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Cardiac optical mapping, also known as optocardiography, employs parameter-sensitive fluorescence dye(s) to image cardiac tissue and resolve the electrical and calcium oscillations that underly cardiac function. This technique is increasingly being used in conjunction with, or even as a replacement for, traditional electrocardiography. Over the last several decades, optical mapping has matured into a “gold standard” for cardiac research applications, yet the analysis of optical signals can be challenging. Despite the refinement of software tools and algorithms, significant programming expertise is often required to analyze large optical data sets, and data analysis can be laborious and time-consuming. To address this challenge, we developed an accessible, open-source software script that is untethered from any subscription-based programming language. The described software, written in python, is aptly named “KairoSight” in reference to the Greek word for “opportune time” (Kairos) and the ability to “see” voltage and calcium signals acquired from cardiac tissue. To demonstrate analysis features and highlight species differences, we employed experimental datasets collected from mammalian hearts (Langendorff-perfused rat, guinea pig, and swine) dyed with RH237 (transmembrane voltage) and Rhod-2, AM (intracellular calcium), as well as human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) dyed with FluoVolt (membrane potential), and Fluo-4, AM (calcium indicator). We also demonstrate cardiac responsiveness to ryanodine (ryanodine receptor modulator) and isoproterenol (beta-adrenergic agonist) and highlight regional differences after an ablation injury. KairoSight can be employed by both basic and clinical scientists to analyze complex cardiac optical mapping datasets without requiring dedicated computer science expertise or proprietary software.

BACKGROUND The purpose of this study was to determine if body weight supported treadmill training (BWSTT) decreased metabolic and cardiovascular demand in older (50-74 years) healthy adults while walking a self-selected speeds. The results of this study could impact clinician application to exercise therapy. METHODS Twenty subjects (50% female, 58.3+7.3 yr) completed 3, 5-minute treadmill walking trials at a self-selected pace, with 0%, 15%, and 30% body weight support (BWS). Blood pressure (BP), heart rate (HR), and oxygen uptake (VO2) were measured at rest, and during walking trials. Mean data from minutes 3-5 were analyzed for difference by repeated measures ANOVA and Bonferroni post-hoc testing. RESULTS At rest, HR was 70.8+8.2 bpm and BP was 126.8+12.2 / 84.3+8.6 mmHg. Mean walking speed was 67.1 m/min. Tested parameters during exercise trials were significantly (p

The operational impact of using head-up display (HUD) with localizer guidance in lieu of Centerline Lights (CLL) in low visibility conditions were of principal interest for this study. From a human factors perspective, the analyses indicated that Flight Technical Error (FTE) scores while using HUD localizer takeoff guidance without CLL were equal to or less than the corresponding FTE scores with CLL at the RVRs used for this research. The research was conducted on a Boeing 737-800NG Level D simulator at the Federal Aviation Administration (FAA) Flight Technologies and Procedures Division facility in Oklahoma City, Oklahoma.

Respiratory diseases adversely affect infants and are the focus of efforts to develop vaccinations and other modalities to prevent disease. The infant immune system differs from that of older children and adults in many ways that are as yet ill understood. We have used a C57BL/6 mouse model of infection with a laboratory- adapted strain of influenza (PR8) to delineate the importance of the cytokine IL-6 in the innate response to primary infection and in the development of protective immunity in adult mice. Herein, we used this same model in infant (14 days of age) mice to determine the effect of IL-6 deficiency. Infant wild type mice are more susceptible than older mice to infection, similar to the findings in humans. IL-6 is expressed in the lung in the early response to PR8 infection. While intramuscular immunization does not protect against lethal challenge, intranasal administration of heat inactivated virus is protective and correlates with expression of IL-6 in the lung, activation of lung CD8 cells, and development of an influenza-specific antibody response. In IL-6 deficient mice, this response is abrogated, and deficient mice are not protected against lethal challenge. These studies support the importance of the role of the tissue environment in infant immunity, and further suggest that IL-6 may be helpful in the generation of protective immune responses in infants.

Background Abdominal wall hernia is a common surgical condition. Patients may present in an emergency with bowel obstruction, incarceration or strangulation. Small bowel obstruction (SBO) is a serious surgical condition associated with significant morbidity. The aim of this study was to describe current management and outcomes of patients with obstructed hernia in the UK as identified in the National Audit of Small Bowel Obstruction (NASBO). Methods NASBO collated data on adults treated for SBO at 131 UK hospitals between January and March 2017. Those with obstruction due to abdominal wall hernia were included in this study. Demographics, co‐morbidity, imaging, operative treatment, and in‐hospital outcomes were recorded. Modelling for factors associated with mortality and complications was undertaken using Cox proportional hazards and multivariable regression modelling. Results NASBO included 2341 patients, of whom 415 (17·7 per cent) had SBO due to hernia. Surgery was performed in 312 (75·2 per cent) of the 415 patients; small bowel resection was required in 198 (63·5 per cent) of these operations. Non‐operative management was reported in 35 (54 per cent) of 65 patients with a parastomal hernia and in 34 (32·1 per cent) of 106 patients with an incisional hernia. The in‐hospital mortality rate was 9·4 per cent (39 of 415), and was highest in patients with a groin hernia (11·1 per cent, 17 of 153). Complications were common, including lower respiratory tract infection in 16·3 per cent of patients with a groin hernia. Increased age was associated with an increased risk of death (hazard ratio 1·05, 95 per cent c.i. 1·01 to 1·10; P = 0·009) and complications (odds ratio 1·05, 95 per cent c.i. 1·02 to 1·09; P = 0·001). Conclusion NASBO has highlighted poor outcomes for patients with SBO due to hernia, highlighting the need for quality improvement initiatives in this group., This study shows that small bowel obstruction due to abdominal wall hernia is common, typically involves a co‐morbid group of patients and has poor outcomes, including high mortality rates. High mortality from this problem

Genomic simulations are an important technique used in population genetics to infer demographic history, test for regions under selection, and create datasets to validate software. However, running thousands of simulations and manipulating large loci can present computational challenges. We present SimPrily, a Python tool optimized for high throughput computing (HTC), which facilitates simulation of whole chromosomes. SimPrily can use prior distributions of parameters to run simulations, incorporate single nucleotide polymorphism array ascertainment bias into the simulated model, and calculate a variety of genomic summary statistics. We include with SimPrily high-throughput workflows that leverage free computing resources through the Open Science Grid and CyVerse Discovery Environment, allowing researchers to run thousands or millions of large-locus simulations with minimal or no prior command line knowledge. Keywords: Genomics, Coalescent simulation, High-throughput computing, Demographic history

Latino families face increased risk for hypertension. Serum-based uric acid and C-reactive protein have been linked to hypertension. However, a paucity of salivary biomarker data exists in this area for Latino families. Using salivary biomarkers enables less invasive options for biomedical and biosocial research, which is especially important among vulnerable populations facing increased health disparities. This study examined the associations between salivary uric (sUA) acid, salivary C-reactive protein (sCRP), and hypertension among 151 participants (57 children, 57 mothers, 37 fathers) from 57 Midwestern Latino families. Participants self-administered the salivary samples, and blood pressure was measured by researchers. Results showed sUA was associated across family members, and child hypertension was related to parents' hypertension. sCRP was only related to sUA in fathers. Findings highlight the family-level health connections, along with the importance for further investigations using salivary biomarkers with Latinos, and the need for a robust sUA cut-off for hyperuricemia.

Sport activities can account for up to one-third of all orofacial injuries. Mouthguards (MGs) have been proposed as a way to reduce these injuries. To present a systematic review and meta-analysis of the effectiveness of MGs for the prevention of sports-related orofacial injuries and concussions. Using specific search terms, PubMed, Ovid Embase, and the Cumulative Index to Nursing and Allied Health Literature were searched to find studies that (1) contained original quantitative data on MGs and orofacial injuries and/or concussions, (2) included groups involved in sports or exercise activities, (3) included MG users and non-MG users, and (4) provided either risk ratios (RRs) and 95% confidence intervals (95% CIs) comparing injuries among MG users and non-MG users, or data that could be used to calculate RRs and 95% CIs. Twenty-six studies met the review criteria. Investigations employed a variety of study designs, utilized different types of MGs, used widely varying injury case definitions, and had multiple methodological weaknesses. Despite these limitations, meta-analyses indicated that the use of MGs reduced the overall risk of orofacial injuries in 12 cohort trials (summary RR [nonusers/users] = 2.33, 95% CI 1.59–3.44), and 11 trials involving self-report questionnaires (summary RR [nonusers/users] = 2.32, 95% CI 1.04–5.13). The influence of MGs on concussion incidence in five cohort studies was modest (summary RR [nonusers/users] = 1.25, 95% CI 0.90–1.74). These data indicate that MGs should be used in sports activities where there is significant orofacial injury risk.

• Family chaos and lack of meal planning distinguished food insecure from food secure households.

Programming in the large allows composition of processes executing code written using programming in the small. Traditionally, systems supporting programming in the large have included interpreters of OS command languages, but today, with the emergence of collaborative “big data” science, these systems also include cyberinfrastructures, which allow computations to be carried out on remote machines in the “cloud”. The rationale for these systems, even the traditional command interpreters, is human-centric computing, as they are designed to support quick, interactive development and execution of process workflows. Some cyberinfrastructures extend this human-centricity by also providing manipulation of visualizations of these workflows. To further increase the human-centricity of these systems, we have started a new project on cyber training - instruction in the use of command languages and visual components of cyberinfrastructures. Our objective is to provide scalable remote awareness of trainees' progress and difficulties, as well as collaborative and automatic resolution of their difficulties. Our current plan is to provide awareness based on a subway workflow metaphor, allow a trainer to collaborate with multiple trainees using a single instance of a command interpreter, and combine research in process and interaction workflows to support automatic help. These research directions can be considered an application of the general principle of integrating programming in the small and large

IntroductionRacial/ethnic minority school-age children are at risk for unhealthy weight gain during the summer, and there is a dearth of information regarding the underlying behavioural and environmental factors. The study objective is to provide an in-depth examination of dietary and physical activity behaviours and food, physical activity, and social environments of African American and Hispanic school-age children during the summer.Methods and analysisAn observational study will be conducted using a multistate (Ohio and Indiana, USA) prospective design examining the weight gain trajectory among a racially/ethnically diverse convenience sample of economically disadvantaged school-age children. In addition, a subset of these children will be evaluated to learn their daily health behaviours and food, physical activity, and social environments during the summer. Comparisons will be made between children who routinely attend programming and those who do not, both in the larger sample and subset. Determinants of programme participation and factors that may enhance the beneficial effects of programme participation will also be identified. Data collection at the Indiana site is planned for summer 2018.Ethics and disseminationThis study is approved by The Ohio State University Behavioral and Social Sciences Institutional Review Board. Results from this study will be disseminated in publications for practitioners, scientists and stakeholders.Trial registration numberNCT03010644; Pre-results.

Introduction: Abdominal aortic aneurysm (AAA) rupture has a mortality rate of 64% and intracranial aneurysm (IA) rupture has a mortality rate of 50%. Despite the high mortality rates, early detection and treatment of these vascular lesions prior to rupture can prevent devastating clinical outcomes, underscoring the need to identify high-risk populations for screening. Current evidence demonstrates shared genetic and environmental risk factors for both AAA and IA. Methods: The BAAS study sought to establish the co-prevalence of AAA and IA. In one arm of BAAS, we recruited patients presenting with AAA and screened them for IA. All participants underwent a detailed interview to collect demographic, radiographic, and clinical data and also had genetic counseling. Results: Of the 126 individuals with an AAA enrolled, 65% (82/126) completed the MRA. Difficulty with logistics of obtaining the research MRA with long distance travel to clinic was the principal reason for failure to obtain MRA. We identified 20.7% (17/82) with one or more IA, including 21 aneurysms found during systematic screening. IA ranged in size from 1.5-14 mm (height) x 1.4-7 mm (width) and varied in location. 9.5% (2/21) had a maximum diameter of 7 mm or more. One participant with a positive MRA underwent early coil embolization with the remainder undergoing continued clinical surveillance. Of the 15 individuals completing the genetic counseling screening, two underwent recommended clinical genetic testing, revealing one negative screen and one variant of unknown significance in the MYH11 gene. Conclusion: Consistent with our prior cost effectiveness models, these prospective data support the clinical utility of routine screening for IA in patients presenting with AAA.

Introduction: Aneurysm rupture is associated with high mortality and morbidity, including both intracranial aneurysms (IA) and abdominal aortic aneurysms (AAA). Despite potential preemptive treatment in those identified prior to IA or AAA rupture, the evidence for whom to screen remains limited. IA and AAA share both environmental and genetic risk, and prior cost-effectiveness models suggest the potential efficacy of screening in these high-risk individuals. We hypothesized that reciprocal screening in those presenting with IA for AAA would yield positive results. Methods: The BAAS study sought to establish the co-prevalence of IA and AAA. In this arm of BAAS, we recruited patients presenting with IA and screened them for AAA using abdominal ultrasound (aU/S) at two sites: Mayo Clinic and the University of Virginia (UVA). All participants underwent a detailed interview to collect demographic, radiographic, and clinical data. At UVA, participants also received genetic counseling. Results: At Mayo Clinic, we enrolled and screened 81 consecutive patients with aSAH (3 patients with known AAA were excluded) with 3 (3.7%) positive aU/S for AAA. At UVA, we recruited 195 consecutive patients presenting with ruptured or unruptured IA and completed screening aU/S in 178 (93%). Only one (0.6%) had an AAA. Conclusion: The lower positive screening at UVA (0.6%) which enrolled both ruptured and unruptured IA compared to the 3.7% positive results at Mayo suggests that future efforts to identify who with IA might benefit from AAA screening should focus on those with aneurysmal subarachnoid hemorrhage (aSAH).

Summary Following polyploidy events, genomes undergo massive reduction in gene content through a process known as fractionation. Importantly, the fractionation process is not always random, and a bias as to which homeologous chromosome retains or loses more genes can be observed in some species. The process of characterizing whole genome fractionation requires identifying syntenic regions across genomes followed by post-processing of those syntenic datasets to identify and plot gene retention patterns. We have developed a tool, FractBias, to calculate and visualize gene retention and fractionation patterns across whole genomes. Through integration with SynMap and its parent platform CoGe, assembled genomes are pre-loaded and available for analysis, as well as letting researchers integrate their own data with security options to keep them private or make them publicly available. Availability and Implementation FractBias is freely available as a web application at https://genomevolution.org/CoGe/SynMap.pl. The software is open source (MIT license) and executable with Python 2.7 or iPython notebook, and available on GitHub (https://goo.gl/PaAtqy). Documentation for FractBias is available on CoGepedia (https://goo.gl/ou9dt6) Supplementary information Supplementary data are available at Bioinformatics online.

This workflow allows novice researchers to leverage advanced computational resources such as cloud computing to carry out pairwise comparative transcriptomics. It also serves as a primer for biologists to develop data scientist computational skills, e.g. executing bash commands, visualization and management of large data sets. All command line code and further explanations of each command or step can be found on the wiki (https://wiki.cyverse.org/wiki/x/dgGtAQ). The Discovery Environment and Atmosphere platforms are connected together through the CyVerse Data Store. As such, once the initial raw sequencing data has been uploaded there is no more need to transfer large data files over an Internet connection, minimizing the amount of time needed to conduct analyses. This protocol is designed to analyze only two experimental treatments or conditions. Differential gene expression analysis is conducted through pairwise comparisons, and will not be suitable to test multiple factors. This workflow is also designed to be manual rather than automated. Each step must be executed and investigated by the user, yielding a better understanding of data and analytical outputs, and therefore better results for the user. Once complete, this protocol will yield de novo assembled transcriptome(s) for underserved (non-model) organisms without the need to map to previously assembled reference genomes (which are usually not available in underserved organism). These de novo transcriptomes are further used in pairwise differential gene expression analysis to investigate genes differing between two experimental conditions. Differentially expressed genes are then functionally annotated to understand the genetic response organisms have to experimental conditions. In total, the data derived from this protocol is used to test hypotheses about biological responses of underserved organisms.

Background: The risk for intracranial (IA) and abdominal aortic aneurysms (AAA) is partially heritable, with evidence mounting in favor of shared genetic risk for both. Methods: The Brain and Aortic Aneurysm Study (BAAS, NCT#17341) at University of Virginia seeks to determine the coprevalence of IA and AAA recruiting patients presenting with an aneurysm at one site and screening for aneurysm at the other. Participants undergo genetic screening and an interview where clinical, demographic, and radiographic data are collected. Recruitment and screening are ongoing, so preliminary demographic data regarding between group differences (IA vs. AAA) are presented. All clinical and demographic data were collected and recorded in REDCap and exported to Excel. We compared a total of 256 participants (IA=164, AAA=92) for demographic factors: age, sex, smoking and past medical history. Results: The AAA cohort was older (70.98 vs. 58.51, p.05). Conclusions: These data suggest that there may be subtle differences in the clinical profile of patients presenting with IA and AAA, especially when considering known aneurysmal risk factors like hypertension, diabetes, and smoking history. Further analyses will consider whether these factors modulate the coprevalence of the two types of aneurysms.

Identification of risk factors is critical to preventing the childhood obesity epidemic. Risk factors that contribute to obesity are multifactorial. However, limited research has focused on identifying obesity risk factors using an ecological approach.Baseline self-report survey data from the STRONG Kids program were used. The sample consisted of 329 parent-child dyads recruited from childcare programs in east-central Illinois. Child height and weight were measured and converted to age- and sex-specific z-scores using standard growth charts. An ecological model provided the theoretical framework for the selection of 22 previously reported childhood obesity risk factors. Multiple logistic regression analyses were used to identify risk factors.Of 22 potential risk factors, three were found to be significantly associated with child overweight/obesity. These included child nighttime sleep duration (χ(2)=8.56; p=0.003), parent BMI (χ(2)=5.62; p=0.01), and parental restrictive feeding for weight control (χ(2)=4.77; p=0.02). Children who slept for 8 hours and less were 2.2 times more likely to be overweight/obese [95% confidence interval (CI): 1.3-3.7), whereas children with an overweight/obese parent were 1.9 times more likely to be overweight/obese (95% CI: 1.12-3.2). Finally, children whose parents used restrictive feeding practices were 1.75 times more likely to be overweight/obese (95% CI: 1.06-2.9).Using an ecological approach, we conclude that childhood obesity prevention efforts may benefit from targeting the key risk factors of child sleep duration, parent BMI, and parental restrictive feeding practices as focus areas for obesity prevention.

Magical. A common adjective used to describe places. But does the magic of place spring from genius loci? Or could it be that we are the magicians, casting spells to transform places into what we desire (or what we fear)? Our sense of place is not a mirror on reality. We come to know places by inscribing our fantasies atop them, by writing onto the landscape our own imagined geographies. C.S. Lewis provides an intriguing glimpse into sense of place through the Pevensie children and their experience in The Lion, the Witch, and the Wardrobe: a mere wardrobe becomes a complex fantasy world in which the children play and interact. As adults, and as societies, we take real geographies and treat them as Lewis's wardrobe, creating Narnias in the depths of our most mundane landscapes. In this paper I explore the magic of place through an autobiographical photo essay set in a nature preserve in eastern Kansas. The stories I tell highlight in a literary and artistic way the phenomenological aspects of sense of plac...

Objective To investigate the safety, pharmacokinetics (PK), binding activity and immunogenicity of CR002, a human monoclonal antibody (mAb) directed against platelet-derived growth factor-D (PDGF-D), administered as a single intravenous (i.v.) infusion over a range of doses. Subjects 40 healthy male subjects received increasing doses of CR002 at 0.3, 1, 3, 10, 30 mg/kg or placebo. Method This was a randomized, double-blind, placebo-controlled, dose-escalation Phase I study. The trial had a duration of 90 days, with dosing on Day 1 and follow-up visits on Days 2, 4, 7, 14, 21, 30, 45 and 90. Serum was collected for PK, binding activity and immunogenicity analysis at screening and up to Day 90. Safety was recorded throughout the study by performing laboratory tests, recording vital signs and electrocardiograms (ECGs), by monitoring the occurrence of adverse events (AEs). The use of concomitant medications was also recorded. Results All 40 subjects received CR002 or placebo, and completed the trial. No dose-limiting toxicities (DLTs) occurred, the maximum tolerated dose (MTD) was not reached and was estimated as > 30 mg/kg. There were no deaths during this study and no SAEs or other significant AEs reported. The most frequent drug-related treatment-emergent AE (TEAE) was headache in 4 of 30 subjects (13.3%) in the CR002 group vs. 0 of 10 subjects in the placebo group. CR002 exhibited linear PK parameters, had a long half-life (t1/2 in the range 15.5 â 48.1 days) and a volume of distribution at steady state in the range 4.7 â 6.5. Free PDGF-D in the serum bound to CR002 in a reversible manner, as shown in the lowest dose cohort. However, levels of total circulating PDGF-D remained constant throughout the study. There were no anti-CR002 antibodies detected in subjects dosed with CR002. Conclusions CR002 was safe and well-tolerated at all doses tested as a single i.v. administration. The MTD was estimated to be above 30 mg/kg, the highest dose tested. CR002 had a long half-life, low clearance and a limited tissue distribution. Although total levels of PDGF-D at all dose levels remained relatively constant, there was no detectable circulating free PDGF-D after CR002 administration. At the lowest CR002 dose tested (0.3 mg/kg), PDGF-D was detectable again by Day 21 and the levels increased near to pre-infusion levels by Day 90. In this study, CR002 was not immunogenic during the 90-day study period.

Triamterene, because of its potassium-sparing properties, is frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the cortical collecting duct, triamterene reduces potassium secretion, thus reducing the risk of hypokalemia. Whether triamterene has an independent effect on blood pressure (BP) has not been well studied. To determine if triamterene provides an effect to further lower BP in patients treated with HCTZ. We conducted an observational study using electronic medical record data from the Indiana Network for Patient Care. Participants were 17,291 patients with the diagnosis of hypertension between 2004 and 2012. BP was the primary outcome. We compared the BP between patients who were taking HCTZ, with and without triamterene, either alone or in combination with other antihypertensive medications, by using a propensity score analysis. For each medication combination, we estimated the propensity score (i.e., probability) of a patient receiving triamterene using a logistic regression model. Patients with similar propensity scores were stratified into subclasses and BP was compared between those taking triamterene or not within each subclass; the effect of triamterene was then assessed by combining BP differences estimated from all subclasses. The mean systolic BP in the triamterene + HCTZ group was 3.8 mmHg lower than in the HCTZ only group (p

Higher protein intake has been implicated in weight management because of its appetitive properties. However, the effects of protein intake on appetitive sensations such as fullness have not been systematically assessed. Meta-analysis is a useful technique to evaluate evidence of an intervention's effect on testable outcomes, but it also has important limitations.The primary aim of this study was to synthesize the available evidence on the effect of protein intake on fullness using a quantitative meta-analysis and a secondary directional analysis using the vote-counting procedure. A tertiary aim was to address limitations of meta-analyses as they pertain to findings from this meta-analysis.We searched multiple databases for interventional studies that evaluated the effect of increased protein intake on fullness ratings. Inclusion criteria for both analyses were as follows: healthy human participants, preload studies that utilized intact dietary protein, delivery of protein load orally, and studies reporting fullness as an outcome. For the meta-analysis, an additional criterion was that the studies also needed to report 2- to 4-hour area under the curve value for fullness.Five studies met all criteria for the meta-analysis. Twenty-eight studies met all criteria for the directional analysis. The meta-analysis indicated higher protein preloads have a greater effect on fullness than lower protein preloads (overall effect estimate: 2,435.74 mm.240 min, (95% CI 1,375.18 to 3,496.31 mm.240 min; P0.0001). The directional analysis also revealed a positive effect on fullness with higher protein preloads (P0.01). Many related scientifically rigorous studies were excluded from the analysis because analytical criteria required a narrowly focused research question.The present analyses show that higher protein preloads increase fullness ratings more than lower protein preloads under tightly defined conditions. Extrapolation of findings to common conditions outside the specified criteria of this analysis must be made cautiously, as must speculation about the influence of fullness sensations on ingestive behavior, body weight, and various health outcomes.

To present the case of a patient with a history of thyroid cancer, postsurgical hypoparathyroidism, chronic calcitriol use, and normal renal function who presented with painful skin lesions secondary to calciphylaxis.We describe the history, biochemistry, histopathology, evaluation, and management of this patient.A 47-year-old female with hypoparathyroidism, chronically treated with calcitriol and calcium, presented with exquisitely painful skin ulcerations. Four months prior to the onset of symptoms, she had initiated warfarin therapy for atrial fibrillation. Review of laboratory data from the past year revealed elevated calcium and phosphorus levels. A diagnosis of calciphylaxis was made based upon pathologic evaluation of a skin biopsy. Management included titration of calcitriol and calcium to maintain serum calcium and phosphate levels in the low-normal range. Sodium thiosulfate was administered at a dose of 25 mg intravenously 3 times a week with some resolution in the patient's pain. Unfortunately, the patient battled recurrent bacteremia and sepsis, presumably related to her calciphylaxis wounds, and ultimately succumbed to complications from sepsis.Although calciphylaxis is typically associated with renal insufficiency and secondary hyperparathyroidism, we highlight the case of a patient with normal renal function and hypoparathyroidism. Patients treated with chronic calcitriol should have serum calcium and phosphorus monitored closely and may benefit from non-calcium-based phosphate binders if hyperphosphatemia becomes unavoidable. This is especially important in the presence of other risk factors for calciphylaxis, including warfarin use.

BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS: The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P = 0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P = 0.04). The primary and secondary outcome results were similar in the two aspirin strata. CONCLUSIONS: Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.) Copyright © 2014 Massachusetts Medical Society.

Background: Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability. Methods: We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. Results: Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P

Purpose: To demonstrate that high-dimensional voxel-to-voxel transformations, derived from continuum mechanics models of the underlying pelvic tissues, can be used to register computed tomography (CT) serial examinations into a single anatomic frame of reference for cumulative dose calculations. Methods and Materials: Three patients with locally advanced cervix cancer were treated with CT-compatible intracavitary (ICT) applicators. Each patient underwent five volumetric CT examinations: before initiating treatment, and immediately before and after the first and second ICT insertions, respectively. Each serial examination was rigidly registered to the patient’s first ICT examination by aligning the bony anatomy. Detailed nonrigid alignment for organs (or targets) of interest was subsequently achieved by deforming the CT exams as a viscous-fluid, described by the Navier-Stokes equation, until the coincidence with the corresponding targets on CT image was maximized. In cases where ICT insertion induced very large and topologically complex rearrangements of pelvic organs, e.g., extreme uterine canal reorientation following tandem insertion, a viscous-fluid-landmark transformation was used to produce an initial registration. Results: For all three patients, reasonable registrations for organs (or targets) of interest were achieved. Fluid-landmark initialization was required in 4 of the 11 registrations. Relative to the best rigid bony landmark alignment, the viscous-fluid registration resulted in average soft-tissue displacements from 2.8 to 28.1 mm, and improved organ coincidence from the range of 5.2% to 72.2% to the range of 90.6% to 100%. Compared to the viscous-fluid transformation, global registration of bony anatomy mismatched 5% or more of the contoured organ volumes by 15–25 mm. Conclusion: Pelvic soft-tissue structures undergo large deformations and displacements during the external-beam and multiple-ICT course of radiation therapy for locally advanced cervix cancer. These changes cannot be modeled by the conventional rigid landmark transformation method. In the current study, we found that the deformable anatomic template registration method, based on continuum-mechanics models of deformation, successfully described these large anatomic shape changes before and after ICT. These promising modeling results indicate that realistic registration of the cumulative dose distribution to the organs (or targets) of interest for radiation therapy of cervical cancers is achievable.

Triamterene is a potassium-sparing diuretic, often used in combination with thiazide diuretics for treatment of hypertension. By inhibiting the epithelial sodium channel (ENaC) in collecting duct, it reduces potassium secretion, thus reducing the risk of hypokalemia. But it is unclear whether triamterene also has a blood pressure (BP)-lowering effect. We conducted an observational study to examine the BP effect of triamterene. We extracted medical records of 1723 patients diagnosed with hypertension from an urban hospital. There were 1375 patients on hydrochlorothiazide (HCTZ) alone and 348 patients on a combination of HCTZ and triamterene. We compared the recorded BP using regression analysis and the propensity score method. Patient characteristics of the two treatment groups were largely comparable, except for patients on the combination therapy were more likely to be female (83% vs 66%; p

Automatic speech recognition (ASR) is finding many new applications in both products and services. Designing good user interfaces with ASR poses a variety of challenges. This paper: — Addresses basic principles in designing for the user, — Describes the need for appropriate dialogues between the user and ASR-based systems, — Discusses how these user-machine transactions are changing due to improved ASR technology, and — Discusses the direction ASR should take to provide the kind of “natural” user-machine dialogue that is expected in Vision 2001.

Petroleum-derived liquid fuels and commodities play a part in nearly every aspect of modern daily life. However, dependence on this one natural resource to maintain modern amenities has caused negative environmental and geopolitical ramifications. In an effort to replace petroleum, technologies to synthesize liquid fuels and other commodities from renewable biomass are being developed. Current technologies, however, only use a portion of plant biomass feedstocks for fuel and useful products. "Using the whole feedstock buffalo" or optimally using all portions and biochemicals present in renewable biomass will enhance the economic and environmental feasibility of biofuels and coproducts. To accomplish this optimization, greater understanding of the relationship between liquid fuel and bioproduct properties and plant chemistries is needed. Liquid fuel properties and how they relate to biochemistry and petrochemistry are discussed. Enhanced biofuel yields and high-value commodities from biomass are needed to sustainably replace petroleum-based products. Several metabolic engineering strategies are discussed. We will describe paths of possible fuel and product diversification using dedicated lignocellulosic biomass (e.g., switchgrass).

Over the past 5 years, ORNL has run 95 diesel range fuels in homogeneous charge compression ignition (HCCI), including 40 bio-diesels and associated diesel fuels in their blending. The bio-diesel blends varied in oxygen content, iodine number, cetane, boiling point distribution, chemical composition, and some contained nitrogen. All fuels were run in an HCCI engine at 1800 rpm, in the power range of 2.5 to 4.5 bar IMEP, using intake air heating for combustion phasing control, and at a compression ratio of 10.6. The engine response to fuel variables has been analyzed statistically. Generally, the engine responded well to fuels with lower nitrogen and oxygen, lower cetane, and lower aromatics. Because of the wide range of fuels combined in the model, it provides only a broad overview of the engine response. It is recommended that data be truncated and re-modeled to obtain finer resolution of engine response to particular fuel variables

This paper explores the human-factors issues in designing human/machine interfaces employing automatic speech recognition (ASR) technology. It describes how a designer of a product or service who uses this technology must ensure successful interactions between computers and end-users, leading to customer satisfaction and success of the product or service. The paper discusses how ASR technology can support human/machine interactions in telecommunications applications, if the human-factors issues that arise in ASR user-interface (UI) design can be appropriately addressed.

Microsprinkler irrigation is often the preferred method of irrigation for tree and vine crops since it provides a greater degree of freeze protection than drip irrigation and provides water and energy savings over sprinkler and flood irrigation methods. With chemigation, microirrigation also provides an economical method of applying fertilizer and other agricultural chemicals on a timely basis. However, microsprinkler systems generally require more maintenance than drip or overhead systems, and they require a higher level of management expertise than sprinkler or flood irrigation methods. This paper discusses the current status of design, operation, and maintenance of microsprinkler systems and the benefits and limitations of these systems for several agricultural crops. Types and characteristics of available microsprinklers are discussed in relation to appropriate application considering crops, soils, and management philosophy. Topics include uniformity, clogging, insect problems, wetting patterns, emitter maintenance, chemigation, system evaluation, management for both young and mature trees, crop response, and freeze protection.

In order to investigate the effect of memory load on reaction time (RT), choice RT trials were embedded in a binary character classification task using the varied set procedure. Twelve Ss performed in experimental blocks, as well as in control blocks consisting of character classification trials only. In experimental blocks, every trial began as a classification trial with the presentation of a new positive set. On a random half of these trials, however, a choice RT stimulus was presented instead of a probe letter and S simply made the indicated response. Results indicated that memory load had no effect on the choice RT trials. Embedding choice RT trials in the classification task affected the intercept (but not the slope) of the function relating classification RT to memory load. This result implies that the increase in latency usually obtained in classification experiments is entirely due to an increase in the duration of the memory searching stage of processing.

BACKGROUND: Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. METHODS: We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5-15 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. FINDINGS:15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34·5%) underwent appendicectomy. The normal appendicectomy rate was 15·9% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0·84 (95% CI 0·82-0·86). Applying score cutoffs of 3 points or lower for children aged 5-10 years and girls aged 11-15 years, and 2 points or lower for boys aged 11-15 years, the failure rate was 3·3% (95% CI 2·0-5·2; 18 of 539 patients), specificity was 44·3% (95% CI 41·4-47·2; 521 of 1176), and positive predictive value was 41·4% (38·5-44·4; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72·6%, 67·4-77·4) was similar to that of ultrasound scan (75·0%, 65·3-83·1). INTERPRETATION: The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. FUNDING: None.