bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term financing needs for HIV control in sub-Saharan Africa in 2015–2050: a modelling study
Authors: Atun Rifat , Chang Angela Y , Ogbuoji Osondu , Silva Sachin , Resch Stephen , Hontelez Jan , Bärnighausen Till 
Published: March 2016

ObjectivesTo estimate the present value of current and future funding needed for HIV treatment and prevention in 9 sub-Saharan African (SSA) countries that account for 70% of HIV burden in Africa under different scenarios of intervention scale-up. To analyse the gaps between current expenditures and funding obligation, and discuss the policy implications of future financing needs.DesignWe used the Goals module from Spectrum, and applied the most up-to-date cost and coverage data to provide a range of estimates for future financing obligations. The four different scale-up scenarios vary by treatment initiation threshold and service coverage level. We compared the model projections to current domestic and international financial sources available in selected SSA countries.ResultsIn the 9 SSA countries, the estimated resources required for HIV prevention and treatment in 2015–2050 range from US$98 billion to maintain current coverage levels for treatment and prevention with eligibility for treatment initiation at CD4 count of <500/mm3to US$261 billion if treatment were to be extended to all HIV-positive individuals and prevention scaled up. With the addition of new funding obligations for HIV—which arise implicitly through commitment to achieve higher than current treatment coverage levels—overall financial obligations (sum of debt levels and the present value of the stock of future HIV funding obligations) would rise substantially.ConclusionsInvesting upfront in scale-up of HIV services to achieve high coverage levels will reduce HIV incidence, prevention and future treatment expenditures by realising long-term preventive effects of ART to reduce HIV transmission. Future obligations are too substantial for most SSA countries to be met from domestic sources alone. New sources of funding, in addition to domestic sources, include innovative financing. Debt sustainability for sustained HIV response is an urgent imperative for affected countries and donors.
Why patients’ disruptive behaviours impair diagnostic reasoning: a randomised experiment
Authors: Mamede Sílvia , Van Gog Tamara , Schuit Stephanie C E , Van den Berge Kees , Van Daele Paul L A , Bueving Herman , Van der Zee Tim , Van den Broek Walter W , Van Saase Jan L C M , Schmidt H G 
Published: March 2016

BackgroundPatients who display disruptive behaviours in the clinical encounter (the so-called ‘difficult patients’) may negatively affect doctors’ diagnostic reasoning, thereby causing diagnostic errors. The present study aimed at investigating the mechanisms underlying the negative influence of difficult patients’ behaviours on doctors’ diagnostic performance.MethodsA randomised experiment with 74 internal medicine residents. Doctors diagnosed eight written clinical vignettes that were exactly the same except for the patients’ behaviours (either difficult or neutral). Each participant diagnosed half of the vignettes in a difficult patient version and the other half in a neutral version in a counterbalanced design. After diagnosing each vignette, participants were asked to recall the patient's clinical findings and behaviours. Main measurements were: diagnostic accuracy scores; time spent on diagnosis, and amount of information recalled from patients’ clinical findings and behaviours.ResultsMean diagnostic accuracy scores (range 0–1) were significantly lower for difficult than neutral patients’ vignettes (0.41 vs 0.51; p<0.01). Time spent on diagnosing was similar. Participants recalled fewer clinical findings (mean=29.82% vs mean=32.52%; p<0.001) and more behaviours (mean=25.51% vs mean=17.89%; p<0.001) from difficult than from neutral patients.ConclusionsDifficult patients’ behaviours induce doctors to make diagnostic errors, apparently because doctors spend part of their mental resources on dealing with the difficult patients’ behaviours, impeding adequate processing of clinical findings. Efforts should be made to increase doctors’ awareness of the potential negative influence of difficult patients’ behaviours on diagnostic decisions and their ability to counteract such influence.
A systematic review and meta-analysis of immunohistochemical biomarkers that differentiate chromophobe renal cell carcinoma from renal oncocytoma
Authors: Ng Keng Lim , Morais Christudas , Bernard Anne , Saunders Nicholas , Samaratunga Hemamali , Gobe Glenda , Wood Simon 
Published: March 2016

BackgroundNumerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities.MethodsPubMed database was used to identify relevant literature. Primary end point was comparison of positive immunostaining of the biomarkers in chRCC and RO, with extracted data used to calculate OR and 95% CI and statistical I2test of heterogeneity for multiple studies.ResultsOne hundred and nine manuscripts were available for review. Data extracted were subjected to quantitative meta-analysis. Ten most effective biomarkers (OR of chRCC/RO and CI) are: amylase α1A (n=129, OR=0.001, 95% CI 0.0001 to 0.019); Wnt-5a (n=38, OR=0.0076, 95% CI 0.0004 to 0.015); FXYD2 (n=57, OR=130, 95% CI 14.2 to 1192.3); ankyrin-repeated protein with a proline-rich region (ARPP) (n=25, OR=0.0054, 95% CI 0.0002 to 0.12); cluster of differentiation 63 (CD63) (n=62, diffuse (chRCC) vs apical/polar (RO) stain pattern); transforming growth factor β 1 (TGFβ1) (n=34, membranous (chRCC) vs cytoplasmic (RO)); cytokeratin 7 (CK7) (11 studies, n=448, pooled OR=44.22, 95% CI 22.52 to 86.64, I2=15%); S100A1 (4 studies, n=124, pooled OR=0.01, 95% CI 0 to 0.03, I2=0%); caveolin-1 (2 studies, n=102, pooled OR=32.95, 95% CI 3.67 to 296.1, I2=70%) and claudin-7 (3 studies, n=89, pooled OR=24.7, 95% CI 6.28 to 97.1, I2=0%).ConclusionsWe recommend a panel of IHC biomarkers of amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.
Progress on Covalent Inhibition of KRASG12C
Authors: Westover Kenneth D. , Jänne Pasi A. , Gray Nathanael S. 
Published: March 2016

Abstract
Summary: Recent reports of small-molecule approaches to directly inhibit oncogenic KRASG12C have invigorated the RAS research community by raising the possibility of drugging a protein that was long considered “undruggable.” A new iteration of covalent compounds targeting the allosteric switch II pocket of KRASG12C showed improved potency and selectivity and enabled studies demonstrating that KRASG12C rapidly cycles its nucleotide substrate. This report illustrates the value of chemical probes in dissecting RAS biology and raises additional hope for development of viable pharmacologic strategies for directly targeting KRASG12C. Cancer Discov; 6(3); 233–4. ©2016 AACR.
See related article by Patricelli et al., p. 316.
Cardiac Magnetic Resonance Reveals Signs of Subclinical Myocardial Inflammation in Asymptomatic HIV-Infected Patients
Authors: Luetkens Julian A. , Doerner Jonas , Schwarze-Zander Carolynne , Wasmuth Jan-Christian , Boesecke Christoph , Sprinkart Alois M. , Schmeel Frederic C. , Homsi Rami , Gieseke Juergen , Schild Hans H. , Rockstroh Jürgen K. , Naehle Claas P. 
Published: March 2016

Background—
People living with chronic HIV infection are at an increased risk for cardiovascular disease. With this study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients by a comprehensive cardiac magnetic resonance (CMR) approach.

Methods and Results—

Asymptomatic patients with chronic HIV infection undergoing combination antiretroviral therapy (n=28) and control subjects (n=22) underwent CMR. HIV-infected patients were successfully controlled for the disease with a consistent plasma viremia of <200 copies/mL (mean CD4
+
-cell count, 475.1±307.9 cells/μL). CMR protocol allowed for the determination of cardiac function, myocardial inflammation, myocardial fibrosis, aortic stiffness, and pericardial fat volume. When compared with healthy controls, HIV-infected patients showed alterations in left ventricular function as demonstrated by a lower ejection fraction (60.9±7.1% versus 65.2±5.5%;
P
=0.023) and lower global peak systolic longitudinal and circumferential strain values (longitudinal strain, −17.7±3.4% versus −20.2±3.2%, circumferential strain, −21.2±4.6% versus −24.7±5.1%;
P
<0.001, respectively). CMR parameters indicating myocardial inflammation were elevated in HIV-infected patients (native T1 relaxation times, 1128.3±53.4 ms versus 1086.5±54.5 ms;
P
=0.009; relative T2 signal intensity ratio, 1.6±0.3 versus 1.4±0.3;
P
=0.046; early gadolinium enhancement ratio, 3.1±1.2 versus 2.1±0.6;
P
=0.003). Myocardial fibrosis, predominantly at the subepicardium of the midventricular and basal inferolateral wall, was prevalent in 82.1% of HIV-infected patients, but only in 27.3% of healthy controls (
P
<0.001).

Conclusions—
Comprehensive CMR revealed a high burden of cardiovascular disease in asymptomatic HIV-infected patients. Subclinical myocardial inflammation as detected by CMR may be a potential precursor of the increased cardiovascular morbidity and mortality observed in patients with chronic HIV infection.
HIV-1–Related Cardiovascular Disease Is Associated With Chronic Inflammation, Frequent Pericardial Effusions, and Probable Myocardial Edema
Authors: Ntusi Ntobeko , O’Dwyer Eoin , Dorrell Lucy , Wainwright Emma , Piechnik Stefan , Clutton Genevieve , Hancock Gemma , Ferreira Vanessa , Cox Pete , Badri Motasim , Karamitsos Theodoros , Emmanuel Sam , Clarke Kieran , Neubauer Stefan , Holloway Cameron 
Published: March 2016

Background—
Patients with treated HIV infection have clear survival benefits although with increased cardiac morbidity and mortality. Mechanisms of heart disease may be partly related to untreated chronic inflammation. Cardiovascular magnetic resonance imaging allows a comprehensive assessment of myocardial structure, function, and tissue characterization. We investigated, using cardiovascular magnetic resonance, subclinical inflammation and myocardial disease in asymptomatic HIV-infected individuals.

Methods and Results—

Myocardial structure and function were assessed using cardiovascular magnetic resonance at 1.5-T in treated HIV-infected individuals without known cardiovascular disease (n=103; mean age, 45±10 years) compared with healthy controls (n=92; mean age, 44±10 years). Assessments included left ventricular volumes, ejection fraction, strain, regional systolic, diastolic function, native T1 mapping, edema, and gadolinium enhancement. Compared with controls, subjects with HIV infection had 6% lower left ventricular ejection fraction (
P
<0.001), 7% higher myocardial mass (
P
=0.02), 29% lower peak diastolic strain rate (
P
<0.001), 4% higher short-tau inversion recovery values (
P
=0.02), and higher native T1 values (969 versus 956 ms in controls;
P
=0.01). Pericardial effusions and myocardial fibrosis were 3 and 4× more common, respectively, in subjects with HIV infection (both
P
<0.001).

Conclusions—
Treated HIV infection is associated with changes in myocardial structure and function in addition to higher rates of subclinical myocardial edema and fibrosis and frequent pericardial effusions. Chronic systemic inflammation in HIV, which involves the myocardium and pericardium, may explain the high rate of myocardial fibrosis and increased cardiac dysfunction in people living with HIV.
Strong Ocean–Atmosphere Interactions during a Short-Term Hot Event over the Western Pacific Warm Pool in Response to El Niño
Authors: Chen Guixing , Qin Huiling 
Published: March 2016

Abstract
A short-term hot event with a very high sea surface temperature (SST ≥ 30°C) occurred in the western Pacific warm pool during November 2006. The interactions between this ocean hot event, atmospheric convection, and large-scale dynamics are studied using satellite observations, buoy measurements, air–sea fluxes analysis, and global reanalysis. It is shown that SST variation and deep convection over the western Pacific behave like a remote response to the El Niño warm SST anomaly in the central Pacific that induces westward-moving atmospheric convection and equatorial waves. The large-scale subsidence associated with propagating convection not only promotes high SSTs in the western Pacific through establishing cloud-free conditions and increasing heat content in a thin ocean mixed layer, but also produces convective instability through capping substantial water vapor in the lower troposphere. Under the precondition of convective instability and the steering of tropical easterlies, some convective systems propagate coherently from the central to western Pacific and intensify. In particular, new cloud clusters are dynamically attracted to the warmest oceans with maximum atmospheric instability. The enhanced convective activity then transfers oceanic energy into the atmosphere, strengthens upper-ocean mixing, and returns the positive SST anomalies to more typical values. In such a coupled system, synoptic-scale convective activities at an interval of 5–8 days are selectively amplified and thus are filtered to an intraseasonal (20–30-day) oscillation, depending on the phase of the hot event over the western Pacific. The observed evidence has implications for the predictability of short-term climate, and it offers critical information for validating the coupled ocean–atmosphere dynamics in climate models.
A Dynamically Based Climatology of Subtropical Cyclones that Undergo Tropical Transition in the North Atlantic Basin
Authors: Bentley Alicia M. , Keyser Daniel , Bosart Lance F. 
Published: March 2016

Subtropical cyclones (STCs) derive a considerable portion of their energy from baroclinic and diabatic processes. The opportunity to investigate the roles of baroclinic and diabatic processes during the evolution of STCs from a potential vorticity (PV) perspective motivates this study. The roles of baroclinic and diabatic processes during the evolution of STCs are determined by calculating three PV metrics from the 0.5° NCEP Climate Forecast System Reanalysis dataset. The three PV metrics quantify the relative contributions of lower-tropospheric baroclinic processes, midtropospheric latent heat release, and upper-tropospheric dynamical processes during the evolution of individual cyclones. An evaluation of the three PV metrics, as well as the sign of the upper-tropospheric thermal vorticity, during the evolution of individual cyclones is used to devise an objective STC identification technique and construct a 1979–2010 climatology of North Atlantic (NATL) STCs that undergo tropical transition. An investigation of the intraseasonal variability associated with the location and frequency of STCs identified in the 1979–2010 climatology shows that STCs typically form over the southern Gulf of Mexico and western NATL during April–June; over the northern Gulf of Mexico and western NATL during July–September; and over the western, central, and eastern NATL during October–December. STC formation occurs most frequently during September, when baroclinic and convectively driven forcings overlap across portions of the NATL. The frequency of STC formation is sensitive to the phase of ENSO and is maximized during periods of anomalously low SSTs in the eastern equatorial Pacific.
External Validation of the Acoustic Voice Quality Index Version 03.01 With Extended Representativity
Authors: Barsties Ben , Maryn Youri 
Published: March 2016

Objectives: The Acoustic Voice Quality Index (AVQI) is an objective method to quantify the severity of overall voice quality in concatenated continuous speech and sustained phonation segments. Recently, AVQI was successfully modified to be more representative and ecologically valid because the internal consistency of AVQI was balanced out through equal proportion of the 2 speech types. The present investigation aims to explore its external validation in a large data set. Methods: An expert panel of 12 speech-language therapists rated the voice quality of 1058 concatenated voice samples varying from normophonia to severe dysphonia. The Spearman rank-order correlation coefficients ( r) were used to measure concurrent validity. The AVQI’s diagnostic accuracy was evaluated with several estimates of its receiver operating characteristics (ROC). Results: Finally, 8 of the 12 experts were chosen because of reliability criteria. A strong correlation was identified between AVQI and auditoryperceptual rating ( r = 0.815, P = .000). It indicated that 66.4% of the auditory-perceptual rating’s variation was explained by AVQI. Additionally, the ROC results showed again the best diagnostic outcome at a threshold of AVQI = 2.43. Conclusions: This study highlights external validation and diagnostic precision of the AVQI version 03.01 as a robust and ecologically valid measurement to objectify voice quality.
Well-Being and Agency in Parents of Children With Congenital Heart Disease
Authors: López Rodrigo , Frangini Patricia , Ramírez Muriel , Valenzuela Patricia M. , Terrazas Claudia , Pérez Carolina A. , Borchert Evelyn , Trachsel Manuel 
Published: March 2016

Background: Parents of children having congenital heart diseases (CHDs) develop symptoms of depression, distress, anxiety, and hopelessness more frequently than parents of healthy children. Associated with the described symptoms, parents may experience a lack of control and disempowerment, which decreases the parent’s agency, a construct from development studies, and which may have negative consequences on adherence to treatment. The primary aim of this study was to assess the effect of medical treatment on well-being and agency in parents of children having CHDs, in Chile, and to compare it with reference values. Methods: Forty parents of children having CHDs (before surgery and before hospital discharge) and 115 parents of healthy children were surveyed. The following scales were applied to this population: the General Health Questionnaire, the Basic Psychological Needs Scales, the Self-Determination Scale, the Beck Hopelessness Scale, and a socioeconomic survey. Results: Children’s surgery decreased parents’ hopelessness (3.13 ± 0.35 and 2.18 ± 0.40, P = .04), and no significant differences were found in the remaining scales. Parents of children with CHDs scored significantly worse than parents of healthy children on the General Health Questionnaire (13.82 ± 1.03 and 9.21 ± 0.64, P = .001). This difference was not found using the others scales. Conclusion: Children’s surgery has a positive effect on parent’s hopelessness, but it does not have any impact on their well-being nor agency. Parents of children with CHD have a decreased well-being compared to parents of healthy children but have a similar level of agency. Socioeconomic level and gender may influence this association.
Understanding variation in length of hospital stay for COPD exacerbation: European COPD audit
Authors: Ruparel Mamta , López-Campos Jose Luis , Castro-Acosta Ady , Hartl Sylvia , Pozo-Rodriguez Francisco , Roberts C. Michael 
Published: March 2016

Chronic obstructive pulmonary disease (COPD) care across Europe has high heterogeneity with respect to cost and the services available. Variations in length of stay (LOS) may be attributed to patient characteristics, resource and organisational characteristics, and/or the so-called hospital cluster effect.The European COPD Audit in 13 countries included data from 16 018 hospitalised patients. The recorded variables included information on patient and disease characteristics, and resources available. Variables associated with LOS were evaluated by a multivariate, multilevel analysis.Mean±sdLOS was 8.7±8.3 days (median 7 days, interquartile range 4–11 days). Crude variability between countries was reduced after accounting for clinical factors and the clustering effect. The main factors associated with LOS being longer than the median were related to disease or exacerbation severity, including GOLD class IV (OR 1.77) and use of mechanical ventilation (OR 2.15). Few individual resource variables were associated with LOS after accounting for the hospital cluster effect.This study emphasises the importance of the patients' clinical severity at presentation in predicting LOS. Identifying patients at risk of a long hospital stay at admission and providing targeted interventions offers the potential to reduce LOS for these individuals. The complex interactions between factors and systems were more important that any single resource or organisational factor in determining differences in LOS between hospitals or countries.
Evolution of Randomized Trials in Advanced/Metastatic Soft Tissue Sarcoma: End Point Selection, Surrogacy, and Quality of Reporting
Authors: Zer Alona , Prince Rebecca M. , Amir Eitan , Abdul Razak Albiruni 
Published: March 2016

Purpose Randomized controlled trials (RCTs) in soft tissue sarcoma (STS) have used varying end points. The surrogacy of intermediate end points, such as progression-free survival (PFS), response rate (RR), and 3-month and 6-month PFS (3moPFS and 6moPFS) with overall survival (OS), remains unknown. The quality of efficacy and toxicity reporting in these studies is also uncertain. Methods A systematic review of systemic therapy RCTs in STS was performed. Surrogacy between intermediate end points and OS was explored using weighted linear regression for the hazard ratio for OS with the hazard ratio for PFS or the odds ratio for RR, 3moPFS, and 6moPFS. The quality of reporting for efficacy and toxicity was also evaluated. Results Fifty-two RCTs published between 1974 and 2014, comprising 9,762 patients, met the inclusion criteria. There were significant correlations between PFS and OS (R = 0.61) and between RR and OS (R = 0.51). Conversely, there were nonsignificant correlations between 3moPFS and 6moPFS with OS. A reduction in the use of RR as the primary end point was observed over time, favoring time-based events (P for trend = .02). In 14% of RCTs, the primary end point was not met, but the study was reported as being positive. Toxicity was comprehensively reported in 47% of RCTs, whereas 14% inadequately reported toxicity. Conclusion In advanced STS, PFS and RR seem to be appropriate surrogates for OS. There is poor correlation between OS and both 3moPFS and 6moPFS. As such, caution is urged with the use of these as primary end points in randomized STS trials. The quality of toxicity reporting and interpretation of results is suboptimal.