Showing papers by "Saint Francis University published in 2018"

Functional variants in the LRRK2 gene confer shared effects on risk for Crohn's disease and Parkinson's disease.

Abstract: Crohn’s disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10−10) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10−8). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson’s disease (PD), and healthy controls revealed extensive pleiotropy, with shared genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant was associated with increased kinase activity, whereas neither N551K nor R1398H variants on the protective haplotype altered kinase activity. We also confirmed that R1398H, but not N551K, increased guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.

Validation of a novel non-hyperaemic index of coronary artery stenosis severity: the Resting Full-cycle Ratio (VALIDATE RFR) study.

Abstract: AIMS: Randomised controlled trials have reported instantaneous wave-free ratio (iFR) to be non-inferior to fractional flow reserve (FFR) for major adverse cardiovascular events at one year; however, iFR is limited by sensitive landmarking of the pressure waveform, and the assumption that maximal flow and minimal resistance occur during a fixed period of diastole We sought to validate the resting full-cycle ratio (RFR), a novel non-hyperaemic index of coronary stenosis severity based on unbiased identification of the lowest distal coronary pressure to aortic pressure ratio (Pd/Pa), independent of the ECG, landmark identification, and timing within the cardiac cycle METHODS AND RESULTS: VALIDATE-RFR was a retrospective study designed to derive and validate the RFR The primary endpoint was the agreement between RFR and iFR RFR was retrospectively determined in 651 waveforms in which iFR was measured using a proprietary Philips/Volcano wire RFR was highly correlated to iFR (R2=099, p<0001), with a mean bias of -0002 (95% limits of agreement -0023 to 0020) The diagnostic performance of RFR versus iFR was diagnostic accuracy 974%, sensitivity 982%, specificity 969%, positive predictive value 945%, negative predictive value 990%, area under the receiver operating characteristic curve of 0996, and diagnostically equivalent within 1% (mean difference -0002; 95% CI: -0009 to 0006, p=003) The RFR was detected outside diastole in 122% (341/2,790) of all cardiac cycles and 324% (167/516) of cardiac cycles in the right coronary artery where the sensitivity of iFR compared to FFR was lowest (406%) CONCLUSIONS: RFR is diagnostically equivalent to iFR but unbiased in its ability to detect the lowest Pd/Pa during the full cardiac cycle, potentially unmasking physiologically significant coronary stenoses that would be missed by assessment dedicated to specific segments of the cardiac cycle

Rationale and Design of the CONCERT-HF Trial (Combination of Mesenchymal and c-kit+ Cardiac Stem Cells As Regenerative Therapy for Heart Failure).

Abstract: Rationale: Autologous bone marrow (BM) mesenchymal stem cells (MSCs) and c-kit + cardiac progenitor cells (CPCs) are two promising cell types being evaluated for patients with heart failure (HF) secondary to ischemic cardiomyopathy. No information is available in humans regarding the relative efficacy of MSCs and CPCs and whether their combination is more efficacious than either cell type alone. Objective: CONCERT-HF (Combination Of meseNchymal and c-kit + Cardiac stEm cells as Regenerative Therapy for Heart Failure) is a Phase II trial aimed at elucidating these issues by assessing the feasibility, safety, and efficacy of transendocardial administration of autologous MSCs and CPCs, alone and in combination, in patients with HF caused by chronic ischemic cardiomyopathy (coronary artery disease and old myocardial infarction). Methods and Results: Using a randomized, double-blinded, placebo-controlled, multi-center, multi-treatment, and adaptive design, CONCERT-HF examines whether administration of MSCs alone, CPCs alone, or MSCs + CPCs in this population alleviates left ventricular (LV) remodeling and dysfunction, reduces scar size, improves quality of life, or augments functional capacity. The four-arm design enables comparisons of MSCs alone with CPCs alone and with their combination. CONCERT-HF consists of 162 patients, 18 in a safety lead-in phase (Stage 1) and 144 in the main trial (Stage 2). Stage 1 is complete and Stage 2 is currently randomizing patients from seven centers across the US. Conclusions: CONCERT-HF will provide important insights into the potential therapeutic utility of MSCs and CPCs, given alone and in combination, for patients with HF secondary to ischemic cardiomyopathy. Clinicaltrials.gov : NCT02501811.

Deconstructing the notion of "global health research partnerships" across Northern and African contexts.

Abstract: Global health conceives the notion of partnership between North and South as central to the foundations of this academic field. Indeed, global health aspires to an equal positioning of Northern and Southern actors. While the notion of partnership may be used to position the field of global health morally, this politicization may mask persisting inequalities in global health. In this paper, we reflect on global health partnerships by revisiting the origins of global health and deconstructing the notion of partnership. We also review promising initiatives that may help to rebalance the relationship. Historical accounts are helpful in unpacking the genesis of collaborative research between Northerners and Southerners – particularly those coming from the African continent. In the 1980s, the creation of a scientific hub of working relationships based on material differences created a context that was bound to create tensions between the alleged “partners”. Today, partnerships provide assistance to underfunded African research institutions, but this assistance is often tied with hypotheses about program priorities that Northern funders require from their Southern collaborators. African researchers are often unable to lead or contribute substantially to publications for lack of scientific writing skills, for instance. Conversely, academics from African countries report frustrations at not being consulted when the main conceptual issues of a research project are discussed. However, in the name of political correctness, these frustrations are not spoken aloud. Fortunately, initiatives that shift paternalistic programs to formally incorporate a mutually beneficial design at their inception with equal input from all stakeholders are becoming increasingly prominent, especially initiatives involving young researchers. Several concrete steps can be undertaken to rethink partnerships. This goes hand in hand with reconceptualizing global health as an academic discipline, mainly through being explicit about past and present inequalities between Northern and Southern universities that this discipline has thus far eluded. Authentic and transformative partnerships are vital to overcome the one-sided nature of many partnerships that can provide a breeding-ground for inequality.

Clinical Efficacy and Safety of Baminercept, a Lymphotoxin β Receptor Fusion Protein, in Primary Sjögren's Syndrome: Results From a Phase II Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract: OBJECTIVE To evaluate the clinical efficacy and safety of baminercept, a lymphotoxin β receptor IgG fusion protein (LTβR-Ig), for the treatment of primary Sjogren's syndrome (SS), and to explore the possible mechanisms of action of this treatment. METHODS In this multicenter trial, 52 patients with primary SS were randomized in a 2:1 ratio to receive subcutaneous injections of 100 mg of baminercept every week for 24 weeks or matching placebo. The primary end point was the change between screening and week 24 in the stimulated whole salivary flow (SWSF) rate. Secondary end points included the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI), as well as measurements of select chemokines and cytokines and enumeration of peripheral blood B and T cell subsets. RESULTS The change from baseline to week 24 in the SWSF rate was not significantly different between the baminercept and placebo treatment groups (baseline-adjusted mean change -0.01 versus 0.07 ml/minute; P = 0.332). The change in the ESSDAI during treatment was also not significantly different between the treatment groups (baseline-adjusted mean change -1.23 versus -0.15; P = 0.104). Although the incidence of adverse events was similar between the treatment groups, baminercept therapy was associated with a higher incidence of liver toxicity, including 2 serious adverse events. Baminercept also produced a significant decrease in plasma levels of CXCL13 and significant changes in the number of circulating B and T cells, consistent with its known inhibitory effects on LTβR signaling. CONCLUSION In this trial, treatment with baminercept failed to significantly improve glandular and extraglandular disease in patients with primary SS, despite evidence from mechanistic studies showing that it blocks LTβR signaling.

Modeling the Kinetics of Hydrogen Formation by Zerovalent Iron: Effects of Sulfidation on Micro- and Nano-Scale Particles.

Abstract: The hydrogen evolution reaction (HER) that generates H2 from the reduction of H2O by Fe0 is among the most fundamental of the processes that control reactivity in environmental systems containing zerovalent iron (ZVI). To develop a comprehensive kinetic model for this process, a large and high-resolution data set for HER was measured using five types of ZVI pretreated by acid-washing and/or sulfidation (in pH 7 HEPES buffer). The data were fit to four alternative kinetic models using nonlinear regression analysis applied to the whole data set simultaneously, which allowed some model parameters to be treated globally across multiple experiments. The preferred model uses two independent reactive phases to match the two-stage character of most HER data, with rate constants ( k's) for each phase fitted globally by iron type and phase quantities ( S's) fitted as fully local (independent) parameters. The first, faster stage was attributed to a reactive mineral intermediate (RMI) phase like Fe(OH)2, which may form in all experiments during preequilibration, but is rapidly consumed, leaving the second, slower stage of HER, which is due to reaction of Fe0. In addition to providing a deterministic model to explain the kinetics of HER by ZVI over a wide range of conditions, the results provide an improved quantitative basis for comparing the effects of sulfidation on ZVI.

Effects of the hippopotamus on the chemistry and ecology of a changing watershed

Abstract: Cross-boundary transfers of nutrients can profoundly shape the ecology of recipient systems. The common hippopotamus, Hippopotamus amphibius, is a significant vector of such subsidies from terrestrial to river ecosystems. We compared river pools with high and low densities of H. amphibius to determine how H. amphibius subsidies shape the chemistry and ecology of aquatic communities. Our study watershed, like many in sub-Saharan Africa, has been severely impacted by anthropogenic water abstraction reducing dry-season flow to zero. We conducted observations for multiple years over wet and dry seasons to identify how hydrological variability influences the impacts of H. amphibius. During the wet season, when the river was flowing, we detected no differences in water chemistry and nutrient parameters between pools with high and low densities of H. amphibius. Likewise, the diversity and abundance of fish and aquatic insect communities were indistinguishable. During the dry season, however, high-density H. amphibius pools differed drastically in almost all measured attributes of water chemistry and exhibited depressed fish and insect diversity and fish abundance compared with low-density H. amphibius pools. Scaled up to the entire watershed, we estimate that H. amphibius in this hydrologically altered watershed reduces dry-season fish abundance and indices of gamma-level diversity by 41% and 16%, respectively, but appears to promote aquatic invertebrate diversity. Widespread human-driven shifts in hydrology appear to redefine the role of H. amphibius, altering their influence on ecosystem diversity and functioning in a fashion that may be more severe than presently appreciated.

Global prevalence of percutaneous injuries among healthcare workers: a systematic review and meta-analysis

Abstract: Background Healthcare workers (HCWs) are at risk of occupational exposure to blood-borne pathogens through contact with human blood and other body fluids. This study was conducted to estimate the global and regional 1-year prevalence of percutaneous injuries (PCIs) among HCWs. Methods We systematically searched EMBASE, PubMed, CINAHL and PsychInfo databases for studies published from January 2008 to January 2018 that reported the prevalence of PCIs among HCWs. A random-effects meta-analysis was conducted to estimate pooled prevalence of PCIs among HCWs. Results Of the 5205 articles identified, 148 studies from 43 countries met the inclusion criteria. The pooled global 1-year prevalence estimate of PCIs was 36.4% [95% confidence interval (CI): 32.9–40.0]. There were substantial regional variations in the 1-year prevalence of PCIs, ranging from 7.7% (95% CI: 3.1–12.4) in South America to 43.2% (95% CI: 38.3–48.0) in Asia. The estimates for Africa and Europe were comparable with values of 34.5% (95% CI: 29.9–39.1) and 31.8% (95% CI: 25.0–38.5), respectively. The highest 1-year prevalence by job category was among surgeons, at 72.6% (95% CI: 58.0–87.2). The estimates for medical doctors (excluding surgeons), nurses (including midwives) and laboratory staff (including laboratory technicians) were 44.5% (95% CI: 37.5–51.5), 40.9% (95% CI: 35.2–46.7) and 32.4% (95% CI: 20.9–49.3), respectively. PCIs commonly occurred among HCWs working in hospital (41.8%, 95% CI: 37.6–46.0) than non-hospital (7.5%, 95% CI: 5.9–9.1) settings. Conclusions Our findings suggest high rates of PCIs among HCWs with direct patient care across many regions of the world. However, paucity of data from some countries was a major limitation.

A phase IB/II randomized study of mFOLFIRINOX (mFFOX) + pegylated recombinant human hyaluronidase (PEGPH20) versus mFFOX alone in patients with good performance status metastatic pancreatic adenocarcinoma (mPC): SWOG S1313 (NCT #01959139).

Abstract: 208Background: PEGPH20 degrades hyaluronan (HA), a major component of the stroma, increases delivery of gemcitabine and prolongs survival in preclinical models. We evaluated the activity of PEGPH20...

Safety and efficacy of the next generation Resolute Onyx zotarolimus-eluting stent: Primary outcome of the RESOLUTE ONYX core trial

Abstract: Objectives To assess the safety and efficacy of the novel Resolute (R-) Onyx drug-eluting stent (DES). Background The R-Onyx DES consists of a composite wire with an outer shell of cobalt chromium alloy and a platinum-iridium inner core to enhance radiopacity, with thinner, swaged struts and modified stent geometry compared with the predicate Resolute DES, resulting in a slightly lower total drug load in most sizes. Methods This was a prospective, single-arm non-inferiority trial compared with a historical control. Patients with stable angina/ischemia and up to 2 de novo target lesions ≤35 mm long with reference vessel diameter (RVD) of 2.25–4.2 mm were enrolled. The primary endpoint was late lumen loss at 8-month follow-up. Propensity-score adjusted outcomes from the single-arm RESOLUTE-US trial served as the control. Results Seventy-five patients (85 lesions) were enrolled. Mean patient age was 66 ± 9 years, 73% were male, and 32% had diabetes. Mean lesion length was 14.28 ± 6.68 mm, mean RVD was 2.57 ± 0.48 mm, and 86% of lesions were class B2/C. In-stent late lumen loss at 8 months was 0.24 ± 0.39 mm with R-Onyx DES compared with 0.36 ± 0.52 mm with Resolute DES (P < 0.001 for noninferiority, P = 0.029 for superiority). At 8 months, clinically driven target lesion revascularization occurred in 3 patients (4.0%) and target lesion failure occurred in 5 patients (6.7%). Conclusions In-stent late lumen loss is non-inferior, and appears to be superior, with the thin-strut novel composite wire R-Onyx DES compared with Resolute DES. Continued evolution of stent design can improve angiographic outcomes in complex lesions, even in the current era of next-generation DES.

Prevalence and correlates of abdominal obesity among adults in Uganda: findings from a national cross-sectional, population based survey 2014

Abstract: Overweight and obesity are associated with health complications the gravity of which, vary with the regional deposition of the excess fat. The Body Mass Index (BMI) is often used to measure obesity although is an inferior predictor of cardiovascular disease risk mortality and morbidity compared with measures of abdominal obesity. We analyzed data from Uganda’s 2014 World Health Organization (WHO) STEPwise approach to surveillance of Non-communicable diseases (NCDs) survey to estimate the prevalence of abdominal obesity and associated factors to provide information on the prevention and control of overweight and obesity. Data were collected using the WHO STEPS protocol. Waist measurement was taken using a non-stretchable standard tape measure mid-way between the lowest rib and iliac crest with the subject standing at the end of gentle expiration. Participants with waist circumference > 102 cm for men and 88 cm for women were classified as abdominally obese. We used weighted modified Poisson regression with robust error variance to estimate the prevalence of abdominal obesity and associated factors. Of the 3676 participants, 432 (11.8%) were abdominally obese; with the prevalence higher among females 412 (19.5%) compared with males 20 (1.3%). Compared with males, female participants were more likely to be abdominally obese Adjusted Prevalence Rate Ratio (APRR) 7.59 [5.58–10.33]. Participants who were married or cohabiting APRR 1.82 [1.29–2.57] and participants who were separated or divorced APRR 1.69 [1.17–2.46] were more likely to be abdominally obese compared with those who had never married before. Compared with rural dwellers, participants from urban areas were more likely to be abdominally obese APRR 1.29 [1.09–1.53]. Compared with participants with normal blood pressure, those with elevated blood pressure were more likely to be abdominally obese APRR 1.83 [1.57–2.14].Compared with participants without any education, those with secondary education were more likely to be abdominally obese APRR 1.42 [1.12–1.78]. There is a high prevalence of abdominal obesity among adults in Uganda which puts many at risk of developing associated metabolic complications. These data provide useful information for developing interventions and formulation of policies for the control and prevention of abdominal obesity in Uganda.

Factors Influencing Contraceptives Use among Women in the Juba City of South Sudan

Abstract: Understanding birth control and child spacing methods used by inhabitants of conflict afflicted settings is important in designing interventions to improve uptake of family planning services In addressing the dearth of knowledge on family planning use in these settings, this study aimed at identifying the influencing factors of contraceptives use among women in the Juba city of South Sudan Using a population based cross-sectional study, 380 women aged 15–49 years filled a guided questionnaire between April and May in 2015 We collected contraceptive use data and factors influencing family planning uptake Data analysis was performed using descriptive statistics and binary logistic regression Lifetime reported contraceptive use stood at 42% whereas contraceptive use in the last three months was 36% Logistic regression revealed attitudes (AOR = 1375, 95 CI 1246–1518) and parity (AOR = 1242, 95% CI 1000–1544) as significant determinants of lifetime contraceptive use whereas only attitude (AOR = 1348, ) determined contraceptive use in last three months The findings indicate optimal uptake of family planning and point to the influence of attitudes and parity on contraceptive use Changing attitudes and embedded sociocultural and political structures influencing attitudes is important to promote contraceptive uptake in these settings

Hospital Complications and Causes of 90-Day Readmissions After Implantation of Left Ventricular Assist Devices.

Abstract: Left ventricular assist devices (LVADs) have emerged as an attractive option in patients with advance heart failure. Nationwide readmission database 2013 to 2014 was utilized to identify LVAD recipients using ICD-9 procedure code 37.66. The primary outcome was 90-day readmission. Readmission causes were identified using ICD-9 codes in primary diagnosis field. The secondary outcomes were LVAD associated with hospital complications. Hierarchic 2-level logistic models were used to evaluate study outcomes. We identified 4,693 LVAD recipients (mean age 57 years, 76.2% males). Of which 53.9% were readmitted in first 90 days of discharge. Cardiac causes (33.3%), bleeding (21.3%), and infections (12.4%) were leading etiologies of 90-day readmissions. Significant predictors (odds ratio, 95% confidence interval, p value) of readmission were disposition to nursing facilities (1.33, 1.09 to 1.63, p = 0.01) and longer length of stay (1.01, 1.00 to 1.01, p <0.01). Although private insurance (0.75, 0.66 to 0.86, p <0.01), and self-pay (0.58, 0.42 to 0.81, p <0.01) predicted lower readmissions. Cardiac complications (36.3%), major bleeding (29.8%), and postoperative infections (10.4%) were most common LVAD-related complications. In conclusion, high early readmission rate was observed among LVAD recipients with Cardiac complications, bleeding complications, and infections were driving force for major complications and most of readmissions.

Heart diseases and echocardiography in rural Tanzania: Occurrence, characteristics, and etiologies of underappreciated cardiac pathologies

Abstract: Background Little is known about heart diseases and their treatment in rural sub-Saharan Africa. This study aimed to describe the occurrence, characteristics, and etiologies of heart diseases, and the medication taken before and prescribed after echocardiography in a rural referral Hospital in Tanzania. Methods This prospective descriptive cohort study included all adults and children referred for echocardiography. Clinical and echocardiographic data were collated for analysis. Results From December 2015 to October 2017, a total of 1'243 echocardiograms were performed. A total of 815 adults and 59 children ≤15 years had abnormal echocardiographic findings; in adults 537/815 (66%) had hypertension, with 230/537(43%) on antihypertensive drugs, and 506/815 (62%) were not on regular cardiac medication; 346/815 (42%) had severe eccentric or concentric left ventricular hypertrophy, and 182/815 (22%) had severe systolic heart failure. Only 44% demonstrated normal left ventricular systolic function. The most frequent heart diseases were hypertensive heart disease (41%), valvular heart disease (18%), coronary heart disease (18%), peripartum cardiomyopathy (7%), and other non-hypertensive dilated cardiomyopathies (6%) in adults, and congenital heart disease (34%) in children. Following echocardiography, 802/815 (98%) adults and 40/59 (68%) children had an indication for cardiac medication, 70/815 (9%) and 2/59 (3%) for oral anticoagulation, and 35/815 (4%) and 23/59 (39%) for cardiac surgery, respectively. Conclusion Hypertension is the leading etiology of heart diseases in rural Tanzania. Most patients present with advanced stages of heart disease, and the majority are not treated before echocardiography. There is an urgent need for increased awareness, expertise and infrastructure to detect and treat hypertension and heart failure in rural Africa.

Utility of initial procalcitonin values to predict urinary tract infection.

Abstract: Background Urinary tract infections (UTIs) are one of the most common reasons women seek treatment in the emergency department (ED). The biomarker procalcitonin (PCT) has gained popularity over the last decade to improve the diagnosis of bacterial infections and reduce unnecessary exposure to antibiotics. PCT has been extensively studied in patients with pneumonia and sepsis and may have additional role in UTI. Methods A retrospective study of patients who presented to the ED in which a urinalysis test and a PCT level was obtained within the first 24 h of presentation. Signs and symptoms of UTI and urine cultures were reviewed to determine a positive diagnosis of UTI. The area under the receiver operating curve was used to calculate the test characteristics of PCT. Different breakpoints were analyzed to determine which PCT level corresponded to the highest sensitivity and specificity. Results 293 patients were included in this single center, retrospective study. The AUC of PCT to predict UTI was 0.717; 95% CI: 0.643–0.791 (p Conclusions A PCT threshold

Phase II Study to Evaluate the Efficacy and Safety of Rilotumumab and Bevacizumab in Subjects with Recurrent Malignant Glioma

Abstract: LESSONS LEARNED Due to evolving imaging criteria in brain tumors and variation in magnetic resonance imaging evaluation, it is not ideal to use response rate as a primary objective. Future studies involving antiangiogenic agents should use overall survival.Disease-expected toxicities should be considered when defining the clinical significance of an adverse event. For example, vascular thromboembolic events are common in brain tumor patients and should not be attributed to the study drug in the safety analysis. BACKGROUND Recurrent malignant glioma (rMG) prognosis is poor, with a median patient survival of 3-11 months with bevacizumab (BEV)-containing regimens. BEV in rMG has 6-month progression free survival (PFS-6) of ∼40% and an objective response rate of 21.2%. BEV-containing regimens improve PFS-6 to 42.6%-50.3%, indicating that BEV combination therapies may be superior to single agent. Rilotumumab, a hepatocyte growth factor (HGF) antibody, inhibits angiogenesis and expression of angiogenic autocrine factors (e.g., vascular endothelial growth factor [VEGF]) by c-Met inhibition. Combination of rilotumumab with BEV to block vascular invasion and tumor proliferation may synergistically inhibit tumor growth. METHODS Thirty-six BEV-naive rMG subjects received rilotumumab (20 mg/kg and BEV (10 mg/kg) every 2 weeks. Endpoints included objective response rate (using Response Assessment in Neuro-Oncology [RANO] criteria), PFS-6, overall survival (OS), and toxicity. RESULTS Median patient follow-up was 65.0 months. Objective response rate was 27.8% (95% confidence interval [CI]: 15.7%-44.1%). Median OS was 11.2 months (95% CI: 7-17.5). PFS-6 was 41.7% (95% CI: 25.6%-57.0%). Most frequent treatment-related grade ≤2 events included weight gain, fatigue, allergic rhinitis, and voice alteration; grade ≥3 events included venous thromboembolism (four patients), including one death from pulmonary embolism. CONCLUSION Rilotumumab with BEV did not significantly improve objective response compared with BEV alone, and toxicity may preclude the use of rilotumumab in combination BEV regimens.

A Fiber-Optic Assisted Multilayer Perceptron Reservoir Production Modeling: A Machine Learning Approach in Prediction of Gas Production From the Marcellus Shale

Abstract: This study utilized the recorded data of a distributed temperature sensing (DTS) and distributed acoustic sensing (DAS) fiber-optic system from a gas producing horizontal well in the Marcellus Shale, in Northern West Virginia. A predictive data-driven model was developed to understand the well’s performance and forecast the gas production using DTS data and daily flowing time as dynamic inputs, from May 2016 to May 2018. We used 1320 DTS measurements along the lateral of the well MIP-3H for each day and upscaled to a stage scale by an averaging method. A multi-layer perceptron neural network (MLPNN) was trained with stage-based daily DTS data, and daily flowing time to predict gas production for the next day. We carried out a sensitivity analysis by removing each stage DTS attribute from the input dataset to identify the most influential stages in predicting gas production. The sensitivity analysis (SA) shows that several stages carry higher weights in predicting gas production, while several stages have less impact on prediction accuracy. In contrast to DTS, DAS data was only recorded during hydraulic fracturing of the well. DAS energy variance attribute, which could be inversely related to stage stimulation efficiency, was computed for each stage and compared with the results of the neural network SA. Stages with higher variance in DAS energy (less efficient stimulation) have less effect on neural network accuracy. This relationship is more significant for stages that are completed with limited entry approach in zones with similar minimum horizontal stress. The results of the sensitivity analysis was also compared with flow scanner production logging data. Results suggests that DAS data is more correlated with sensitivity analysis results than production logging data.

Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features

Abstract: PCGF2 encodes the polycomb group ring finger 2 protein, a transcriptional repressor involved in cell proliferation, differentiation, and embryogenesis. PCGF2 is a component of the polycomb repressive complex 1 (PRC1), a multiprotein complex which controls gene silencing through histone modification and chromatin remodelling. We report the phenotypic characterization of 13 patients (11 unrelated individuals and a pair of monozygotic twins) with missense mutations in PCGF2. All the mutations affected the same highly conserved proline in PCGF2 and were de novo, excepting maternal mosaicism in one. The patients demonstrated a recognizable facial gestalt, intellectual disability, feeding problems, impaired growth, and a range of brain, cardiovascular, and skeletal abnormalities. Computer structural modeling suggests the substitutions alter an N-terminal loop of PCGF2 critical for histone biding. Mutant PCGF2 may have dominant-negative effects, sequestering PRC1 components into complexes that lack the ability to interact efficiently with histones. These findings demonstrate the important role of PCGF2 in human development and confirm that heterozygous substitutions of the Pro65 residue of PCGF2 cause a recognizable syndrome characterized by distinctive craniofacial, neurological, cardiovascular, and skeletal features.

Measurements of radiation exposure of radiography students during their clinical training using thermoluminescent dosimetry.

Abstract: Radiation dose monitoring for radiography students during clinical training is necessary to demonstrate the extent of radiation protection issues present, as well as to instill in them an awareness of safe practices that they will carry with them throughout their careers. The study assess the radiation dose incurred by the undergraduate during clinical training. 312 students were monitored using (thermoluminescence dosimetry) between 2009 and 2015. The results establish that the radiation dose received by the students is well below the dose recommended by national and international authorities. Findings indicate that the dose did not reach the value of 1 mSv, which indicate that current radiation protection measures are acceptable and there was no risk of overexposure, as well as reinforces the importance of nuturing a culture of radiation protection and provides evidence to students that their future as professionals will be a safe one.

Vaccine-Preventable Diseases in Hospitalized Patients With Inflammatory Bowel Disease: A Nationwide Cohort Analysis

Abstract: BACKGROUND Inflammatory bowel disease (IBD) entails a higher risk of infections, including those that could be prevented with immunizations. Current Advisory Committee on Immunization Practices and American College of Gastroenterology vaccine recommendations for patients with IBD are based on low levels of evidence. METHODS We conducted a population-based descriptive cohort study using the US National Inpatient Sample ICD-9 codes from 2012 to 2015. We measured the frequency of patients with IBD who were admitted to the hospital with a vaccine-preventable disease (VPD). Frequencies and demographics were determined and compared between patients with IBD and patients without IBD. RESULTS Of discharges, 596,485 (2.08%) were secondary to a VPD, and 7180 (1.2%) were found to have both a VPD and IBD (including Crohn disease and ulcerative colitis). The most common VPDs among patients with IBD were herpes zoster virus (HZV) (34.9%) and hepatitis B virus (31.6%), followed by influenza (22.1%). Pneumococcal pneumonia (9.1%) and hepatitis A virus (2.4%) were less common. Inpatients with IBD were twice as likely to have HZV when compared to non-IBD inpatients (odds ratios [OR] = 2.30 [95% CI, 2.06-2.58], P < 0.0001) This finding was consistent for every study year. Pneumococcal pneumonia [OR = 0.62 (95% CI, 0.52-0.74), P < 0.0001] and influenza [OR = 0.72 (95% CI, 0.63-0.81), P < 0.0001] were significantly lower in the IBD population. There was no difference for other VPDs. CONCLUSIONS HZV was the most frequent VPD in IBD inpatients. Patients with IBD have a higher rate of hospital admissions with HZV and a lower rate of pneumococcal pneumonia and influenza admissions when compared with non-IBD patients. For other VPDs, patients with IBD have the same rate of admission as the general population.

Pharmacokinetics of a Single Dose of Oral and Intramuscular Meloxicam in African Penguins ( Spheniscus demersus).

Abstract: Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that has been used orally and intramuscularly in numerous avian species, but not studied to date, in African penguins ( Spheniscus demersus). The study describes the pharmacokinetic parameters of meloxicam after oral and intramuscular administration to African penguins. Several pilot studies were conducted initially where meloxicam (1, 0.5, and 0.25 mg/kg) was given intramuscularly to 4 birds, and orally (1 mg/kg) to 2 birds. Based on pilot study results, one group of 8 penguins was given meloxicam 0.5 mg/kg intramuscularly and one group of 8 penguins was given 1 mg/kg orally. Blood samples were collected at baseline and at 11 time intervals per group after administration of meloxicam. Meloxicam time to maximum plasma concentration (Tmax), maximum concentration (Cmax), and half-life (t1/2) after intramuscular administration were 1.00 hour, 8.03 μg/mL, and 31.87 hours, respectively, while oral administration produced a Tmax, Cmax, and t1/2 of 12.00 hours, 10.84 μg/mL, and 28.59 hours, respectively. Based on plasma meloxicam concentrations found to be therapeutic in other bird species and humans, the recommended dosage and frequency for African penguins is 1 mg/kg orally every 48 hours and 0.5 mg/kg intramuscularly every 24 hours. Further studies are needed to determine the multiple-dose pharmacokinetics of meloxicam in African penguins.

Inhaled glycopyrrolate for the treatment of chronic obstructive pulmonary disease.

Abstract: Long-acting muscarinic antagonists (LAMAs), along with long-acting β2-agonists (LABAs), are the mainstay for treatment of patients with COPD. Glycopyrrolate, or glycopyrronium bromide, like other LAMAs, inhibits parasympathetic nerve impulses by selectively blocking the binding of acetylcholine to muscarinic receptors. Glycopyrrolate is unusual in that it preferentially binds to M3 over M2 muscarinic receptors, thereby specifically targeting the primary muscarinic receptor responsible for bronchoconstriction occurring in COPD. Inhaled glycopyrrolate is slowly absorbed from the lungs and rapidly eliminated from the bloodstream, most likely by renal excretion in its unmetabolized form, limiting the potential for systemic adverse events. Inhaled glycopyrrolate is a fast-acting, efficacious treatment option for patients with moderate-severe COPD. It improves lung function, reduces the risk of exacerbations, and alleviates the symptoms of breathlessness, which in turn may explain the improvement seen in patients' quality of life. Inhaled formulations containing glycopyrrolate are well tolerated, and despite being an anticholinergic, few cardiovascular-related events have been reported. Inhaled glycopyrrolate is thus of value as both monotherapy and in combination with other classes of medication for maintenance treatment of COPD. This review covers the mechanism of action of inhaled glycopyrrolate, including its pharmacokinetic, pharmacodynamic, and safety profiles, and effects on mucus secretion. It also discusses the use of inhaled glycopyrrolate in the treatment of COPD, as monotherapy and in fixed-dose combinations with LABAs and inhaled corticosteroid-LABAs, including a triple therapy recently approved in Europe.

Caesarean section audit to improve quality of care in a rural referral hospital in Tanzania

Abstract: Caesarean section (CS) is often a life-saving procedure, but can also lead to serious complications, even more so in low-resource settings. Therefore unnecessary CS should be avoided and optimal circumstances for vaginal delivery should be created. In this study, we aim to audit indications for Caesarean sections and improve decision-making and obstetric management. Audit of all cases of CS performed from January to August 2013 was performed in a rural referral hospital in Tanzania. The study period was divided in three audit blocks; retrospective (before auditing), prospective 1 and prospective 2. A local audit panel (LP) and an external auditor (EA) judged if obstetric management was adequate and indications were appropriate or if CS could have been prevented and yet retain good pregnancy outcome. Furthermore, changes in modes of deliveries, overall pregnancy outcome and decision-to-delivery interval were monitored. During the study period there were 1868 deliveries. Of these, 403 (21.6%) were Caesarean sections. The proportions of unjustified CS prior to introduction of audit were as high as 34 and 75%, according to the respective judgments of LP and EA. Following introduction of audit, the proportions of unjustified CS decreased to 23% (p = 0.29) and 52% (p = 0.01) according to LP and EA respectively. However, CS rate did not change (20.2 to 21.7%), assisted vacuum delivery rate did not increase (3.9 to 1.8%) and median decision-to-delivery interval was 83 min (range 10 - 390 min). Although this is a single center study, these findings suggest that unnecessary Caesarean sections exist at an alarming rate even in referral hospitals and suggest that a vast number can be averted by introducing a focused CS audit system. Our findings indicate that CS audit is a useful tool and, if well implemented, can enhance rational use of resources, improve decision-making and harmonise practice among care providers.

Bringing the Effects of Occupational Licensing into Focus: Optician Licensing in the United States

Abstract: The labor market institution of occupational licensing continues to grow in scope in the United States and abroad. In this paper, we estimate the effects of occupational licensing on opticians using data from the US Census and American Community Survey. Our results suggest that optician licensing is associated with opticians receiving as much as 16.9 percent more in annual earnings. In an examination of malpractice insurance premiums in all states and participation rates in optician certification programs in Texas, we find little evidence that optician licensing has enhanced the quality of services delivered to consumers. By and large, optician licensing appears to be reducing consumer welfare by raising the earnings of opticians without enhancing the quality of services delivered to consumers.

Application of horizontal wells in three-dimensional shale reservoir modeling: A case study of Longmaxi–Wufeng shale in Fuling gas field, Sichuan Basin: Reply

Abstract: Three-dimensional reservoir modeling is an important aspect to determine the heterogeneity of organic-rich shale reservoirs, an area of study that continues to be explored and refined. A large proportion of data acquired from horizontal wells causes issues in the structural and property modeling for shale reservoirs. Since horizontal wells are designed to drill into a specific, narrow zone, their horizontal section tends to parallel or nearly parallel formation surfaces. As a result, formation surfaces have a much more complex spatial location relationship with horizontal wellbores than with vertical wellbores. The existing algorithms are not good at addressing this issue during structural modeling. The major problem of using horizontal well data in property modeling is the biased data set because their horizontal section tends to stay within a narrow zone. The property distribution feature estimated from this biased data set, as a significant, default input of geostatistical simulation algorithms, causes the constructed property models to deviate away from the real case in the subsurface. A method to infer more formation tops in pseudovertical wells according to a series of assumptions was developed to provide more constraint points for structural modeling within the areas of the horizontal well section. To use the biased database from horizontal wells, distribution function and trend model methods were developed for continuous property modeling, and percentage and probability trend models were developed for discrete property modeling. The Longmaxi–Wufeng shale in the Fuling gas field of Sichuan Basin was used as an example to express and verify these methods.

Assessment of sulphate and iron reduction rates during reactor start-up for passive anaerobic co-treatment of acid mine drainage and sewage

Abstract: Passive co-treatment of municipal wastewater (MWW) and acid mine drainage (AMD) has shown promise over the past decade for simultaneous remediation of these widespread waste streams. To investigate the efficiency and rates of iron and sulphate reduction during the start-up of anaerobic co-treatment using a novel, process-based kinetic modeling approach, twenty-four replicate 1L-cubitainers containing a 5:2 MWW:AMD mixture and Kaldnes plastic media were sealed, incubated and sacrificially sampled for key water quality parameters over 30 days. Alkalinity generation, pH increase and efficient removal of iron, aluminum and phosphate were observed. The observed sulphate and iron reduction rates were relatively slow, and the removal of sulphate, organic carbon and nitrogen was modest and incomplete. Overall, the results confirm the efficacy of AMD-MWW co-treatment for removal of key pollutants, but also highlight factors that may limit this emerging technology. Supplementary material: The fitted model parameters used to describe the behaviour of Fe, H 2 S and SO 4 2− are available at https://doi.org/10.6084/m9.figshare.c.3841279