bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental and social benefits of the targeted intraoperative radiotherapy for breast cancer: data from UK TARGIT-A trial centres and two UK NHS hospitals offering TARGIT IORT
Authors: Coombs Nathan J , Coombs Joel M , Vaidya Uma J , Singer Julian , Bulsara Max , Tobias Jeffrey S , Wenz Frederik , Joseph David J , Brown Douglas A , Rainsbury Richard , Davidson Tim , Adamson Douglas J A , Massarut Samuele , Morgan David , Potyka Ingrid , Corica Tammy , Falzon Mary , Williams Norman , Baum Michael , Vaidya Jayant S 
Published: May 2016

ObjectiveTo quantify the journeys and CO2emissions if women with breast cancer are treated with risk-adapted single-dose targeted intraoperative radiotherapy (TARGIT) rather than several weeks' course of external beam whole breast radiotherapy (EBRT) treatment.Setting(1) TARGIT-A randomised clinical trial (ISRCTN34086741) which compared TARGIT with traditional EBRT and found similar breast cancer control, particularly when TARGIT was given simultaneously with lumpectomy, (2) 2 additional UK centres offering TARGIT.Participants485 UK patients (249 TARGIT, 236 EBRT) in the prepathology stratum of TARGIT-A trial (where randomisation occurred before lumpectomy and TARGIT was delivered simultaneously with lumpectomy) for whom geographical data were available and 22 patients treated with TARGIT after completion of the TARGIT-A trial in 2 additional UK breast centres.Outcome measuresThe shortest total journey distance, time and CO2emissions from home to hospital to receive all the fractions of radiotherapy.MethodsDistances, time and CO2emissions were calculated using Google Maps and assuming a fuel efficiency of 40 mpg. The groups were compared using the Student t test with unequal variance and the non-parametric Wilcoxon rank-sum (Mann-Whitney) test.ResultsTARGIT patients travelled significantly fewer miles: TARGIT 21 681, mean 87.1 (SE 19.1) versus EBRT 92 591, mean 392.3 (SE 30.2); had lower CO2emissions 24.7 kg (SE 5.4) vs 111 kg (SE 8.6) and spent less time travelling: 3 h (SE 0.53) vs 14 h (SE 0.76), all p<0.0001. Patients treated with TARGIT in 2 hospitals in semirural locations were spared much longer journeys (753 miles, 30 h, 215 kg CO2per patient).ConclusionsThe use of TARGIT intraoperative radiotherapy for eligible patients with breast cancer significantly reduces their journeys for treatment and has environmental benefits. If widely available, 5 million miles (8 000 000 km) of travel, 170 000 woman-hours and 1200 tonnes of CO2(a forest of 100 hectares) will be saved annually in the UK.Trial registration numberISRCTN34086741; Post-results.
Economic analysis of endovascular drug-eluting treatments for femoropopliteal artery disease in the UK
Authors: Katsanos Konstantinos , Geisler Benjamin P , Garner Abigail M , Zayed Hany , Cleveland Trevor , Pietzsch Jan B 
Published: May 2016

ObjectivesTo estimate the clinical and economic impact of drug-eluting endovascular treatment strategies for femoropopliteal artery disease compared with current standard of care.DesignSystematic literature search to pool target lesion revascularisations (TLR). Model-based per-patient cost impact and quasi-cost-effectiveness projection over 24 months based on pooled TLRs and current reimbursement.SettingThe UK's National Health Service (NHS).ParticipantsPatients presenting with symptomatic femoropopliteal disease eligible for endovascular treatment.InterventionsCurrent National Institute for Health and Care Excellence (NICE) guideline-recommended treatment with percutaneous transluminal balloon angioplasty (PTA) and bailout bare metal stenting (BMS) versus primary BMS placement, or drug-coated balloon (DCB), or drug-eluting stent (DES) treatment.Primary and secondary outcome measures24-month per-patient cost impact to NHS (primary outcome). Secondary outcomes: pooled 24-month TLR rates; numbers needed to treat (NNTs); cost per TLR avoided and estimated incremental cost-effectiveness ratio (ICER) in £ per quality-adjusted life year (QALY).ResultsN=28 studies were identified, reporting on 5167 femoropopliteal lesions. Over 24 months, DCB, DES and BMS reduced TLRs of de novo lesions from 36.2% to 17.6%, 19.4% and 26.9%, respectively, at an increased cost of £43, £44 and £112. NNTs to avoid 1 TLR in 24 months were 5.4, 6.0 and 10.8, resulting in cost per TLR avoided of £231, £264 and £1204. DCB was estimated to add 0.011 QALYs, DES 0.010 QALYs and BMS 0.005 QALYs, resulting in estimated ICERs of £3983, £4534 and £20 719 per QALY gained. A subset analysis revealed more favourable clinical and economic outcomes for a 3.5 µg/mm2DCB with urea excipient, compared with the rest of DCBs. A modest reduction of 10% in DCB and DES prices made drug-eluting treatments dominant.ConclusionsWidespread adoption of drug-eluting endovascular therapies for femoropopliteal disease would add meaningful clinical benefit at reasonable additional costs to the NHS. Based on currently available data, DCBs offer the highest clinical and economic value.
Asthma in Primary Care: Making Guidelines Work
Authors: Putnam Wayne , Burge Fred , Tatemichi Sue , Twohig Peter 
Published: May 2016

OBJECTIVE: To determine the views of family physicians regarding selected asthma recommendations from a Canadian practice guideline and the supporting evidence, and to identify issues needing further development if family physicians are to find guideline recommendations to be truly useful clinical tools.SETTING: Four urban communities in Nova Scotia, Prince Edward Island and New Brunswick.PARTICIPANTS: Twenty community family physicians representing different practice settings, and varying according to age and sex, were recruited to participate.DATA COLLECTION: Four focus groups were held, each lasting 2 h, at which recommendations from a published asthma guideline were presented for discussion on the applicability to their practices. The data were analyzed using a grounded theory method.RESULTS: Physicians rely on clinical judgment in lieu of objective measures in diagnosing asthma and resist treating every exacerbation with steroids. They thought that the recommendations on smoking and patient education should have been stronger or more prominent. Patient noncompliance limits the usefulness of home peak flow measures. Topics such as allergy assessment and most pharmacological therapies triggered little discussion.DISCUSSION: Asthma guideline developers and those interested in enhancing compliance with recommendations will need to attend to factors such as physician attitudes and beliefs on a variety of issues, including the use of objective measures and the availability of adequate resources to conduct the tests. Similarly, negative patient attitudes toward an increased use of corticosteroids suggest that a public education program would be most helpful regarding that group of recommendations.
Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma
Authors: Yokoyama Shintaro , Miyoshi Hiroaki , Nakashima Kazutaka , Shimono Joji , Hashiguchi Toshihiro , Mitsuoka Masahiro , Takamori Shinzo , Akagi Yoshito , Ohshima Koichi 
Published: May 2016

Abstract
Purpose: The immune checkpoint of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is believed to play an important role in evasion of host antitumor immune surveillance in various malignancies; however, little is known about its role in thymic carcinoma. This study investigated PD-1/PD-L1 expression and its association with clinicopathologic features, the expression of immune-related proteins in tumor-infiltrating lymphocytes (TIL), and patient prognosis.
Experimental Design: PD-L1 and PD-1 expression was evaluated by IHC in 25 thymic carcinoma tissue specimens. Copy number alterations of the PD-L1 gene in 11 cases were assessed in formalin-fixed, paraffin-embedded material using qRT-PCR.
Results: Compared with normal subjects, 3 thymic carcinoma patients showed an increase in PD-L1 copy number, whereas 8 did not. PD-L1 was significantly overexpressed in cases with copy number gain as compared with normal cases. High PD-L1 expression was associated with higher disease-free and overall survival rates as compared to cases with low expression. Prognostic analysis revealed low PD-L1 expression and high number of PD-1+ TILs as significant predictors of poor survival, together with Masaoka–Koga stage IVa/IVb disease and incomplete resection. In the quantitative analysis of TILs, PD-L1 expression correlated proportionally with the number of infiltrating CTLs.
Conclusions: Here, for the first time, we report that PD-L1 and PD-1 expression might be useful prognostic predictors in thymic carcinoma. Further studies are expected to substantiate the prognostic value of PD-L1 and PD-1 expression, and the potential efficacy of targeting the PD-1/PD-L1 pathway in thymic carcinoma via immunotherapy. Clin Cancer Res; 22(18); 4727–34. ©2016 AACR.
Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation
Authors: Sirish Padmini , Li Ning , Timofeyev Valeriy , Zhang Xiao-Dong , Wang Lianguo , Yang Jun , Lee Kin Sing Stephen , Bettaieb Ahmed , Ma Sin Mei , Lee Jeong Han , Su Demetria , Lau Victor C. , Myers Richard E. , Lieu Deborah K. , López Javier E. , Young J. Nilas , Yamoah Ebenezer N. , Haj Fawaz , Ripplinger Crystal M. , Hammock Bruce D. , Chiamvimonvat Nipavan 
Published: May 2016

Background—
Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation.

Methods and Results—
For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-β.

Conclusions—
This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation.
Frequency and Outcomes of Postrandomization Atrial Tachyarrhythmias in the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial
Authors: Wilton Stephen B. , Exner Derek V. , Wyse D. George , Yetisir Elizabeth , Wells George , Tang Anthony S.L. , Healey Jeffrey S. 
Published: May 2016

Background—
Whether adding cardiac resynchronization therapy (CRT-D) to an implanted cardioverter–defibrillator alters the risk of atrial fibrillation or other atrial tachyarrhythmias (AF/AT), or if postimplantation AF/AT modulate the benefits of CRT-D, remain unknown.

Methods and Results—

We studied 972 Resynchronization/Defibrillation in Ambulatory Heart Failure Trial (RAFT) participants without permanent AF, who were randomized to CRT-D (n=495) versus nonresynchronization defibrillator (implanted cardioverter–defibrillator; n=477) within the predefined stratum eligible for an atrial lead. Occurrence of postrandomization AF/AT was prospectively assessed, and Cox models were used to test the independent association between the postrandomization AF/AT and the RAFT primary composite outcome of all-cause mortality or hospitalization for heart failure. Over 41 (±19) months, postrandomization AF/AT occurred in 216 (45.3%) patients randomized to implanted cardioverter–defibrillator and 249 (50.3%) randomized to CRT-D. After adjusting for competing risk of death, randomization to CRT-D increased risk of postrandomization AF/AT (hazard ratio, 1.20; 95% confidence interval, 1.00–1.42;
P
=0.045). Postrandomization AF/AT, which remained paroxysmal in 69.5%, did not reduce biventricular pacing percentage. In adjusted models, postrandomization AF/AT was not associated with the primary outcome (hazard ratio, 1.04; 95% confidence interval, 0.84–1.30). However, AF/AT was associated with a borderline decreased risk of mortality (hazard ratio, 0.75; 95% confidence interval, 0.58–1.00) but increased risk of heart failure hospitalization (hazard ratio, 1.43; 95% confidence interval, 1.08–1.90).

Conclusions—
In RAFT, nearly half of the patients developed postrandomization AF/AT, and those randomized to CRT-D had borderline significant higher risk. Postrandomization AF/AT was associated with risk of heart failure hospitalization, but not with the primary composite outcome.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00251251.
Short-Term Risk of Serious Fall Injuries in Older Adults Initiating and Intensifying Treatment With Antihypertensive Medication
Authors: Shimbo Daichi , Barrett Bowling C. , Levitan Emily B. , Deng Luqin , Sim John J. , Huang Lei , Reynolds Kristi , Muntner Paul 
Published: May 2016

Background—
Antihypertensive medication use has been associated with an increased risk of falls in some but not all studies. Few data are available on the short-term risk of falls after antihypertensive medication initiation and intensification.

Methods and Results—
We examined the association between initiating and intensifying antihypertensive medication and serious fall injuries in a case-crossover study of 90 127 Medicare beneficiaries who were ≥65 years old and had a serious fall injury between July 1, 2007, and December 31, 2012, based on emergency department and inpatient claims. Antihypertensive medication initiation was defined by a prescription fill with no fills in the previous year. Intensification was defined by the addition of a new antihypertensive class, and separately, titration by the addition of a new class or increase in dosage of a current class. Exposures were ascertained for the 15 days before the fall (case period) and six 15-day earlier periods (control periods). Overall, 272, 1508, and 3113 Medicare beneficiaries initiated, added a new class of antihypertensive medication or titrated therapy within 15 days of their serious fall injury. The odds for a serious fall injury was increased during the 15 days after antihypertensive medication initiation (odds ratio, 1.36 [95% confidence interval, 1.19–1.55]), adding a new class (odds ratio, 1.16 [95% confidence interval, 1.10–1.23]), and titration [odds ratio, 1.13 [95% confidence interval, 1.08–1.18]). These associations were attenuated beyond 15 days.

Conclusions—
Antihypertensive medication initiation and intensification was associated with a short-term, but not long-term, increased risk of serious fall injuries among older adults.
Hospitalized Infection as a Trigger for Acute Ischemic Stroke
Authors: Cowan Logan T. , Alonso Alvaro , Pankow James S. , Folsom Aaron R. , Rosamond Wayne D. , Gottesman Rebecca F. , Lakshminarayan Kamakshi 
Published: May 2016

Background and Purpose—
Acute triggers for ischemic stroke, which may include infection, are understudied, as is whether background cardiovascular disease (CVD) risk modifies such triggering. We hypothesized that infection increases acute stroke risk, especially among those with low CVD risk.

Methods—
Hospitalized strokes and infections were identified in the Atherosclerosis Risk in Communities (ARIC) cohort. A case-crossover design and conditional logistic regression were used to compare hospitalized infections among patients with stroke (14, 30, 42, and 90 days before stroke) with corresponding control periods 1 year and 2 years before stroke. Background CVD risk was assessed at both visit 1 and the visit most proximal to stroke, with risk dichotomized at the median.

Results—
A total of 1008 adjudicated incident ischemic strokes were included. Compared with control periods, hospitalized infection was more common within 2 weeks before stroke (14-day odds ratio [OR], 7.7; 95% CI, 2.1–27.3); the strength of association declined with increasing time in the exposure window before stroke (30-day OR, 5.7 [95% CI, 2.3–14.3]; 42-day OR, 4.5 [95% CI, 2.0–10.2]; and 90-day OR, 3.6 [95% CI, 2.1–6.5]). Stroke risk was higher among those with low compared with high CVD risk, with this interaction reaching statistical significance for some exposure periods.

Conclusions—
These results support the hypothesis that hospitalized infection is a trigger of ischemic stroke and may explain some cryptogenic strokes. Infection control efforts may prevent strokes. CVD preventive therapies may prevent strokes if used in the peri-infection period, but clinical trials are needed.
Social Cognition as Reinforcement Learning: Feedback Modulates Emotion Inference
Authors: Zaki Jamil , Kallman Seth , Wimmer G. Elliott , Ochsner Kevin , Shohamy Daphna 
Published: May 2016

Abstract
Neuroscientific studies of social cognition typically employ paradigms in which perceivers draw single-shot inferences about the internal states of strangers. Real-world social inference features much different parameters: People often encounter and learn about particular social targets (e.g., friends) over time and receive feedback about whether their inferences are correct or incorrect. Here, we examined this process and, more broadly, the intersection between social cognition and reinforcement learning. Perceivers were scanned using fMRI while repeatedly encountering three social targets who produced conflicting visual and verbal emotional cues. Perceivers guessed how targets felt and received feedback about whether they had guessed correctly. Visual cues reliably predicted one target's emotion, verbal cues predicted a second target's emotion, and neither reliably predicted the third target's emotion. Perceivers successfully used this information to update their judgments over time. Furthermore, trial-by-trial learning signals—estimated using two reinforcement learning models—tracked activity in ventral striatum and ventromedial pFC, structures associated with reinforcement learning, and regions associated with updating social impressions, including TPJ. These data suggest that learning about others' emotions, like other forms of feedback learning, relies on domain-general reinforcement mechanisms as well as domain-specific social information processing.
Response of the East Asian Winter Monsoon to Strong Tropical Volcanic Eruptions
Authors: Miao Jiapeng , Wang Tao , Zhu Yali , Min Jinzhong , Wang Huijun , Guo Dong 
Published: May 2016

Abstract
In this study, a 600-yr integration performed with the Bergen Climate Model (BCM), version 2.0, was used to investigate the impact of strong tropical volcanic eruptions (SVEs) on the East Asian winter monsoon (EAWM). It is found that SVEs have an important influence on the East Asian winter climate. The volcanic forcing can cause changes in surface heat fluxes and tropospheric circulation, particularly over the tropics and high-latitude regions. As a result, Arctic Oscillation enters into its positive phase in the first two winters after SVEs. The associated circulation weakens the Siberian high and reduces the cold air transport to East Asia, which is not conducive to the enhancement of the EAWM during this period. At the same time, the North Pacific Ocean gradually cools and shapes La Niña–like sea surface temperature (SST) anomalies in the third winter after SVEs. The Walker circulation is strengthened over the Pacific, and two anomalous lower-tropospheric cyclones are located over the South China Sea and southeast of Japan, respectively. Therefore, related northeasterly wind anomalies appear along the East Asian coast, indicating a strengthened EAWM during this period. Meanwhile, the enhanced Siberian high and East Asian trough further contribute to the enhancement of EAWM in the third winter. It is therefore concluded that the SVEs-induced climate changes over the tropical Pacific and north polar regions play an important role in regulating the EAWM in the posteruption winters.
Influence of Below-Cloud Evaporation on Deuterium Excess in Precipitation of Arid Central Asia and Its Meteorological Controls
Authors: Wang Shengjie , Zhang Mingjun , Che Yanjun , Zhu Xiaofan , Liu Xuemei 
Published: May 2016

AbstractThe deuterium excess is a second-order parameter linking water-stable oxygen and hydrogen isotopes and has been widely used in hydrological studies. The deuterium excess in precipitation is greatly influenced by below-cloud evaporation through unsaturated air, especially in an arid climate. Based on an observation network of isotopes in precipitation of arid central Asia, the difference in deuterium excess from cloud base to ground was calculated for each sampling site. The difference on the southern slope of the Tian Shan is generally larger than that on the northern slope, and the difference during the summer months is greater than that during the winter months. Generally, an increase of 1% in evaporation of raindrops causes deuterium excess to decrease by approximately 1‰. Under conditions of low air temperature, high relative humidity, heavy precipitation, and large raindrop diameter, a good linear correlation is exhibited between evaporation proportion and difference in deuterium excess, and a linear regression slope of <1‰ %−1 can be seen; in contrast, under conditions of high air temperature, low relative humidity, light precipitation, and small raindrop diameter, the linear relationship is relatively weak, and the slope is much larger than 1‰ %−1. A sensitivity analysis under different climate scenarios indicates that, if air temperature has increased by 5°C, deuterium excess difference decreases by 0.3‰–4.0‰ for each site; if relative humidity increases by 10%, deuterium excess difference increases by 1.1‰–10.3‰.