Measuring vascular reactivity with breath-holds after stroke: a method to aid interpretation of group-level BOLD signal changes in longitudinal fMRI studies

Blood oxygenation level dependent (BOLD) contrast fMRI is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath-hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task-related BOLD signal changes. Three methods of analyzing the breathhold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue, and the peri-infarct tissue, both sub-acutely (~two weeks) and chronically (~four months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri-infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared to the controls may be confounded by a reduced CVR, longitudinal grouplevel BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath-hold based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity

A survey of UK optometry trainees' smoking cessation training

BACKGROUND: Smoking is a risk factor for a number of eye conditions, including age-related macular degeneration, cataracts and thyroid eye disease. Smoking cessation interventions have been shown to be highly cost-effective when delivered by a range of healthcare professionals. Optometrists are well placed to deliver smoking cessation advice to a wide population of otherwise healthy smokers. Yet optometrists remain a relatively neglected healthcare professional group in smoking cessation research and policy. Surveys of UK medical/nursing schools and of optometrists' training internationally demonstrate significant deficits in current curricular coverage regarding smoking cessation. This study aimed to identify the extent of smoking cessation training in UK optometry trainees' undergraduate and pre-registration training. METHODS: All undergraduate optometry schools in the UK (n = 9) were invited to participate in a web-based survey of their curricular coverage and assessment related to smoking cessation, and of perceived barriers to delivering smoking cessation training. A content analysis of the College of Optometrists Scheme for Registration Trainee Handbook 2014 was conducted to identify competence indicators related to smoking cessation. RESULTS: Nine undergraduate optometry schools (100%) responded to the survey. The majority reported dedicating limited hours (0-3) to teaching smoking cessation, and predominantly focused on teaching the harmful effects of smoking (89%). Only one school provides practical skills training for delivering evidence-based smoking cessation interventions, including very brief advice. The majority of schools (78%) reported that they did not formally examine students on their knowledge or skills for supporting smoking cessation, and rated confidence in their graduates' abilities to deliver smoking cessation interventions as 'poor' (78%). Lack of knowledge amongst staff was identified as the key barrier to teaching about smoking cessation support. The pre-registration competency framework does not include any competence indicators related to providing support for quitting smoking. CONCLUSIONS: There are substantial gaps in the current curricula of UK optometry training, particularly regarding practical skills for supporting smoking cessation. Increased curricular coverage of these issues is essential to ensure trainee optometrists are adequately trained and competent in supporting patients to quit smoking

The ACTA PORT-score for predicting perioperative risk of blood transfusion for adult cardiac surgery.

BACKGROUND: A simple and accurate scoring system to predict risk of transfusion for patients undergoing cardiac surgery is lacking. METHODS: We identified independent risk factors associated with transfusion by performing univariate analysis, followed by logistic regression. We then simplified the score to an integer-based system and tested it using the area under the receiver operator characteristic (AUC) statistic with a Hosmer-Lemeshow goodness-of-fit test. Finally, the scoring system was applied to the external validation dataset and the same statistical methods applied to test the accuracy of the ACTA-PORT score. RESULTS: Several factors were independently associated with risk of transfusion, including age, sex, body surface area, logistic EuroSCORE, preoperative haemoglobin and creatinine, and type of surgery. In our primary dataset, the score accurately predicted risk of perioperative transfusion in cardiac surgery patients with an AUC of 0.76. The external validation confirmed accuracy of the scoring method with an AUC of 0.84 and good agreement across all scores, with a minor tendency to under-estimate transfusion risk in very high-risk patients. CONCLUSIONS: The ACTA-PORT score is a reliable, validated tool for predicting risk of transfusion for patients undergoing cardiac surgery. This and other scores can be used in research studies for risk adjustment when assessing outcomes, and might also be incorporated into a Patient Blood Management programme

Factors associated with timeliness of post-primary care referral, diagnosis and treatment for lung cancer: population-based, data-linkage study

BACKGROUND: The NHS Cancer Plan for England set waiting time targets for cancer referral (14 days from GP referral to first hospital appointment) and treatment (31 days from diagnosis, 62 days from urgent GP referral). Interim diagnostic intervals can also be calculated. The factors that influence timely post-primary care referral, diagnosis and treatment for lung cancer are not known. METHODS: Northern and Yorkshire Cancer Registry, Hospital Episode Statistics and lung cancer audit data sets were linked. Logistic regression was used to investigate the factors (socioeconomic position, age, sex, histology, co-morbidity, year of diagnosis, stage and performance status (PS)) that may influence the likelihood of referral, diagnosis and treatment within target, for 28 733 lung cancer patients diagnosed in 2006–2010. RESULTS: Late-stage, poor PS and small-cell histology were associated with a higher likelihood of post-primary care referral, diagnosis and treatment within target. Older patients were significantly less likely to receive treatment within the 31-day (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.69–0.91) and 62-day target (OR=0.80, 95% CI 0.67–0.95) compared with younger patients. CONCLUSIONS: Older patients waited longer for treatment and this may be unjustified. Patients who appeared ill were referred, diagnosed and treated more quickly and this ‘sicker quicker’ effect may cancel out system socioeconomic inequalities that might result in longer time intervals for more deprived patients

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

Ecological Guild Evolution and the Discovery of the World's Smallest Vertebrate

Living vertebrates vary drastically in body size, yet few taxa reach the extremely minute size of some frogs and teleost fish. Here we describe two new species of diminutive terrestrial frogs from the megadiverse hotspot island of New Guinea, one of which represents the smallest known vertebrate species, attaining an average body size of only 7.7 mm. Both new species are members of the recently described genus Paedophryne, the four species of which are all among the ten smallest known frog species, making Paedophryne the most diminutive genus of anurans. This discovery highlights intriguing ecological similarities among the numerous independent origins of diminutive anurans, suggesting that minute frogs are not mere oddities, but represent a previously unrecognized ecological guild

Transgenerational Effects of Stress Exposure on Offspring Phenotypes in Apomictic Dandelion

Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various stresses was previously shown to heritably alter DNA methylation patterns. In this study we explore whether these induced changes are accompanied by heritable effects on offspring phenotypes. We observed effects of parental jasmonic acid treatment on offspring specific leaf area and on offspring interaction with a generalist herbivore; and of parental nutrient stress on offspring root-shoot biomass ratio, tissue P-content and leaf morphology. Some of the effects appeared to enhance offspring ability to cope with the same stresses that their parents experienced. Effects differed between apomictic genotypes and were not always consistently observed between different experiments, especially in the case of parental nutrient stress. While this context-dependency of the effects remains to be further clarified, the total set of results provides evidence for the existence of transgenerational effects in apomictic dandelions. Zebularine treatment affected the within-generation response to nutrient stress, pointing at a role of DNA methylation in phenotypic plasticity to nutrient environments. This study shows that stress exposure in apomictic dandelions can cause transgenerational phenotypic effects, in addition to previously demonstrated transgenerational DNA methylation effects

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity

Anthropogenic trade and development have broken down dispersal barriers, facilitating the spread of diseases that threaten Earth's biodiversity. We present a global, quantitative assessment of the amphibian chytridiomycosis panzootic, one of the most impactful examples of disease spread, and demonstrate its role in the decline of at least 501 amphibian species over the past half-century, including 90 presumed extinctions. The effects of chytridiomycosis have been greatest in large-bodied, range-restricted anurans in wet climates in the Americas and Australia. Declines peaked in the 1980s, and only 12% of declined species show signs of recovery, whereas 39% are experiencing ongoing decline. There is risk of further chytridiomycosis outbreaks in new areas. The chytridiomycosis panzootic represents the greatest recorded loss of biodiversity attributable to a disease