Tackling discrimination in medicine head on: The impact of bystander intervention training.

PURPOSE: A mixed-methods study to evaluate Bystander Intervention Training (BiT), a simulation-based small-group training programme designed to teach skills to tackle discrimination. MATERIALS AND METHODS: Norwich Medical School delivered the intervention online between January 2020 and June 2023 to medical students, physician associate trainees, and qualified doctors. A sample of 569 participants was used in the main analysis. Participants completed pre- and post-training and follow-up evaluations. RESULTS: Paired post-training scores were significantly different (all p < 0.001) from the pre-training scores for all 12 questions, in favour of the post-training scores. Of the 159 participants who completed follow-up questionnaires, 27 (17.9%) reported having the opportunity to be an active bystander; of those, 23 (85%) intervened. Scores in the follow-up questionnaire were significantly higher than those in the pre-training survey and significantly lower than those in the post-training questionnaire (p < 0.001). Participants had an increased sense of responsibility to be an active bystander and were empowered to challenge discrimination. Participants from marginalised groups expressed positive views about the training. CONCLUSIONS: Interventions that allow open discussion and carefully supported personal disclosure in safe spaces, where difficult and uncomfortable discussions can occur, with an opportunity to change behaviour, must be developed to tackle discrimination.

Alcohol Consumption and Measures of Sarcopenic Muscle Risk: Cross-Sectional and Prospective Associations Within the UK Biobank Study.

Alcohol intake is a major modifiable risk factor for many diseases. Alcohol can also damage skeletal muscle health during ageing which in turn increases risk of sarcopenia, frailty and falls but this relationship is understudied. The aim of this study was to model the relationship between a full range of alcohol consumption and components of sarcopenic risk, skeletal muscle mass and function, in middle-aged and younger older-aged men and women. A cross-sectional analyses was undertaken of 196,561 white participants from the UK Biobank with longitudinal analysis also in 12,298 of these participants, with outcome measures for the latter repeated after around four years. For the cross-sectional analysis fractional polynomial curves were fitted in models of measures of skeletal muscle mass, appendicular lean mass/body mass index (ALM/BMI), fat-free mass as a percentage of body weight (FFM%) and grip strength, all predicted from alcohol consumption with models fitted for men and women separately. Alcohol consumption at baseline was based on the mean of up to five dietary recalls, typically over 16 months. Linear regression was used for longitudinal analyses to model the effects of alcohol consumption groups on these measures. All models were adjusted for covariates. In the cross-sectional analysis, modelled values of the muscle mass measures all showed a peak at medium levels of alcohol consumption and a steep decline with increasing alcohol consumption. Modelled differences in muscle mass from zero consumption of alcohol to 160 g/d ranged from 3.6 to 4.9% for ALM/BMI for men and women, respectively, and 3.6 to 6.1% for FFM%. Grip strength consistently increased with alcohol consumption. No association between alcohol consumption and muscle measures were seen in the longitudinal results. Our results suggest that higher levels of alcohol consumption could have detrimental effects on muscle mass in middle- and older-aged men and women.

The Association Between Atypical Speech Development and Adolescent Self-Harm.

BACKGROUND: Adolescent self-harm is a major public health issue internationally. Various factors associated with adolescent self-harm have been identified, including being bullied and experiencing mental health problems. Stuttering and speech sound disorder are associated with both of these factors. It was hypothesized that both stuttering and speech sound disorder would be associated with self-harm. This is the first study to explore the relationship between communication disorders and adolescent self-harm. METHOD: Secondary analysis of a large, longitudinal, prospective, community sample, the Avon Longitudinal Study of Parents and Children, was carried out. Clinicians identified children who stuttered or exhibited speech sound disorder at the age of 8 years. When the cohort members were 16 years old, they were asked to complete a questionnaire about self-harm. Multinomial logistic regression was used to examine the associations between stuttering and speech sound disorder and the self-harm outcomes, adjusting for other relevant factors. RESULTS: Of 3,824 participants with data for both speech status and self-harm, 94 (2.5%; 95% confidence interval [CI; 2.0, 3.0]) stuttered at 8 years of age and 127 (3.3%; 95% CI [2.8, 3.9]) displayed speech sound disorder. Speech sound disorder at the age of 8 years was associated with self-harm with suicidal intent in both unadjusted and adjusted models. Differences between the adjusted and unadjusted models were small, suggesting that speech sound disorder is largely an independent risk factor for self-harm with suicidal intent. Stuttering at the age of 8 years was not associated with adolescent self-harm, and there was no association between speech sound disorder and self-harm without suicidal intent. CONCLUSION: Compared with individuals without speech sound disorder, adolescents with speech sound disorder at the age of 8 years have twice the risk of reporting self-harm with suicidal intent, even when other important predictors are taken into account. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22573030.

Mental health, well-being and support interventions for UK ambulance services staff: an evidence map, 2000 to 2020.

BACKGROUND: Prior to COVID-19 there had been a renewed policy focus in the National Health Service on the health and well-being of the healthcare workforce, with the ambulance sector identified as a priority area. This focus is more important than ever as the sector deals with the acute and longer-term consequences of a pandemic. AIM: To systematically identify, summarise and map the evidence regarding mental health, well-being and support interventions for United Kingdom ambulance services staff and to identify evidence gaps. METHOD: Evidence mapping methodology of published and grey original research published in English from 1 January 2000 to 23 May 2020 describing the health risk, mental health and/or well-being of UK ambulance services staff including retired staff, volunteers and students. MEDLINE, EMBASE, PsychINFO, CINAHL and AMED databases, plus EThOS, Zetoc, OpenGrey and Google, were searched, alongside hand-searching of grey literature and bibliographies. Information was extracted on study aims, sample, design and methodology, funding source, country and key findings. Included studies were categorised into seven a priori theme areas. RESULTS: Of 1862 identified articles, 45 peer-reviewed studies are included as well as 24 grey literature documents. Peer-reviewed research was largely observational and focused on prevalence studies, post-traumatic stress disorder or organisational and individual social factors related to health and well-being. Most grey literature reported the development and testing of interventions. Across all study types, underpinning theory was often not cited. CONCLUSION: To date, intervention research has largely been funded by charities and published in the grey literature. Few studies were identified on self-harm, bullying, sleep and fatigue or alcohol and substance use. Theoretically informed intervention development and testing, including adaptation of innovations from other countries and 24-hour workforces, is needed. This evidence map provides important context for planning of staff well-being provision and research as the sector responds to and recovers from the pandemic. PROSPERO REGISTRATION NUMBER: CRD42018104659.

Fracture Incidence and the Relevance of Dietary and Lifestyle Factors Differ in the United Kingdom and Hong Kong: An International Comparison of Longitudinal Cohort Study Data.

Geographic variation in fracture risk may be due to divergent profiles of dietary, lifestyle, and other risk factors between populations. We investigated differences in fracture rates between two older-population cohorts: the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk cohort (n = 7732) in the United Kingdom (UK), and the Mr and Ms Os cohort (n = 3956) in Hong Kong (HK). Data were collected by questionnaires, laboratory assessments, and hospital records. Incidence of hip, spine, and wrist fractures in the two cohorts was calculated and multivariable regression was used to explore variables important to fracture risk. Total hip, spine, and wrist fracture incidence was higher in the UK vs HK for women (13.70 vs 8.76 per 1000 person-years; p < 0.001), but not men (5.95 vs 5.37 per 1000 person-years; p = 0.337), and the proportions of different fractures also varied between cohorts (p < 0.001). Hip fracture was the most common UK fracture (accounting for 56.8% fractures in men and 52.6% in women), while wrist fracture was most common in HK (42.9% in men and 57.9% in women). The major contributor to total fracture risk in multivariable regression models of both cohorts and sexes, was age; with BMI also an important contributor to fracture risk HK men and UK women. The distribution of factors relevant to fracture risk, and the rates of different fractures, varied significantly between UK and HK cohorts. However, the importance of each factor in contributing to fracture risk was similar between the cohorts. The differences in fracture rates suggest targeted approaches may be required when developing interventions and public health recommendations to reduce the burden of osteoporosis in these two countries.

REP1 deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia.

Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations in CHM, encoding for Rab escort protein 1 (REP1). Loss of functional REP1 leads to the accumulation of unprenylated Rab proteins and defective intracellular protein trafficking, the putative cause for photoreceptor, retinal pigment epithelium (RPE), and choroidal degeneration. CHM is ubiquitously expressed, but adequate prenylation is considered to be achieved, outside the retina, through the isoform REP2. Recently, the possibility of systemic features in CHM has been debated; therefore, in this study, whole metabolomic analysis of plasma samples from 25 CHM patients versus age- and sex-matched controls was performed. Results showed plasma alterations in oxidative stress-related metabolites, coupled with alterations in tryptophan metabolism, leading to significantly raised serotonin levels. Lipid metabolism was disrupted with decreased branched fatty acids and acylcarnitines, suggestive of dysfunctional lipid oxidation, as well as imbalances of several sphingolipids and glycerophospholipids. Targeted lipidomics of the chmru848 zebrafish provided further evidence for dysfunction, with the use of fenofibrate over simvastatin circumventing the prenylation pathway to improve the lipid profile and increase survival. This study provides strong evidence for systemic manifestations of CHM and proposes potentially novel pathomechanisms and targets for therapeutic consideration.

Association between heart rate variability and haemodynamic response to exercise in chronic heart failure.

OBJECTIVES: Heart rate variability (HRV) and haemodynamic response to exercise (i.e. peak cardiac power output) are strong predictors of mortality in heart failure. The present study assessed the relationship between measures of HRV and peak cardiac power output. DESIGN: In a prospective observational study of 33 patients (age 54 ± 16 years) with chronic heart failure with reduced left ventricular ejection fraction (29 ± 11%), measures of the HRV (i.e. R-R interval and standard deviation of normal R-R intervals, SDNN) were recorded in a supine position. All patients underwent maximal graded cardiopulmonary exercise testing with non-invasive (inert gas rebreathing) cardiac output assessment. Cardiac power output, expressed in watts, was calculated as the product of cardiac output and mean arterial blood pressure. RESULTS: The mean RR and SDNN were 837 ± 166 and 96 ± 29 ms, peak exercise cardiac power output 2.28 ± 0.85 watts, cardiac output 10.34 ± 3.14 L/min, mean arterial blood pressure 98 ± 14 mmHg, stroke volume 91.43 ± 40.77 mL/beat, and oxygen consumption 19.0 ± 5.6 mL/kg/min. There was a significant but only moderate relationship between the RR interval and peak exercise cardiac power output (r = 0.43, p = .013), cardiac output (r = 0.35, p = .047), and mean arterial blood pressure (r = 0.45, p = .009). The SDNN correlated with peak cardiac power output (r = 0.42, p = .016), mean arterial blood arterial (r = 0.41, p = .019), and stroke volume (r = 0.35, p = .043). CONCLUSIONS: Moderate strength of the relationship between measures of HRV and cardiac response to exercise suggests that cardiac autonomic function is not good indicator of overall function and pumping capability of the heart in chronic heart failure.

Nonsense-mediated mRNA decay efficiency varies in choroideremia providing a target to boost small molecule therapeutics.

Choroideremia (CHM) is an x-linked recessive chorioretinal dystrophy, with 30% caused by nonsense mutations in the CHM gene resulting in an in-frame premature termination codon (PTC). Nonsense-mediated mRNA decay (NMD) is the cell's natural surveillance mechanism that detects and destroys PTC-containing transcripts, with UPF1 being the central NMD modulator. NMD efficiency can be variable amongst individuals with some transcripts escaping destruction, leading to the production of a truncated non-functional or partially functional protein. Nonsense suppression drugs, such as ataluren, target these transcripts and read-through the PTC, leading to the production of a full length functional protein. Patients with higher transcript levels are considered to respond better to these drugs, as more substrate is available for read-through. Using Quantitative reverse transcription PCR (RT-qPCR), we show that CHM mRNA expression in blood from nonsense mutation CHM patients is 2.8-fold lower than controls, and varies widely amongst patients, with 40% variation between those carrying the same UGA mutation [c.715 C>T; p.(R239*)]. These results indicate that although NMD machinery is at work, efficiency is highly variable and not wholly dependent on mutation position. No significant difference in CHM mRNA levels was seen between two patients' fibroblasts and their induced pluripotent stem cell-derived retinal pigment epithelium. There was no correlation between CHM mRNA expression and genotype, phenotype or UPF1 transcript levels. NMD inhibition with caffeine was shown to restore CHM mRNA transcripts to near wild-type levels. Baseline mRNA levels may provide a prognostic indicator for response to nonsense suppression therapy, and caffeine may be a useful adjunct to enhance treatment efficacy where indicated.

Effectiveness of virtual reality in the treatment of hand function in children with cerebral palsy: A systematic review.

STUDY DESIGN: Systematic review. INTRODUCTION: Children with cerebral palsy (CP) may have limited use of their hands for functional activities and for fine motor skills. Virtual reality (VR) is a relatively new and innovative approach to facilitate hand function in children with CP. PURPOSE OF THE STUDY: The primary purpose of this study was to determine the effectiveness of VR as an intervention to improve hand function in children with CP compared to either conventional physiotherapy or other therapeutic interventions. The secondary purpose was to classify the outcomes evaluated according to the International Classification of Functioning, Disability and Health (ICF) dimensions. METHODS: A International prospective register of systematic reviews (PROSPERO)-registered literature search was carried out in August 2015 in MEDLINE, CINAHL, ERIC, HealthSTAR, AMED, BNI, Embase, PsycINFO, PEDro, Cochrane Central Register, DARE, OTSeeker, REHABDATA, HaPI, CIRRIE, and Scopus. PRISMA guidelines were followed. Only randomized controlled trials (RCTs) were included, and their methodological qualities were examined using the Cochrane collaboration's risk of bias (RoB) tool. A narrative synthesis was performed. RESULTS: The 6 RCTs published on this topic provide conflicting results. Four studies reported improved hand function (2 low RoB, 1 high RoB, and 1 unclear RoB), whereas 2 studies reported no improvement. All of the RCTs reported the activity element of ICF, but no study explicitly described the effect of VR intervention based on the ICF model. CONCLUSION: The role of VR ti imrpove hand fucntion in children with CP is unclear due to limited evidence; use as an adjunct has some support.

A novel cardiac output response to stress test developed to improve diagnosis and monitoring of heart failure in primary care.

AIMS: Primary care physicians lack access to an objective cardiac function test. This study for the first time describes a novel cardiac output response to stress (CORS) test developed to improve diagnosis and monitoring of heart failure in primary care and investigates its reproducibility. METHODS AND RESULTS: Prospective observational study recruited 32 consecutive primary care patients (age, 63 ± 9 years; female, n = 18). Cardiac output was measured continuously using the bioreactance method in supine and standing positions and during two 3 min stages of a step-exercise protocol (10 and 15 steps per minute) using a 15 cm height bench. The CORS test was performed on two occasions, i.e. Test 1 and Test 2. There was no significant difference between repeated measures of cardiac output and stroke volume at supine standing and Stage 1 and Stage 2 step exercises (all P > 0.3). There was a significant positive relationship between Test 1 and Test 2 cardiac outputs (r = 0.92, P = 0.01 with coefficient of variation of 7.1%). The mean difference in cardiac output (with upper and lower limits of agreement) between Test 1 and Test 2 was 0.1 (-1.9 to 2.1) L/min, combining supine, standing, and step-exercise data. CONCLUSIONS: The CORS, as a novel test for objective evaluation of cardiac function, demonstrates acceptable reproducibility and can potentially be implemented in primary care.

Use of dietary indices to control for diet in human gut microbiota studies.

BACKGROUND: Environmental factors have a large influence on the composition of the human gut microbiota. One of the most influential and well-studied is host diet. To assess and interpret the impact of non-dietary factors on the gut microbiota, we endeavoured to determine the most appropriate method to summarise community variation attributable to dietary effects. Dietary habits are multidimensional with internal correlations. This complexity can be simplified by using dietary indices that quantify dietary variance in a single measure and offer a means of controlling for diet in microbiota studies. However, to date, the applicability of different dietary indices to gut microbiota studies has not been assessed. Here, we use food frequency questionnaire (FFQ) data from members of the TwinsUK cohort to create three different dietary measures applicable in western-diet populations: The Healthy Eating Index (HEI), the Mediterranean Diet Score (MDS) and the Healthy Food Diversity index (HFD-Index). We validate and compare these three indices to determine which best summarises dietary influences on gut microbiota composition. RESULTS: All three indices were independently validated using established measures of health, and all were significantly associated with microbiota measures; the HEI had the highest t values in models of alpha diversity measures, and had the highest number of associations with microbial taxa. Beta diversity analyses showed the HEI explained the greatest variance of microbiota composition. In paired tests between twins discordant for dietary index score, the HEI was associated with the greatest variation of taxa and twin dissimilarity. CONCLUSIONS: We find that the HEI explains the most variance in, and has the strongest association with, gut microbiota composition in a western (UK) population, suggesting that it may be the best summary measure to capture gut microbiota variance attributable to habitual diet in comparable populations.

Dietary Magnesium May Be Protective for Aging of Bone and Skeletal Muscle in Middle and Younger Older Age Men and Women: Cross-Sectional Findings from the UK Biobank Cohort.

Although fragility fractures, osteoporosis, sarcopenia, and frailty are becoming more prevalent in our aging society the treatment options are limited and preventative strategies are needed. Despite magnesium being integral to bone and muscle physiology, the relationship between dietary magnesium and skeletal muscle and bone health has not been investigated concurrently to date. We analysed cross-sectional associations between dietary magnesium and skeletal muscle mass (as fat free mass-FFM), grip strength, and bone density (BMD) in 156,575 men and women aged 39-72 years from the UK Biobank cohort. FFM was measured with bioelectrical impedance and was expressed as the percentage of body weight (FFM%) or as divided by body mass index (FFMBMI). Adjusted mean grip strength, FFM%, FFMBMI, and BMD were calculated according to quintiles of dietary magnesium, while correcting for covariates. Significant inter-quintile differences across intakes of magnesium existed in men and women, respectively, of 1.1% and 2.4% for grip strength, 3.0% and 3.6% for FFM%, 5.1% and 5.5% for FFMBMI, and 2.9% and 0.9% for BMD. These associations are as great or greater than annual measured losses of these musculoskeletal outcomes, indicating potential clinical significance. Our study suggests that dietary magnesium may play a role in musculoskeletal health and has relevance for population prevention strategies for sarcopenia, osteoporosis, and fractures.

Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia.

Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001). CONCLUSION: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: • Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). • The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: • Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. • An elevated CRP concentration during the first postnatal week may be regarded as an expected finding in moderate and severe HIE and, in the overwhelming majority of cases, occurs secondary to hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis.

Stuttering, alcohol consumption and smoking.

PURPOSE: Limited research has been published regarding the association between stuttering and substance use. An earlier study provided no evidence for such an association, but the authors called for further research to be conducted using a community sample. The present study used data from a community sample to investigate whether an association between stuttering and alcohol consumption or regular smoking exists in late adolescence and adulthood. METHODS: Regression analyses were carried out on data from a birth cohort study, the National Child Development Study (NCDS), whose initial cohort included 18,558 participants who have since been followed up until age 55. In the analyses, the main predictor variable was parent-reported stuttering at age 16. Parental socio-economic group, cohort member's sex and childhood behavioural problems were also included. The outcome variables related to alcohol consumption and smoking habits at ages 16, 23, 33, 41, 46, 50 and 55. RESULTS: No significant association was found between stuttering and alcohol consumption or stuttering and smoking at any of the ages. It was speculated that the absence of significant associations might be due to avoidance of social situations on the part of many of the participants who stutter, or adoption of alternative coping strategies. CONCLUSION: Because of the association between anxiety and substance use, individuals who stutter and are anxious might be found to drink or smoke excessively, but as a group, people who stutter are not more likely than those who do not to have high levels of consumption of alcohol or nicotine.

Does resuscitation status affect decision making in a deteriorating patient? Results from a randomised vignette study.

AIMS AND OBJECTIVES: The aim of this paper is to determine the influence of do not attempt cardiopulmonary resuscitation (DNACPR) orders and the Universal Form of Treatment Options ('UFTO': an alternative approach that contextualizes the resuscitation decision within an overall treatment plan) on nurses' decision making about a deteriorating patient. METHODS: An online survey with a developing case scenario across three timeframes was used on 231 nurses from 10 National Health Service Trusts. Nurses were randomised into three groups: DNACPR, the UFTO and no-form. Statements were pooled into four subcategories: Increasing Monitoring, Escalating Concern, Initiating Treatments and Comfort Measures. RESULTS: Reported decisions were different across the three groups. Nurses in the DNACPR group agreed or strongly agreed to initiate fewer intense nursing interventions than the UFTO and no-form groups (P < 0.001) overall and across subcategories of Increase Monitoring, Escalate Concern and Initiate Treatments (all P < 0.001). There was no difference between the UFTO and no-form groups overall (P = 0.795) or in the subcategories. No difference in Comfort Measures were observed (P = 0.201) between the three groups. CONCLUSION: The presence of a DNACPR order appears to influence nurse decision making in a deteriorating patient vignette. Differences were not observed in the UFTO and no-form group. The UFTO may improve the way nurses modulate their behaviours towards critically ill patients with DNACPR status. More hospitals should consider adopting an approach where the resuscitation decisions are contextualised within overall goals of care.

Metastatic Midgut Carcinoid in the Myocardium.

Metastasis of neuroendocrine tumor to the myocardium is rare. We present a case of 64-year-old woman, who presented initially with abdominal pain and large adnexal mass. The image-guided biopsy showed low-grade neuroendocrine tumor with Ki67 less than 2% within the ovarian tissue. CT staging revealed bilateral adnexal masses, liver metastases, and primary lesion in the terminal ileum. Octreoscan showed marked tracer uptake within the lower esophagus not related to obvious mass on CT scan; the echocardiography confirmed the presence of a 2.7 cm LV/LA mass. In this case, close correlation between ECHO and the octreoscan obviated need for myocardial biopsy.

Correction: evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines.

[This corrects the article DOI: 10.1371/journal.pone.0078053.].

Observational gait assessment tools in paediatrics--a systematic review.

Instrumented gait analysis (IGA) is an expensive technique used to objectively detect gait abnormalities in children. Observational gait assessment is considered as a cost effective alternate for IGA in regular clinical practice. This article is aimed at systematically reviewing the available paediatric gait analysis tools and examines their reliability and validity compared to IGA. This review also examines the structure of these tools, their clinical use and limitations. Articles were searched from PubMed, CINHL, AMED, BNI, EMBASE, PEDro and Cochrane library from the earliest record on the database to December 2012. Hand searches were carried out in a few journals. Studies that examined children's gait using a structured assessment tool were included and analysed for their quality, reliability and validity. Pre-established criteria were used to judge the quality of methodology and reliability and validity. Five observational gait tools for children with Cerebral Palsy (CP) and one for children with Downs Syndrome were identified. Nine studies related to children with CP were enrolled for this review. None of the tools have accomplished the level of IGA's consistency. Edinburgh Visual Gait Score (EVGS) was found to have better reliability and validity than the other tools. Very limited studies were available for most of the gait assessment tools therefore their clinical use cannot be judged based on the existing evidence. EVGS was found to have better concurrent validity and reliability and it should be considered to assess CP gait in regular practice. Future work to investigate the use of low cost technology to improve observers' accuracy of EVGS is suggested.

Low copy number of the salivary amylase gene predisposes to obesity.

Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10(-14)) and serum enzyme levels (P < 2.20 × 10(-16)), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 × 10(-10)) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10(-10)). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies.