bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing the number of unnecessary routine laboratory tests through education of internal medicine residents
Authors: Faisal Annum , Andres Kayla , Rind Jubran Afzal Khan , Das Aparna , Alter David , Subramanian Jeevarathna , Koehler Tracy J , Parker Jessica , Bernicchi Nathan 
Published: January 2019

AbstractIntroductionThe Choosing Wisely guidelines advise against ordering routine blood tests for hospitalised patients unless they change management. Unnecessary testing can lead to adverse effects (eg, iatrogenic anaemia, poor sleep quality, risk for infections and increased cost of care).MethodsAn 8-week quality initiative aimed at reducing unnecessary blood tests was implemented in three internal medicine resident inpatient services. The initiative included a 30 min educational session, reminders prior to rotation and midrotation and posters in work areas that displayed lab pricing and urged judicious testing. Residents were encouraged to justify the purpose of ordering tests in their daily progress notes. Attending physicians were made aware of the initiative. Preintervention and postintervention time points were used to compare key metrics. A &gt;10% decrease between time periods was used as an evaluation criterion.ResultsThere were 293 patient records reviewed in the preintervention period and 419 in the postintervention period. The two groups were similar in terms of age and gender. Median blood test count (complete blood count/basic metabolic profile/comprehensive metabolic profile) decreased from 4 to 2 tests per patient per day (50 % decrease) after the intervention. The median length of hospital stay decreased from 4.9 to 3.9 days (21% decrease). A decreased percentage of people requiring transfusions was also noted (2016: 6.1%, 2017: 2.9%).ConclusionThe frequency of unnecessary routine blood tests ordered in the hospital can be decreased by educating resident physicians, making them cost conscious and aware of the indications for ordering routine labs. Frequent reminders are needed to sustain the educational benefit.
Loop Unrolling for Energy Efficiency in Low-Cost Field-Programmable Gate Arrays
Authors: Dumpala Naveen Kumar , Patil Shivukumar B. , Holcomb Daniel , Tessier Russell 
Published: January 2019

Field-programmable gate arrays (FPGAs) are used for a wide variety of computations in low-cost embedded systems. Although these systems often have modest performance constraints, their energy consumption must typically be limited. Many FPGA applications employ repetitive loops that cannot be straightforwardly split into parallel computations. Performing a loop sequentially generally requires high-speed clocks that consume considerable clock power and sometimes require clock generation using a phase-locked loop (PLL). Loop unrolling addresses the high-speed clock issue, but its use often leads to significant combinational glitch power.
In this work, a computer-aided design (CAD) approach that unrolls loops for designs targeted to low-cost FPGAs is described. Our approach considers latency constraints in an effort to minimize energy consumption for loop-based computation. To reduce glitch power, a glitch-filtering approach is introduced that provides a balance between glitch reduction and design performance. Glitch-filter enable signals are generated and routed to the filters using resources best suited to the target FPGA. Our approach automatically inserts glitch filters and associated control logic into a design prior to processing with FPGA synthesis, place, and route tools. Our energy-saving loop-unrolling approach has been evaluated using five benchmarks often used in low-cost FPGAs. The energy-saving capabilities of the approach have been evaluated for an Intel Cyclone IV and a Xilinx Artix-7 FPGA using board-level power measurement. The use of unrolling and glitch filtering is shown to reduce energy by at least 65% for an Artix-7 device and 50% for a Cyclone IV device while meeting design latency constraints.
EGFR/Notch Antagonists Enhance the Response to Inhibitors of the PI3K-Akt Pathway by Decreasing Tumor-Initiating Cell Frequency
Authors: Fu Wenyan , Lei Changhai , Yu Yue , Liu Shuowu , Li Tian , Lin Fangxing , Fan Xiaoyan , Shen Yafeng , Ding Min , Tang Ying , Ye Xuting , Yang Yongji , Hu Shi 
Published: January 2019

Abstract

Purpose:
Both EGFR and PI3K-Akt signaling pathways have been used as therapeutically actionable targets, but resistance is frequently reported. In this report, we show that enrichment of the cancer stem cell (CSC) subsets and dysregulation of Notch signaling underlie the challenges to therapy and describe the development of bispecific antibodies targeting both HER and Notch signaling.

Experimental Design:
We utilized cell-based models to study Notch signaling in drug-induced CSC expansion. Both cancer cell line models and patient-derived xenograft tumors were used to evaluate the antitumor effects of bispecific antibodies. Cell assays, flow cytometry, qPCR, and in vivo serial transplantation assays were employed to investigate the mechanisms of action and pharmacodynamic readouts.

Results:
We found that EGFR/Notch targeting bispecific antibodies exhibited a notable antistem cell effect in both in vitro and in vivo assays. Bispecific antibodies delayed the occurrence of acquired resistance to EGFR inhibitors in triple-negative breast cancer cell line–based models and showed efficacy in patient-derived xenografts. Moreover, the EGFR/Notch bispecific antibody PTG12 in combination with GDC-0941 exerted a stronger antitumor effect than the combined therapy of PI3K inhibitor with EGFR inhibitors or tarextumab in a broad spectrum of epithelial tumors. Mechanistically, bispecific antibody treatment inhibits the stem cell–like subpopulation, reduces tumor-initiating cell frequency, and downregulates the mesenchymal gene expression.

Conclusions:
These findings suggest that the coblockade of EGFR and Notch signaling has the potential to increase the response to PI3K inhibition, and PTG12 may gain clinical efficacy when combined with PI3K blockage in cancer treatment.
irRECIST for the Evaluation of Candidate Biomarkers of Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma: Analysis of a Phase II Prospective Clinical Trial
Authors: Pignon Jean-Christophe , Jegede Opeyemi , Shukla Sachet A. , Braun David A. , Horak Christine E. , Wind-Rotolo Megan , Ishii Yuko , Catalano Paul J. , Grosha Jonian , Flaifel Abdallah , Novak Jesse S. , Mahoney Kathleen M. , Freeman Gordon J. , Sharpe Arlene H. , Hodi F. Stephen , Motzer Robert J. , Choueiri Toni K. , Wu Catherine J. , Atkins Michael B. , McDermott David F. , Signoretti Sabina 
Published: January 2019

Abstract

Purpose:
Immune-related RECIST (irRECIST) were designed to capture atypical responses seen with immunotherapy. We hypothesized that, in patients with metastatic clear cell renal cell carcinoma (mccRCC), candidate biomarkers for nivolumab response would show improved association with clinical endpoints capturing atypical responders (irRECIST) compared with standard clinical endpoints (RECISTv1.1).

Experimental Design:
Endpoints based on RECISTv1.1 [objective response rate (ORR)/progression-free survival (PFS)] or irRECIST [immune-related ORR (irORR)/immune-related PFS (irPFS)] were compared in patients enrolled in the CheckMate-010 trial. Pretreatment tumors were analyzed by PD-L1 and PD-L2 IHC, and by multiplex immunofluorescence for CD8, PD-1, TIM-3, and LAG-3. T-cell activation signatures were assessed by RNA sequencing.

Results:
Median irPFS was significantly longer than median PFS. irORR was not significantly different from ORR, but immune-related progressive disease (irPD) rate was significantly lower than progressive disease (PD) rate. Tumor cell (TC) PD-L1 expression was not associated with PFS or ORR, but patients with TC PD-L1 ≥1% had longer median irPFS and higher irORR. High percentage of CD8+ tumor-infiltrating cells (TIC) that are PD-1+TIM-3−LAG-3− (% CD8+PD-1+TIM-3−LAG-3− TIC) correlated with high levels of T-cell activation and was associated with longer median irPFS and higher irORR. Notably, combination of TC PD-L1 expression with % CD8+PD-1+TIM-3−LAG-3− TIC identified three groups of patients for which irPFS and irORR were significantly different.

Conclusions:
Atypical responders to nivolumab were identified in the CheckMate-010 trial. We observed improved association of candidate biomarkers for nivolumab response with endpoints defined by irRECIST compared with RECISTv1.1. TC PD-L1 expression in combination with PD-1 expression on CD8+ TIC may predict outcome on nivolumab in mccRCC.
РОЗРОБКА СПЕКТРОФОТОМЕТРИЧНОЇ МЕТОДИКИ ВИЗНАЧЕННЯ ФЛАВОНОЇДІВ У ПАГОНАХ ЧОРНИЦІ ЗВИЧАЙНОЇ
Authors: Vronska L. V. 
Published: January 2019

Мета роботи. Розробка спектрофотометричної методики визначення флавоноїдів у пагонах чорниці звичайної.
Матеріали і методи. У дослідженнях застосовувались зразки пагонів чорниці, зібрані у Закарпатській, Івано-Франківській, Тернопільській і Волинській областях впродовж 2014-2018 років, і зразки лікарського засобу «Чорниці пагони» (ПрАТ "Ліктрави", Україна). Визначення вмісту флавоноїдів проводили методом абсорбційної спектрофотометрії, вимірюючи абсорбцію комплексу флавоноїдів з алюміній хлоридом. Для вимірювання абсорбції і запису електронних спектрів поглинання застосовували спектрофотометр Cary 50 UV-Vis (Agilent Technologies).
Результати й обговорення. Електронні спектри поглинання, отримані для випробовуваних розчинів і стандартного розчину рутину в умовах комплексоутворення флавоноїдів з алюміній хлоридом, були ідентичними за ходом кривих світлопоглинання і характеризувались положенням максимуму поглинання при 410 ± 2 нм і 412 ± 2 нм відповідно, що дозволило обрати рутин за стандарт для перерахунку вмісту флавоноїдів у досліджуваній сировині. При дослідженні впливу концентрації етанолу на вилучення флавоноїдів, встановлено, що для приготування вихідного розчину проби слід застосовувати 70% (об/об) етанол. Вилучення флавоноїдів з аналітичною метою слід виконувати при нагріванні зі зворотнім холодильником трикратно – почергово з 60, 20 і 15 мл етанолу впродовж 30, 15 і 15 хв відповідно. Важливим моментом методики є підготовка сировини – для аналізу слід застосовувати дрібну фракцію (355) подрібненої сировини, враховуючи її вміст у розрахунковій формулі. Знайдено, що вміст флавоноїдів у досліджуваних дикорослих зразках є в межах 1,14-1,86%, а в промислових серіях (за винятком сировини серії 20614) – в межах 0,7-1,0%.
Висновки. Розроблено спектрофотометричну методику кількісного визначення флавоноїдів у сировині пагонів чорниці звичайної. Здійснено кількісне визначення вмісту флавоноїдів у 17 зразках сировини різного походження. Для оцінки якості пагонів чорниці запропоновано ввести додатковий показник «Вміст флавоноїдів» з критерієм – не менше 0,6% флавоноїдів у перерахунку на рутин і суху сировину.
Stroke Outcomes in the COMPASS Trial
Authors: Sharma Mukul , Hart Robert G. , Connolly Stuart J. , Bosch Jackie , Shestakovska Olga , Ng Kelvin K.H. , Catanese Luciana , Keltai Katalin , Aboyans Victor , Alings Marco , Ha Jong-Won , Varigos John , Tonkin Andrew , O’Donnell Martin , Bhatt Deepak L. , Fox Keith , Maggioni Aldo , Berkowitz Scott D. , Bruns Nancy Cook , Yusuf Salim , Eikelboom John W. 
Published: January 2019

Background:
Strokes were significantly reduced by the combination of rivaroxaban plus aspirin in comparison with aspirin in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies). We present detailed analyses of stroke by type, predictors, and antithrombotic effects in key subgroups.

Methods:
Participants had stable coronary artery or peripheral artery disease and were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117), or rivaroxaban 2.5 mg twice daily plus aspirin (n=9152). Patients who required anticoagulation or had a stroke within 1 month, previous lacunar stroke, or intracerebral hemorrhage were excluded.

Results:

During a mean follow-up of 23 months, fewer patients had strokes in the rivaroxaban plus aspirin group than in the aspirin group (83 [0.9% per year] versus 142 [1.6% per year]; hazard ratio [HR], 0.58; 95% CI, 0.44–0.76;
P
<0.0001). Ischemic/uncertain strokes were reduced by nearly half (68 [0.7% per year] versus 132 [1.4% per year]; HR, 0.51; 95% CI, 0.38–0.68;
P
<0.0001) by the combination in comparison with aspirin. No significant difference was noted in the occurrence of stroke in the rivaroxaban alone group in comparison with aspirin: annualized rate of 0.7% (HR, 0.82; 95% CI, 0.65–1.05). The occurrence of fatal and disabling stroke (modified Rankin Scale, 3–6) was decreased by the combination (32 [0.3% per year] versus 55 [0.6% per year]; HR, 0.58; 95% CI, 0.37–0.89;
P
=0.01). Independent predictors of stroke were prior stroke, hypertension, systolic blood pressure at baseline, age, diabetes mellitus, and Asian ethnicity. Prior stroke was the strongest predictor of incident stroke (HR, 3.63; 95% CI, 2.65–4.97;
P
<0.0001) and was associated with a 3.4% per year rate of stroke recurrence on aspirin. The effect of the combination in comparison with aspirin was consistent across subgroups with high stroke risk, including those with prior stroke.

Conclusions:
Low-dose rivaroxaban plus aspirin is an important new antithrombotic option for primary and secondary stroke prevention in patients with clinical atherosclerosis.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01776424.
Systemic Inflammation and Cardio-Renal Organ Damage Biomarkers in Middle Age Are Associated With Physical Capability Up to 9 Years Later
Authors: Kuh Diana , Cooper Rachel , Sattar Naveed , Welsh Paul , Hardy Rebecca , Ben-Shlomo Yoav 
Published: January 2019

Background:
Physical capability, a key component of healthy aging, is associated with cardiovascular and other risk factors across life. We investigated whether midlife biomarkers of heart and kidney damage capturing the cumulative impact of long-term adverse exposures were associated with the level and decline in physical capability over 9 years of follow-up, taking account of systemic inflammatory biomarkers and conventional cardiovascular risk factors.

Methods:
We used data on 1736 men and women from the oldest British birth cohort study with walking speed, chair rise speed, balance time, and grip strength assessed at ages 60 to 64 and 69 years. We tested associations between logged and standardized measures of cystatin C, NT-proBNP (N-terminal pro-B-type natriuretic peptide), interleukin (IL)-6, and E-selectin at age 60 to 64 years with performance at age 69 years, adjusting for sex, height, and body mass index; then for performance at age 60 to 64 years. These biomarkers were mutually adjusted, and additionally adjusted for cardiovascular risk factors (pulse pressure, total/high density lipoprotein cholesterol, glycosylated hemoglobin), diabetes mellitus, cardiovascular and kidney disease, smoking status, and lifetime socioeconomic position.

Results:
Cystatin C, NT-proBNP, and IL-6 (but not E-selectin) were inversely associated with all outcomes, adjusted for sex, height, and body mass index. For example, a 1-SD increase in logged NT-proBNP was associated with weaker grip (−0.63 kg, 95% CI, −0.99 to −0.28); the equivalent association for cystatin C was −0.60 kg (95% CI, −0.94 to −0.25) and for IL-6 was −0.76 kg (95% CI, −1.11 to −0.41). Most associations remained, albeit attenuated, after adjustment for previous performance and mutual adjustment of the biomarkers. NT-proBNP and IL-6 (but not cystatin C) were more strongly associated with the outcomes than many of the conventional risk factors after mutual adjustment.

Conclusions:
Higher levels of NT-proBNP may identify those in midlife at risk of accelerated physical decline. Before considering the use of NT-proBNP for risk stratification, further research should untangle whether these associations exist because the biomarker is an integrated measure of cumulative exposures to relevant stressors across life, or whether it is marking additional risk pathways. Randomized trials to reduce the rate of decline in physical capability or delay incident disability could benefit from including middle-aged adults and adding NT-proBNP and IL-6 as intermediate outcomes.
Long-term outcome and quality of life in patients with iliac vein compression syndrome after endovascular treatment
Authors: Bi Yonghua , Yu Zepeng , Chen Hongmei , Ren Jianzhuang , Han Xinwei 
Published: January 2019

Purpose Deep venous thrombosis induced by iliac vein compression syndrome often interferes with patients’ work or daily living. This study aims to investigate the long-term outcome and quality of life in patients with iliac vein compression syndrome after endovascular treatment. Methods From October 2011 until June 2016, 28 patients with acute deep venous thrombosis diagnosed as iliac vein compression syndrome by ultrasonography were enrolled in this perspective study. Fifteen patients underwent balloon dilation and stent insertion (group A); 13 patients received anticoagulation treatment, thrombolysis, or balloon dilation without stenting (group B). The Medical Outcomes Study-Short Form-36 was used to assess the quality of life preoperatively and after endovascular treatment. The follow-up of Short Form-36 questionnaire was obtained within 12.13 ± 12.04 months after repair. Results There was no operative mortality in two groups, and technical success was achieved in 14 (93.3%) patients in group A. Thirteen (86.7%) patients were cured in group A, which was significantly higher than that of group B (46.2%, p = 0.042). Only one patient showed occlusion of stent in group A, with a secondary patency rate of 93.3%. Except for ‘Role emotion’, all remaining domains were significantly improved in group A when compared with preoperative score ( p < 0.01). The scores of ‘Physical functioning’, ‘Role physical’, and ‘General health’ in group A were significantly higher than those of group B ( p < 0.05). Conclusions Endovascular stenting to treat iliac vein compression syndrome shows beneficial clinical outcome, cumulative patency rate, and quality of life, with high technical success and low complications.
Adverse Reactions to Human Plasma Proteins
Authors: Wells J. Vivian , King M. A. 
Published: January 2019

Adverse reactions to human plasma proteins range from mild urticaria to fatal anaphylaxis and may occur with virtually any blood product. The most common clinical settings appear to be whole blood transfusion in subjects with no previous history of reactions, or the infusion of fresh frozen plasma or injection of human immune serum globulin (HISG) to patients with known immunodeficiency. The immunological processes involved and the management of reactions are discussed.
Effect of Ranitidine Given before Atropine Sulphate on Lower Oesophageal Sphincter Tone
Authors: Brock-Utne J. G. , Downing J. W. , Humphrey D. 
Published: January 2019

The effects on lower oesophageal sphincter tone of intravenous ranitidine 150 mg followed by atropine 0.6 mg were studied in six healthy volunteers. Ranitidine increased the mean lower oesophageal sphincter pressure by 21.2 cm H2O (p <0.01). Subsequent injection of atropine lowered the lower oesophageal sphincter pressure but not significantly, mean sphincter pressure remaining 14.2 cm H2O above control. Barrier pressure to reflux (lower oesophageal sphincter pressure minus gastric pressure) increased significantly after intravenous ranitidine injection, and although it fell after intravenous atropine it was still above control levels. The results of this study suggest that ranitidine increases lower oesophageal sphincter tone. When it is given prior to atropine injection within 20 minutes before induction of anaesthesia it counteracts the deleterious effect of the latter on sphincter tone and barrier pressure to reflux.
Neurological Monitoring during Anaesthesia and Surgery
Authors: McMeniman W. J. , Purcell G. J. 
Published: January 2019

The ability to monitor the electrical activity of the central nervous system and to record responses to stimulation allows for a more immediate assessment of the functional integrity of the nervous system during anaesthesia than do conventional techniques. These monitoring methods, however, have been slow to find acceptance in clinical practice. The reasons include the difficulty with standardization and reproducibility of results from such monitoring techniques as the electroencephalogram (EEG) and evoked potentials, along with the level of expertise necessary for accurate interpretation of the voluminous data collected. Anaesthetic agents along with variations in physiological parameters can markedly alter the recordings not to mention the influence of diathermy, other electrical devices, muscle activity and artifact. Because of these inherent difficulties, most anaesthetists still rely on optimising such physiological parameters as arterial, venous and intracranial pressures, oxygen and carbon dioxide tensions, to ensure the functional integrity of the nervous system. This brief review explores the potential areas of application of electrophysiologic monitoring in surgery and anaesthesia. 1–5
A Five-Year Prospective Analysis of the Efficacy, Safety and Morbidity of Epidural Anaesthesia Performed by a General Practitioner Anaesthetist in an Isolated Rural Hospital
Authors: Watts R. W. 
Published: January 2019

During a five-year period, 324 epidurals were performed by a general practitioner anaesthetist in an isolated rural hospital. Of these 160 were for obstetric purposes, 72% in primagravida patients, the majority in early and established labour (median cervical dilatation of 3.0 cm). The median epidural insertion time was seven minutes: 80% were free of all complications, there were no dural taps and there was a failure rate of 2%. The median visual analogue pain score (VAPS) was 8.3 prior to insertion and at peak of epidural blockade it was reduced to 0.5. Ten per cent of patients had unblocked segments, half of these were corrected and 90% of patients had even blocks. Despite higher pain scores in the 6–10 cm cervical dilatation group, epidural analgesia was just as effective when compared to the 0.5 cm group. Seventy-seven percent of women interviewed the day after delivery were fully satisfied with the epidural: 19% said it was considerable help, 2% some help and 2% said no help at all. During epidural caesarean section (n = 72), 75% of patients were comfortable, 17% had some discomfort and 7% required general or spinal anaesthesia. The incidence of hypotension (systolic blood pressure < 90 mmHg), was 24.6% with a median ephedrine dose of 10 mg; however, with a greater than 20% drop in systolic blood pressure, the dose of ephedrine required to maintain blood pressure increased in a log-dose fashion. For women who received epidurals in labour, the caesarean section rate was 25%, instrumental vaginal delivery 34% and spontaneous vaginal delivery 41%. There were no adverse neonatal outcomes.