Genetic dissection of photoperiod response based on GWAS of pre-anthesis phase duration in spring barley

Heading time is a complex trait, and natural variation in photoperiod responses is a major factor controlling time to heading, adaptation and grain yield. In barley, previous heading time studies have been mainly conducted under field conditions to measure total days to heading. We followed a novel approach and studied the natural variation of time to heading in a world-wide spring barley collection (218 accessions), comprising of 95 photoperiod-sensitive (Ppd-H1) and 123 accessions with reduced photoperiod sensitivity (ppd-H1) to long-day (LD) through dissecting pre-anthesis development into four major stages and sub-phases. The study was conducted under greenhouse (GH) conditions (LD; 16/8 h; ∼20/∼16°C day/night). Genotyping was performed using a genome-wide high density 9K single nucleotide polymorphisms (SNPs) chip which assayed 7842 SNPs. We used the barley physical map to identify candidate genes underlying genome-wide association scans (GWAS). GWAS for pre-anthesis stages/sub-phases in each photoperiod group provided great power for partitioning genetic effects on floral initiation and heading time. In addition to major genes known to regulate heading time under field conditions, several novel QTL with medium to high effects, including new QTL having major effects on developmental stages/sub-phases were found to be associated in this study. For example, highly associated SNPs tagged the physical regions around HvCO1 (barley CONSTANS1) and BFL (BARLEY FLORICAULA/LEAFY) genes. Based upon our GWAS analysis, we propose a new genetic network model for each photoperiod group, which includes several newly identified genes, such as several HvCO-like genes, belonging to different heading time pathways in barley

Evaluation of the safety of C-spine clearance by paramedics: design and methodology

<p>Abstract</p> <p>Background</p> <p>Canadian Emergency Medical Services annually transport 1.3 million patients with potential neck injuries to local emergency departments. Less than 1% of those patients have a c-spine fracture and even less (0.5%) have a spinal cord injury. Most injuries occur before the arrival of paramedics, not during transport to the hospital, yet most patients are transported in ambulances immobilized. They stay fully immobilized until a bed is available, or until physician assessment and/or X-rays are complete. The prolonged immobilization is often unnecessary and adds to the burden of already overtaxed emergency medical services systems and crowded emergency departments.</p> <p>Methods/Design</p> <p>The goal of this study is to evaluate the safety and potential impact of an active strategy that allows paramedics to assess very low-risk trauma patients using a validated clinical decision rule, the Canadian C-Spine Rule, in order to determine the need for immobilization during transport to the emergency department.</p> <p>This cohort study will be conducted in Ottawa, Canada with one emergency medical service. Paramedics with this service participated in an earlier validation study of the Canadian C-Spine Rule. Three thousand consecutive, alert, stable adult trauma patients with a potential c-spine injury will be enrolled in the study and evaluated using the Canadian C-Spine Rule to determine the need for immobilization. The outcomes that will be assessed include measures of safety (numbers of missed fractures and serious adverse outcomes), measures of clinical impact (proportion of patients transported without immobilization, key time intervals) and performance of the Rule.</p> <p>Discussion</p> <p>Approximately 40% of all very low-risk trauma patients could be transported safely, without c-spine immobilization, if paramedics were empowered to make clinical decisions using the Canadian C-Spine Rule. This safety study is an essential step before allowing all paramedics across Canada to selectively immobilize trauma victims before transport. Once safety and potential impact are established, we intend to implement a multi-centre study to study actual impact.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01188447">NCT01188447</a></p

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Cost-effectiveness of adding vaccination with the AS04-adjuvanted human papillomavirus 16/18 vaccine to cervical cancer screening in Hungary

<p>Abstract</p> <p>Background</p> <p>The cervical cancer screening program implemented in Hungary to date has not been successful. Along with screening, vaccination is an effective intervention to prevent cervical cancer. The aim of this study was to assess the cost-effectiveness of adding vaccination with the human papillomavirus 16/18 vaccine to the current cervical cancer screening program in Hungary.</p> <p>Methods</p> <p>We developed a cohort simulation state-transition Markov model to model the life course of 12-year-old girls. Eighty percent participation in the HPV vaccination program at 12 years of age was assumed. Transitional probabilities were estimated using data from the literature. Local data were used regarding screening participation rates, and the costs were estimated in US $. We applied the purchasing power parity exchange rate of 129 HUF/$ to the cost data. Only direct health care costs were considered. We used a 3.7% discount rate for both the cost and quality-adjusted life years (QALYs). The time horizon was 88 years.</p> <p>Results</p> <p>Inclusion of HPV vaccination at age 12 in the cervical cancer prevention program was predicted to be cost-effective. The incremental cost-effectiveness ratio (ICER) of adding HPV vaccination to the current national cancer screening program was estimated to be 27 588 $/QALY. The results were sensitive to the price of the vaccine, the discount rate, the screening participation rate and whether herd immunity was taken into account.</p> <p>Conclusions</p> <p>Our modeling analysis showed that the vaccination of 12-year-old adolescent girls against cervical cancer with the AS04-adjuvanted human papillomavirus 16/18 vaccine would be a cost-effective strategy to prevent cervical cancer in Hungary.</p