bluuebunny/crossref_metadata_2025_split huggingface dataset:
Masterful Antibodies: Checkpoint Blockade
Authors: Lonberg Nils , Korman Alan J. 
Published: April 2017

Abstract
Cancer therapeutics that target the immune system rather than the cancer cell itself are becoming standard of care in a growing number of different malignancies. Although cancer immunotherapy is not a new concept, the potential importance of this class of drugs was probably not fully appreciated as recently as a decade ago when much of the focus of cancer drug discovery was on cancer cell–targeted medicines. The authors were lucky enough to be able to witness and participate in the discovery and development of ipilimumab and nivolumab, two relatively early examples of immune system–targeted drugs. The challenges associated with discovering and developing these molecules may be of historical interest and instructive for moving cancer immunotherapy forward for greater numbers of patients. Cancer Immunol Res; 5(4); 275–81. ©2017 AACR.
Invariance of the Double-Moment Normalized Raindrop Size Distribution through 3D Spatial Displacement in Stratiform Rain
Authors: Raupach Timothy H. , Berne Alexis 
Published: April 2017

AbstractDouble-moment normalization of the drop size distribution (DSD) summarizes the DSD in a compact way, using two of its statistical moments and a “generic” double-moment normalized DSD function. Results are presented of an investigation into the invariance of the double-moment normalized DSD through horizontal and vertical displacement in space, using data from disdrometers, vertically pointing K-band Micro Rain Radars, and an X-band polarimetric weather radar. The invariance of the double-moment normalized DSD is tested over a vertical range of up to 1.8 km and a horizontal range of up to approximately 100 km. The results suggest that for practical use, with well-chosen input moments, the double-moment normalized DSD can be assumed invariant in space in stratiform rain. The choice of moments used to characterize the DSD affects the amount of DSD variability captured by the normalization. It is shown that in stratiform rain, it is possible to capture more than 85% of the variability in DSD moments zero to seven using the technique. Most DSD variability in stratiform rain can thus be explained through the variability of two of its statistical moments. The results suggest similar behavior exists in transition and convective rain, but the limited data samples available do not allow for robust conclusions for these rain types. The results have implications for practical uses of double-moment DSD normalization, including the study of DSD variability and microphysics, DSD-retrieval algorithms, and DSD models used in rainfall retrieval.
The North Atlantic Eddy Heat Transport and Its Relation with the Vertical Tilting of the Gulf Stream Axis
Authors: Treguier A. M. , Lique C. , Deshayes J. , Molines J. M. 
Published: April 2017

AbstractCorrelations between temperature and velocity fluctuations are a significant contribution to the North Atlantic meridional heat transport, especially at the northern boundary of the subtropical gyre. In satellite observations and in a numerical model at ⅞° resolution, a localized pattern of positive eddy heat flux is found northwest of the Gulf Stream, downstream of its separation at Cape Hatteras. It is confined to the upper 500 m. A simple kinematic model of a meandering jet can explain the surface eddy flux, taking into account a spatial shift between the maximum velocity of the jet and the maximum cross-jet temperature gradient. In the Gulf Stream such a spatial shift results from the nonlinear temperature profile and the vertical tilting of the velocity profile with depth. The numerical model suggests that the meandering of the Gulf Stream could account, at least in part, for the large eddy heat transport (of order 0.3 PW) near 36°N in the North Atlantic and for its compensation by the mean flow.
Observations and Modeling of Typhoon Waves in the South China Sea
Authors: Xu Yao , He Hailun , Song Jinbao , Hou Yijun , Li Funing 
Published: April 2017

AbstractBuoy-based observations of surface waves during three typhoons in the South China Sea were used to obtain the wave characteristics. With the local wind speeds kept below 35 m s−1, the surface waves over an area with a radius 5 times that of the area in which the maximum sustained wind was found were mainly dominated by wind-wave components, and the wave energy distribution was consistent with fetch-limited waves. Swells dominated the surface waves at the front of and outside the central typhoon region. Next, the dynamics of the typhoon waves were studied numerically using a state-of-the-art third-generation wave model. Wind forcing errors made a negligible contribution to the surface wave results obtained using hindcasting. Near-realistic wind fields were constructed by correcting the idealized wind vortex using in situ observational data. If the different sets of source terms were further considered for the forcing stage of the typhoon, which was defined as the half inertial period before and after the typhoon arrival time, the best model performance had mean relative biases and root-mean-square errors of −0.7% and 0.76 m, respectively, for the significant wave height, and −3.4% and 1.115 s, respectively, for the peak wave period. Different sets of source terms for wind inputs and whitecapping breaking dissipation were also used and the results compared. Finally, twin numerical experiments were performed to investigate the importance of nonlinear wave–wave interactions on the spectrum formed. There was evidence that nonlinear wave–wave interactions efficiently transfer wave energy from high frequencies to low frequencies and prevent double-peak structures occurring in the frequency-based spectrum.
Bulk versus Spectral Wave Parameters: Implications on Stokes Drift Estimates, Regional Wave Modeling, and HF Radars Applications
Authors: Kumar Nirnimesh , Cahl Douglas L. , Crosby Sean C. , Voulgaris George 
Published: April 2017

AbstractAccurate estimates of Stokes drift are necessary to quantify Lagrangian transport and upper-ocean mixing. These can be estimated from directional wave spectra. Here, a methodology for the reconstruction of such spectra is developed using partitioned bulk wave parameters provided by global wave models. These reconstructed spectra agree well with global wave model–simulated full spectra. Regional wave model simulations with reconstructed spectra as open boundary conditions lead to more accurate estimates of bulk wave parameters in the coastal ocean. Furthermore, the reconstructed directional spectra can be used to improve high-frequency (HF) radar–derived surface Lagrangian current estimates. Stokes drift vertical profiles from complete directional spectra are more accurate, and therefore coupled ocean circulation and wave models should incorporate spectral estimates for wave–current interaction studies. Based on model simulations conducted here, it is recommended that regional wave modeling studies use partitioned rather than bulk wave parameter products from global wave simulations to reconstruct complete directional spectra for open boundary conditions. Finally, this study shows that inclusion of the peak spectral energy for each partition improves the ability to reconstruct more accurately directional spectra and surface Stokes drift. It is recommended that the global wave model hindcast/forecast include this additional bulk parameter.
Turbulence Measurements from Compliant Moorings. Part I: Motion Characterization
Authors: Harding Samuel , Kilcher Levi , Thomson Jim 
Published: April 2017

AbstractHigh-fidelity measurements of turbulence in the ocean have long been challenging to collect, in particular in the middle of the water column. In response, a measurement technique has been developed to deploy an acoustic Doppler velocimeter (ADV) to midwater locations on a compliant mooring. A variety of instrumentation platforms have been deployed as part of this work with a range of dynamic motion characteristics. The platforms discussed herein include the streamlined StableMoor buoy (SMB), the Tidal Turbulence Mooring (TTM) system based on a conventional 0.9-m spherical buoy, and a 100-lb sounding weight suspended from the stern of a research vessel. The ADV head motion is computed from inertial motion sensors integrated into an ADV, and the spectra of these signals are investigated to quantify the motion of each platform. The SMB with a single ADV head mounted on the nose provided the most stable platform for the measurement of tidal turbulence in the inertial subrange for flow speeds exceeding 1.0 m s−1. The modification of the SMB with a transverse wing configuration for multiple ADVs showed a similar frequency response to the nose configuration in the horizontal plane but with large contamination in the vertical direction as a result of platform roll. While the ADV motion on the TTM was significant in the horizontal directions, the vertical motion of this configuration was the most stable of all configurations tested. The sounding weight measurements showed the greatest motion at the ADV head but are likely to be influenced by both prop-wash and vessel motion.
Formative research on a teacher accompaniment model to promote youth mental health in Haiti: Relevance to mental health task-sharing in low-resource school settings
Authors: Eustache Eddy , Gerbasi Margaret E , Severe Jennifer , Fils-Aimé J Reginald , Smith Fawzi Mary C , Raviola Giuseppe J , Darghouth Sarah , Boyd Kate , Thérosmé Tatiana , Legha Rupinder , Pierre Ermaze L , Affricot Emmeline , Alcindor Yoldie , Grelotti David J , Becker Anne E 
Published: April 2017

Background: Task-sharing with teachers to promote youth mental health is a promising but underdeveloped strategy in improving care access in low-income countries. Aims: To assess feasibility, acceptability and utility of the teacher accompaniment phase of a school-based Teacher- Accompagnateur Pilot Study (TAPS) in Haiti. Methods: We assigned student participants, aged 18–22 years ( n = 120), to teacher participants ( n = 22) within four Haitian schools; we instructed participants to arrange meetings with their assigned counterparts to discuss mental health treatment, academic skills, and/or well-being. We measured student and teacher perceived feasibility, acceptability and utility of meetings with self-report Likert-style questions. We examined overall program feasibility by the percentage of students with a documented meeting, acceptability by a composite measure of student satisfaction and utility by the percentage with identified mental health need who discussed treatment with a teacher. Results: Favorable ratings support feasibility, acceptability and utility of teacher- accompagnateur meetings with students. The majority of students (54%) met with a teacher. Among students with an identified mental disorder, 43.2% discussed treatment during a meeting. Conclusion: This accompaniment approach to mental health task-sharing with teachers provided a school-based opportunity for students with mental health need to discuss treatment and has potential relevance to other low-income settings.
High burden of mental illness and low utilization of care among school-going youth in Central Haiti: A window into the youth mental health treatment gap in a low-income country
Authors: Eustache Eddy , Gerbasi Margaret E , Smith Fawzi Mary C , Fils-Aimé J Reginald , Severe Jennifer , Raviola Giuseppe J , Legha Rupinder , Darghouth Sarah , Grelotti David J , Thérosmé Tatiana , Pierre Ermaze L , Affricot Emmeline , Alcindor Yoldie , Becker Anne E 
Published: April 2017

Background: The mental health treatment gap for youth in low- and middle-income countries (LMICs) is substantial; strategies for redress are urgently needed to mitigate the serious health and social consequences of untreated mental illness in youth. Aims: To estimate the burden of major depressive episode (MDE) and posttraumatic stress disorder (PTSD) as well as utilization of care among Haitian youth in order to describe the mental health treatment gap in a LMIC setting. Methods: We estimated the point prevalence of MDE, PTSD, and subthreshold variants in a school-based sample of youth ( n = 120, ages 18–22 years) using a modified Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID)-based interview and examined treatment utilization among those receiving one of these diagnoses. We assessed additional psychopathology with self-report measures to examine validity of study diagnostic assignments. Results: The combined prevalence of full-syndrome or subthreshold MDE or PTSD was high (36.7%). A large majority of affected individuals (88.6%) had accessed no mental health services in the health sector, and 36.4% had accessed no care of any kind in either the health or folk sectors in the past year. Conclusion: Findings demonstrate a high mental health burden among Haiti’s youth and that many youth with MDE and PTSD are not accessing mental health care.
Novel approach to classifying patients with pulmonary arterial hypertension using cluster analysis
Authors: Parikh Kishan S. , Rao Youlan , Ahmad Tariq , Shen Kai , Felker G. Michael , Rajagopal Sudarshan 
Published: April 2017

Pulmonary arterial hypertension (PAH) patients have distinct disease courses and responses to treatment, but current diagnostic and treatment schemes provide limited insight. We aimed to see if cluster analysis could distinguish clinical phenotypes in PAH. An unbiased cluster analysis was performed on 17 baseline clinical variables of PAH patients from the FREEDOM‐M, FREEDOM‐C, and FREEDOM‐C2 randomized trials of oral treprostinil versus placebo. Participants were either treatment‐naïve (FREEDOM‐M) or on background therapy (FREEDOM‐C, FREEDOM‐C2). We tested for association of clusters with outcomes and interaction with respect to treatment. Primary outcome was 6‐minute walking distance (6MWD) change. We included 966 participants with 12‐week (FREEDOM‐M) or 16‐week (FREEDOM‐C and FREEDOM‐C2) follow‐up. Four patient clusters were identified. Compared with Clusters 1 (n = 131) and 2 (n = 496), Clusters 3 (n = 246) and 4 (n = 93) patients were older, heavier, had worse baseline functional class, 6MWD, Borg Dyspnea Index, and fewer years since PAH diagnosis. Clusters also differed by PAH etiology and background therapies, but not gender or race. Mean treatment effect of oral treprostinil differed across Clusters 1–4 increased in a monotonic fashion (Cluster 1: 10.9 m; Cluster 2: 13.0 m; Cluster 3: 25.0 m; Cluster 4: 50.9 m; interaction P value = 0.048). We identified four distinct clusters of PAH patients based on common patient characteristics. Patients who were older, diagnosed with PAH for a shorter period, and had worse baseline symptoms and exercise capacity had the greatest response to oral treprostinil treatment.
Start as you mean to carry on: The emerging evidence base for the treatment of conflict-related mental health difficulties in children and adolescents
Authors: Meiser-Stedman Richard , Allen Leila R. 
Published: April 2017

SummaryIn this editorial, we discuss Morina and colleagues' meta-analysis of psychological therapies for youth with post-traumatic stress disorder (PTSD) and depression following conflict. Recent years have seen significantly more randomised controlled trial evidence addressing the needs of this population. More work is needed to understand post-traumatic depression, dissemination, timing of intervention and whether trauma-focused interventions are essential.
[5.5]-P-Spirocyclic Chiral Triaminoiminophosphorane-Catalyzed Asymmetric Hydrophosphonylation of Aldehydes and Ynones
Authors: Uraguchi Daisuke , Ito Takaki , Kimura Yuto , Nobori Yumiko , Sato Makoto , Ooi Takashi 
Published: April 2017

Abstract
Development of highly efficient and enantioselective hydrophosphonylations of aldehydes and ynones mediated by [5.5]-P-spirocyclic chiral triaminoiminophosphoranes as base catalysts is described. The strong basicity of the iminophosphoranes and hydrogen-bond donating ability of their conjugate acids, tetraaminophosphonium ions, are critical for the facile generation of aminophosphonium phosphites with substantial nucleophilicity as well as for the subsequent selective, yet productive, P-C bond formation by suppressing undesired side reactions. The scope and limitations of these catalytic asymmetric methodologies are also reported.
Treatment with penicillin G and hydrocortisone reduces ALS-associated symptoms: a case series of three patients
Authors: Tuk Bert , Jousma Harmen , Gaillard Pieter J. 
Published: April 2017

Three male Caucasian patients with ALS were admitted to the hospital due to progressive dysphagia and dysarthria. During two 21-day courses of penicillin G and hydrocortisone, these patients’ dysphagia and dysarthria resolved. The patient’s other ALS-associated symptoms also improved, including respiratory function, coordination, walking, and muscle strength. This is the first report of a treatment with a protocol for treating dysphagia, dysarthria, respiratory depression and other ALS-related symptoms. Furthermore, the observations are consistent with the recent hypothesis that the successful treatment of ALS symptoms with this treatment course in six patients with syphilitic ALS was not directly due to the treatment of syphilis; but that the administered penicillin G and/or hydrocortisone treated these patients’ ALS symptoms due the off-target pharmacological activity of penicillin G and/or hydrocortisone. This report therefore underscores the need to evaluate the efficacy of this treatment course in a clinical trial.
Midlife interventions are critical in prevention, delay, or improvement of Alzheimer’s disease and vascular cognitive impairment and dementia
Authors: Gandy Sam , Bartfai Tamas , Lees Graham V. , Sano Mary 
Published: April 2017

The basic strategy for focusing exclusively on genetically identified targets for intervening in late life dementias was formulated 30 years ago. Three decades and billions of dollars later, all efforts at disease-modifying interventions have failed. Over that same period, evidence has accrued pointing to dementias as late-life clinical phenotypes that begin as midlife pathologies. Effective prevention therefore may need to begin in midlife, in order to succeed. No current interventions are sufficiently safe to justify their use in midlife dementia prevention trials. Observational studies could be informative in testing the proposal that amyloid imaging and APOEε4 genotype can predict those who are highly likely to develop Alzheimer’s disease and in whom higher risk interventions might be justifiable. A naturally occurring, diet-responsive cognitive decline syndrome occurs in canines that closely resembles human Alzheimer’s. Canine cognitive dysfunction could be useful in estimating how early intervention must begin in order to succeed. This model may also help identify and assess novel targets and strategies. New approaches to dementia prevention are urgently required, since none of the world’s economies can sustain the costs of caring for this epidemic of brain failure that is devastating half of the over 85-year-olds globally.
“[We] had not the ties of blood to unite us”
Authors: Turner Beatrice 
Published: April 2017

Beatrice Turner, “‘[We] had not the ties of blood to unite us’: Family Genius and Family Blood in William Godwin Jr.’s Transfusion” (pp. 457–484)
This essay recuperates Transfusion; or, the Orphans of Unwalden (1835), the posthumously published and forgotten novel of William Godwin’s only son, William Godwin Jr. It argues that Godwin Jr.’s absence from Godwin-Shelley circle scholarship is a critical oversight given the complex personal and intellectual relationship between writing and family, which, as numerous critics have noted, defines this circle of authors. Attention to Transfusion reveals a Gothic novel expressly concerned with articulating a biological idea of the family, dramatizing the fatal consequences of “porous” family arrangements that transgress the absolute boundaries erected by blood. Godwin Jr. mobilizes early-nineteenth-century proto-evolutionary discourses and biomedical theories in order to reject the viability of socially constructed or affective familial structures, reflecting cultural anxieties about how to define the family and, ultimately, the species. However, the novel’s deterministic account of family relations appears also directly to oppose the contractual family ideal that characterized both how Godwin Sr. imagined the family and, to a lesser extent, how the Godwin-Shelley family constituted itself. I argue that Transfusion speaks directly to Godwin Jr.’s “outsider” position in the family, interrogating how the Godwin-Shelley family imagines itself and its family “canon,” and opens up opportunities for significant further work on this writing family.
Influenza Vaccine Effectiveness Against Pediatric Deaths: 2010–2014
Authors: Flannery Brendan , Reynolds Sue B. , Blanton Lenee , Santibanez Tammy A. , O’Halloran Alissa , Lu Peng-Jun , Chen Jufu , Foppa Ivo M. , Gargiullo Paul , Bresee Joseph , Singleton James A. , Fry Alicia M. 
Published: April 2017

BACKGROUND AND OBJECTIVES:
Surveillance for laboratory-confirmed influenza-associated pediatric deaths since 2004 has shown that most deaths occur in unvaccinated children. We assessed whether influenza vaccination reduced the risk of influenza-associated death in children and adolescents.

METHODS:
We conducted a case–cohort analysis comparing vaccination uptake among laboratory-confirmed influenza-associated pediatric deaths with estimated vaccination coverage among pediatric cohorts in the United States. Case vaccination and high-risk status were determined by case investigation. Influenza vaccination coverage estimates were obtained from national survey data or a national insurance claims database. We estimated odds ratios from logistic regression comparing odds of vaccination among cases with odds of vaccination in comparison cohorts. We used Bayesian methods to compute 95% credible intervals (CIs) for vaccine effectiveness (VE), calculated as (1 − odds ratio) × 100.

RESULTS:
From July 2010 through June 2014, 358 laboratory-confirmed influenza-associated pediatric deaths were reported among children aged 6 months through 17 years. Vaccination status was determined for 291 deaths; 75 (26%) received vaccine before illness onset. Average vaccination coverage in survey cohorts was 48%. Overall VE against death was 65% (95% CI, 54% to 74%). Among 153 deaths in children with underlying high-risk medical conditions, 47 (31%) were vaccinated. VE among children with high-risk conditions was 51% (95% CI, 31% to 67%), compared with 65% (95% CI, 47% to 78%) among children without high-risk conditions.

CONCLUSIONS:
Influenza vaccination was associated with reduced risk of laboratory-confirmed influenza-associated pediatric death. Increasing influenza vaccination could prevent influenza-associated deaths among children and adolescents.
Több-billentyűs redoműtét felnőtt betegen komplex pulmonalis atresiában
Authors: Hartyánszky István , Babik Barna , Kádár Krisztina , Tóth Attila , Göbölös László , Bogáts Gábor 
Published: April 2017

Abstract: 30-year-old adult with complex pulmonary atresia (previous surgical procedures: in infancy: exploration, at age of 10: ventricular septal defect closing, unifocalization, homograft implantation between right ventricular outflow tract and pulmonary artery) has biventricular dysfunction because of aortic valve regurgitation, ascending aortic aneurysm, and homograft insufficienty. Multivalve surgery: aortic valve plasty, pulmonary homograft changes for homograft and ascending aortic reconstruction by graft were carried out successfully. In Hungary this was the first case of this type of surgery. Management of special problems (follow-up, correct diagnostics (echocardiography, MR, CT), indication and necessity of reoperation, optimal age) in adult patients with complex congenital heart defects produces excellent early and late surgical results. Orv. Hetil., 2017, 158(14), 546–549.