Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

Academic selection and Northern Ireland

An overview of research and public policy debate on academic selection in Northern Ireland. The chapter examines the outcomes of the major investigation of the effects of the selective system of secondary education published in 2000, including a consideration of comparative evidence collected in Scotland. The paper outlines the debate which followed the publication of the Burns Report and presents the current state of play in policy and practice.

Academic and Practitioners perspectives on Organisation Development – a UK study

This paper reports on a research study to identify the nature of the profession of Organisation Development (OD) in the UK and how it has evolved over four decades. The study is designed to compare academic perspectives on OD with what is happening in the professional practice world. Three forms of data were collected for this study, content analysis of job advertisements from a four decade period, a bibliometric search and interviews with subject experts. The findings were analysed through the theory lens of institutional theory, the dissemination of ideas and fads and fashions in management. Emerging insights are that there is a difference between academic and practitioners development of the OD profession in the UK. The reasons for the difference have been explored in the discussion.

Technological aids for the rehabilitation of memory and executive functioning in children and adolescents with acquired brain injury (Review).

Background The use of technology in healthcare settings is on the increase and may represent a cost-effective means of delivering rehabilitation. Reductions in treatment time, and delivery in the home, are also thought to be benefits of this approach. Children and adolescents with brain injury often experience deficits in memory and executive functioning that can negatively affect their school work, social lives, and future occupations. Effective interventions that can be delivered at home, without the need for high-cost clinical involvement, could provide a means to address a current lack of provision. We have systematically reviewed studies examining the effects of technology-based interventions for the rehabilitation of deficits in memory and executive functioning in children and adolescents with acquired brain injury. Objectives To assess the effects of technology-based interventions compared to placebo intervention, no treatment, or other types of intervention, on the executive functioning and memory of children and adolescents with acquired brain injury. Search methods We ran the search on the 30 September 2015. We searched the Cochrane Injuries Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic + EMBASE (OvidSP), ISI Web of Science (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), CINAHL Plus (EBSCO), two other databases, and clinical trials registers. We also searched the internet, screened reference lists, and contacted authors of included studies. Selection criteria Randomised controlled trials comparing the use of a technological aid for the rehabilitation of children and adolescents with memory or executive-functioning deficits with placebo, no treatment, or another intervention. Data collection and analysis Two review authors independently reviewed titles and abstracts identified by the search strategy. Following retrieval of full-text manuscripts, two review authors independently performed data extraction and assessed the risk of bias. Main results Four studies (involving 206 participants) met the inclusion criteria for this review. Three studies, involving 194 participants, assessed the effects of online interventions to target executive functioning (that is monitoring and changing behaviour, problem solving, planning, etc.). These studies, which were all conducted by the same research team, compared online interventions against a 'placebo' (participants were given internet resources on brain injury). The interventions were delivered in the family home with additional support or training, or both, from a psychologist or doctoral student. The fourth study investigated the use of a computer program to target memory in addition to components of executive functioning (that is attention, organisation, and problem solving). No information on the study setting was provided, however a speech-language pathologist, teacher, or occupational therapist accompanied participants. Two studies assessed adolescents and young adults with mild to severe traumatic brain injury (TBI), while the remaining two studies assessed children and adolescents with moderate to severe TBI. Risk of bias We assessed the risk of selection bias as low for three studies and unclear for one study. Allocation bias was high in two studies, unclear in one study, and low in one study. Only one study (n = 120) was able to conceal allocation from participants, therefore overall selection bias was assessed as high. One study took steps to conceal assessors from allocation (low risk of detection bias), while the other three did not do so (high risk of detection bias). Primary outcome 1: Executive functioning: Technology-based intervention versus placebo Results from meta-analysis of three studies (n = 194) comparing online interventions with a placebo for children and adolescents with TBI, favoured the intervention immediately post-treatment (standardised mean difference (SMD) -0.37, 95% confidence interval (CI) -0.66 to -0.09; P = 0.62; I2 = 0%). (As there is no 'gold standard' measure in the field, we have not translated the SMD back to any particular scale.) This result is thought to represent only a small to medium effect size (using Cohen’s rule of thumb, where 0.2 is a small effect, 0.5 a medium one, and 0.8 or above is a large effect); this is unlikely to have a clinically important effect on the participant. The fourth study (n = 12) reported differences between the intervention and control groups on problem solving (an important component of executive functioning). No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. The quality of evidence for this outcome according to GRADE was very low. This means future research is highly likely to change the estimate of effect. Primary outcome 2: Memory One small study (n = 12) reported a statistically significant difference in improvement in sentence recall between the intervention and control group following an eight-week remediation programme. No means or standard deviations were presented for this outcome, therefore an effect size could not be calculated. Secondary outcomes Two studies (n = 158) reported on anxiety/depression as measured by the Child Behavior Checklist (CBCL) and were included in a meta-analysis. We found no evidence of an effect with the intervention (mean difference -5.59, 95% CI -11.46 to 0.28; I2 = 53%). The GRADE quality of evidence for this outcome was very low, meaning future research is likely to change the estimate of effect. A single study sought to record adverse events and reported none. Two studies reported on use of the intervention (range 0 to 13 and 1 to 24 sessions). One study reported on social functioning/social competence and found no effect. The included studies reported no data for other secondary outcomes (that is quality of life and academic achievement). Authors' conclusions This review provides low-quality evidence for the use of technology-based interventions in the rehabilitation of executive functions and memory for children and adolescents with TBI. As all of the included studies contained relatively small numbers of participants (12 to 120), our findings should be interpreted with caution. The involvement of a clinician or therapist, rather than use of the technology, may have led to the success of these interventions. Future research should seek to replicate these findings with larger samples, in other regions, using ecologically valid outcome measures, and reduced clinician involvement.

Explaining the success of karmic religions

One of the central claims of Norenzayan et al.’s article is that supernatural monitoring and intergroup competition have facilitated the rise of large-scale prosocial religions. Although the authors outline in detail how social instincts that govern supernatural monitoring are honed by cultural evolution and have given rise to Big Gods, they do not provide a clear explanation for the success of karmic religions. Therefore, to test the real scope of their model, Norenzayan et al. need to seriously engage with questions concerning the evolution of karmic prosocial religions.

Factors influencing the success of rural cataract surgery programs in China:The study of hospital administration and relative productivity (SHARP)

PURPOSE. To explore factors potentially influencing the success or failure of rural Chinese hospitals in increasing cataract surgical output and quality. METHODS. Focus groups (FGs, n = 10) were conducted with hospital administrators, doctors, and nurses at 28 county hospitals in Guangdong Province. Discussions explored respondents' views on increasing surgical volume and quality and improving patient satisfaction. Respondents numerically ranked possible strategies to increase surgical volume and quality and patient satisfaction. FG transcripts were independently coded by two reviewers utilizing the constant comparative method following the grounded theory approach, and numerical responses were scored and ranked. RESULTS. Ten FGs and 77 ranking questionnaires were completed by 33 administrators, 23 doctors, and 21 nurses. Kappa values for the two coders were greater than 0.7 for all three groups. All groups identified a critical need for enhanced management training for hospital directors. Doctors and nurses suggested reducing surgical fees to enhance uptake, although administrators were resistant to this. Although doctors saw the need to improve equipment, administrators felt current material conditions were adequate. Respondents agreed that patient satisfaction was generally high, and did not view increasing patient satisfaction as a priority. CONCLUSIONS. Our findings highlight agreements and disagreements among the three stakeholder groups about improving surgical output and quality, which can inform strategies to improve cataract programs in rural China. Respondents' beliefs about high patient satisfaction are not in accord with other studies in the area, highlighting a potential area for intervention. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Outcomes of surgical bleb revision for complications of trabeculectomy.

OBJECTIVE: To describe the results of revision surgery for complications of trabeculectomy in a case series from an academic glaucoma service. DESIGN: Retrospective case series. PARTICIPANTS: A total of 177 eyes of 167 adult patients who underwent revision of trabeculectomy at the Wilmer Eye Institute between 1994 and 2007. METHODS: Three indications for surgery were identified: hypotony without leak, bleb leak, and bleb dysesthesia. Revision was deemed successful when all of the following were true: the primary indication was eliminated, further intraocular pressure (IOP)-lowering surgery was not required, no major complication occurred, and a new bleb-related problem did not develop. Patients with less than 3 months of follow-up were excluded unless failure occurred earlier. Surgical procedures included variations on excision of thin or leaking conjunctiva with advancement. MAIN OUTCOME MEASURES: Change in IOP, change in visual acuity, need for further IOP-lowering surgery, and complications after bleb revision. RESULTS: Subjects' mean age was 67+/-14 years, 54% were female, and mean follow-up was 2.8+/-2.7 years, with a mean interval from trabeculectomy to revision of 3.5+/-3.7 years. Overall success rate was 63% (112/177), which was slightly higher for leak repair (65%; 64/98) and hypotony (63%; 32/51) than for dysesthesia (57%; 16/28) indications. By Kaplan-Meier analysis, overall cumulative success rates at 1, 2, 5, and 10 years after bleb revision were 80%, 75%, 50%, and 41%, respectively. IOP and visual acuity improved significantly in both hypotony and leak groups (P values ranging from 0.004 to <0.0001). Additional IOP-lowering surgery was required in 9%. In multivariate regression analysis adjusting for age, gender, and number of prior surgeries, patients with glaucoma other than primary open-angle glaucoma were twice as likely to have failed bleb revision. CONCLUSIONS: Surgical bleb revision often provides successful resolution of bleb-related complications. Most patients maintain IOP control without need for further IOP-lowering surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Reproductive success of parasitized males in a marine reef fish

Parasitism is hypothesized to reduce reproductive success in heavily parasitized males because females
may preferentially mate with less parasitized males (parasite-mediated sexual selection) or parasites may compromise
male competitiveness. In marine systems, this hypothesis is largely unexplored. This paper provides the first confirmed record of a copepod ectoparasite (Caligus buechlerae Hewitt 1964) on the common triplefin (Forsterygion lapillum) and evaluates the hypothesis that males parasitized with C. buechlerae experience lower reproductive success than unparasitized males (as determined
by the presence and area of eggs within male nests). We found that 38 % of males we surveyed were infected with
at least one C. buechlerae, with a median of two individuals per infected male. About 32 % of males were defending
eggs, with 62.5 % of those males infected with at least one parasite. Males of greater total length (TL) were both
more likely to be infected and more likely to be defending eggs. However, when statistically accounting for the effects
of TL, parasite infection had no effect on the probability of defending eggs, or the average surface area of eggs when
present. Positive covariation in fish length, the presence of eggs and parasite infection observed here potentially suggest
that the importance of parasitic infection on reproductive success may depend upon the strength of selection for larger male body size. Our study is one of the few studies to investigate the effects of ectoparasites on reproductive success in reef fish and also provides a quantitative measure of infection for a widespread species within New Zealand.

The Effect of Seat Location in Lecture Theatres on Academic Performance

The purpose of this research study was to investigate and identify possible patterns relating to academic performance on the effects of university students self-selecting where to sit in a lecture theatre.
The key research questions are:
1. Does seating position affect student performance?
2. Do the most academically able and engaged students regularly sit at the front of lecture theatres?
Academic achievement
Preliminary results suggest significant assessment score differences between those that sit at the front and those that sit further the back. Of those that received a grade of 75%+ (Grade A) 6.67% regularly sat at the back. With the same group 46.67% regularly sat at the front. Of the group that scored less than 50% (Grade D) 0% of students regularly sat at the front. 12.50% regularly sat in the middle zones with 37.50% sitting at the back. It was also observed that the remaining numbers did not consistently sit in the same zone.

Temporal movement
There is little evidence of movement between seating zones of the Grade A group throughout the 24 week period. However there was considerable movement with the Grade D group. Although still under analysis there appears be a pattern of students in this group graduating towards the back seating positions over the course of the programme.

Engagement
The frequency of completed entries on PinPoint was also used as an indicator of engagement. With the Grade A group 75% of them regularly completed an entry whereas in the Grade D group this drops to less than 50%.
Further analysis on the attitudinal factors in relational to seating position and performance are ongoing, but preliminary results suggest that those students that scored highly in attitude tended to sit at the front and middle sections.
It would indeed appear that the more highly engaged and academically capable students voluntarily sit at the front for most lectures. Interestingly as the course progresses those who had lesser engagement and below average midterm results tend to began to sit progressively toward the back. If this is a repeatable pattern then a linear regression analysis of the seating positions and midterm results could help predict students in danger of failing.

Critical Success Factors of Construction Project Quality in Brunei Darussalam

This research concentrates on the critical success factors driving construction quality and the barriers that must be overcome to achieve quality in Brunei. It hopes to identify methods of quality improvement and clearly justify investment in this area of local industry. Over the past number of years, Brunei has attempted to diversify its industry from the dominant oil and gas sector into secondary sectors,
including construction. To date, very little research has been carried out in many areas of construction management that take into account the specific industry context in Brunei. A comprehensive literature review has been employed to enable a questionnaire to be constructed and distributed among Brunei construction
professionals. The results have been analyzed through mean testing. This analysis reveals that the key barriers to construction quality in Brunei relate to lack of skills, lack of clarity in responsibility and communication and poor commitment among the design team. The critical success factors include issues relating to competency, capability, commitment and effectiveness, primarily among managers and decision-makers. The results of this study will hopefully contribute to fill the knowledge gap related to construction management in the context of Brunei and facilitate movement towards improved techniques and strategies that will foster higher quality in construction. The findings can be generalised across similar
developing economies and it is suggested that in general, the management concepts governing construction quality remain similar across the borders of East and West.