A four-week dietary intervention with mycoprotein-containing food products reduces serum cholesterol concentrations in community-dwelling, overweight adults: A randomised controlled trial.

BACKGROUND: Substituting dietary meat and fish for mycoprotein, a fungal-derived food source rich in protein and fibre, decreases circulating cholesterol concentrations in laboratory-controlled studies. However, whether these findings can be translated to a home-based setting, and to decrease cholesterol concentrations in overweight and hypercholesterolemic individuals, remains to be established. OBJECTIVE: We investigated whether a remotely-delivered, home-based dietary intervention of mycoprotein-containing food products would affect various circulating cholesterol moieties and other markers of cardio-metabolic health in overweight (BMI >27.5 kg⋅m-2) and hypercholesterolaemic (>5.0 mmol⋅L-1) adults. METHODS: Seventy-two participants were randomized into a controlled, parallel-group trial conducted in a free-living setting, in which they received home deliveries of either meat/fish control products (CON; n = 39; BMI 33 ± 1 kg⋅m-2; 13 males, 26 females) or mycoprotein-containing food products (MYC; n = 33; BMI 32 ± 1 kg⋅m-2; 13 males, 20 females) for 4 weeks. Fingertip blood samples were collected and sent via postal service before and after the dietary intervention period and analysed for concentrations of serum lipids, blood glucose and c-peptide. RESULTS: Serum total cholesterol concentrations were unchanged throughout the intervention in CON, but decreased by 5 ± 2 % in MYC (from 5.4 ± 0.2 to 5.1 ± 0.2 mmol⋅L-1; P < 0.05). Serum low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol concentrations were also unchanged in CON, but decreased in MYC by 10 ± 3 % and 6 ± 2 % (both by 0.3 ± 0.1 mmol⋅L-1; P < 0.05). Serum high-density lipoprotein cholesterol and free triglyceride concentrations were unaffected in CON or MYC. Post-intervention, MYC displayed lower mean blood glucose (3.7 ± 0.2 versus 4.3 ± 0.2 mmol⋅L-1) and c-peptide (779 ± 76 vs. 1064 ± 86 pmol⋅L-1) concentrations (P < 0.05) vs. CON. CONCLUSIONS: We show that a home-based dietary intervention of mycoprotein-containing food products effectively lowers circulating cholesterol concentrations in overweight, hypercholesterolemic adults. This demonstrates that mycoprotein consumption is a feasible and ecologically valid dietary strategy to improve markers of cardio-metabolic health in an at-risk population under free living conditions. CLINICAL TRIAL REGISTRATION: NCT04773483 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04773483).

The effect of the Mid-Day Meal programme on the longitudinal physical growth from childhood to adolescence in India.

The study aims to examine the effect of the world's largest school-feeding programme, the Mid-Day Meal (MDM) programme, on the changes in the underweight prevalence among school-children in India. Data from the Indian Human Development Survey (IHDS) Rounds 1 (2004-05) and 2 (2011-12) were utilized. The sample included individual-level information of children aged 6 to 9 years in IHDS-1 who then turned 13 to 16 years in IHDS-2. The sample was categorised into four groups based on their MDM consumption history (Group 1: no MDM support in IHDS-1 and IHDS-2, Group 2: MDM support in IHDS-1, Group 3: MDM support in IHDS-2, Group 4: persistent MDM support in IHDS-1 and IHDS-2). The dependent variable was underweight status as defined by the World Health Organisation Child Growth Standards Body Mass Index for age (BMI Z-score) < -2 SD of the median. Bivariate analysis was used to examine the prevalence of underweight and establish associations between underweight status and socio-demographic characteristics. Logistic regression was performed to assess the strength of the association of socio-demographic characteristics and MDM consumption patterns with underweight across poor and non-poor asset groups. The findings suggest that early and persistent MDM support among respondents reduced the likelihood of low BMI Z-scores compared to those without MDM support. Respondents from the poor asset group who received MDM support in at least one of the two survey rounds had higher odds of being underweight in comparison with those who did not receive MDM support at all. Girls and adolescents residing in the Eastern region of India were less likely to be underweight. The study shows that the MDM programme was effective in reducing the rate of underweight among school children. However, continuous programme upscaling with a special focus on children from poor households will significantly benefit India's school-aged children.

The evolution of nutritional care in children and young people with acute lymphoblastic leukaemia: a narrative review.

BACKGROUND: Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy in the world. Advances in treatment protocols have resulted in survival rates of >80% in most high-income countries (HIC); however, children and young people (CYP) with ALL continue to face significant nutrition-related challenges during treatment. METHODS: This narrative review outlines the changing landscape of treatment and survivorship for CYP with ALL and the advances in nutrition knowledge that call for changes to clinical nutrition practice. RESULTS: The incidence of ALL has remained stable in HIC; however, there have been significant advances in survival over the past 30 years. Overweight and obesity are increasingly prevalent in CYP with ALL at diagnosis, during treatment and in survivorship. Coupled with poor diet quality, high-energy and saturated fat intakes, altered eating behaviours and inactivity, this necessitates the need for a shift in nutrition intervention. Undernutrition remains a concern for CYP with high-risk treatment protocols where oral or enteral nutrition support remains a cornerstone of maintaining nutrition status. CONCLUSIONS: With improved treatment protocols and high survival rates, a shift to focusing on diet quality, prevention of excessive weight gain and obesity during treatment and survivorship is necessary.

Maximal sustainable energy intake during transatlantic ocean rowing is insufficient for total energy expenditure and skeletal muscle mass maintenance.

Studies of extreme endurance have suggested that there is an alimentary limit to energy intake (EI) of ∼2.5 × resting metabolic rate (RMR). To gain further insight, this study aimed to simultaneously measure EI, total energy expenditure (TEE) body mass and muscle mass in a large cohort of males and females of varying ages during a transatlantic rowing race. Forty-nine competitors (m = 32, f = 17; age 24-67 years; time at sea 46 ± 7 days) in the 2020 and 2021 Talisker Whisky Atlantic Challenge rowed 12-18 hday-1 for ∼3000 miles. TEE was assessed in the final week of the row using 2 H2 18 O doubly labelled water, and EI was analysed from daily ration packs over this period. Thickness of relatively active (vastus lateralis, intermedius, biceps brachaii and rectus abdominus) and inactive (gastrocnemius, soleus and triceps) muscles was measured pre (<7 days) and post (<24 h) row using ultrasound. Body mass was measured and used to calculate RMR from standard equations. There were no sex differences in males and females in EI (2.5 ± 0.5 and 2.3 ± 0.4 × RMR, respectively, P = 0.3050), TEE (2.5 ± 1.0 and 2.3 ± 0.4 × RMR, respectively, P = 0.5170), or body mass loss (10.2 ± 3.1% and 10.0 ± 3.0%, respectively, P = 0.8520), and no effect of age on EI (P = 0.5450) or TEE (P = 0.9344). Muscle loss occurred exclusively in the calf (15.7% ± 11.4% P < 0.0001), whilst other muscles remained unchanged. After 46 days of prolonged ultra-endurance ocean rowing incurring 10% body mass loss, maximal sustainable EI of ∼2.5 × RMR was unable to meet total TEE suggesting that there is indeed a physiological capacity to EI.

Systematic review and meta-analysis: Associations of vitamin D with pulmonary function in children and young people with cystic fibrosis.

BACKGROUND: Increasing evidence suggests that vitamin D is associated with pulmonary health, which may benefit children and young people diagnosed with Cystic Fibrosis (cypCF). Therefore, the aim of this systematic review was to evaluate primary research to establish associations between 25OHD and pulmonary health in cypCF. METHODS: Electronic databases were searched with keywords related to CF, vitamin D, children/young people and pulmonary function. Included studies were cypCF (aged ≤21 years) treated in a paediatric setting. The primary outcome was lung function [forced expiratory volume in 1 s (FEV1% predicted)] and secondary outcomes were rate of pulmonary exacerbations, 25OHD status and growth. Evidence was appraised for risk of bias using the CASP tool, and quality using the EPHPP tool. A Meta-analysis was performed. RESULTS: Twenty-one studies were included with mixed quality ratings and heterogeneity of reported outcomes. The Meta-analysis including 5 studies showed a significantly higher FEV1% predicted in the 25OHD sufficiency compared to the deficiency group [FEV1% predicted mean difference (95% CI) was 7.71 (1.69-13.74) %; p = 0.01]. The mean ± SD FEV1% predicted for the sufficient (≥75 nmol/L) vs. deficient (<50 nmol/L) group was 94.7 ± 31.9% vs. 86.9 ± 13.2%; I2 = 0%; χ2 = 0.5; df = 4). Five studies (5/21) found significantly higher rate of pulmonary exacerbations in those who were 25OHD deficient when compared to the sufficient group and negative associations between 25OHD and FEV% predicted. The effects of vitamin D supplementation dosages on 25OHD status (10/21) varied across studies and no study (12/21) showed associations between 25OHD concentration and growth. CONCLUSION: This systematic review suggests that 25OHD concentration is positively associated with lung function and a concentration of >75 nmol/L is associated with reduced frequency of pulmonary exacerbations, which may slow lung function decline in cypCF. Future randomised clinical trials and mechanistic studies are warranted.

A shortened surface electromyography recording is sufficient to facilitate home fasciculation assessment.

INTRODUCTION/AIMS: Fasciculations are an early clinical hallmark of amyotrophic lateral sclerosis (ALS), amenable to detection by high-density surface electromyography (HDSEMG). In conjunction with the Surface Potential Quantification Engine (SPiQE), HDSEMG offers improved spatial resolution for the analysis of fasciculations. This study aims to establish an optimal recording duration to enable longitudinal remote monitoring in the home. METHODS: Twenty patients with ALS and five patients with benign fasciculation syndrome (BFS) underwent serial 30 min HDSEMG recordings from biceps brachii and gastrocnemii. SPiQE was independently applied to abbreviated epochs within each 30-min recording (0-5, 0-10, 0-15, 0-20, and 0-25 min), outputting fasciculation frequency, amplitude median and amplitude interquartile range. Bland-Altman plots and intraclass correlation coefficients (ICC) were used to assess agreement with the validated 30-min recording. RESULTS: In total, 506 full recordings were included. The 5 min recordings demonstrated diverse and relatively poor agreement with the 30 min baselines across all parameters, muscles and patient groups (ICC = 0.32-0.86). The 15-min recordings provided more acceptable and stable agreement (ICC = 0.78-0.98), which did not substantially improve in longer recordings. DISCUSSION: For the detection and quantification of fasciculations in patients with ALS and BFS, HDSEMG recordings can be halved from 30 to 15 min without significantly compromising the primary outputs. Reliance on a shorter recording duration should lead to improved tolerability and repeatability among patients, facilitating longitudinal remote monitoring in patients' homes.

Vitamin D Status and Health Outcomes in School Children in Northern Ireland: Year One Results from the D-VinCHI Study.

(1) Background: Vitamin D status has never been investigated in children in Northern Ireland (UK). (2) Methods: Children (4-11 years) (n = 47) were recruited from November 2019 to March 2020 onto the cross-sectional study. Anthropometry was assessed. Plasma 25-hydroxyvitamin D (25(OH)D) was analysed. Vitamin D intake, parental knowledge and perceptions, participant habits, physical activity and sedentary behaviour were established via questionnaire. Muscle strength was assessed via isometric grip strength dynamometry and balance via dominant single-leg and tandem stance. Parathyroid hormone, bone turnover markers (OC, CTX and P1NP), glycated haemoglobin and inflammatory markers (CRP, IFN-γ, IL-10, IL-12p70, IL-13, IL-1ß, IL-2, IL-4, IL-6, IL-8 and TNF-α) were analysed. (3) Results: Mean (SD) 25(OH)D was 49.17 (17.04) nmol/L (n = 47); 44.7% of the children were vitamin D sufficient (25(OH)D >50 nmol/L), 48.9% were insufficient (25-50 nmol/L) and 6.4% were deficient (<25 nmol/L). 25(OH)D was positively correlated with vitamin D intake (µg/day) (p = 0.012, r = 0.374), spring/summer outdoor hours (p = 0.006, r = 0.402) and dominant grip strength (kg) (p = 0.044, r = 0.317). Vitamin D sufficient participants had higher dietary vitamin D intake (µg/day) (p = 0.021), supplement intake (µg/day) (p = 0.028) and spring/summer outdoor hours (p = 0.015). (4) Conclusion: Over half of the children were vitamin D deficient or insufficient. Wintertime supplementation, the consumption of vitamin D rich foods and spring/summer outdoor activities should be encouraged to minimise the risk of vitamin D inadequacy.

The impact of plasma 25-hydroxyvitamin D on pulmonary function and exercise physiology in cystic fibrosis: A multicentre retrospective study.

BACKGROUND: A 25-hydroxyvitamin D (25OHD) may exert immunomodulatory effects on respiratory health, which may translate to improvements in exercise physiology. Thus, we aimed to investigate whether plasma 25OHD is associated with lung function and aerobic fitness in people with cystic fibrosis (pwCF). METHODS: A multicentre retrospective review of pwCF (> 9 years old) attending the Royal Hospital for Sick Children (Edinburgh) or Wessex CF-Unit (Southampton) was performed between July 2017 and October 2019. Demographic and clinical data were collected. Plasma 25OHD measured closest in time to clinical cardiopulmonary exercise testing and/or spirometry [forced expiratory volume (FEV1 )% predicted] was recorded. Pancreatic insufficiency was diagnosed based on faecal elastase of < 100 µg g-1 . We performed multiple-regression analysis with aerobic fitness outcomes [peak oxygen uptake (VO2 peak )] and FEV1 % predicted as primary outcomes. RESULTS: Ninety pwCF [mean ± SD age: 19.1 ± 8.6 years, 54 (60%) children, 48 (53%) males and 88 (98%) Caucasian] were included. 25OHD deficiency and insufficiency was 15 (17%) and 44 (49%), respectively. 25OHD deficiency and insufficiency was significantly associated with pancreatic insufficiency (χ2  = 4.8, p = 0.02). Plasma 25OHD was not significantly associated with FEV1 % predicted (r2  = 0.06, p = 0.42, 95% CI = -0.09 to 0.19) or VO2 peak (r2  = 0.04, p = 0.07, 95% CI = -011 to 0.005) in all pwCF. However, 25OHD was significantly associated with both FEV1 % (r2  = 0.15, p = 0.02, 95% CI = 1.99-2.64) and VO2 peak (r2  = 0.13, p = 0.05, 95% CI = -0.26 to -0.005) in the paediatric cohort. CONCLUSIONS: We showed that 25OHD is associated with improved lung function and aerobic fitness in children and adolescents with CF. Mechanistic and high-quality prospective studies including both lung function and aerobic fitness as primary outcomes are now warranted.

Identifying homogeneous subgroups of patients and important features: a topological machine learning approach.

BACKGROUND: This paper exploits recent developments in topological data analysis to present a pipeline for clustering based on Mapper, an algorithm that reduces complex data into a one-dimensional graph. RESULTS: We present a pipeline to identify and summarise clusters based on statistically significant topological features from a point cloud using Mapper. CONCLUSIONS: Key strengths of this pipeline include the integration of prior knowledge to inform the clustering process and the selection of optimal clusters; the use of the bootstrap to restrict the search to robust topological features; the use of machine learning to inspect clusters; and the ability to incorporate mixed data types. Our pipeline can be downloaded under the GNU GPLv3 license at https://github.com/kcl-bhi/mapper-pipeline .

First-recruited motor units adopt a faster phenotype in amyotrophic lateral sclerosis.

KEY POINTS: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder of motor neurons, carrying a short survival. High-density motor unit recordings permit analysis of motor unit size (amplitude) and firing behaviour (afterhyperpolarization duration and muscle fibre conduction velocity). Serial recordings from biceps brachii indicated that motor units fired faster and with greater amplitude as disease progressed. First-recruited motor units in the latter stages of ALS developed characteristics akin to fast-twitch motor units, possibly as a compensatory mechanism for the selective loss of this motor unit subset. This process may become maladaptive, highlighting a novel therapeutic target to reduce motor unit vulnerability. ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with a median survival of 3 years. We employed serial high-density surface electromyography (HDSEMG) to characterize voluntary and ectopic patterns of motor unit (MU) firing at different stages of disease. By distinguishing MU subtypes with variable vulnerability to disease, we aimed to evaluate compensatory neuronal adaptations that accompany disease progression. Twenty patients with ALS and five patients with benign fasciculation syndrome (BFS) underwent 1-7 assessments each. HDSEMG measurements comprised 30 min of resting muscle and 1 min of light voluntary activity from biceps brachii bilaterally. MU decomposition was performed by the progressive FastICA peel-off technique. Inter-spike interval, firing pattern, MU potential area, afterhyperpolarization duration and muscle fibre conduction velocity were determined. In total, 373 MUs (ALS = 287; BFS = 86) were identified from 182 recordings. Weak ALS muscles demonstrated a lower mean inter-spike interval (82.7 ms) than strong ALS muscles (96.0 ms; P = 0.00919) and BFS muscles (95.3 ms; P = 0.0039). Mean MU potential area (area under the curve: 487.5 vs. 98.7 µV ms; P < 0.0001) and muscle fibre conduction velocity (6.2 vs. 5.1 m/s; P = 0.0292) were greater in weak ALS muscles than in BFS muscles. Purely fasciculating MUs had a greater mean MU potential area than MUs also under voluntary command (area under the curve: 679.6 vs. 232.4 µV ms; P = 0.00144). These results suggest that first-recruited MUs develop a faster phenotype in the latter stages of ALS, likely driven by the preferential loss of vulnerable fast-twitch MUs. Inhibition of this potentially maladaptive phenotypic drift may protect the longevity of the MU pool, stimulating a novel therapeutic avenue.

The promise of machine learning in predicting treatment outcomes in psychiatry.

For many years, psychiatrists have tried to understand factors involved in response to medications or psychotherapies, in order to personalize their treatment choices. There is now a broad and growing interest in the idea that we can develop models to personalize treatment decisions using new statistical approaches from the field of machine learning and applying them to larger volumes of data. In this pursuit, there has been a paradigm shift away from experimental studies to confirm or refute specific hypotheses towards a focus on the overall explanatory power of a predictive model when tested on new, unseen datasets. In this paper, we review key studies using machine learning to predict treatment outcomes in psychiatry, ranging from medications and psychotherapies to digital interventions and neurobiological treatments. Next, we focus on some new sources of data that are being used for the development of predictive models based on machine learning, such as electronic health records, smartphone and social media data, and on the potential utility of data from genetics, electrophysiology, neuroimaging and cognitive testing. Finally, we discuss how far the field has come towards implementing prediction tools in real-world clinical practice. Relatively few retrospective studies to-date include appropriate external validation procedures, and there are even fewer prospective studies testing the clinical feasibility and effectiveness of predictive models. Applications of machine learning in psychiatry face some of the same ethical challenges posed by these techniques in other areas of medicine or computer science, which we discuss here. In short, machine learning is a nascent but important approach to improve the effectiveness of mental health care, and several prospective clinical studies suggest that it may be working already.

Micronutrient status influences clinical outcomes of paediatric cancer patients during treatment: A prospective cohort study.

BACKGROUND: Research reporting plasma micronutrient status and its impact on clinical outcomes in paediatric cancer is scarce. Therefore, we investigated the prevalence of plasma micronutrient abnormalities and their impact on clinical outcomes and treatment complications. METHODS: A multicentre prospective-cohort study of children aged <18 years diagnosed with cancer was performed between Aug 2010-Jan 2014. Clinical and nutritional data were collected at diagnosis, 3, 6, 9, 12 and 18 months. Micronutrient status was established using in-house laboratory references (vitamin B12, vitamin A and Vitamin E/Ch) and aged adjusted Z-scores (Mg, Se, Zn and Cu) generated from a cohort of healthy Scottish children. Clinical outcomes were classified as "event free survival (EFS)" or "event" (relapse, death, new metastasis or becoming palliative) and treatment complications. Descriptive statistics, logistic regression and multilevel analysis were performed. RESULTS: Eighty-two patients [median (IQR) 3.9 (1.9-8.8) years, 56% males] were recruited. Of these, 72 (88%) samples were available, 74% (53/72) patients had micronutrient abnormalities at baseline; deficiencies (25%, 18/72), excesses (19%, 14/72) and a combination of both (29%, 21/72), which continued for 18 months. Vitamin A deficiency (15%, 3/20) and excess (50%, 10/20) were most prevalent at 18 months, whilst vitamin E/Cholesterol and vitamin B12 were mostly within the normal range. Prevalence of Zn deficiency at diagnosis was 36% (16/44 adjusted for CRP), which remained at these levels throughout the study. Reduction in each selenium concentration unit increased the odds of an event by 2% (OR 0.02) and lower Se predicted higher complications at diagnosis [ß (-1.2); t (-2.1); 95% CI (-2.9 - (-0.04)); p = 0.04], 3 months [ß (-3.9); t (-4.2); 95% CI (-5.57 - (-2.02)); p < 0.001] and 12 months [ß (-2.3); t (-2.4); 95% CI (-4.10 - (-0.34)); p = 0.02]. CONCLUSIONS: Given the prevalence of micronutrient abnormalities and the negative impact of low selenium on clinical outcome, micronutrient status should be assessed and monitored in paediatric cancer patients. Larger multicentre population based studies and clinical trials are now warranted.

Fasciculation analysis reveals a novel parameter that correlates with predicted survival in amyotrophic lateral sclerosis.

INTRODUCTION: Prognostic uncertainty in amyotrophic lateral sclerosis (ALS) confounds clinical management planning, patient counseling, and trial stratification. Fasciculations are an early clinical hallmark of disease and can be quantified noninvasively. Using an innovative analytical method, we correlated novel fasciculation parameters with a predictive survival model. METHODS: Using high-density surface electromyography, we collected biceps recordings from ALS patients on their first research visit. By accessing an online survival prediction tool, we provided eight clinical and genetic parameters to estimate individual patient survival. Fasciculation analysis was performed using an automated algorithm (Surface Potential Quantification Engine), with a Cox proportional hazards model to calculate hazard ratios. RESULTS: The median predicted survival for 31 patients was 41 (interquartile range, 31.5-57) months. Univariate hazard ratios were 1.09 (95% confidence interval [CI], 1.03-1.16) for the rate of change of fasciculation frequency (RoCoFF) and 1.10 (95% CI, 1.01-1.19) for the amplitude dispersion rate. Only the RoCoFF remained significant (P = .04) in a multivariate model. DISCUSSION: Noninvasive measurement of fasciculations at a single time-point could enhance prognostic models in ALS, where higher RoCoFF values indicate shorter survival.

The rise and fall of fasciculations in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a median survival of 3 years from symptom onset. Accessible and reliable biomarkers of motor neuron decline are urgently needed to quicken the pace of drug discovery. Fasciculations represent an early pathophysiological hallmark of amyotrophic lateral sclerosis and can be reliably detected by high-density surface electromyography. We set out to quantify fasciculation potentials prospectively over 14 months, seeking comparisons with established markers of disease progression. Twenty patients with amyotrophic lateral sclerosis and five patients with benign fasciculation syndrome underwent up to seven assessments each. At each assessment, we performed the amyotrophic lateral sclerosis-functional rating scale, sum power score, slow vital capacity, 30-min high-density surface electromyography recordings from biceps and gastrocnemius and the motor unit number index. We employed the Surface Potential Quantification Engine, which is an automated analytical tool to detect and characterize fasciculations. Linear mixed-effect models were employed to account for the pseudoreplication of serial measurements. The amyotrophic lateral sclerosis-functional rating scale declined by 0.65 points per month (P < 0.0001), 35% slower than average. A total of 526 recordings were analysed. Compared with benign fasciculation syndrome, biceps fasciculation frequency in amyotrophic lateral sclerosis was 10 times greater in strong muscles and 40 times greater in weak muscles. This was coupled with a decline in fasciculation frequency among weak muscles of -7.6/min per month (P = 0.003), demonstrating the rise and fall of fasciculation frequency in biceps muscles. Gastrocnemius behaved differently, whereby strong muscles in amyotrophic lateral sclerosis had fasciculation frequencies five times greater than patients with benign fasciculation syndrome while weak muscles were increased by only 1.5 times. Gastrocnemius demonstrated a significant decline in fasciculation frequency in strong muscles (2.4/min per month, P < 0.0001), which levelled off in weak muscles. Fasciculation amplitude, an easily quantifiable surrogate of the reinnervation process, was highest in the biceps muscles that transitioned from strong to weak during the study. Pooled analysis of >900 000 fasciculations revealed inter-fasciculation intervals <100 ms in the biceps of patients with amyotrophic lateral sclerosis, particularly in strong muscles, consistent with the occurrence of doublets. We hereby present the most comprehensive longitudinal quantification of fasciculation parameters in amyotrophic lateral sclerosis, proposing a unifying model of the interactions between motor unit loss, muscle power and fasciculation frequency. The latter showed promise as a disease biomarker with linear rates of decline in strong gastrocnemius and weak biceps muscles, reflecting the motor unit loss that drives clinical progression.

Nutritional screening and assessment of paediatric cancer patients: A quality improvement project (baseline results).

BACKGROUND: The department of Haematology and Oncology at the Royal Hospital for Sick Children (RHSC) in Edinburgh have developed their own nutritional standards specific to paediatric cancer. We aimed to audit the current nutritional practice in anthropometry, nutritional biochemistry and malnutrition screening for paediatric cancer patients against nutritional standards to identify areas for nutritional-practice improvement and progress nutrition-related clinical outcomes. METHODS: A Clinical audit was conducted >20 weeks between 2015 and 2017 in three data collection locations (inpatient (IP), day-care (DC), or outpatient (OP)) at RHSC. We included patients aged 0-18 years and undergoing treatment for diagnosed malignant childhood cancer (ICCC-3 or Langerhans Cell Histiocytosis). Data were collected by analysing documentation and observing clinical practice for frequency and mode of administration of anthropometry, malnutrition screening, nutritional biochemistry and resulting documentation completion. Results were presented as descriptive statistics and stratified by percentage of standard met (100%, 99-70%, <70%). RESULTS: 185 audited patient records (22 IP, 54 DC and 109 OP) were analysed. The areas which were <70% of the standard were: height and weight documentation for DC; head-circumference for IP; arm anthropometry assessment for all locations; initial PYMS screening and re-screening in IP; malnutrition screening in DC and OP; and initial assessment and re-assessment for serum vitamins D, A, E, B12 and parathyroid hormone levels. CONCLUSION: Baseline nutritional practice was successfully established, identifying areas for practice improvement in the RHSC Paediatric Oncology and Haematology Department; this will be implemented in the next step of the audit to optimise patient care.

Fasciculations demonstrate daytime consistency in amyotrophic lateral sclerosis.

INTRODUCTION: Fasciculations represent early neuronal hyperexcitability in amyotrophic lateral sclerosis (ALS). To aid calibration as a disease biomarker, we set out to characterize the daytime variability of fasciculation firing. METHODS: Fasciculation awareness scores were compiled from 19 ALS patients. In addition, 10 ALS patients prospectively underwent high-density surface electromyographic (HDSEMG) recordings from biceps and gastrocnemius at three time-points during a single day. RESULTS: Daytime fasciculation awareness scores were low (mean: 0.28 muscle groups), demonstrating significant variability (coefficient of variation: 303%). Biceps HDSEMG recordings were highly consistent for fasciculation potential frequency (intraclass correlation coefficient [ICC] = 95%, n = 19) and the interquartile range of fasciculation potential amplitude (ICC = 95%, n = 19). These parameters exhibited robustness to observed fluctuations in data quality parameters. Gastrocnemius demonstrated more modest levels of consistency overall (44% to 62%, n = 20). DISCUSSION: There was remarkable daytime consistency of fasciculation firing in the biceps of ALS patients, despite sparse and intermittent awareness among patients' accounts.

Working Towards a Blood-Derived Gene Expression Biomarker Specific for Alzheimer's Disease.

BACKGROUND: The typical approach to identify blood-derived gene expression signatures as a biomarker for Alzheimer's disease (AD) have relied on training classification models using AD and healthy controls only. This may inadvertently result in the identification of markers for general illness rather than being disease-specific. OBJECTIVE: Investigate whether incorporating additional related disorders in the classification model development process can lead to the discovery of an AD-specific gene expression signature. METHODS: Two types of XGBoost classification models were developed. The first used 160 AD and 127 healthy controls and the second used the same 160 AD with 6,318 upsampled mixed controls consisting of Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, bipolar disorder, schizophrenia, coronary artery disease, rheumatoid arthritis, chronic obstructive pulmonary disease, and cognitively healthy subjects. Both classification models were evaluated in an independent cohort consisting of 127 AD and 687 mixed controls. RESULTS: The AD versus healthy control models resulted in an average 48.7% sensitivity (95% CI = 34.7-64.6), 41.9% specificity (95% CI = 26.8-54.3), 13.6% PPV (95% CI = 9.9-18.5), and 81.1% NPV (95% CI = 73.3-87.7). In contrast, the mixed control models resulted in an average of 40.8% sensitivity (95% CI = 27.5-52.0), 95.3% specificity (95% CI = 93.3-97.1), 61.4% PPV (95% CI = 53.8-69.6), and 89.7% NPV (95% CI = 87.8-91.4). CONCLUSIONS: This early work demonstrates the value of incorporating additional related disorders into the classification model developmental process, which can result in models with improved ability to distinguish AD from a heterogeneous aging population. However, further improvement to the sensitivity of the test is still required.

Genetic and Inflammatory Biomarkers Classify Small Intestine Inflammation in Asymptomatic First-degree Relatives of Patients With Crohn's Disease.

BACKGROUND & AIMS: Relatives of individuals with Crohn's disease (CD) carry CD-associated genetic variants and are often exposed to environmental factors that increase their risk for this disease. We aimed to estimate the utility of genotype, smoking status, family history, and biomarkers can calculate risk in asymptomatic first-degree relatives of patients with CD. METHODS: We recruited 480 healthy first-degree relatives (full siblings, offspring or parents) of patients with CD through the Guy's and St Thomas' NHS Foundation Trust and from members of Crohn's and Colitis, United Kingdom. DNA samples were genotyped using the Immunochip. We calculated a risk score for 454 participants, based on 72 genetic variants associated with CD, family history, and smoking history. Participants were assigned to highest and lowest risk score quartiles. We assessed pre-symptomatic inflammation by capsule endoscopy and measured 22 markers of inflammation in stool and serum samples (reference standard). Two machine-learning classifiers (elastic net and random forest) were used to assess the ability of the risk factors and biomarkers to identify participants with small intestinal inflammation in the same dataset. RESULTS: The machine-learning classifiers identified participants with pre-symptomatic intestinal inflammation: elastic net (area under the curve, 0.80; 95% CI, 0.62-0.98) and random forest (area under the curve, 0.87; 95% CI, 0.75-1.00). The elastic net method identified 3 variables that can be used to calculate odds for intestinal inflammation: combined family history of CD (odds ratio, 1.31), genetic risk score (odds ratio, 1.14), and fecal calprotectin (odds ratio, 1.04). These same 3 variables were among the 5 factors associated with intestinal inflammation in the random forest model. CONCLUSION: Using machine learning classifiers, we found that genetic variants associated with CD, family history, and fecal calprotectin together identify individuals with pre-symptomatic intestinal inflammation who are therefore at risk for CD. A tool for detecting people at risk for CD before they develop symptoms would help identify the individuals most likely to benefit from early intervention.

Non-invasive measurement of fasciculation frequency demonstrates diagnostic accuracy in amyotrophic lateral sclerosis.

Delayed diagnosis of amyotrophic lateral sclerosis prevents early entry into clinical trials at a time when neuroprotective therapies would be most effective. Fasciculations are an early hallmark of amyotrophic lateral sclerosis, preceding muscle weakness and atrophy. To assess the potential diagnostic utility of fasciculations measured by high-density surface electromyography, we carried out 30-min biceps brachii recordings in 39 patients with amyotrophic lateral sclerosis, 7 patients with benign fasciculation syndrome, 1 patient with multifocal motor neuropathy and 17 healthy individuals. We employed the surface potential quantification engine to compute fasciculation frequency, fasciculation amplitude and inter-fasciculation interval. Inter-group comparison was assessed by Welch's analysis of variance. Logistic regression, receiver operating characteristic curves and decision trees discerned the diagnostic performance of these measures. Fasciculation frequency, median fasciculation amplitude and proportion of inter-fasciculation intervals <100 ms showed significant differences between the groups. In the best-fit regression model, increasing fasciculation frequency and median fasciculation amplitude were independently associated with the diagnosis of amyotrophic lateral sclerosis. Fasciculation frequency was the single best measure predictive of the disease, with an area under the curve of 0.89 (95% confidence interval 0.81-0.98). The cut-off of more than 14 fasciculation potentials per minute achieved 80% sensitivity (95% confidence interval 63-90%) and 96% specificity (95% confidence interval 78-100%). In conclusion, non-invasive measurement of fasciculation frequency at a single time-point reliably distinguished amyotrophic lateral sclerosis from its mimicking conditions and healthy individuals, warranting further research into its diagnostic applications.