A cattle graph genome incorporating global breed diversity.

Despite only 8% of cattle being found in Europe, European breeds dominate current genetic resources. This adversely impacts cattle research in other important global cattle breeds, especially those from Africa for which genomic resources are particularly limited, despite their disproportionate importance to the continent's economies. To mitigate this issue, we have generated assemblies of African breeds, which have been integrated with genomic data for 294 diverse cattle into a graph genome that incorporates global cattle diversity. We illustrate how this more representative reference assembly contains an extra 116.1 Mb (4.2%) of sequence absent from the current Hereford sequence and consequently inaccessible to current studies. We further demonstrate how using this graph genome increases read mapping rates, reduces allelic biases and improves the agreement of structural variant calling with independent optical mapping data. Consequently, we present an improved, more representative, reference assembly that will improve global cattle research.

Survival and variability over time from out of hospital cardiac arrest across large geographically diverse communities participating in the Resuscitation Outcomes Consortium.

BACKGROUND: The Resuscitation Outcomes Consortium (ROC)epidemiological registry (Epistry) provides opportunities to assess trends in out-of-hospital cardiac arrest treatment and outcomes. METHODS: Patient, event, system, treatment, and outcome data from adult (≥18 years) out-of-hospital cardiac arrest (OHCA) from 10 geographically diverse North American ROC sites over four 12-month epochs, from July 1, 2011 to June 30, 2015, were assessed. Descriptive statistics were used to characterize the sample and logistic regression assessed the association of study epoch and key covariates on survival. RESULTS: Overall, 85,553 patients were assessed by Emergency Medical Services (EMS) and 45,516 (53.2%, site range 30.4%-69.9%) had resuscitation attempted by EMS. Patient and event characteristics were consistent except for increases in bystander CPR (41.3%-44.9%) and bystander AED application (3.9%-5.2%). EMS CPR depth and compression fraction increased while pre-shock pause interval decreased. Targeted temperature management was performed in 51.1% of admitted patients and early coronary angiography in 30.2%. Survival to hospital discharge improved (from 10.9% to 11.3% across epochs) with epoch significantly associated with survival (p < 0.001) showing an increasing trend in survival over time. (p = 0.02). Marked site variation in survival persisted within and across epochs (overall site range: 4.2%-19.8%). Patients with an initially shockable rhythm (VT/VF) had an overall survival of 32.2% (site range: 11.9%-47.1%) while survival in bystander witnessed VT/VF was 35.8% (site range: 12.9%-53.1%). CONCLUSIONS: Survival from adult OHCA in multiple large geographically-separate sites improved over the study period. Marked site differences in survival persist and addressing this variation is essential to improve outcomes from OHCA across North America.

Prehospital cooling to improve successful targeted temperature management after cardiac arrest: A randomized controlled trial.

RATIONALE: Targeted temperature management (TTM) improves survival with good neurological outcome after out-of-hospital cardiac arrest (OHCA), but is delivered inconsistently and often with delay. OBJECTIVE: To determine if prehospital cooling by paramedics leads to higher rates of 'successful TTM', defined as achieving a target temperature of 32-34°C within 6h of hospital arrival. METHODS: Pragmatic RCT comparing prehospital cooling (surface ice packs, cold saline infusion, wristband reminders) initiated 5min after return of spontaneous circulation (ROSC) versus usual resuscitation and transport. The primary outcome was rate of 'successful TTM'; secondary outcomes were rates of applying TTM in hospital, survival with good neurological outcome, pulmonary edema in emergency department, and re-arrest during transport. RESULTS: 585 patients were randomized to receive prehospital cooling (n=279) or control (n=306). Prehospital cooling did not increase rates of 'successful TTM' (30% vs 25%; RR, 1.17; 95% confidence interval [CI] 0.91-1.52; p=0.22), but increased rates of applying TTM in hospital (68% vs 56%; RR, 1.21; 95%CI 1.07-1.37; p=0.003). Survival with good neurological outcome (29% vs 26%; RR, 1.13, 95%CI 0.87-1.47; p=0.37) was similar. Prehospital cooling was not associated with re-arrest during transport (7.5% vs 8.2%; RR, 0.94; 95%CI 0.54-1.63; p=0.83) but was associated with decreased incidence of pulmonary edema in emergency department (12% vs 18%; RR, 0.66; 95%CI 0.44-0.99; p=0.04). CONCLUSIONS: Prehospital cooling initiated 5min after ROSC did not increase rates of achieving a target temperature of 32-34°C within 6h of hospital arrival but was safe and increased application of TTM in hospital.

Systematic review and meta-analysis of hemodynamic-directed feedback during cardiopulmonary resuscitation in cardiac arrest.

BACKGROUND/OBJECTIVE: Physiologic monitoring of resuscitative efforts during cardiac arrest is gaining in importance, as it provides a real-time window into the cellular physiology of patients. The aim of this review is to assess the quality of evidence surrounding the use of physiologic monitoring to guide cardiopulmonary resuscitation (CPR), and to examine whether the evidence demonstrates an improvement in patient outcome when comparing hemodynamic-directed CPR versus standard CPR. METHODS: Studies were obtained through a search of the PubMed, Embase and Cochrane databases. Peer-reviewed randomized trials, case-control studies, systematic reviews, and cohort studies that titrated CPR to physiologic measures, compared results to standard CPR, and examined patient outcome were included. RESULTS: Six studies met inclusion criteria, with all studies conducted in animal populations. Four studies examined the effects of hemodynamic-directed CPR on survival, with 35/37 (94.6%) animals surviving in the hemodynamic-directed CPR groups and 12/35 (34.3%) surviving in the control groups (p<0.001). Two studies examined the effects of hemodynamic-directed CPR on ROSC, with 22/30 (73.3%) achieving ROSC in the hemodynamic-directed CPR group and 19/30 (63.3%) achieving ROSC in the control group (p=0.344). DISCUSSION/CONCLUSION: These results suggest a trend in survival from hemodynamic-directed CPR over standard CPR, however the small sample size and lack of human data make these results of limited value. Future human studies examining hemodynamic-directed CPR versus current CPR standards are needed to enhance our understanding of how to effectively use physiologic measures to improve resuscitation efforts and ultimately incorporate concrete targets into international resuscitation guidelines.

Cattle trypanosomosis: the diversity of trypanosomes and implications for disease epidemiology and control.

Trypanosomosis is one of the most significant infectious threats to cattle in sub-Saharan Africa, and one form has also spread to Asia and South America. The disease is caused by a complex of trypanosome species, and the species and strain of parasite can have a profound influence upon the epidemiology of the host-parasite-vector relationships, the severity and course of infection, and, consequently, the implementation and development of control methods. This review will summarise our current knowledge of the relationship between trypanosome species/genotype and the phenotype of disease in cattle, and the implications that this has for ongoing efforts to develop diagnostics, drugs and vaccines for the control of cattle trypanosomosis.

The Canadian National EMS Research Agenda: Impact and Feasibility of Implementation of Previously Generated Recommendations.

BACKGROUND: A recent mixed-methods study on the state of emergency medical services (EMS) research in Canada led to the generation of nineteen actionable recommendations. As part of the dissemination plan, a survey was distributed to EMS stakeholders to determine the anticipated impact and feasibility of implementing these recommendations in Canadian systems. METHODS: An online survey explored both the implementation impact and feasibility for each recommendation using a five-point scale. The sample consisted of participants from the Canadian National EMS Research Agenda study (published in 2013) and additional EMS research stakeholders identified through snowball sampling. Responses were analysed descriptively using median and plotted on a matrix. Participants reported any planned or ongoing initiatives related to the recommendations, and required or anticipated resources. Free text responses were analysed with simple content analysis, collated by recommendation. RESULTS: The survey was sent to 131 people, 94 (71.8%) of whom responded: 30 EMS managers/regulators (31.9%), 22 researchers (23.4%), 15 physicians (16.0%), 13 educators (13.8%), and 5 EMS providers (5.3%). Two recommendations (11%) had a median impact score of 4 (of 5) and feasibility score of 4 (of 5). Eight recommendations (42%) had an impact score of 5, with a feasibility score of 3. Nine recommendations (47%) had an impact score of 4 and a feasibility score of 3. CONCLUSIONS: For most recommendations, participants scored the anticipated impact higher than the feasibility to implement. Ongoing or planned initiatives exist pertaining to all recommendations except one. All of the recommendations will require additional resources to implement.

IR action spectroscopy shows competitive oxazolone and diketopiperazine formation in peptides depends on peptide length and identity of terminal residue in the departing fragment.

The interplay between the entropically and enthalpically favored products of peptide fragmentation is probed using a combined experimental and theoretical approach. These b2 ion products can take either an oxazolone or diketopiperazine structure. Cleavage after the second amide bond is often a favorable process because the products are small ring structures that are particularly stable. These structures are structurally characterized by action IRMPD spectroscopy and semi-quantified using gas-phase hydrogen-deuterium exchange. The formation of the oxazolone and diketopiperazine has been thought to be largely governed by the identity of the first two residues at the N-terminus of the peptide. We show here that the length of the precursor peptide and identity of the third residue play a significant role in the formation of the diketopiperazine structure in peptides containing an N-terminal asparagine residue. This is additionally the first instance showing an N-terminal residue with an amide side chain can promote formation of the diketopiperazine b2 ion structure.

Are the 2010 guidelines on cardiopulmonary resuscitation lost in translation? A call for increased focus on implementation science.

Despite significant resources spent on rigorous evidence review and resuscitation guideline development, an important gap remains in our understanding of effective strategies and tools for implementing resuscitation guidelines. The lack of evidence about effective guideline implementation for resuscitation is likely reducing the impact of the incredible amount of work that goes into the production of such guidelines. This commentary draws attention to knowledge translation learnings from other content areas and within the area of resuscitation science to support a call for increased attention and innovation in implementation science as an equally important investment for the future of resuscitation medicine.

Parasite-driven pathogenesis in Trypanosoma brucei infections.

Trypanosomes are protozoan parasites of medical and veterinary importance. It is well established that different species, subspecies and strains of trypanosome can cause very different disease in the mammalian host, exemplified by the two human-infective subspecies of Trypanosoma brucei that cause either acute or chronic disease. We are beginning to understand how the host response shapes the course of the disease and how genetic variation in the host can be a factor in disease severity, particularly in the mouse model, but until recently the role of parasite genetic variation that determines differential disease outcome has been a neglected area. This review will discuss the recent advances in this field, covering both our current knowledge of the T. brucei genes involved and the approaches that are leading towards the identification of T. brucei virulence genes. Finally, the potential for using parasite genotype variation to examine the evolutionary context of virulence will be discussed.

What the genome sequence is revealing about trypanosome antigenic variation.

African trypanosomes evade humoral immunity through antigenic variation, whereby they switch expression of the gene encoding their VSG (variant surface glycoprotein) coat. Switching proceeds by duplication of silent VSG genes into a transcriptionally active locus. The genome project has revealed that most of the silent archive consists of hundreds of subtelomeric VSG tandem arrays, and that most of these are not functional genes. Precedent suggests that they can contribute combinatorially to the formation of expressed, functional genes through segmental gene conversion. These findings from the genome project have major implications for evolution of the VSG archive and for transmission of the parasite in the field.

International Resuscitation Network Registry: design, rationale and preliminary results.

There is a lack of high-quality information about the effectiveness of resuscitation interventions and international differences in structure, process and outcome after out-of-hospital cardiac arrest and cardiopulmonary resuscitation because data are not collected uniformly. An internet-based international registry could make such evaluations possible, and enable the conduct of large randomized controlled trials of resuscitation therapies. A prospective international cohort study was performed that included 571 infants, children and adults (a) who experienced cardiac arrest requiring chest compressions or external defibrillation, (b) outside the hospital in the study communities and (c) upon whom resuscitation was attempted by EMS personnel. Cardiac arrest was defined as lack of responsiveness, breathing or movement in individuals for whom the EMS system is activated for whom an arrest record is completed. All data were collated via a secure and confidential web-based method by using automated forms processing software with appropriate variable range checks, logic checks and skip rules. Median number of missing responses for each variable was 0 (interquartile range 0, 0). Twenty-seven percent of the patients had a first recorded rhythm of ventricular fibrillation or ventricular tachycardia, 60% had a witnessed arrest, and 34% received bystander CPR. Mean time from call to arrival on scene was 7.1+/-5.1 min. Six percent of the patients survived to hospital discharge. The resuscitation process was highly variable across centers, and survival and neurological outcome were also significantly and independently different across centers. This study shows that it is possible to collect data prospectively describing the structure, process and outcome associated with cardiac arrest in multiple international sites via the internet. Therefore, it is feasible to conduct adequately powered randomized trials of resuscitation therapies in international settings.

Clinical value of obtaining sputum and cough swab samples following inhaled hypertonic saline in children with cystic fibrosis.

Prompt detection and treatment of lower respiratory tract infection are essential in the management of patients with cystic fibrosis (CF), who often have signs or symptoms of respiratory infection without any pathogens being isolated from sputum or cough swab specimens. The aims of this study were to assess the efficacy and clinical value of obtaining sputum and oropharyngeal cough swab samples following induction with hypertonic saline (HS) in this group of patients. Forty-three outpatients with CF, mean age 7.2 years (range, 1.8-12.9 years), were recruited over a 2-year period. Nebulized salbutamol was administered, followed by 6% HS. Sputum was preferentially obtained before and after HS induction if possible. If the patient was not able to expectorate, oropharyngeal cough swabs were taken instead. Four patients were able to expectorate sputum before and 19 after HS induction. The procedure was tolerated in 41 of 43 patients. Pathogens were isolated from 13 patients' HS-induced samples, but not from their corresponding preinduced specimens, and 4 patients' preinduced specimens cultured organisms which were not identified from their HS-induced samples. Significant changes were made in the management of 13 (30.2%) patients directly resulting from the positive culture of pathogens only from HS-induced samples. Cultures from oropharyngeal cough swab or expectorated sputum specimens following inhalation of HS provide additional microbiological information which is of clinical value and may lead to changes in patient management.

Conversion rates for prehospital paroxysmal supraventricular tachycardia (PSVT) with the addition of adenosine: a before-and-after trial.

OBJECTIVE: To determine whether the prehospital administration of adenosine to adults with stable and unstable paroxysmal supraventricular tachycardia (PSVT) influences conversion rate (CR) to sinus rhythm, scene time, use of synchronized electrical cardioversion (SEC), and accuracy of rhythm strip interpretation by paramedics. METHODS: This before-and-after study compared a retrospective control group (CG) prior to the introduction of adenosine with a prospective treatment group (TG) following the addition of adenosine to the PSVT treatment protocol in a large urban advanced life support emergency medical services system. The population represented patients > or = 18 years of age with PSVT diagnosed by the paramedic (defined as spontaneous onset of a regular narrow-complex tachycardia between 140 and 250 beats/minute). RESULTS: The CG comprised 74 calls and the TG 137 calls. The overall CR was higher in the TG (59% vs 32%, p < 0.001). The SEC and spontaneous conversion rates remained unchanged. The proportion of untreated patients with PSVT decreased from 26% CG to 12% TG (p < 0.01). Scene times were longer in the TG (26 vs 19 minutes, p < 0.001). Agreement between paramedic and physician rhythm strip interpretations was fair to moderate (CG kappa 0.43 [95% CI: 0.14, 0.72]; TG kappa 0.37 [95% CI: 0.13, 0.61]). CONCLUSIONS: The introduction of adenosine was associated with a significant increase in the prehospital CR of stable and unstable PSVT, while the SEC and spontaneous conversion rates were similar in each group; however, scene times were longer in the TG and paramedic accuracy in rhythm strip interpretation remained fair to moderate.

Redefining emergency medicine procedures: Canadian competence and frequency survey.

OBJECTIVE: To redefine the Royal College of Physicians and Surgeons (RCPS) procedural skills list for Canadian emergency medicine (EM) residents through a national survey of EM specialists to determine procedural performance frequency and self-assessment of competence. METHODS: The survey instrument was developed in three phases: 1) an EM program directors survey identified inappropriate or dated procedures, endorsing 127 skills; 2) a search of EM literature added 98 skills; and 3) an expert panel designed the survey instrument and finalized a list of 150 skills. The survey instrument measured the frequency of procedure performance or supervision, self-reported competence (yes/no), and endorsement of one of four training levels for each skill: undergraduate (UG), postgraduate (PG), knowledge only, or unnecessary (i.e., too infrequently performed to maintain competence). RESULTS: All 289 Canadian EM specialists were surveyed by mail; 231 (80%) responded, 221 completed surveys, and 10 were inactive. More than 60% reported competence in 125 (83%) procedures, and 55 procedures were performed at least three times a year. The mean competence score was 121 (SD +/- 17.7, median = 122) procedures. Competence score correlation with patient volume was r = 0.16 (p = 0.02) and with hours worked was r = 0.19 (p = 0.01). Competence score was not associated with year or route (residency vs grandfather) of certification. Each procedure was assigned to a training level using response consensus and decision rules (UG: 1%; PG: 82%; unnecessary: 17%). CONCLUSIONS: A survey of EM clinicians reporting competence and frequency of skill performance defined 127 procedural skills appropriate for Canadian RCPS postgraduate training and EM certification.

Improving the emergency department detection rate of domestic violence using direct questioning.

The purpose of this study was to compare the domestic violence (DV) rate identified with simple direct questioning to a historical cohort of patients receiving routine emergency department (ED) care. One thousand ED charts of female patients were retrospectively reviewed. Each patient in the prospective cohort was asked five DV specific questions. The historical cohort revealed a DV prevalence rate of 0.4%. The prospective study group of 302 patients identified 11 (3.6%) patients who admitted to acute DV on direct questioning. Ten of these patients accepted help. Twenty (6.6%) were identified as probable DV and 12 (4%) admitted to past violence. The total number of victims of DV, past, present, and probable was 43 (14.2%). This increase in detection from 0.4% (4/1000) to 14.2% (43/302) is significant at p < 0.001. Only 1.3% of patients refused to participate in the DV specific questions. The conclusion of the study indicated that the use of simple, direct questioning significantly improves the detection rate of DV in the ED.

Mortality and prehospital thrombolysis for acute myocardial infarction: A meta-analysis.

CONTEXT: Early administration of thrombolysis for acute myocardial infarction (AMI) may improve survival if safely and appropriately delivered. No systematic reviews that have comprehensively examined this topic exist in the literature. OBJECTIVE: To perform a meta-analysis of randomized controlled trials of prehospital vs in-hospital thrombolysis for AMI measuring in-hospital mortality. DATA SOURCES: The Cochrane search strategy was used to search MEDLINE, EMBASE, and the Science Citation Index (1982-1999); Dissertation Abstracts (1987-1999); and Current Contents (1994-1999) for the terms thrombolysis, thrombolysis therapy, prehospital, and acute myocardial infarction. In addition, text and journal article bibliographies were hand searched, the National Institutes of Health Web site was reviewed, and primary authors and thrombolytic drug manufacturers were contacted for unpublished studies. STUDY SELECTION: Randomized controlled trials of prehospital vs in-hospital thrombolysis for AMI measuring all-cause hospital mortality were included. Two authors independently reviewed 175 citations by title, abstract, or complete article. After exclusion of 30 duplicate citations, 145 studies remained, of which 6 studies and 3 follow-up studies met the inclusion criteria. DATA EXTRACTION: Independent data abstraction by 2 reviewers blinded to the journal, title, and author was confirmed by consensus. Trial quality was independently assessed by 2 other coauthors, blinded to the author, title, journal, introduction, and discussion. DATA SYNTHESIS: The results of the 6 randomized trials (n=6434) were pooled and indicated significantly decreased all-cause hospital mortality among patients treated with prehospital thrombolysis compared with in-hospital thrombolysis (odds ratio, 0.83; 95% confidence interval, 0.70-0.98). Results were similar regardless of trial quality or training and experience of the provider. Estimated (SE) time to thrombolysis was 104 (7) minutes for the prehospital group and 162 (16) minutes for the in-hospital thrombolysis group (P=.007). CONCLUSIONS: Our meta-analysis suggests that prehospital thrombolysis for AMI significantly decreases the time to thrombolysis and all-cause hospital mortality. JAMA. 2000;283:2686-2692.

Facial composite production: a comparison of mechanical and computer-driven systems.

Computer-driven systems for constructing composite faces of suspects (E-fit; Mac-a-Mug) have largely replaced mechanical systems (Photofit; the Identikit) in police use, yet little is known of their comparative effectiveness in rendering an accurate likeness. Participants (N = 24) constructed 2 of 4 familiar or unfamiliar faces, for one of which they used Photofit and for the other, E-fit. A likeness of each face was made first under target-absent conditions and then with photographs of the target present. The accuracy of the resulting composites was assessed by familiarity ratings, names elicited, and matching accuracy. The computer-driven system showed consistent superiority only when a familiar face was constructed in the presence of photographs; when participants worked from memory, E-fit was no better than Photofit. The implications of these findings for theories of face retrieval and the operational use of composites are discussed.