How do I sound to me? Perceived changes in communication in Parkinson's disease

Objective: To examine self and carer perceived changes in communication associated with Parkinson's disease and relate these to speech intelligibility, gender, age and other disease measures. Design: Cross-sectional survey of a hospital- and community-based sample of 176 people with Parkinson's disease and their carers using a questionnaire based on semantic differential techniques. Participants: One hundred and four people with Parkinson's disease with no history of communication difficulties prior to onset of their Parkinson's disease and 45 primary carers who returned completed questionnaires. Main outcome measures: Differences in ratings for `before' the onset of Parkinson's disease versus present status. Results: There was a strong perception of negative impact on communication between `before' and `now', irrespective of age and gender and largely independent of disease severity and duration, intelligibility and cognitive status. Activities of daily living (assessed by Unified Parkinson's Disease Rating Scale (UPDRS) II) and depression rating scale scores had the strongest association with change (adjusted R 2 0.27). There was a significant correlation between the rank order of perceived change in features examined in people with Parkinson's disease versus their carers, though in general carers rated change as having less impact. Conclusions: Parkinson's disease exercises a strong influence on communication even before apparent alterations to intelligibility or motor status

Universal cannabis outcomes from the Climate and Preventure (CAP) study : a cluster randomised controlled trial

Background: The Climate and Preventure (CAP) study was the first trial to assess and demonstrate the effectiveness of a combined universal and selective approach for preventing alcohol use and related harms among adolescents. The current paper reports universal effects from the CAP study on cannabis-related outcomes over three years. Methods: A cluster randomized controlled trial was conducted with 2190 students from twenty-six Australian high schools (mean age: 13.3 yrs., SD 0.48). Participants were randomised to one of four conditions; universal prevention for all students (Climate); selective prevention for high-risk students (Preventure); combined universal and selective prevention (Climate and Preventure; CAP); or health education as usual (Control). Participants were assessed at baseline, post intervention (6–9 months post baseline), and at 12-, 24- and 36-months, on measures of cannabis use, knowledge and related harms. This paper compares cannabis-related knowledge, harms and cannabis use in the Control, Climate and CAP groups as specified in the protocol, using multilevel mixed linear models to assess outcomes. Results: Compared to Control, the Climate and CAP groups showed significantly greater increases in cannabis-related knowledge initially (p < 0.001), and had higher knowledge at the 6, 12 and 24-month follow-ups. There was no significant difference between the Climate and CAP groups. While no differences were detected between Control and the CAP and Climate groups on cannabis use or cannabis-related harms, the prevalence of these outcomes was lower than anticipated, possibly limiting power to detect intervention effects. Additional Bayesian analyses exploring confidence in accepting the null hypothesis showed there was insufficient evidence to conclude that the interventions had no effect, or to conclude that they had a meaningfully large effect. Conclusions: Both the universal Climate and the combined CAP programs were effective in increasing cannabisrelated knowledge for up to 2 years. The evidence was inconclusive regarding whether the interventions reduced cannabis use and cannabis-related harms. A longer-term follow-up will ascertain whether the interventions become effective in reducing these outcomes as adolescents transition into early adulthood

The validity of the Substance Use Risk Profile Scale (SURPS) among Australian adolescents

Aims: This study investigated the validity of a brief personality screening measure for substance use in adolescents, the Substance Use Risk Profile Scale (SURPS), among Australian adolescents. Design and participants: A total of 527 adolescents (mean age: 13.38 years, SD=0.43) from seven Australian schools were assessed at two time points 24 months apart. The concurrent and predictive validity of the SURPS was determined using a series of linear and logistic regressions, and was compared to the results in a United Kingdom (UK) sample. SURPS subscale scores for the Australian population were also reported and compared to those in the UK. Findings: Overall, the SURPS subscale scores for Australian adolescents were similar to those for adolescents from the UK. Tests of concurrent and predictive validity in the Australian sample demonstrated that the all four personality profiles - Hopelessness (H), Anxiety Sensitivity (AS), Impulsivity (IMP), and Sensation Seeking (SS) - were related to measures of substance use and other behavioural and emotional characteristics. In addition, all the predicted specific prospective relationships between the personality profiles and particular substance use and other behavioural problems were confirmed except that H was not associated with illicit drug use. Overall, the results were similar between the Australian and UK samples. Conclusions: The SURPS is a valid and useful measure for identifying Australian adolescents at high-risk for substance use and other emotional and behavioural problems. Implications for prevention are discussed

Variability of Dosing and Number of Medications Needed to Achieve Adequate Sedation in Mechanically Ventilated Pediatric Intensive Care Patients.

Children admitted to the pediatric intensive care unit (PICU) often require multiple medications to achieve comfort and sedation. Although starting doses are available, these medications are typically titrated to the desired effect. Both oversedation and undersedation are associated with adverse events. The aim of this retrospective study was to evaluate cumulative medication burden necessary to achieve comfort in patients in the PICU and determine relevant predictors of medication needs. In order to account for all of the sedative medications, z-scores were used to assess the population average dose of each medication and compare each patient day to this population average. Sedation regimens for 130 patients in the PICU were evaluated. Mean overall infusion rates of fentanyl, morphine, and hydromorphone were 1.67 ± 0.81 µg/kg/hour, 0.12 ± 0.08 mg/kg/hour, and 17.84 ± 13.4 µg/kg/hour, respectively. The mean infusion rate of dexmedetomidine was 0.59 ± 0.28 µg/kg/hour, and midazolam was 0.14 ± 0.1 mg/kg/hour. Summation z-sores were used to rank the amount of sedation medication needed to achieve comfort for each individual patient for his/her PICU stay in relation to the entire sample. Patient age, weight, and length of mechanical ventilation were all significant predictors of sedation requirement. This study will provide data necessary to develop a model of cumulative medication burden needed to achieve appropriate sedation in this population. This descriptive model in appropriately ranking patients based on sedative needs is the first step in exploring potential genetic factors that may provide an insight into homing in on the appropriate sedation regimen

The Early Years

Policy concentration on the early years is of vital importance for the wellbeing of children now and for their future health outcomes and life chances. Evidence-based research points to the need for a focus that is properly holistic and to precipitate intervention to promote a healthy diet, regular patterns of activity and rest and give children the best start in life. In 2005, The United Nations Committee on the Rights of the Child (General Comment No. 7) acknowledged the need for a fresh strategy, pinpointing research findings indicating that a failure to prioritise early years’ welfare exposes children to the ills of ‘malnutrition, disease, poverty, neglect, social exclusion and a range of other adversities.’ Professor Dame Sally Davies, Chief Medical Officer of the United Kingdom, considers that robust early years’ policies make both social and economic sense: ‘Too many children and young people do not have the start in life they need, leading to high costs for society, and too many affected lives’ (Forward to ‘The 1001 Critical Days’, June 16th 2014). This observation is significant because there remains much to do. In 2012, the NSPCC reviewed the United Kingdom policy scenario for babies and very young children and concluded that identifiable advances in maternity and early years’ provision did not detract from the fact that: ‘babies are still particularly vulnerable’ and ‘their rights are not always recognised or realised’. (‘All Babies Count – But what about their rights?’ Sally Knock and Lorriann Robinson, January 2012). Knock and Robinson highlight glaring gaps of support and provision – especially in maternity services whereby the fostering of a strong parent-child bond is invariably sacrificed to a concentration upon purely medical practicalities such as labour, birth and the immunisation programme. The All Party Group on a Fit and Healthy Childhood aims, in this report, to offer the incoming Government recommendations for an early years’ strategy that are credible, feasible and evidence-based and will enable the United Kingdom to set the standard in a crucial policy field both at home and abroad. In defining ‘early childhood’, we follow the example of The United Nations (2005) Convention on the Right of the Child by examining the period of 0-8 including, as it does, the vital transition phase from pre-school to primary school. We consider the antenatal period and maternal physical and mental health, methods of feeding the newborn, parental support services both hospital and home-based and infant nutrition and socioeconomic factors that may impact upon the health and wellbeing of young children. The report examines the optimum balance between sleep, rest and activity, the need for freely-chosen play, safeguarding measures and the importance of respecting cultural diversity in all early years’ settings. Above all, we analyse the relationship between young families and the professionals whose role it is to ensure that babies have the very best start in life, supported by parents who have confidence in the choices that they make and the advice that they are given. Just as new families require mentoring so that they can act in the best interests of their children, so the early years’ workforce needs training and continuous professional development to ensure that the advice given is of the highest possible quality and specifically tailored to the individual family. Early Years’ students from The University of Northampton (interviewed) explain what a positive difference their newly acquired knowledge has made to their performance in the settings and Government recognition of The Early Years as a developmental stage in its own right and the creation of the new posts of Early Years Teacher and Early Years Educator have been positive. Yet as the Ilkeston ‘Mums Group’ (interviewed) makes clear, there is still no guarantee of uniform excellence in the delivery of services nationwide and no assurance of continuity between, for example, advice on feeding from the midwife and the health visitor, or the emphasis put on freely-chosen play in an early years’ setting and a primary school. If young children are to thrive, we believe it is essential that there is a national consensus and political will behind multi-disciplinary working in the early years. We see the early years as a window of opportunity and make no apology for the fact that each section of this report is accompanied by many policy recommendations. It has not been possible to produce a uniform handful of ‘asks’, just as the early years itself is a rich, complex and multifarious developmental phase. However, neither do we consider it to be feasible to achieve everything that we recommend in the lifespan of a single Government. This is a two, even three term journey. However, if the nation’s families and the early years workforce are to embark upon it, the Government must be prepared to provide the resources; the Cabinet Minister for Children and Families, the commitment to multi-disciplinary co-operation to achieve an early years workforce that is truly ‘joined up’ and, above all, the finance to make well–intentioned aspiration a reality. In an age of austerity, by spending early, the later savings to education, health, social or criminal justice services will be immense. Investing in the children of today is not a gambl

iPrevent®: a tailored, web-based, decision support tool for breast cancer risk assessment and management

We aimed to develop a user-centered, web-based, decision support tool for breast cancer risk assessment and personalized risk management. Using a novel model choice algorithm, iPrevent&reg; selects one of two validated breast cancer risk estimation models (IBIS or BOADICEA), based on risk factor data entered by the user. Resulting risk estimates are presented in simple language and graphic formats for easy comprehension. iPrevent&reg; then presents risk-adapted, evidence-based, guideline-endorsed management options. Development was an iterative process with regular feedback from multidisciplinary experts and consumers. To verify iPrevent&reg;, risk factor data for 127 cases derived from the Australian Breast Cancer Family Study were entered into iPrevent&reg;, IBIS (v7.02), and BOADICEA (v3.0). Consistency of the model chosen by iPrevent&reg; (i.e., IBIS or BOADICEA) with the programmed iPrevent&reg; model choice algorithm was assessed. Estimated breast cancer risks from iPrevent&reg; were compared with those attained directly from the chosen risk assessment model (IBIS or BOADICEA). Risk management interventions displayed by iPrevent&reg; were assessed for appropriateness. Risk estimation model choice was 100% consistent with the programmed iPrevent&reg;logic. Discrepant 10-year and residual lifetime risk estimates of &gt;1% were found for 1 and 4 cases, respectively, none was clinically significant (maximal variation 1.4%). Risk management interventions suggested by iPrevent&reg; were 100% appropriate. iPrevent&reg; successfully integrates the IBIS and BOADICEA risk assessment models into a decision support tool that provides evidence-based, risk-adapted risk management advice. This may help to facilitate precision breast cancer prevention discussions between women and their healthcare providers

The effects of vitamin C and E on exercise-induced physiological adaptations: a systematic review and Meta-analysis of randomized controlled trials

We conducted a systematic review and meta-analysis of randomized controlled trials examining the effect of vitamin C and/or E on exercise-induced training adaptations. Medline, Embase and SPORTDiscus databases were searched for articles from inception until June 2019. Inclusion criteria was studies in adult humans where vitamin C and/or E had to be consumed alongside a supervised exercise training program of ≥4 weeks. Nine trials were included in the analysis of aerobic exercise adaptations and nine for resistance training (RT) adaptations. Vitamin C and/or E did not attenuate aerobic exercise induced improvements in maximal aerobic capacity (V̇ O2max) (SMD −0.14, 95% CI: −0.43 to 0.15, P = 0.35) or endurance performance (SMD −0.01, 95% CI: −0.38 to 0.36, P = 0.97). There were also no effects of these supplements on lean mass and muscle strength following RT (SMD −0.07, 95% CI: −0.36 to 0.23, P = 0.67) and (SMD −0.15, 95% CI: −0.16 to 0.46, P = 0.35), respectively. There was also no influence of age on any of these outcomes (P > 0.05). These findings suggest that vitamin C and/or E does not inhibit exercise-induced changes in physiological function. Studies with larger sample sizes and adequate power are still required

Exploring rumen microbe-derived fibre-degrading activities for improving feed digestibility

Ruminal fibre degradation is mediated by a complex community of rumen microbes, and its efficiency is crucial for optimal dairy productivity. Enzymes produced by rumen microbes are primarily responsible for degrading the complex structural polysaccharides that comprise fibre in the plant cell walls of feed materials. Because rumen microbes have evolved with their ruminant hosts over millions of years to perform this task, their enzymes are hypothesised to be optimally suited for activity at the temperature, pH range, and anaerobic environment of the rumen. However, fibre-rich diets are not fully digested, which represents a loss in potential animal productivity. Thus, there is opportunity to improve fibre utilisation through treating feeds with rumen microbe-derived fibrolytic enzymes and associated activities that enhance fibre degradation. This research aims to gain a better understanding of the key rumen microbes involved in fibre degradation and the mechanisms they employ to degrade fibre, by applying cultivation-based and culture-independent genomics approaches to rumen microbial communities of New Zealand dairy cattle. Using this knowledge, we aim to identify new opportunities for improving fibre degradation to enhance dairy productivity. Rumen content samples were taken over the course of a year from a Waikato dairy production herd. Over 1,000 rumen bacterial cultures were obtained from the plant-adherent fraction of the rumen contents. Among these cultures, two, 59 and 103 potentially new families, genera and species of rumen bacteria were identified, respectively. Many of the novel strains are being genome sequenced within the Hungate 1000 rumen microbial reference genome programme, which is providing deeper insights into the range of mechanisms used by the individual strains for fibre degradation. This information has been used to guide the selection of rumen bacterial strains with considerable potential as fibrolytic enzyme producers in vitro, with the intent of developing the strains so that their enzymes may be used as feed pre-treatments for use on farm. Culture-independent metagenomic approaches were also used to explore the activities involved in fibre degradation from the rumen microbial communities. Functional screening has revealed a range of novel enzymes and a novel fibre disrupting activity. Enrichment for the cell-secreted proteins from the community revealed evidence of a diverse range of cellulosomes, which are cell-surface associated multi-enzyme complexes that efficiently degrade plant cell wall polysaccharides. Biochemical and structural characterisation of these proteins has been conducted. In conclusion, cultivation and culture-independent genomic approaches have been applied to New Zealand bovine rumen microbial communities, and have provided considerable new insights into ruminal fibre degradation processes. Novel activities and bacterial species that display desirable activities on fibrous substrates in vitro are now being explored for their potential to improve ruminal fibre degradation, to allow the development of new technologies that will enhance dairy productivity

Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum

Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology