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The objective of this study was to determine whether the magnitude of the peripheral inflammatory response to cardiovascular surgery is associated with increases in blood–brain barrier (BBB) permeability as reflected by changes in cerebrospinal fluid (CSF)/plasma S100B concentrations. We conducted a secondary analysis from a prospective cohort study of 35 patients undergoing elective thoracoabdominal aortic aneurysm repair with (n = 17) or without (n = 18) cardiopulmonary bypass (CPB). Plasma and CSF S100B, interleukin-6 (IL-6), and albumin concentrations were measured at baseline (C0) and serially for up to five days. Following CPB, the median [interquartile range] plasma S100B concentration increased from 58 [32–88] pg·mL-1 at C0 to a maximum concentration (Cmax) of 1,131 [655–1,875] pg·mL-1 over a median time (tmax) of 6.3 [5.9–7.0] hr. In the non-CPB group, the median plasma S100B increased to a lesser extent. There was a delayed increase in CSF S100B to a median Cmax of 436 [406–922] pg·mL-1 in the CPB group at a tmax of 23.7 [18.5–40.2] hr. In the non-CPB group, the CSF concentrations were similar at all time points. In the CPB group, we did not detect significant correlations between plasma and CSF S100B with plasma IL-6 [r = 0.52 (95% confidence interval [CI], -0.061 to 0.84)] and CSF IL-6 [r = 0.53 (95% CI, -0.073 to 0.85)] concentrations, respectively. Correlations of plasma or CSF S100B levels with BBB permeability were not significant. The lack of parallel increases in plasma and CSF S100B following CPB indicates that S100B may not be a reliable biomarker for BBB disruption after thoracoabdominal aortic aneurysm repair employing CPB. www.clinicaltrials.gov (NCT00878371); registered 7 April 2009.

In New Zealand, the introduced honey bee (Apis mellifera) is a valuable production animal, providing pollination services for horticultural crops and significant export volumes of honey, especially...

To what extent do gender and culture impact people’s attitudes towards help-seeking? It has been well documented that gender plays a large role in determining the likelihood that an individual will look to external agencies in order to remedy issues of physical or mental health and that women tend to have more positive attitudes towards help-seeking than do men. However, this paper looks to investigate the intersection between gender and culture to understand the impact that different societies have on the formation and maintenance of attitudes towards help-seeking. In order to do this, this study utilised thematic analysis to highlight the attitudes of 3 Muslim Arab men, aged 24 - 32, in the United Arab Emirates, towards issues of mental illness and physical injury (as both are often temporary and treatable). Although much of the findings of this study were consistent with previous studies using Western participants, there were also cultural repertoires utilised which suggested that social stigma and cultural practices may further impact men’s tendency to seek help from external agencies. Recognition of these differences may impact upon the promotion and delivery of healthcare in Arab countries by suggesting that providing Western treatments to Arab men, particularly for mental illness, is unlikely to be effective without cultural-specific adaptations.

Objectives To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. Design A multicenter randomized sham-controlled clinical trial. Setting Twelve ICUs in Canada. Patients We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. Interventions Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. Measurements and main results The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). Conclusions Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.

Background The optimal treatment duration for patients with bloodstream infection is understudied. The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) pilot randomized clinical trial (RCT) determined that it was feasible to enroll and randomize intensive care unit (ICU) patients with bloodstream infection to 7 versus 14 days of treatment, and served as the vanguard for the ongoing BALANCE main RCT. We performed this BALANCE-Ward pilot RCT to examine the feasibility and impact of potentially extending the BALANCE main RCT to include patients hospitalized on non-ICU wards. Methods We conducted an open pilot RCT among a subset of six sites participating in the ongoing BALANCE RCT, randomizing patients with positive non-Staphylococcus aureus blood cultures on non-ICU wards to 7 versus 14 days of antibiotic treatment. The co-primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. We compared feasibility outcomes, patient/pathogen characteristics, and overall outcomes among those enrolled in this BALANCE-Ward and prior BALANCE-ICU pilot RCTs. We estimated the sample size and non-inferiority margin impacts of expanding the BALANCE main RCT to include non-ICU patients. Results A total of 134 patients were recruited over 47 site-months (mean 2.9 patients/site-month, median 1.0, range 0.1–4.4 patients/site-month). The overall recruitment rate exceeded the BALANCE-ICU pilot RCT (mean 1.10 patients/site-month, p p = 0.0003). BALANCE-Ward patients were older, with lower Sequential Organ Failure Assessment scores, and higher proportions of infections caused by Escherichia coli and genito-urinary sources of bloodstream infection. The BALANCE-Ward pilot RCT patients had an overall 90-day mortality rate of 17/133 (12.8%), which was comparable to the 90-day mortality rate in the ICU pilot RCT (17/115, 14.8%) (p = 0.65). Simulation models indicated there would be minimal sample size and non-inferiority margin implications of expanding enrolment to increasing proportions of non-ICU versus ICU patients. Conclusion It is feasible to enroll non-ICU patients in a trial of 7 versus 14 days of antibiotics for bloodstream infection, and expanding the BALANCE RCT hospital-wide has the potential to improve the timeliness and generalizability of trial results. Trial registration Clinicaltrials.gov, NCT02917551. Registered on September 28, 2016.

IMPORTANCE: Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. OBJECTIVE: To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). INTERVENTIONS: Enteral L rhamnosus GG (1 × 10(10) colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. MAIN OUTCOMES AND MEASURES: The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. RESULTS: Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, –2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P

Neurologic abnormality after cardiac surgery is common, and neurologic complications after cardiac surgery are among the most devastating problems that can occur in the postoperative period. Disruption of the blood-brain barrier (BBB) plays an important role in these complications. Assessment of the BBB integrity relies on cognitive testing, MRI, and measurement of brain biomarkers. In applying these methods, up to 50% of cardiac patients show some degree of BBB disruption and most of these abnormalities are short lived. To date there is no single test or measure that can predict BBB disruption in cardiac surgery.

by Philip E. Nelson, 2007 World Food Prize Laureate; Professor Emeritus, Food Science Dept., Purdue Univ. Just as society has evolved over time, our food system has also evolved over centuries into a global system of immense size and complexity. The commitment of food science and technology professionals to advancing the science of food, ensuring a safe and abundant food supply, and contributing to healthier people everywhere is integral to that evolution. Food scientists and technologists are versatile, interdisciplinary, and collaborative practitioners in a profession at the crossroads of scientific and technological developments. As the food system has drastically changed, from one centered around family food production on individual farms and home food preservation to the modern system of today, most people are not connected to their food nor are they familiar with agricultural production and food manufacturing designed for better food safety and quality. The Institute of Food Technologists-a nonprofit scientific society of individual members engaged in food science, food technology, and related professions in industry, academia, and government-has the mission to advance the science of food and the long-range vision to ensure a safe and abundant food supply contributing to healthier people everywhere. IFT convened a task force and called on contributing authors to develop this scientific review to inform the general public about the importance and benefits of food science and technology in IFT's efforts to feed a growing world. The main objective of this review is to serve as a foundational resource for public outreach and education and to address misperceptions and misinformation about processed foods. The intended audience includes those who desire to know more about the application of science and technology to meet society's food needs and those involved in public education and outreach. It is IFT's hope that the reader will gain a better understanding of the goals or purposes for various applications of science and technology in the food system, and an appreciation for the complexity of the modern food supply. Abstract: This Institute of Food Technologists scientific review describes the scientific and technological achievements that made possible the modern production-to-consumption food system capable of feeding nearly 7 billion people, and it also discusses the promising potential of ongoing technological advancements to enhance the food supply even further and to increase the health and wellness of the growing global population. This review begins with a historical perspective that summarizes the parallel developments of agriculture and food technology, from the beginnings of modern society to the present. A section on food manufacturing explains why food is processed and details various food processing methods that ensure food safety and preserve the quality of products. A section about potential solutions to future challenges briefly discusses ways in which scientists, the food industry, and policy makers are striving to improve the food supply for a healthier population and feed the future. Applications of science and technology within the food system have allowed production of foods in adequate quantities to meet the needs of society, as it has evolved. Today, our production-to-consumption food system is complex, and our food is largely safe, tasty, nutritious, abundant, diverse, convenient, and less costly and more readily accessible than ever before. Scientific and technological advancements must be accelerated and applied in developed and developing nations alike, if we are to feed a growing world population.

Being able to predict the mechanical properties of vertebrae in patients with osteoporosis and other relevant pathologies is essential to prevent fractures and to develop the most favorable fracture treatments. Furthermore, a reliable prediction is important for developing more patient‐ and pathology‐specific biomaterials. A plethora of studies correlating bone density to mechanical properties has been reported; however, the results are variable, due to a variety of factors, including anatomical site and methodological differences. The aim of this study was to provide a comprehensive literature review on density and mechanical properties of human vertebral trabecular bone as well as relationships found between these properties. A literature search was performed to include studies, which investigated mechanical properties and bone density of trabecular bone. Only studies on vertebral trabecular bone tissue, reporting bone density or mechanical properties, were kept. A large variation in reported vertebral trabecular bone densities, mechanical properties, and relationships between the two was found, as exemplified by values varying between 0.09 and 0.35 g/cm3 for the wet apparent density and from 0.1 to 976 MPa for the elastic modulus. The differences were found to reflect variations in experimental and analytical processes that had been used, including testing protocol and specimen geometry. The variability in the data decreased in studies where bone tissue testing occurred in a standardized manner (eg, the reported differences in average elastic modulus decreased from 400% to 10%). It is important to take this variability into account when analyzing the predictions found in the literature, for example, to calculate fracture risk, and it is recommended to use the models suggested in the present review to reduce data variability.

To describe current practices and safety concerns regarding cardiac emergency medications in cardiac anesthesia.An anonymous survey with multiple-choice questions.Online survey using Opinio platform.Cardiac anesthesiologists from United States and Canada.None.Response rate was 12% (n = 320), with 78% of respondents from the United States and 22% from Canada. The majority of the respondents were experienced (66%), academic (60%), and worked in large cardiac institutions (81%). Most cardiac emergency medications were prepared in the operating room (53.4%), followed by the pharmacy (34%) and industry (8.2%). American respondents had more medications prepared by a pharmacy (53%) versus Canadian (10%, p0.001). The majority (85%) considered expiration time of cardiac medications prepared in the operating room to be more than 12 hours. Familiarity with the American Society of Anesthesiologists guidelines on labeling was 58%, other medication safety guidelines 25%, and 34% were not familiar with any guidelines. The majority used color-coded labeling (95%), and a minority (11%) used bar-code systems. Most respondents (69%) agreed that lack of availability of preprepared medications could compromise patient safety. Having to prepare medications by themselves was a concern for respondents based on distractions (66%), lack of availability for emergencies (53%), labeling errors (41%), incorrect concentration (36%), sterility (33%), and stability (30%).This survey found that cardiac emergency medications commonly are prepared in the operating room. The authors identified gaps in familiarity with parenteral medications safety guidelines. Most safety concerns could be addressed with the application of current medication safety guidelines.

1. Angela L. Chandler, MD* 2. Jared C. Beavers, MD* 3. Richard Whit Hall, MD* 1. *University of Arkansas for Medical Science and Arkansas Children’s Hospital, Little Rock, AR Telemedicine has been defined as “the use of medical information exchanged from one site to another via electronic communications to improve a patient’s clinical health status.” The most common clinical application and the greatest potential of telemedicine lie in its ability to connect patients with providers in underserved areas with pediatric subspecialists, saving time and travel expenses for the patient while supporting community providers. Educational applications lie in the ability to connect academic with community practices, allowing bidirectional flow of information. Research applications include the ability to recruit patients and engage community providers as well as study an intervention’s usefulness in the community. Subsequently, telemedicine can be used to disseminate research findings. A growing area for telemedicine is commercially available direct access for patients, but this application will need modification. Barriers to wider adoption do exist, including technical issues, which are typically less significant, time demands and reluctance by providers, and reimbursement and political concerns such as licensing issues, which vary from state to state. Telemedicine provides an avenue to imbed general pediatric care in the community. Many programs have been able to implement telemedicine in schools, child care centers, summer camps, youth homes, and juvenile detention centers. Despite initial concerns regarding lack of communication with the primary care physician, telemedicine, when used in the context of the medical home, has significant advantages: enhanced patient satisfaction, cost savings, fewer emergency department visits, and less time off work for parents. Current subspecialty uses for telemedicine include pediatric dermatology, emergency medicine, intensive care, neonatology, cardiology, surgery, and psychiatry. The primary benefit for patients who receive pediatric subspecialty care via telemedicine is …

Optimal perinatal regionalization is a proven evidence-based strategy to lower infant mortality. Telemedicine can engage community stakeholders, providers, and patients to facilitate optimal perinatal regionalization leading to lower infant mortality. Rural community caregivers and administrators can participate in forming optimal perinatal guidelines without leaving their community. The visual picture created by telemedicine facilitates better transport decisions; ensuring infants who are transferred to larger centers truly need it while supporting smaller nurseries by providing better consultation services and back transport of patients when appropriate. Telemedicine can also provide educational opportunities to community practices, leading to better evidence-based care.

To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study.Phase 2, multicenter, randomized, double-blind, placebo-controlled study.Medical-surgical ICUs.Adult, critically ill patients receiving invasive mechanical ventilation.Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days.Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [SD], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; p = 0.91) and nosocomial infections (0.3 [0.7] vs 0.4 [0.6] per patient; p = 0.48) did not differ between lactoferrin and placebo groups, respectively. Clinical outcomes for lactoferrin versus placebo were as follows: ICU length of stay (14.5 [18.0] vs 15.0 [37.3] d; p = 0.82), hospital length of stay (25.0 [25.9] vs 28.1 [44.6] d; p = 0.57), hospital mortality (41.1% vs 30.5%; p = 0.11), and 90-day mortality (44.9% vs 32.4%; p = 0.06). Biomarker levels did not differ between the groups.Lactoferrin did not improve the primary outcome of antibiotic-free days, nor any of the secondary outcomes. Our data do not support the conduct of a larger phase 3 trial.

Objective The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival (OS) responses, to the use of one such system, implantable macrobeads [RENCA macrobeads (RMBs)], in phase I and IIa clinical trials in advanced, treatment-resistant metastatic colorectal cancer (mCRC) are described here. Methods Forty-eight mCRC patients (30 females; 18 males), who had failed all available, approved treatments, underwent RMB implantation (8 RMB/kg body weight) up to 4 times in phase I and phase IIa open-label trials. Physicals, labs [tumor and inflammation markers, lactate dehydrogenase (LDH)] and positron emission tomography-computed tomography (PET-CT) imaging to measure number/volume and metabolic activity of the tumors were performed pre- and 3-month-post-implantation to evaluate safety and initial efficacy (as defined by biological responses). PET-CT maximum standard uptake value (SUVmax) (baseline and d 90; SUVmax ≥2.5), LDH, and carcinoembryonic antigen (CEA) and/or cancer antigen 19-9 (CA 19-9) response (baseline, d 30 and/or d 60) were assessed and compared to OS. Results Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in 75% of patients. Fluorodeoxyglucose (FDG)-positive lesions (phase I, 39; 2a, 82) were detected in 37/48 evaluable patients, with 35% stable volume and stable or decreased SUV (10) plus four with necrosis; 10, increased tumor volume, SUV. LDH levels remained stable and low in Responders (R) (d 0-60, 290.4-333.9), but increased steadily in Non-responders (NR) (d 0-60, 382.8-1,278.5) (d 60, P=0.050). Responders to RMBs, indicated by the changes in the above markers, correlated with OS (R mean OS=10.76 months; NR mean OS=4.9 months; P=0.0006). Conclusions The correlations of the tumor marker, tumor volume and SUV changes on PET-CT, and LDH levels themselves, and with OS, support the concept of a biological response to RMB implantation and the validity of the biological-systems approach to mCRC. A phase III clinical trial is planned.

Clinicians' current practice patterns in the management of acute respiratory distress syndrome (ARDS) and refractory hypoxemia are not well described.To describe mechanical ventilation strategies and treatment adjuncts for adults with ARDS, including refractory hypoxemia.This was a prospective cohort study (March 2014-February 2015) of mechanically ventilated adults with moderate-to-severe ARDS requiring an FiWe enrolled 664 patients: 222 (33%) with moderate and 442 (67%) with severe ARDS. On Study Day 1, mean Vt was 7.5 (SD = 2.1) ml/kg predicted body weight (n = 625); 80% (n = 501) received Vt greater than 6 ml/kg. Mean positive end-expiratory pressure (PEEP) was 10.5 (3.7) cm HPatients with moderate-to-severe ARDS receive treatment adjuncts frequently, especially with refractory hypoxemia. Paradoxically, therapies with less evidence supporting their use (e.g., pulmonary vasodilators) were over-used, whereas those with more evidence (e.g., prone positioning, neuromuscular blockade) were under-used. Patients received higher Vts and lower PEEP than would be suggested by the evidence.

Established invasions have wide-ranging negative impacts but constraints relating to invader detectability, cost, and efficacy of control may hamper management efforts. One choice that managers face is whether to target control efforts at heavily invaded areas that are sources of invasive propagules or to re-treat previously controlled areas that may be cheaper to control and in which local elimination may be achieved. We developed a mathematical model for the dynamics and control of a plant invasion to determine whether prioritizing heavily invaded or recently controlled areas better achieves each of two management objectives: minimizing the total number of detectable invaded sites (eradication) or heavily invaded sites only (beautification). We provide general guidelines for management by considering how invader traits, budgetary and time constraints, and control efficacy influence prioritization of control efforts and discuss their applicability to long-established invasive plants. For a wide range of invaders and control types, we find that prioritizing heavily-invaded sites performs better for meeting the beautification objective, while re-treating previously controlled sites better achieves eradication. However, combinations of invader traits can lead to the alternate strategy being favored for each management objective, while the optimal choice of management strategy can switch depending on the time horizon of control and annual budget. We summarize model findings to provide general guidelines for invasion managers on how to efficiently allocate limited resources based on invader life history, control cost, and mode of action.

This article examined factors associated with the adoption of smart wearable devices. More specifically, this research explored the contributing and inhibiting factors that influence the adoption o...

Morphine is administered intravenously for pain management in the perioperative period. The effect of the inflammatory response to surgery on morphine distribution across the blood-brain barrier (BBB) in humans was investigated. We hypothesized that a graded surgically induced, systemic inflammatory response alters cerebrospinal fluid (CSF) levels of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) through a temporary reduction in BBB drug efflux transporter function. We conducted a prospective pharmacokinetic study of the plasma and CSF distribution of the P-glycoprotein (PGP) substrate morphine in 33 patients undergoing open thoracic (n = 18) or endovascular (n = 15) aortic aneurysm repair. Morphine was administered with induction of anesthesia and in the intensive care unit. Plasma and CSF concentrations of interleukin (IL)-6, morphine, M3G, M6G, and albumin were measured prior to surgery (baseline), during surgery, and postoperatively every six hours until removal of the CSF drain. The area under the curve (AUC) was determined for plasma and CSF IL-6, morphine, M3G, and M6G concentrations vs time. The primary endpoint measures were the correlations between the morphine, M6G, and M3G AUC CSF/plasma ratios and systemic inflammation as quantified by the time-normalized IL-6 exposure, which was calculated for each individual by dividing the total exposure (AUC) by time (t). A Bonferroni corrected P

A decreased frequency of upper gastrointestinal bleeding and a possible association of proton pump inhibitor use with Clostridium difficile and ventilator-associated pneumonia have raised concerns recently. The Reevaluating the Inhibition of Stress Erosions Pilot Trial determined the feasibility of undertaking a larger trial investigating the efficacy and safety of withholding proton pump inhibitors in critically ill patients.In 10 ICUs, we randomized adult ICU patients anticipated to be mechanically ventilated for greater than or equal to 48 hours to receive 40 mg of IV pantoprazole daily or placebo. We excluded patients who had acute or recent gastrointestinal bleed, used dual antiplatelet agents, had a medical condition requiring proton pump inhibitor treatment, or had already received more than one dose of acid suppression daily. Patients, families, clinicians, and research staff were blinded. We conducted a systematic review and meta-analysis of similar trials.Ninety-one patients (49 pantoprazole and 42 placebo) from 10 centers in Canada, Saudi Arabia, and Australia were enrolled. All feasibility goals were met: 1) recruitment rate was 2.6 patients per month; 2) consent rate was 77.8%; and 3) protocol adherence was 97.7%. Upper gastrointestinal bleeding developed in 6.1% of patients in the pantoprazole group and 4.8% in the placebo group (p = 1.0). Ventilator-associated pneumonia developed in 20.4% of patients in the pantoprazole group and 14.3% in the placebo group (p = 0.58). C. difficile was identified in 4.1% pantoprazole patients and in 2.4% placebo patients (p = 1.0). We meta-analyzed five trials (604 patients) of proton pump inhibitors versus placebo; there was no statistically significant difference in the risk of upper gastrointestinal bleeding, infections, or mortality.Our results support the feasibility of a larger trial to evaluate the safety of withholding stress ulcer prophylaxis. Although the results are imprecise, there was no alarming increase in the risk of upper gastrointestinal bleeding; the effect of proton pump inhibitors on ventilator-associated pneumonia and C. difficile remain unclear.

The purpose of this survey was to determine how Canadian healthcare professionals perceive their deficiencies and educational requirements related to organ and tissue donation. We surveyed 641 intensive care unit (ICU) physicians, 1,349 ICU nurses, 1,561 emergency room (ER) physicians, and 1,873 ER nurses. The survey was distributed by the national organization for each profession (the Canadian Association of Emergency Physicians, the Canadian Association of Critical Care Nurses, and the National Emergency Nurses Association). Canadian Blood Services developed the critical care physician list in collaboration with the Canadian Critical Care Society. Survey development included questions related to comfort with, and knowledge of, key competencies in organ and tissue donation. Eight hundred thirty-one (15.3%) of a possible 5,424 respondents participated in the survey. Over 50% of respondents rated the following topics as highly important: knowledge of general organ and tissue donation, neurological determination of death, donation after cardiac death, and medical-legal donation issues. High competency comfort levels ranged from 14.7-50.9% for ICU nurses and 8.0-34.6% for ER nurses. Competency comfort levels were higher for ICU physicians (67.5-85.6%) than for ER physicians who rated all competencies lower. Respondents identified a need for a curriculum on national organ donation and preferred e-learning as the method of education. Both ICU nurses and ER practitioners expressed low comfort levels with their competencies regarding organ donation. Intensive care unit physicians had a much higher level of comfort; however, the majority of these respondents were specialty trained and working in academic centres with active donation and transplant programs. A national organ donation curriculum is needed.

The purpose of this research is to review the literation on the relationship between internet use and happiness, updating a previous review [1], and building upon a series of longitudinal studies following this initial review [2, 3, 4]. Reasons for studying happiness, and happiness definitions and measurement are discussed. This is followed by a discussion of early research which found a negative relationship between internet use and happiness, followed by studies indicating a more positive relationship, supporting a “stimulation hypothesis” that poses that the internet can act to facilitate face-to-face interactions. More recent research has focused on social networking. With some important exceptions, these most recent studies continue to find that internet use is positively related to happiness, while identifying a number of important mediating and moderating variables, such as experience with the internet and social networking; wealth; health; number of “friends”; the nature of interactions; extroversion, and the ways in which users represent themselves online.

Humans provide supplemental food to wildlife under many contexts, ranging from professional feeding areas for game species to backyard bird feeders. Such resources benefit wildlife by providing reliable resources during periods of food shortages, but may also alter the risk of pathogen transmission and development of disease. While several reviews have summarized the detrimental effects of supplemental food on infection risk, we conducted a comprehensive review to quantify support for mechanisms by which intentional wildlife feeding influences host condition (i.e. malnutrition and stress) and pathogen transmission on a global scale and provide a framework to mitigate these risks. We also examined whether the purpose of feeding, whether for game management, conservation, tourism, or in residential areas, influenced health outcomes. We found 115 studies that evaluated the health of wildlife with supplementary feeding, representing 68 species in 35 countries, although nearly half (46% of studies) were from North America. Supplemental feeding tended to increase the risk of pathogen transmission by increasing contact rates between hosts (95%) and promoting pathogen accumulation at feeders or the surrounding environment (77%). Provisioned food was also often a source of immunosuppressive contaminants (80%). Feeding associated with tourism frequently increased wildlife stress, rates of injury, pathogen prevalence, or malnutrition (85%), while feeding for conservation purposes had mostly positive effects on wildlife health (63%). We recommend adopting feeding practices that validate the nutritional appropriateness of wildlife feed for the target species, make food available at lower densities for short periods at unpredictable times and places to prevent aggregation, and avoid feeding during times of migration, pulses of new recruits, and epidemics. These strategies will help retain the recreational and management benefits of wildlife provisioning while mitigating negative effects for many species around the world.

Purpose: Nanocrystalline hydroxyapatite (nHA) cages have emerged as a new alternative to carbon fiber or polyether ether ketone (PEEK) devices to promote intervertebral fusion. No evidence has been published to date regarding rates of fusion for these devices after anterior cervical discectomy and fusion (ACDF). Methods: Eight patients underwent one- or two-level ACDF with nHA intervertebral cages (Nanoss®-Cervical, Pioneer® Surgical Technology, Inc., Marquette, MI). Radiographs, neck disability index (NDI) and visual analog scores (VAS) for pain were taken preoperatively and at a minimum of 19 months postoperatively. Results: At an average follow-up of 21 months, all eight patients (100%) achieved fusion as assessed by plain radiographs. Reduction in preoperative symptomology was comparable to previously published data with a mean reduction of neck VAS of 3, arm VAS of 6 and NDI reduced by 27%. Radiographs showed clear evidence of bridging bone. Conclusions: This series provides evidence that nHA...

Stress ulcer prophylaxis (SUP) using histamine-2-receptor antagonists has been a standard of care in intensive care units (ICUs) for four decades. Proton pump inhibitors (PPIs) are increasingly used despite apparently lower background rates of gastrointestinal bleeding and growing concerns about PPI-associated complications. Our objective was to understand the views and prescribing habits amongst Canadian physicians regarding SUP in the ICU and to gauge interest in a future randomized-controlled trial (RCT). We created a short self-administered survey about SUP for critically ill adults, evaluated its clinical sensibility, and pilot tested the instrument. We surveyed all physician members of the Canadian Critical Care Trials Group (CCCTG) by e-mail and sent reminders three and five weeks later. We received 94 of 111 (85%) surveys from the validated respondent pool between May and June, 2015. Respondents reported use of SUP most commonly in patients 1) receiving invasive mechanical ventilation (62, 66%), 2) expected to be ventilated for ≥ two days (25, 27%), or 3) receiving mechanical ventilation but nil per os (NPO) (20, 21%). Stress ulcer prophylaxis is discontinued when patients no longer receive mechanical ventilation (75%), no longer are NPO (22%), or are discharged from the ICU (19%). Stress ulcer prophylaxis involves PPIs in 68% of centres. Most respondents endorsed the need for a large rigorous RCT of PPI vs placebo to understand the risks and benefits of this practice. Stress ulcer prophylaxis is reportedly used primarily for the duration of mechanical ventilation. The CCCTG physicians believe that a placebo-controlled RCT is needed to evaluate the effectiveness and safety of contemporary SUP with PPIs.

Background: Until 1990, there was an upward trend in mortality from breast, lung, prostate, and colon cancers in the United Kingdom. With improvements in cancer treatment there has, in general, been a fall in mortality over the last 20 years. We evaluate regional cancer mortality trends in the United Kingdom between 1991 and 2007. Methods: We analysed mortality trends for breast, lung, prostate, and colon cancers using data obtained from the EUREG cancer database. We have described changes in age-standardised rates (using European standard population) per 100 000 for cancer mortality and generated trends in mortality for the 11 regions using Joinpoint regression. Results: Across all regions in the United Kingdom there was a downward trend in mortality for the four most common cancers in males and females. Overall, deaths from colon cancer decreased most rapidly and deaths from prostate cancer decreased at the slowest rate. Similar downward trends in mortality were observed across all regions of the United Kingdom with the data for lung cancer exhibiting the greatest variation. Conclusions: Mortality from the four most common cancers decreased across all regions of the United Kingdom; however, the rate of decline varied between cancer type and in some instances by region.

IntroductionBloodstream infections are a leading cause of mortality and morbidity; the duration of treatment for these infections is understudied.Methods and analysisWe will conduct an international, multicentre randomised clinical trial of shorter (7 days) versus longer (14 days) antibiotic treatment among hospitalised patients with bloodstream infections. The trial will include 3626 patients across 60 hospitals and 6 countries. We will include patients with blood cultures confirming a pathogenic bacterium after hospital admission. Exclusion criteria will include patient factors (severe immunosuppression), infection site factors (endocarditis, osteomyelitis, undrained abscesses, infected prosthetic material) and pathogen factors (Staphylococcus aureus, Staphylococcus lugdunensis, Candida and contaminant organisms). We will leave the selection of specific antibiotics, doses and route of delivery to the discretion of treating physicians; no placebo control will be used given the diversity of pathogens and sources of bacteraemia. The intervention will be assignment of treatment duration to be 7 versus 14 days. We will minimise selection bias via central randomisation with variable block sizes, with concealed allocation until day 7 of adequate antibiotic treatment. The primary outcome is 90-day survival; we will test whether 7 days is non-inferior to 14 days of treatment, with a non-inferiority margin of 4% absolute mortality. Secondary outcomes include hospital and intensive care unit (ICU) mortality, relapse rates of bacteraemia, hospital and ICU length of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile infection, antibiotic allergy and adverse events and colonisation/infection with antibiotic-resistant organisms.Ethics and disseminationThe study has been approved by the ethics review board at each participating site. Sunnybrook Health Sciences Centre is the central ethics committee. We will disseminate study results via the Canadian Critical Care Trials Group and other collaborating networks to set the global paradigm for antibiotic treatment duration for non-staphylococcal Gram-positive, Gram-negative and anaerobic bacteraemia, among patients admitted to hospital.Trial registration numberThe BALANCE (Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness) trial was registered at www.clinicaltrials.gov (registration number: NCT03005145).

Many wildlife species occupy landscapes that vary in the distribution, abundance, and quality of food resources. Increasingly, urbanized and agricultural habitats provide supplemental food resources that can have profound consequences for host distributions, movement patterns, and pathogen exposure. Understanding how host and pathogen dispersal across landscapes is affected by the spatial extent of food-supplemented habitats is therefore important for predicting the consequences for pathogen spread and impacts on host occupancy. Here we develop a generalizable metapopulation model to understand how the relative abundance of provisioned habitats across the landscape and how the host dispersal responses to provisioning and infection influence patch occupancy by hosts and their pathogens. We find that pathogen invasion and landscape-level infection prevalence are greatest when provisioning increases patch attractiveness and disperser production and when infection has minimal costs on dispersal success. Alternatively, if provisioning promotes site fidelity or reduces disperser production, increasing the fraction of food-supplemented habitats can reduce landscape-scale infection prevalence and minimize disease-induced declines in host occupancy. This work highlights the importance of considering how resources and infection jointly influence host dispersal for predicting how changing resource distributions influence the spread of infectious diseases.

Introduction Leptospirosis is the most common occupational zoonosis in New Zealand, with the highest incidence observed in meat processing workers and farm workers. New Zealand has a high incidence of human infection relative to other temperate developed countries, and the organism is widespread in livestock. Serological testing has confirmed infection in livestock presenting to abattoirs and in meat workers. The objective of this study was to determine whether leptospires were present in bioaerosols within the abattoir. Methods Ambient air samples (n=18) were collected in an abattoir from ovine and bovine processing areas, using a SASS 3100 high volume sampler located adjacent to workers performing exsanguination (halal sticking), pelt removal, evisceration, a splitting saw (bovine only) and boning or meat cutting. Nucleic acid (DNA) in the bioaerosol samples was amplified using multiple displacement amplification (MDA) for metagenomic analysis, but the material was also tested for specific pathogenic species including L. interrogans sv Pomona and L. borgpetersenii sv Hardjobovis by quantitative PCR. The original (unamplified) DNA samples were also tested. Result Leptospires were detected in 11 of the (MDA) samples from both ovine and bovine processing areas at the splitting saw, evisceration, exsanguination and pelt removal. There was no evidence of leptospires in samples taken in the boning or meat cutting areas, or in the five blanks taken. Two of the original DNA samples, both from the ovine pelt removal area, also tested positive for leptospires. Discussion This is the first study to show that leptospires can be detected in a bioaerosol within an abattoir, suggesting a possible route of transmission to meat workers. The organism was detected at locations adjacent to slaughter, pelt removal and evisceration, with the strongest evidence near ovine pelt removal. This distribution directly mirrors the pattern of risk shown in serological testing of meat workers.

Background: In rural states there are shortages of medically trained public safety answering point (PSAP) 911 answering stations. Dispatchers in these rural states risk leaving out vital Medical Priority Dispatch System (MPDS) determinants on patient stability and location to emergency medical systems (EMS) paramedics. We developed a smart phone medical education application for PSAP operators in underserved rural areas with a high deficiency of medical training. In Arkansas, as a rural stroke belt state there are 120 PSAP locations and 75 do not require any medical information training from state agencies. Twenty-six of these sites have limited medical training in cardio-pulmonary training. Only five counties have medically trained dispatchers and use MPDS. Following training, certification of dispatchers in any of the remaining underserved 70 counties that provide medical information will be regarded as a success. Hypothesis: The PSAP personnel serving as dispatch operators who utilize a medical dispatch training application will provide training based medical information, and reduce mortality due to stroke, trauma, and ST-elevation myocardial infarction (STEMI). Methods: In our data analysis, we are identifying whether the app intervention training influences telecommunication transition of information such as patient condition and caller location information to emergency medical service (EMS) providers. Other variables include paramedic impression/observation coding and response time to the scene. Baseline data from 2012 to 2014 will be used to compare pre- and post-training and state mortality data for stroke, trauma, and STEMI. Dispatcher to EMS agencies for dispatcher/caller information pre- and post-training will be compared for stroke, trauma, and STEMI mortality data. Results: App downloads have been noted in states across the US and as far as South Africa. At this time, we are still acquiring data for app downloads and user completed course training. Baseline mortality in 2012 to 2014 due to stroke, trauma, and STEMI were 140, 234, and 277 per 100,000, respectively. Conclusion: Currently, non-trained PSAP operators do not provide medical information on 911 calls and risk delayed EMS response time, jeopardizing patient safety.

Background: Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill. Methods/design: This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic-free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence. Discussion: The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large-scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF. Trial registration: The trial was registered at www.ClinicalTrials.gov on 18 November 2013. Trial registration number: NCT01996579 .

This study is an extension of two previous studies, which explored the relationship between happiness and Internet use [1, 2]. An Internet Use Scale (IUS), developed in the initial study, was administered to college students along with the Flourishing Scale [3] and the Satisfaction with Life Scale [4]. I compared changes in the relationship between these measures, and their mean values, across the three samples; assessed the relationship between use factors and happiness over-all, combining data from all samples; and evaluated the relationship between individual usage scale items and happiness. Results indicated that those who reported spending less time on the Internet, and less time expressing negative emotions scored higher on measures of happiness. There was also some indication that those who spend time checking facts on the Internet are happier, but the effect was not as strong nor consistent.

Introduction In a landmark 2013 decision, the Supreme Court of Canada (SCC) ruled that the withdrawal of life support in certain circumstances is a treatment requiring patient or substitute decision maker (SDM) consent. How intensive care unit (ICU) physicians perceive this ruling is unknown. Objectives To determine physician knowledge of and attitudes towards the SCC decision, as well as the self-reported changes in practice attributed to the decision. Methods We surveyed intensivists at university hospitals across Canada. We used a knowledge test and Likert-scale questions to measure respondent knowledge of and attitudes towards the ruling. We used vignettes to assess decision making in cases of intractable physician-SDM conflict over the management of patients with very poor prognoses. We compared management choices pre-SCC decision versus post-SCC decision versus the subjective, respondent-defined most appropriate choice. Responses were compared across predefined subgroups. We performed qualitative analysis on free-text responses. Results We received 82 responses (response rate=42%). Respondents reported providing high levels of self-defined inappropriate treatment. Although most respondents reported no change in practice, there was a significant overall shift towards higher intensity and less subjectively appropriate management after the SCC decision. Attitudes to the SCC decision and approaches to disputes over end-of-life (EoL) care in the ICU were highly variable. There were no significant differences among predefined subgroups. Conclusions Many Canadian ICU physicians report providing a higher intensity of treatment, and less subjectively appropriate treatment, in situations of dispute over EoL care after the Supreme Court of Canada9s ruling in Cuthbertson versus Rasouli .

Many wildlife species persist on a network of ephemerally occupied habitat patches connected by dispersal. Provisioning of food and other resources for conservation management or recreation is frequently used to improve local habitat quality and attract wildlife. Resource improvement can also facilitate local pathogen transmission, but the landscape-level consequences of provisioning for pathogen spread and habitat occupancy are poorly understood. Here, we develop a simple metapopulation model to investigate how heterogeneity in patch quality resulting from resource improvement influences long-term metapopulation occupancy in the presence of a virulent pathogen. We derive expressions for equilibrium host–pathogen outcomes in terms of provisioning effects on individual patches (through decreased patch extinction rates) and at the landscape level (the fraction of high-quality, provisioned patches), and highlight two cases of practical concern. First, if occupancy in the unprovisioned metapopulation is sufficiently low, a local maximum in occupancy occurs for mixtures of high- and low-quality patches, such that further increasing the number of high-quality patches both lowers occupancy and allows pathogen invasion. Second, if the pathogen persists in the unprovisioned metapopulation, further provisioning can result in all patches becoming infected and in a global minimum in occupancy. This work highlights the need for more empirical research on landscape-level impacts of local resource provisioning on pathogen dynamics.

Crop productivity needs to substantially increase to meet global food and feed demand for a rapidly growing world population. Agricultural technology developers are pursuing a variety of approaches based on both traditional technologies such as genetic improvement, pest control and mechanization as well as new technologies such as genomics, gene manipulation and environmental modelling to develop crops that are capable of meeting growing demand. Photosynthesis is a key biochemical process that, many suggest, is not yet optimized for industrial agriculture or the modern global environment. We are interested in identifying control points in maize photoassimilation that are amenable to gene manipulation to improve overall productivity. Our approach encompasses: developing and using novel gene discovery techniques, translating our discoveries into traits and evaluating each trait in a stepwise manner that reflects a modern production environment. Our aim is to provide step change advancement in overall crop productivity and deliver this new technology into the hands of growers. This article is part of the themed issue ‘Enhancing photosynthesis in crop plants: targets for improvement’.

Background: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury. Methods: We conducted a two-part phase II trial comprising an open-label intrapatient dose escalation and a randomized, double-blind, placebo-controlled phase in ten intensive care units in North America. Patients were between the ages of 18 and 80 years, had an American-European Consensus Criteria consensus diagnosis of ARDS, and had been mechanically ventilated for less than 72 h. In part A, open-label GSK2586881 was administered at doses from 0.1 mg/kg to 0.8 mg/kg to assess safety, pharmacokinetics, and pharmacodynamics. Following review of data from part A, a randomized, double-blind, placebo-controlled investigation of twice-daily doses of GSK2586881 (0.4 mg/kg) for 3 days was conducted (part B). Biomarkers, physiological assessments, and clinical endpoints were collected over the dosing period and during follow-up. Results: Dose escalation in part A was well-tolerated without clinically significant hemodynamic changes. Part B was terminated after 39 of the planned 60 patients following a planned futility analysis. Angiotensin II levels decreased rapidly following infusion of GSK2586881, whereas angiotensin-(1–7) and angiotensin-(1–5) levels increased and remained elevated for 48 h. Surfactant protein D concentrations were increased, whereas there was a trend for a decrease in interleukin-6 concentrations in rhACE2-treated subjects compared with placebo. No significant differences were noted in ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, oxygenation index, or Sequential Organ Failure Assessment score. Conclusions: GSK2586881 was well-tolerated in patients with ARDS, and the rapid modulation of RAS peptides suggests target engagement, although the study was not powered to detect changes in acute physiology or clinical outcomes. Trial registration ClinicalTrials.gov, NCT01597635 . Registered on 26 January 2012.

This is an extension of a previous study, which explored the relationship between happiness and Internet use [1]. An Internet Use Scale (IUS), developed in the previous study, was administered to college students along with the Flourishing Scale [2] and the Satisfaction with Life Scale [3]; and three new open-ended questions. We compared changes in the relationship between these measures, and their mean values, across the two samples, and carried out qualitative analyses of the open-ended questions. Results indicated that those who reported spending less time on the internet, less time expressing emotions, and more time checking facts, scored higher on measures of happiness. Further, participants found negative affective expression on the Internet particularly aversive. Finally, those with lower happiness scores were more likely to report playing on-line games; and those with higher happiness scores were more likely to identify Internet disinformation as aversive.

Acute kidney injury (AKI) is a potentially serious complication of cardiac surgery. Anemia and red blood cell (RBC) transfusion have individually been identified as potentially modifiable risk factors, but their interrelationship with AKI has not been clearly defined. The purpose of this study was to explore the interrelationship of preoperative anemia, intraoperative anemia, and RBC transfusion on the day of surgery with AKI in cardiac surgery. This historical cohort study included 16 hospitals, each contributing data on approximately 100 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass. Acute kidney injury was defined as a > 50% increase in creatinine levels during the first postoperative week. Multivariable regression was used to identify the interrelationship between preoperative anemia (hemoglobin

In clinical setting, Sidestream Dark Field (SDF) imaging has provided unprecedented insights into the gut microcirculation mainly by studying the intestinal mucosa of patients with ileostomies. Visualizing microvascular structure and function of ileal mucosa at the bedside brings unique opportunity for clinical research, particularly in critically ill patients. Several papers that were focused on intestinal microcirculation, used different methods of assessment because an accepted scoring systems does not exist so far and it is no surprise that it is rather difficult to compare the results from these studies. The present paper presents recommendations concerning specific aspects of image acquisition and proposes some parameters for the description of the intestinal microcirculation in human studies, as suggested by the participants of a round table meeting.The round table meeting participants reviewed all relevant literature, discussed various aspects of image acquisition by SDF technology in patients with ileostomy and parameters for the description of intestinal mucosa microcirculation. Selected key conditions for high quality and reproducible image recordings were identified. To evaluate quality of intestinal microcirculation, selected parameters and scoring system were suggested and described.For image acquisition in ileostomies, five key points were proposed: optimal timing, optimal SDF device probe positioning, optimal stabilization, optimal number and length of acquired video recordings, and optimal avoidance of pressure artefacts. With regard to image analysis, simplified set of quantitative and qualitative parameters for the description of the intestinal mucosa microcirculation for the clinical studies has been proposed: vessels per villus, microvascular flow index, proportion of perfused villi, and borders of villi. The proposed parameters can be included in a semi-quantitative scoring system; however, this scoring system needs further validation. This simplified analysis does not require sophisticated software and can be performed manually on the video screen.We propose a simple methodology for image acquisition and suggest specific microvascular parameters to analyze SDF imaging studies of the intestinal mucosa microcirculation in patients with ileostomy. Proposed scoring system needs to be validated in further clinical studies.

The encapsulation of porcine islets is an attractive methodology for the treatment of Type I diabetes. In the current study, the use of pravastatin as a mild anti-inflammatory agent was investigated in pancreatectomized diabetic canines transplanted with porcine islets encapsulated in agarose-agarose macrobeads and given 80 mg/day of pravastatin (n=3) while control animals did not receive pravastatin (n=3). Control animals reached preimplant insulin requirements on days 18, 19, and 32. Pravastatin-treated animals reached preimplant insulin requirements on days 22, 27, and 50. Two animals from each group received a second macrobead implant: control animals remained insulin-free for 15 and 21 days (AUC = 3003 and 5078 mg/dL/24 hr days 1 to 15) and reached preimplant insulin requirements on days 62 and 131. Pravastatin treated animals remained insulin-free for 21 and 34 days (AUC = 1559 and 1903 mg/dL/24 hr days 1 to 15) and reached preimplant insulin requirements on days 38 and 192. Total incidence (83.3% versus 64.3%) and total severity (22.7 versus 18.3) of inflammation on tissue surfaces were higher in the control group at necropsy. These findings support pravastatin therapy in conjunction with the transplantation of encapsulated xenogeneic islets for the treatment of diabetes mellitus.

BackgroundVertebroplasty is increasingly used in the treatment of vertebral compression fractures. However there are concerns that this intervention may lead to further fractures in the adjacent vertebral segments. This study was designed to parametrically assess the influence of both treatment factors (cement volume and number of augmentations), and patient factors (bone and disc quality) on the biomechanical effects of vertebroplasty.MethodsSpecimen-specific finite element models of two experimentally-tested human three-vertebral-segments were developed from CT-scan data. Cement augmentation at one and two levels was represented in the respective models and good agreement in the predicted stiffness was found compared to the corresponding experimental specimens. Parametric variations of key variables associated with the procedure were then studied.FindingsThe segmental stiffness increased with disc degeneration, with increasing bone quality and to a lesser extent with increasing cement volume. Cement modulus did not have a great influence on the overall segmental stiffness and on the change in the elemental stress in the adjoining vertebrae. However, following augmentation, the stress distribution in the adjacent vertebra changed, indicating possible load redistribution effects of vertebroplasty.InterpretationThis study demonstrates the importance of patient factors in the outcomes of vertebroplasty and suggests that these may be one reason for the variation in clinical results.

Across sub-Saharan Africa, women and children play major roles as pedestrian load-transporters, in the widespread absence of basic sanitation services, electricity and affordable/reliable motorised transport. The majority of loads, including water and firewood for domestic purposes, are carried on the head. Load-carrying has implications not only for school attendance and performance, women's time budgets and gender relations, but arguably also for health and well-being. We report findings from a comprehensive review of relevant literature, undertaken June–September 2012, focussing particularly on biomechanics, maternal health, and the psycho-social impacts of load-carrying; we also draw from our own research. Key knowledge gaps and areas for future research are highlighted.

All critically ill patients require medication to treat organ dysfunction. However, the pharmacokinetics of drugs used to treat these patients is complex due to frequent alterations in drug absorption, distribution, metabolism, and excretion (ADME).This review examines pharmacokinetic aspects of drug administration for adult intensive care unit (ICU) patients. Specifically, the authors examine the ADME changes that occur and which should be considered by clinicians when delivering drug therapy to critically ill patients.Dosage pharmacokinetics determined from single-dose or limited-duration administration studies in healthy volunteers may not apply to critically ill patients. Organ dysfunction among these patients may be due to pre-existing disease or the effects of a systemic or locoregional inflammatory response precipitated by their illness. Alterations in pharmacokinetics observed among the critically ill include altered bioavailability after enteral administration, increased volume of distribution and blood-brain barrier permeability and changes in P-glycoprotein and cytochrome P450 enzyme function. However, the effect of these changes on clinically important outcomes remains uncertain and poorly studied. Future investigations should examine not only pharmacokinetic changes among the critically ill, but also whether recognition of these changes and alterations in drug therapy directed as a consequence of their observation alters patient outcomes.

Kangaroo care (KC) has possible benefits for promoting physiological stability and positive developmental outcomes in preterm infants. The purpose of this study was to compare bradycardia and oxygen desaturation events in preterm infants in standard incubator care versus KC.Thirty-eight infants 27 to 30 weeks gestational age were randomly assigned to 2 hours of KC daily between days of life 5 to 10 or to standard incubator care. Infants were monitored for bradycardia (heart rate80) or oxygen desaturation (80%). Analysis of hourly events was based on three sets of data: standard care group 24 hours daily, KC group during incubator time 22 hours daily, and KC group during holding time 2 hours daily.The KC group had fewer bradycardia events per hour while being held compared to time spent in an incubator (p = 0.048). The KC group also had significantly fewer oxygen desaturation events while being held than while in the incubator (p = 0.017) and significantly fewer desaturation events than infants in standard care (p = 0.02).KC reduces bradycardia and oxygen desaturation events in preterm infants, providing physiological stability and possible benefits for neurodevelopmental outcomes.

We present preliminary results from an experiment designed to measure the effective pixel positions of a CCD to sub-pixel precision. This technique will be used to characterise the 4k x 4k CCD destined for the HARPS-3 spectrograph. The principle of coherent beam interference is used to create intensity fringes along one axis of the CCD. By sweeping the physical parameters of the experiment, the geometry of the fringes can be altered which is used to probe the pixel structure. We also present the limitations of the current experimental set-up and suggest what will be implemented in the future to vastly improve the precision of the measurements.

Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. We selected relevant literature to illustrate the important concepts contained within. Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach. Genetic variability in response to drugs may occur as a result of alterations of drug-metabolizing (cytochrome P [CYP]) enzymes, receptors, and transport proteins leading to enhancement or delay in the therapeutic response. Of relevance to the ICU, genetic variation in CYP-450 isoenzymes results in altered effects of midazolam, fentanyl, morphine, codeine, phenytoin, clopidogrel, warfarin, carvedilol, metoprolol, HMG-CoA reductase inhibitors, calcineurin inhibitors, non-steroidal anti-inflammatory agents, proton pump inhibitors, and ondansetron. Changes in cholinesterase enzyme function may affect the disposition of succinylcholine, benzylisoquinoline muscle relaxants, remifentanil, and hydralazine. Genetic variation in transport proteins leads to differences in the response to opioids and clopidogrel. Polymorphisms in drug receptors result in altered effects of β-blockers, catecholamines, antipsychotic agents, and opioids. Genetic variation also contributes to the diversity and incidence of diseases and conditions such as sepsis, malignant hyperthermia, drug-induced hypersensitivity reactions, cardiac channelopathies, thromboembolic disease, and congestive heart failure. Application of pharmacogenetics and pharmacogenomics has seen improvements in drug therapy. Ongoing study and incorporation of these concepts into clinical decision making in the ICU has the potential to affect patient outcomes.

Aim Noninvasive electrical stimulation at acupuncture points (NESAP) for analgesia is used in children, but has not been widely studied in neonates. The purpose of this study was to determine if NESAP alone or in combination with sucrose relieved heelstick pain in neonates. Methods Term neonates (n=162) receiving routine heelsticks for newborn screening were enrolled following parental consent. All infants received facilitated tucking and nonnutritive sucking. Neonates were randomized to standard care, sucrose, NESAP, or sucrose plus NESAP. NESAP (3.5 mA, 10 Hz) or sham was administered over 4 acupuncture points. The Premature Infant Pain Profile (PIPP), heart rate variability (HRV), and salivary cortisol were used to measure heelstick pain. Results PIPP scores among all 4 treatment groups increased during heelstick,F (9,119) =1.95, p 0.05, and NESAP therapy had no significant effect on PIPP scores. However, PIPP scores from baseline to heelstick increased the most in the two groups not receiving sucrose (p

Preterm infants undergoing Retinopathy of Prematurity Eye Exams (ROPEE) may experience adverse events, possibly from systemic absorption of cyclopentolate. The purpose of this study was to analyze the association between adverse events and drug levels found in neonates undergoing ROPEE.25 infants were randomized into two groups during routine ROP screening: 5 infants for blood collection before mydriatic drops and 20 for blood collection 1 h after eye drops. Blood was collected onto dried blood spot cards, extracted, and analyzed for cyclopentolate and phenylephrine using liquid chromatography and mass spectrometry. Relationships between drug levels and adverse events were assessed.Cyclopentolate (range 6-53 ng/ml) was observed in 15 of 18 infants, while phenylephrine was not detected. Levels of cyclopentolate were significantly higher in infants who were on oxygen (p = 0.01). There was a significant association between cyclopentolate levels and gastric residuals in tube-fed infants not receiving oxygen (p = 0.01).Cyclopentolate levels varied among preterm infants after ROPEE. Cyclopentolate was positively associated with increased gastric residuals. Underlying medical conditions requiring oxygen administration may affect absorption and metabolism of cyclopentolate. There is a need to predict infants at risk for high blood levels of cyclopentolate in order to prevent or treat adverse events after ROPEE.