Educational outcomes in extremely preterm children : neuropsychological correlates and predictors of attainment

This study assessed the impact of extremely preterm birth on academic attainment at 11 years of age, investigated neuropsychological antecedents of attainment in reading and mathematics, and examined early predictors of educational outcomes. Children born extremely preterm had significantly poorer academic attainment and a higher prevalence of learning difficulties than their term peers. General cognitive ability and specific deficits in visuospatial skills or phoneme deletion at 6 years were predictive of mathematics and reading attainment at 11 years in both extremely preterm and term children. Phonological processing, attention, and executive functions at 6 years were also associated with academic attainment in children born extremely preterm. Furthermore, social factors, neonatal factors (necrotizing enterocolitis, breech delivery, abnormal cerebral ultrasound, early breast milk provision), and developmental factors at 30 months (head circumference, cognitive development), were independent predictors of educational outcomes at 11 years. Neonatal complications combined with assessments of early cognitive function provide moderate prediction for educational outcomes in children born extremely preterm

Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer : a systematic review and overview of reviews

Background: Prophylactic aspirin has been considered to be beneficial in reducing the risks of heart disease and cancer. However, potential benefits must be balanced against the possible harm from side effects, such as bleeding and gastrointestinal (GI) symptoms. It is particularly important to know the risk of side effects when aspirin is used as primary prevention - that is when used by people as yet free of, but at risk of developing, cardiovascular disease (CVD) or cancer. In this report we aim to identify and re-analyse randomised controlled trials (RCTs), systematic reviews and meta-analyses to summarise the current scientific evidence with a focus on possible harms of prophylactic aspirin in primary prevention of CVD and cancer. Objectives: To identify RCTs, systematic reviews and meta-analyses of RCTs of the prophylactic use of aspirin in primary prevention of CVD or cancer. To undertake a quality assessment of identified systematic reviews and meta-analyses using meta-analysis to investigate study-level effects on estimates of benefits and risks of adverse events; cumulative meta-analysis; exploratory multivariable meta-regression; and to quantify relative and absolute risks and benefits. Methods: We identified RCTs, meta-analyses and systematic reviews, and searched electronic bibliographic databases (from 2008 September 2012) including MEDLINE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, NHS Centre for Reviews and Dissemination, and Science Citation Index. We limited searches to publications since 2008, based on timing of the most recent comprehensive systematic reviews. Results: In total, 2572 potentially relevant papers were identified and 27 met the inclusion criteria. Benefits of aspirin ranged from 6% reduction in relative risk (RR) for all-cause mortality [RR 0.94, 95% confidence interval (CI) 0.88 to 1.00] and 10% reduction in major cardiovascular events (MCEs) (RR 0.90, 95% CI 0.85 to 0.96) to a reduction in total coronary heart disease (CHD) of 15% (RR 0.85, 95% CI 0.69 to 1.06). Reported pooled odds ratios (ORs) for total cancer mortality ranged between 0.76 (95% CI 0.66 to 0.88) and 0.93 (95% CI 0.84 to 1.03). Inclusion of the Women's Health Study changed the estimated OR to 0.82 (95% CI 0.69 to 0.97). Aspirin reduced reported colorectal cancer (CRC) incidence (OR 0.66, 95% CI 0.90 to 1.02). However, including studies in which aspirin was given every other day raised the OR to 0.91 (95% CI 0.74 to 1.11). Reported cancer benefits appeared approximately 5 years from start of treatment. Calculation of absolute effects per 100,000 patient-years of follow-up showed reductions ranging from 33 to 46 deaths (all-cause mortality), 60-84 MCEs and 47-64 incidents of CHD and a possible avoidance of 34 deaths from CRC. Reported increased RRs of adverse events from aspirin use were 37% for GI bleeding (RR 1.37, 95% CI 1.15 to 1.62), between 54% (RR 1.54, 95% CI 1.30 to 1.82) and 62% (RR 1.62, 95% CI 1.31 to 2.00) for major bleeds, and between 32% (RR 1.32, 95% CI 1.00 to 1.74) and 38% (RR 1.38, 95% CI 1.01 to 1.82) for haemorrhagic stroke. Pooled estimates of increased RR for bleeding remained stable across trials conducted over several decades. Estimates of absolute rates of harm from aspirin use, per 100,000 patient-years of follow-up, were 99-178 for non-trivial bleeds, 46-49 for major bleeds, 68-117 for GI bleeds and 8-10 for haemorrhagic stroke. Meta-analyses aimed at judging risk of bleed according to sex and in individuals with diabetes were insufficiently powered for firm conclusions to be drawn. Limitations: Searches were date limited to 2008 because of the intense interest that this subject has generated and the cataloguing of all primary research in so many previous systematic reviews. A further limitation was our potential over-reliance on study-level systematic reviews in which the person-years of follow-up were not accurately ascertainable. However, estimates of number of events averted or incurred through aspirin use calculated from data in study-level meta-analyses did not differ substantially from estimates based on individual patient data-level meta-analyses, for which person-years of follow-up were more accurate (although based on less-than-complete assemblies of currently available primary studies). Conclusions: We have found that there is a fine balance between benefits and risks from regular aspirin use in primary prevention of CVD. Effects on cancer prevention have a long lead time and are at present reliant on post hoc analyses. All absolute effects are relatively small compared with the burden of these diseases. Several potentially relevant ongoing trials will be completed between 2013 and 2019, which may clarify the extent of benefit of aspirin in reducing cancer incidence and mortality. Future research considerations include expanding the use of IPD meta-analysis of RCTs by pooling data from available studies and investigating the impact of different dose regimens on cardiovascular and cancer outcomes

Mathematics difficulties in extremely preterm children : evidence of a specific deficit in basic mathematics processing

Background: Extremely preterm (EP, <26 wk gestation) children have been observed to have poor academic achievement in comparison to their term-born peers, especially in mathematics. This study investigated potential underlying causes of this difficulty. Methods: A total of 219 EP participants were compared with 153 term-born control children at 11 y of age. All children were assessed by a psychologist on a battery of standardized cognitive tests and a number estimation test assessing children’s numerical representations. Results: EP children underperformed in all tests in comparison with the term controls (the majority of Ps < 0.001). Different underlying relationships between performance on the number estimation test and mathematical achievement were found in EP as compared with control children. That is, even after controlling for cognitive ability, a relationship between number representations and mathematical performance persisted for EP children only (EP: r = 0.346, n = 186, P < 0.001; control: r = 0.095, n = 146, P = 0.256). Conclusion: Interventions for EP children may target improving children’s numerical representations in order to subsequently remediate their mathematical skills

Does implementation matter if comprehension is lacking? A qualitative investigation into perceptions of advance care planning in people with cancer

Purpose: While advance care planning holds promise, uptake is variable and it is unclear how well people engage with or comprehend advance care planning. The objective of this study was to explore how people with cancer comprehended Advance Care Plans and examine how accurately advance care planning documentation represented patient wishes. Methods: This study used a qualitative descriptive design. Data collection comprised interviews and an examination of participants’ existing advance care planning documentation. Participants included those who had any diagnosis of cancer with an advance care plan recorded: Refusal of Treatment Certificate; Statement of Choices; and/or Enduring Power of Attorney (Medical Treatment) at one cancer treatment centre. Results: Fourteen participants were involved in the study. Twelve participants were female (86%). The mean age was 77 (range: 61-91) and participants had completed their advance care planning documentation between 8 and 72 weeks prior to the interview (mean 33 weeks). Three themes were evident from the data: Incomplete advance care planning understanding and confidence; Limited congruence for attitude and documentation; Advance care planning can enable peace of mind. Complete advance care planning understanding was unusual; most participants demonstrated partial comprehension of their own advance care plan, and some indicated very limited understanding. Participants’ attitudes and their written document congruence was limited, but advance care planning was seen as helpful. Conclusions: This study highlighted advance care planning was not a completely accurate representation of patient wishes. There is opportunity to improve how patients comprehend their own advance care planning documentation

Activation and Oxidation of Mesitylene C−H Bonds by (Phebox)Iridium(III) Complexes

A pincer iridium(III) complex, (Phebox)Ir(OAc)_2OH_2 (1) (Phebox = 3,5-dimethylphenyl-2,6-bis(oxazolinyl)), selectively cleaves the benzylic C–H bond of mesitylene to form an isolable iridium mesityl complex, (Phebox)Ir(mesityl)(OAc) (3), in >90% yield. The trifluoroacetate analogue, (Phebox)Ir(OCOCF_3)_2OH_2 (2), was synthesized to compare with complex 1 for C–H activation, and (Phebox)Ir(mesityl)(OCOCF_3) (4) was synthesized by ligand exchange of complex 3. Both complexes 1 and 2 catalyze H/D exchange between mesitylene and D2O at 180 °C, exclusively at the benzylic position; 2 gave a higher turnover number (11 TO) than 1 (6 TO) in 12 h. Using d4-acetic acid as the source of deuterium, up to 92 turnovers of benzylic H/D exchange of mesitylene were obtained with complex 1. (Phebox)Ir(OCOCF3)_2OH_2 catalyzed the benzylic C–H oxidation of mesitylene using Ag_2O as a terminal oxidant at 130 °C, to form 3,5-dimethylbenzaldehyde and 3,5-dimethylbenzoic acid in 35% ± 4% yield (5.1 ± 0.6 TO). DFT calculations were used to investigate two possible pathways for the catalytic oxidation of mesitylene: (1) C–H activation followed by oxy-functionalization and (2) Ir-oxo formation followed by outer-sphere C–H hydroxylation. Results of calculations of the C–H activation pathway appear to be the more consistent with the experimental observations

Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: Systematic review and meta-analysis

Objective: To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention. Design: Systematic review and meta-analysis. Data sources: Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases. Eligibility criteria: Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible. Results: 26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups. Conclusions Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish

Study protocol: developing a decision system for inclusive housing: applying a systematic, mixed-method quasi-experimental design

Background Identifying the housing preferences of people with complex disabilities is a much needed, but under-developed area of practice and scholarship. Despite the recognition that housing is a social determinant of health and quality of life, there is an absence of empirical methodologies that can practically and systematically involve consumers in this complex service delivery and housing design market. A rigorous process for making effective and consistent development decisions is needed to ensure resources are used effectively and the needs of consumers with complex disability are properly met. Methods/Design This 3-year project aims to identify how the public and private housing market in Australia can better respond to the needs of people with complex disabilities whilst simultaneously achieving key corporate objectives. First, using the Customer Relationship Management framework, qualitative (Nominal Group Technique) and quantitative (Discrete Choice Experiment) methods will be used to quantify the housing preferences of consumers and their carers. A systematic mixed-method, quasi-experimental design will then be used to quantify the development priorities of other key stakeholders (e.g., architects, developers, Government housing services etc.) in relation to inclusive housing for people with complex disabilities. Stakeholders randomly assigned to Group 1 (experimental group) will participate in a series of focus groups employing Analytical Hierarchical Process (AHP) methodology. Stakeholders randomly assigned to Group 2 (control group) will participate in focus groups employing existing decision making processes to inclusive housing development (e.g., Risk, Opportunity, Cost, Benefit considerations). Using comparative stakeholder analysis, this research design will enable the AHP methodology (a proposed tool to guide inclusive housing development decisions) to be tested. Discussion It is anticipated that the findings of this study will enable stakeholders to incorporate consumer housing preferences into commercial decisions. Housing designers and developers will benefit from the creation of a parsimonious set of consumer-led housing preferences by which to make informed investments in future housing and contribute to future housing policy. The research design has not been applied in the Australian research context or elsewhere, and will provide a much needed blueprint for market investment to develop viable, consumer directed inclusive housing options for people with complex disability

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy