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Cellular mitochondrial function has been suggested to contribute to variation in feed efficiency (FE) among animals. The objective of this study was to determine mitochondrial abundance and activities of various mitochondrial respiratory chain complexes (complex I (CI) to complex IV (CIV)) in liver and muscle tissue from beef cattle phenotypically divergent for residual feed intake (RFI), a measure of FE. Individual DM intake (DMI) and growth were measured in purebred Simmental heifers (n = 24) and bulls (n = 28) with an initial mean BW (SD) of 372 kg (39.6) and 387 kg (50.6), respectively. All animals were offered concentrates ad libitum and 3 kg of grass silage daily, and feed intake was recorded for 70 days. Residuals of the regression of DMI on average daily gain (ADG), mid-test BW0.75 and backfat (BF), using all animals, were used to compute individual RFI coefficients. Animals were ranked within sex, by RFI into high (inefficient; top third of the population), medium (middle third of population) and low (efficient; bottom third of the population) terciles. Statistical analysis was carried out using the MIXED procedure of SAS v 9.3. Overall mean ADG (SD) and daily DMI (SD) for heifers were 1.2 (0.4) and 9.1 (0.5) kg, respectively, and for bulls were 1.8 (0.3) and 9.5 (1.02) kg, respectively. Heifers and bulls ranked as high RFI consumed 10% and 15% more (P < 0.05), respectively, than their low RFI counterparts. There was no effect of RFI on mitochondrial abundance in either liver or muscle (P > 0.05). An RFI × sex interaction was apparent for CI activity in muscle. High RFI animals had an increased activity (P < 0.05) of CIV in liver tissue compared to their low RFI counterparts; however, the relevance of that observation is not clear. Our data provide no clear evidence that cellular mitochondrial function within either skeletal muscle or hepatic tissue has an appreciable contributory role to overall variation in FE among beef cattle.
The mild-slope equations, devised to approximate surface wave propagation over water of slowly varying depth, have hitherto been based on either the velocity potential formulation or the streamfunction formulation. By using a more general version of the governing equations, a single framework is developed that relates the existing mild-slope equations and provides new examples and derivations.
The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH MB using immunohistochemical analysis as well as transcriptome data across 763 primary tumors. Characterization of CD271+ and CD271- cells by RNA sequencing revealed that these two subpopulations are molecularly distinct, co-existing cellular subsets both in vitro and in vivo. MAPK/ERK signaling is upregulated in the CD271+ population and inhibiting this pathway reduced CD271 levels, stem/progenitor cell proliferation and cell survival as well as cell migration in vitro. Importantly, the MEK inhibitor selumetinib extends survival and reduces CD271 levels in vivo. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH MB tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH MB cells.
Introduction: Patients with chronic diseases are known to benefit from exercise. Such patients often visit the emergency department (ED). There are few studies examining prescribing exercise in the ED. We wished to study if exercise prescription in the ED is feasible and effective. Methods: In this pilot prospective block randomized trial, patients in the control group received routine care, whereas the intervention group received a combined written and verbal prescription for moderate exercise (150 minutes/week). Both groups were followed up by phone at 2 months. The primary outcome was achieving 150 min of exercise per week. Secondary outcomes included change in exercise, and differences in reported median weekly exercise. Comparisons were made by Mann-Whitney and Fishers tests (GraphPad). Results: Follow-up was completed for 22 patients (11 Control; 11 Intervention). Baseline reported median (with IQR) weekly exercise was similar between groups; Control 0(0-0)min; Intervention 0(0-45)min. There was no difference between groups for the primary outcome of 150 min/week at 2 months (Control 3/11; Intervention 4/11, RR 1.33 (95%CI 0.38-4.6;p=1.0). There was a significant increase in median exercise from baseline in both groups, but no difference between the groups (Control 75(10-225)min; Intervention 120(52.5-150)min;NS). 3 control patients actually received exercise prescription as part of routine care. A post-hoc comparison of patients receiving intervention vs. no intervention, revealed an increase in patients meeting the primary target of 150min/week (No intervention 0/8; Intervention 7/14, RR 2.0 (95%CI 1.2-3.4);p=0.023). Conclusion: Recruitment was feasible, however our study was underpowered to quantify an estimated effect size. As a significant proportion of the control group received the intervention (as part of standard care), any potential measurable effect was diluted. The improvement seen in patients receiving intervention and the increase in reported exercise in both groups (possible Hawthorne effect) suggests that exercise prescription for ED patients may be beneficial.
The morphology of englacial drainage networks and their temporal evolution are poorly characterised, particularly within cold ice masses. At present, direct observations of englacial channels are restricted in both spatial and temporal resolution. Through novel use of a terrestrial laser scanning (TLS) system, the interior geometry of an englacial channel in Austre Brøggerbreen, Svalbard, was reconstructed and mapped. Twenty-eight laser scan surveys were conducted in March 2016, capturing the glacier surface around a moulin entrance and the uppermost 122 m reach of the adjoining conduit. The resulting point clouds provide detailed 3-D visualisation of the channel with point accuracy of 6.54 mm, despite low (<60%) overall laser returns as a result of the physical and optical properties of the clean ice, snow, hoar frost and sediment surfaces forming the conduit interior. These point clouds are used to map the conduit morphology, enabling extraction of millimetre-to-centimetre scale geometric measurements. The conduit meanders at a depth of 48 m, with a sinuosity of 2.7, exhibiting teardrop shaped cross-section morphology. This improvement upon traditional surveying techniques demonstrates the potential of TLS as an investigative tool to elucidate the nature of glacier hydrological networks, through reconstruction of channel geometry and wall composition.
The immune system’s remarkable ability to protect the body from invasion by foreign pathogens stems from its capacity to distinguish biologic “self” from “nonself.” An aberration in this normally well-regulated process leads to so-called autoimmunity, in which immune effector cells are directed against “self” tissues. Persistent abnormal immunologic activation results in autoimmune disease, each type characterized by a typical pattern of clinical signs and symptoms and confirmed by the presence of immune effector cells, usually autoantibodies. In some autoimmune conditions, serologically detected autoantibodies play an active role in tissue damage, while in others they serve only to confirm the existence of an autoimmune process. The pathophysiology leading to autoimmunity likely involves a failure of complex regulatory mechanisms, which normally control activation and deactivation of the immune system. Recent investigations suggest that full expression of autoimmune disease depends on a combination of environmental, genetic, and host factors.
Introduction: Point-of-care-ultrasound is an established tool in the early diagnosis of abdominal aortic aneurysm (AAA), with a reported pooled sensitivity of 97.5% and pooled specificity 98.9%. Despite these impressive numbers, body habitus and bowel gas often render emergency department (ED) PoCUS for AAA inconclusive. We devised a manual aid “the modified peace sign technique” to improve visualization of the aorta, consisting of placing the divided fingers of the free hand of the sonographer around the probe to increase gas dispersion and improve the view of the obscured aorta. We tested the technique on volunteers during a training course when the initial scan was indeterminate due to inability to view the aorta from sub-xiphoid to bifurcation. Methods: In our pilot study, 7 physicians were asked to make a best attempt to perform an aortic scan. If they were unable to visualize the aorta, they were asked to use the modified peace sign technique. Participants recorded the number of times which they used the technique and the frequency that the technique allowed for a complete aortic scan, previously unobtainable. All scans were supervised by certified PoCUS physicians. Results: The technique was used a total of 25 times. Following failure to complete an aortic scan using their best attempt, participants were subsequently able to obtain a complete aortic scan 70% (95% CI 48 to 83%) of the time using the modified peace sign technique. Conclusion: In our pilot study, the modified peace sign technique had an estimated effect size of 70% improvement for visualization of the aorta in volunteers. Further studies are required to validate the technique in clinical practice.
Introduction: The positive health outcomes of exercise have been well-studied, and exercise prescription has been shown to reduce morbidity in several chronic health conditions. However, patient attitudes around the prescription of exercise in the emergency department (ED) have not been explored. The aim of our pilot study is to explore patients’ willingness and perceptions of exercise being discussed and prescribed in the ED. Methods: This study is a survey of patients who had been previously selected for exercise prescription in a pilot study conducted at a tertiary care ED. This intervention group were given a standardized provincial written prescription to perform moderate exercise for 150 minutes per week. Participants answered a discharge questionnaire and were followed up by a telephone interview 2 months later. A structured interview of opinions around exercise prescription was conducted. Questions included a combination of non-closed style interview questions and Likert scale. Patients rated prescription detail, helpfulness and likelihood on a Likert scale from 1-5 (1 being strongly disagree and 5 being strongly agree). Median values (+/-IQRs) are presented, along with dominant themes. Results: 17 people consented to exercise prescription and follow up surveys. 2 were excluded due to hospital admission. 15 participants were enrolled and completed the discharge survey. Two-month follow up survey response rate was 80%. Patients rated the detail given in their prescription as 5 (+/-1). Helpfulness of prescription was rated as 4 (+/-2). Likelihood to continue exercising based on the prescription was rated as 4 (+/-2). 11/12 participants felt that exercise should be discussed in the Emergency Department either routinely or on a case-by-case basis.1 participant felt it should not be discussed at all. Conclusion: Our study demonstrates that most patients are open to exercise being discussed during their Emergency Department visit, and that the prescription format was well-received by study participants.
Introduction: Data regarding adverse events (AEs) (unintended harm to the patient from health care provided) among children seen in the emergency department (ED) are scarce despite the high risk setting and population. The objective of our study was to estimate the risk and type of AEs, and their preventability and severity, among children treated in pediatric EDs. Methods: Our prospective cohort study enrolled children <18 years of age presenting for care during 21 randomized 8 hr-shifts at 9 pediatric EDs from Nov 2014 to October 2015. Exclusion criteria included unavailability for follow-up or insurmountable language barrier. RAs collected demographic, medical history, ED course, and systems level data. At day 7, 14, and 21 a RA administered a structured telephone interview to all patients to identify flagged outcomes (e.g. repeat ED visits, worsening/new symptoms, etc). A validated trigger tool was used to screen admitted patients’ health records. For any patients with a flagged outcome or trigger, 3 ED physicians independently determined if an AE occurred. Primary outcome was the proportion of patients with an AE related to ED care within 3 weeks of their ED visit. Results: We enrolled 6377 (72.0%) of 8855 eligible patients; 545 (8.5%) were lost to follow-up. Median age was 4.4 years (range 3 months to 17.9 yrs). Eight hundred and seventy seven (13.8%) were triaged as CTAS 1 or 2, 2638 (41.4%) as CTAS 3, and 2839 (44.7%) as CTAS 4 or 5. Top entrance complaints were fever (11.2%) and cough (8.8%). Flagged outcomes/triggers were identified for 2047 (32.1%) patients. While 252 (4.0%) patients suffered at least one AE within 3 weeks of ED visit, 163 (2.6%) suffered an AE related to ED care. In total, patients suffered 286 AEs, most (67.9%) being preventable. The most common AE types were management issues (32.5%) and procedural complications (21.9%). The need for a medical intervention (33.9%) and another ED visit (33.9%) were the most frequent clinical consequences. In univariate analysis, older age, chronic conditions, hospital admission, initial location in high acuity area of the ED, having >1 ED MD or a consultant involved in care, (all p<0.001) and longer length of stay (p<0.01) were associated with AEs. Conclusion: While our multicentre study found a lower risk of AEs among pediatric ED patients than reported among pediatric inpatients and adult ED patients, a high proportion of these AEs were preventable.
The anticipated release of EnlistTM cotton, corn, and soybean cultivars likely will increase the use of 2,4-D, raising concerns over potential injury to susceptible cotton. An experiment was conducted at 12 locations over 2013 and 2014 to determine the impact of 2,4-D at rates simulating drift (2 g ae ha−1) and tank contamination (40 g ae ha−1) on cotton during six different growth stages. Growth stages at application included four leaf (4-lf), nine leaf (9-lf), first bloom (FB), FB + 2 wk, FB + 4 wk, and FB + 6 wk. Locations were grouped according to percent yield loss compared to the nontreated check (NTC), with group I having the least yield loss and group III having the most. Epinasty from 2,4-D was more pronounced with applications during vegetative growth stages. Importantly, yield loss did not correlate with visual symptomology, but more closely followed effects on boll number. The contamination rate at 9-lf, FB, or FB + 2 wk had the greatest effect across locations, reducing the number of bolls per plant when compared to the NTC, with no effect when applied at FB + 4 wk or later. A reduction of boll number was not detectable with the drift rate except in group III when applied at the FB stage. Yield was influenced by 2,4-D rate and stage of cotton growth. Over all locations, loss in yield of greater than 20% occurred at 5 of 12 locations when the drift rate was applied between 4-lf and FB + 2 wk (highest impact at FB). For the contamination rate, yield loss was observed at all 12 locations; averaged over these locations yield loss ranged from 7 to 66% across all growth stages. Results suggest the greatest yield impact from 2,4-D occurs between 9-lf and FB + 2 wk, and the level of impact is influenced by 2,4-D rate, crop growth stage, and environmental conditions.
Introduction: Multiples barriers to appropriate analgesia are reported in the paediatric emergency department (PED), including limited accessibility to effective strategies. Our objective: was to evaluate the improvement in the accessibility of pain and anxiety management strategies in Canadian PEDs, after the creation of a national pediatric pain Quality Improvement Collaborative (QIC), through Pediatric Emergency Research Canada (PERC). Methods: In 2013, the TRAPPED 1 survey was administered to Canadian PEDs, in order to evaluate what resources were in place for pain and anxiety management. A pain QIC was then created to stimulate the implementation of new strategies, through information sharing between PEDs. In 2015, the TRAPPED 2 cross sectional survey was administered. Its focus was to evaluate the improvement in the accessibility of specific strategies reported by each centre, after participating in this QIC, and working to implement change within their own PEDs. Results: All 15/15 Canadian PEDs responded to the TRAPPED 1 survey in 2013 and 11 agreed to participate in the national pain QIC. In-person, phone meetings, follow up surveys and email communications were employed for information sharing. Strategies identified by the QIC to be newly introduced in individual centres were educational initiatives, distraction options, nurse-initiated protocols and intranasal (IN) medications. All 15 PEDs completed the TRAPPED 2 survey. Compared to 2013, an increased number of PEDs used face-based pain scales (14/15 vs 6/15) and behavioural scales (5/15 vs 1/15) for pain assessment in 2015. Use of reminder posters on pain management at triage increased from 4/15 to 6/15 PEDs. Availability of tablets for distraction increased from 4/15 to 10/15 PEDs. Nurse-initiated protocols for topical anesthetic and oral sucrose (for needle procedures) increased from 10/15 to 12/15 sites and from 12/15 to 14/15 sites respectively. Availability of IN medications increased; fentanyl from 9/15 to 14/15 sites and midazolam from 8/15 to 10/15 sites. Ten of the 11 PEDs involved in the QIC strategy reported the implementation of at least one of their own identified strategies. Conclusion: This study suggests that the use of a QIC may improve the introduction of new strategies to reduce pain and anxiety in EDs. QICs may also be helpful to other centres when introducing new strategies.
Impaired neuropsychological functioning is a feature of major depression. Previous studies have suggested that at least some aspects of neuropsychological functioning improve with successful treatment of major depression. The extent to which medications may affect the degree of normalization of these functions is unclear. The aim of the current study was to examine the course of neuropsychological functioning during treatment of major depression with cognitive–behaviour therapy (CBT) or schema therapy (ST).
A total of 69 out-patients with a primary diagnosis of major depression and 58 healthy controls completed mood ratings, neuropsychological measures, and measures of emotional processing at baseline and after 16 weeks. Participants were randomized after baseline assessment to a year-long course of CBT or ST. Patients reassessed at 16 weeks were medication-free throughout the study.
Significant neuropsychological impairment was evident at baseline in depressed participants compared with healthy controls. After 16 weeks of psychotherapy, mean depression rating scores fell more than 50%. However, no neuropsychological measures showed convincing evidence of significant improvement and emotional processing did not change.
Persisting impairment in neuropsychological functioning after the first 16 weeks of CBT or ST suggests a need to modify psychological treatments to include components targeting cognitive functioning.
Acinetobacter is a well-recognized nosocomial pathogen. Previous reports of community-associated Acinetobacter infections have lacked clear case definitions and assessment of healthcare-associated (HCA) risk factors. We identified Acinetobacter bacteraemia cases from blood cultures obtained <3 days after hospitalization in rural Thailand and performed medical record reviews to assess HCA risk factors in the previous year and compare clinical and microbiological characteristics between cases with and without HCA risk factors. Of 72 Acinetobacter cases, 32 (44%) had no HCA risk factors. Compared to HCA infections, non-HCA infections were more often caused by Acinetobacter species other than calcoaceticus–baumannii complex species and by antibiotic-susceptible organisms. Despite similar symptoms, the case-fatality proportion was lower in non-HCA than HCA cases (9% vs. 45%, P < 0·01). Clinicians should be aware of Acinetobacter as a potential cause of community-associated infections in Thailand; prospective studies are needed to improve understanding of associated risk factors and disease burden.