward as conclusion are: In order to be at the centre stage of partnering with business, HR and OD have to complement and innovate new-age VUCA strategies. VUCA competencies with appropriate metrics are in the formative stage. The competencies are emerging from the real-time stories of consultants, companies and academia (TATA 26/11 and DuPont safety mandate). Only when HR and OD integrate and work together can the future of leadership or start-up entrepreneurs learn from their insights to ‘thrive in VUCA’.
Schizophrenic Deterioration
Authors: Bleuler Manfred , Ciompi Luc , Crow T. J. , Abrahamson David , Tantam D. 
Published: May 2019

Psychological deterioration, defect state and psychological deficit are all terms introduced this century to replace Kraepelin's idea of dementia praecox. They all express the notion that schizophrenics have some global impairment in psychological functioning, which is different from the presenile dementias or recognised causes of cerebral dysfunction. At the beginning of the century it was generally regarded as organic in nature. In the 1960s the social revolution in psychiatry encouraged the view that the deterioration was psychosocial, the effect of institutionalisation. There has been a recent trend to revive the organic formulation.The five articles which follow examine the idea from different points of view. They were commissioned because correspondence to the editor indicated that the issue was topical and controversial. It is hoped that they may be the first of a series of multi-author contributions on topical issues.Manfred Bleuler presents his view that deterioration is not a progressive condition, but one of several outcomes, and even then liable to remission. Luc Ciompi discusses the relationship between organic and psychosocial factors in its cause, and concludes that it is the result of an interaction between the two. Tim Crow gives a clear account of the organic model. David Abrahamson draws attention to some methodological issues, which have led to a false clinical impression, and wrongly overemphasised the extent of deterioration. Digby Tantam analyses the complex effect of drug treatment.
CD33_PGx6_Score Predicts Gemtuzumab Ozogamicin Response in Childhood Acute Myeloid Leukemia: A Report From the Children’s Oncology Group
Authors: Chauhan Lata , Shin Miyoung , Wang Yi-Cheng , Loken Michael , Pollard Jessica , Aplenc Richard , Hirsch Betsy A. , Raimondi Susana , Ries Rhonda E. , Bernstein Irwin D. , Gamis Alan S. , Alonzo Todd A. , Meshinchi Soheil , Lamba Jatinder K. 
Published: May 2019

PURPOSE The US Food and Drug Administration recently announced reapproval of gemtuzumab ozogamicin (GO) for treatment of CD33-positive acute myeloid leukemia (AML), thus opening up opportunities to develop strategies for effective use of GO. In light of our recent report showing prognostic significance of CD33 splicing single nucleotide polymorphisms (SNPs), the objective of this study was to comprehensively evaluate CD33 SNPs for accurate prediction of patients with AML who are more or less likely to respond to GO. PATIENTS AND METHODS We investigated the five new CD33 SNPs (rs2455069, rs35112940, rs61736475, rs1803254, and rs201074739) for association with CD33 leukemic cell surface expression and clinical response in pediatric patients with AML enrolled in the Children’s Oncology Group AAML0531 trial. We further developed a composite CD33 pharmacogenetics (PGx) score using six CD33 SNPs (CD33_PGx6_score) for association with clinical outcome. RESULTS Four CD33 SNPs were associated with cell surface CD33 levels and clinical response in the GO versus no-GO arms. Therefore, the CD33_PGx6_score was built using directional genotype scores for the previously reported splicing SNP and five new SNPs. Patients with a CD33_PGx6_score of 0 or higher had higher CD33 expression levels compared with patients with a score of less than 0 ( P < .001). In addition, patients with a score of 0 or higher demonstrated an improved disease-free survival in the GO versus no-GO arms (62.5% ± 7.8% v 46.8% ± 8.3%, respectively; P = .008) and a reduced risk of relapse (28.3% ± 7.2% v 49.9% ± 8.4%, respectively; P < .001). No improvement from GO was observed in patients with a CD33-PGx6_score of less than 0. Consistent results were observed across the risk groups. CONCLUSION In this study, we report a composite CD33_PGx6_score using directional genotype scores of CD33 SNPs. Once validated, our findings hold promise for use of the CD33_PGx6_score to guide efficient use of GO in patients with AML. In addition, because the CD33_PGx6_score considers SNPs with varying abundance in different ethnic groups, it has potential for global application.
Maternal and Offspring Genetic Risk of Type 2 Diabetes and Offspring Birthweight Among African Ancestry Populations
Authors: Rahman Mohammad L , Shrestha Deepika , Workalemahu Tsegaselassie , Wu Jing , Zhu Chunming , Zhang Cuilin , Tekola-Ayele Fasil 
Published: May 2019

AbstractObjectivesMaternal genetic risk of type 2 diabetes (T2D) can influence offspring birthweight through shared offspring genetic risk and by altering intrauterine glycemic status. The aim of this study was to estimate the independent effects of maternal and offspring genetic risk scores (GRSs) of T2D on offspring birthweight and the extent to which intrauterine glycemic traits mediate the effect of maternal GRSs on offspring birthweight.DesignThe study involved 949 mother–offspring pairs of African ancestry from the Hyperglycemia Adverse Pregnancy Outcome study. GRSs of T2D were calculated separately for mothers and offspring as the weighted sum of 91 T2D risk alleles identified in a genome-wide association study meta-analysis in African Americans. Linear regression models were fit to estimate changes in birthweight by quartiles of GRSs. Mediation analysis was implemented to estimate the direct and indirect effects of maternal GRS on offspring birthweight through cord blood C-peptide and maternal fasting and postchallenge glucose levels.ResultsMaternal and offspring GRSs were independently and differentially associated with offspring birthweight. Changes (95% CI) in birthweight across increasing quartiles of maternal GRSs were 0 g (reference), 83.1 g (6.5, 159.6), 103.1 g (26.0, 180.2), and 92.7 g (12.6, 172.8) (P trend = 0.041) and those of offspring GRSs were 0 (reference), −92.0 g (−169.2, −14.9), −64.9 g (−142.4, 12.6), and 2.0 g (−77.8, 81.7) (P trend = 0.032). Cord blood C-peptide mediated the effect of maternal GRS on offspring birthweight, whereas maternal postchallenge glucose levels showed additive effects with maternal GRS on birthweight.ConclusionsMaternal and offspring GRSs of T2D were independently and differentially associated with offspring birthweight.
Circulating Biomarkers of Testosterone’s Anabolic Effects on Fat-Free Mass
Authors: Huang Grace , Rocha Guilherme V , Pencina Karol M , Cox Karen , Krishnan Venkatesh , Henriksen Kim , Mitchell Peter , Sissons Sean E , Li Zhuoying , Nedergaard Anders F , Karsdal Morten A , Sun Shu , Storer Thomas W , Basaria Shehzad , Bhasin Shalender 
Published: May 2019

AbstractBackgroundBiomarkers that predict response to anabolic therapies could expedite the development of function-promoting anabolic drugs. This study aimed to identify serum biomarkers that are responsive to testosterone administration and associated with increases in fat-free mass (FFM).MethodsSerum samples were obtained from the 5α-Reductase Trial, a randomized trial that compared the effects of graded doses of testosterone enanthate for 20 weeks in healthy men randomized with placebo or dutasteride (dual SRD5A inhibitor). Testosterone’s effects on FFM or strength measures did not differ between placebo vs dutasteride groups. Accordingly, 54 subjects treated with testosterone plus placebo were included in the discovery cohort, and 48 subjects randomized to dutasteride were included in the validation cohort. A total of 1162 biomarkers were evaluated using prespecified criteria.ResultsIn the discovery cohort, testosterone administration increased propeptide of type III collagen (PRO-C3) and propeptide of type VI collagen (PRO-C6) levels in a dose- and concentration-dependent manner; increases in these biomarkers from baseline to week 12 were associated with changes in FFM from baseline to week 20 (PRO-C3: r2 = 0.437, P < 0.001; PRO-C6: r2 = 0.434, P < 0.001). Changes in PRO-C3 and PRO-C6 levels were significantly associated with changes in chest press strength (PRO-C3: r2 = 0.394, P < 0.001; PRO-C6: r2 = 0.530, P < 0.001). In the SOMAscan, changes in IGF binding protein-6 (IGFBP6) and glypican 3 (GPC3) were associated with changes in total and free testosterone levels and FFM. These findings were replicated in the Validation cohort.ConclusionPRO-C3, PRO-C6, IGFBP6, and GPC3 fulfilled the prespecified criteria for biomarkers of testosterone-induced muscle anabolism. Changes in these biomarkers were associated with changes in total and free testosterone concentrations and with testosterone-induced gains in FFM.
Polymodal Mechanism for TWIK-Related K+ Channel Inhibition by Local Anesthetic
Authors: Pavel Mahmud Arif , Chung Hae-Won , Petersen E. Nicholas , Hansen Scott B. 
Published: May 2019

BACKGROUND:
Local anesthetics cause reversible block of pain and robustly inhibit TWIK-related K+ channel (TREK-1) currents. Before local anesthesia onset, injection of local anesthetics can cause unwanted transient pain. TREK-1 is an anesthetic-sensitive potassium channel that when inhibited produces pain. A disordered C-terminal loop of TREK-1 is thought to contribute to anesthetic sensitivity, but the molecular basis for TREK-1 inhibition by local anesthetics is unknown. Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA) required for TREK-1 activation and also binds to the channel’s C terminus.

METHODS:
Here, we use biophysical and cellular techniques to characterize direct and indirect lipid-mediated mechanism for TREK-1 inhibition (respectively). We characterized direct binding of local anesthetic to TREK-1 by reconstituting the purified channel into artificial membranes and measuring ion flux. We characterized indirect PA-mediated inhibition of TREK-1 by monitoring lipid production in live whole cells using a fluorescent PLD2 product release assay and ion channel current using live whole-cell patch-clamp electrophysiology. We monitored anesthetic-induced nanoscale translocation of PLD2 to TREK-1 channels with super-resolution direct stochastic reconstruction microscopy (dSTORM).

RESULTS:
We find local anesthetics tetracaine, lidocaine, and bupivacaine directly bind to and inhibit PLD2 enzymatic activity. The lack of PLD2 activity indirectly inhibited TREK-1 currents. Select local anesthetics also partially blocked the open pore of TREK-1 through direct binding. The amount of pore block was variable with tetracaine greater than bupivacaine and lidocaine exhibiting a minor effect. Local anesthetics also disrupt lipid rafts, a mechanism that would normally activate PLD2 were it not for their direct inhibition of enzyme catalysis.

CONCLUSIONS:
We propose a mechanism of TREK-1 inhibition comprised of (1) primarily indirect PLD2-dependent inhibition of lipid catalysis and (2) limited direct inhibition for select local anesthetics through partial open pore block. The inhibition through PLD2 explains how the C terminus can regulate the channel despite being devoid of structure and putative binding sites for local anesthetics.
Evaluating Propofol Concentration in Blood From Exhaled Gas Using a Breathing-Related Partition Coefficient
Authors: Dong Hao , Zhang Fengjiang , Chen Jing , Yu Qiwen , Zhong Yinbo , Liu Jun , Yan Min , Chen Xing 
Published: May 2019

BACKGROUND:
The anesthetic side effects of propofol still occur in clinical practice because no reliable monitoring techniques are available. In this regard, continuous monitoring of propofol in breath is a promising method, yet it remains infeasible because there is large variation in the blood/exhaled gas partial pressure ratio (RBE) in humans. Further evaluations of the influences of breathing-related factors on RBE would mitigate this variation.

METHODS:
Correlations were analyzed between breathing-related factors (tidal volume [TV], breath frequency [BF], and minute ventilation [VM]) and RBE in 46 patients. Furthermore, a subset of 10 patients underwent pulmonary function tests (PFTs), and the parameters of the PFTs were then compared with the RBE. We employed a 1-phase exponential decay model to characterize the influence of VM on RBE. We also proposed a modified RBE (RBEM) that was not affected by the different breathing patterns of the patients. The blood concentration of propofol was predicted from breath monitoring using RBEM and RBE.

RESULTS:
We found a significant negative correlation (R = −0.572; P < .001) between VM and RBE (N = 46). No significant correlation was shown between PFTs and RBE in the subset (N = 10). RBEM demonstrated a standard Gaussian distribution (mean, 1.000; standard deviation [SD], 0.308). Moreover, the predicted propofol concentrations based on breath monitoring matched well with the measured blood concentrations. The 90% prediction band was limited to within ±1 μg·mL−1.

CONCLUSIONS:
The prediction of propofol concentration in blood was more accurate using RBEM than when using RBE and could provide reference information for anesthesiologists. Moreover, the present study provided a general approach for assessing the influence of relevant physiological factors and will inform noninvasive and accurate breath assessment of volatile drugs or metabolites in blood.