Analytic regularity for a singularly perturbed system of reaction-diffusion equations with multiple scales: proofs

We consider a coupled system of two singularly perturbed reaction-diffusion equations, with two small parameters $0< \epsilon \le \mu \le 1$, each multiplying the highest derivative in the equations. The presence of these parameters causes the solution(s) to have \emph{boundary layers} which overlap and interact, based on the relative size of $\epsilon$ and $$. We construct full asymptotic expansions together with error bounds that cover the complete range $0 < \epsilon \leq \mu \leq 1$. For the present case of analytic input data, we derive derivative growth estimates for the terms of the asymptotic expansion that are explicit in the perturbation parameters and the expansion order

National trends in retreatment of HCV due to reinfection or treatment failure in Australia

Background & Aims: Population-level uptake of direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection, including retreatment, can be estimated through administrative pharmaceutical dispensation data. However, the reasons for retreatment are not captured in these data. We developed a machine learning model to classify retreatments as reinfection or treatment failure at a national level. Methods: Retreatment data from the REACH-C cohort (n = 10,843 treated with DAAs; n = 320 retreatments with known reason), were used to train a random forest model. Nested cross validation was undertaken to assess model performance and to optimise hyperparameters. The model was applied to data on DAA retreatment dispensed during 2016-2021 in Australia, to identify the reason for retreatment (treatment failure or reinfection). Results: Average predictive accuracy, precision, sensitivity, specificity and F1-score for the model were 96.3%, 96.5%, 96.3%, 96.3% and 96.3%, respectively. Nationally, 95,272 individuals initiated DAAs, with treatment uptake declining from 32,454 in 2016 to 6,566 in 2021. Of those treated, 6,980 (7%) were retreated. Our model classified 51.8% (95% CI 46.7–53.6%; n = 3,614) of cases as reinfection and 48.2% (95% CI 46.4–53.3%; n = 3,366) as treatment failure. Retreatment for reinfection increased steadily over the study period from 14 in 2016 to 1,092 in 2020, stabilising in 2021. Retreatment for treatment failure increased from 73 in 2016 to 1,077 in 2019, then declined to 515 in 2021. Among individuals retreated for treatment failure, 50% had discontinued initial treatment. Conclusions: We used a novel methodology with high classification accuracy to evaluate DAA retreatment patterns at a national level. Increases in retreatment uptake for treatment failure corresponded to the availability of pangenotypic and salvage regimens. Increasing retreatment uptake for reinfection likely reflects increasing reinfection incidence. Impact and implications: This study used machine learning methodologies to analyse national administrative data and characterise trends in HCV retreatment due to reinfection and treatment failure. Retreatment for reinfection increased over time, reflecting increasing numbers of people at risk for reinfection following HCV cure. Increased retreatment for treatment failure corresponded to the availability of pangenotypic and salvage DAA regimens. The findings of this study can be used by public health agencies and policy makers to guide and assess HCV elimination strategies, while the novel methodology for monitoring trends in HCV retreatment has the potential to be used in other settings, and health conditions

Oscillations on the star Procyon

Stars are sphere of hot gas whose interiors transmit acoustic waves very efficiently. Geologists learn about the interior structure of Earth by monitoring how seismic waves propagate through it and, in a similar way, the interior of a star can be probed using the periodic motions on the surface that arise from such waves. Matthews et al. claim that the star Procyon does not have acoustic surface oscillations of the strength predicted. However, we show here, using ground-based spectroscopy, that Procyon is oscillating, albeit with an amplitude that is only slightly greater than the noise level observed by Matthews et al. using spaced-based photometry

The long exercise test as a functional marker of periodic paralysis

Aims: The aim of this study was to evaluate the sensitivity of the long exercise test (LET) in the diagnosis of periodic paralysis (PP) and assess correlations with clinical phenotypes and genotypes. // Methods: From an unselected cohort of 335 patients who had an LET we analyzed 67 patients with genetic confirmation of PP and/or a positive LET. // Results: 32/45 patients with genetically confirmed PP had a significant decrement after exercise (sensitivity of 71%). Performing the short exercise test before the LET in the same hand confounded results in four patients. Sensitivity was highest in patients with frequent (daily or weekly) attacks (8/8, 100%), intermediate with up to monthly attacks (15/21, 71%) and lowest in those with rare attacks (9/16, 56%) (p = .035, Mann–Whitney U-test). Patients with a positive LET without confirmed PP mutation comprised those with typical PP phenotype and a group with atypical features. // Discussion: In our cohort, the LET is strongly correlated with the frequency of paralytic attacks suggesting a role as a functional marker. A negative test in the context of frequent attacks makes a diagnosis of PP unlikely but it does not rule out the condition in less severely affected patients

Simulating quantum statistics with entangled photons: a continuous transition from bosons to fermions

In contrast to classical physics, quantum mechanics divides particles into two classes-bosons and fermions-whose exchange statistics dictate the dynamics of systems at a fundamental level. In two dimensions quasi-particles known as 'anyons' exhibit fractional exchange statistics intermediate between these two classes. The ability to simulate and observe behaviour associated to fundamentally different quantum particles is important for simulating complex quantum systems. Here we use the symmetry and quantum correlations of entangled photons subjected to multiple copies of a quantum process to directly simulate quantum interference of fermions, bosons and a continuum of fractional behaviour exhibited by anyons. We observe an average similarity of 93.6\pm0.2% between an ideal model and experimental observation. The approach generalises to an arbitrary number of particles and is independent of the statistics of the particles used, indicating application with other quantum systems and large scale application.Comment: 10 pages, 5 figure

Muscle MRI reveals distinct abnormalities in genetically proven non-dystrophic myotonias.

We assessed the presence, frequency and pattern of MRI abnormalities in non-dystrophic myotonia patients. We reviewed T1-weighted and STIR (short-tau-inversion-recovery) 3T MRI sequences of lower limb muscles at thigh and calf level in 21 patients with genetically confirmed non-dystrophic myotonia: 11 with CLCN1 mutations and 10 with SCN4A mutations, and 19 healthy volunteers. The MRI examinations of all patients showed hyperintensity within muscles on either T1-weighted or STIR images. Mild extensive or marked T1-weighted changes were noted in 10/21 patients and no volunteers. Muscles in the thigh were equally likely to be affected but in the calf there was sparing of tibialis posterior. Oedema was common in calf musculature especially in the medial gastrocnemius with STIR hyperintensity observed in 18/21 patients. In 10/11 CLCN1 patients this included a previously unreported "central stripe", also present in 3/10 SCN4A patients but no volunteers. Degree of fatty infiltration correlated with age (rho=0.46, p<0.05). Muscle MRI is frequently abnormal in non-dystrophic myotonia providing evidence of fatty infiltration and/or oedema. The pattern is distinct from other myotonic disorders; in particular the "central stripe" has not been reported in other conditions. Correlations with clinical parameters suggest a potential role for MRI as a biomarker

Enhancing the early home learning environment through a brief group parenting intervention: study protocol for a cluster randomised controlled trial.

BACKGROUND: The quality of the home learning environment has a significant influence on children's language and communication skills during the early years with children from disadvantaged families disproportionately affected. This paper describes the protocol and participant baseline characteristics of a community-based effectiveness study. It evaluates the effects of 'smalltalk', a brief group parenting intervention (with or without home coaching) on the quality of the early childhood home learning environment. METHODS/DESIGN: The study comprises two cluster randomised controlled superiority trials (one for infants and one for toddlers) designed and conducted in parallel. In 20 local government areas (LGAs) in Victoria, Australia, six locations (clusters) were randomised to one of three conditions: standard care (control); smalltalk group-only program; or smalltalk plus (group program plus home coaching). Programs were delivered to parents experiencing socioeconomic disadvantage through two existing age-based services, the maternal and child health service (infant program, ages 6-12 months), and facilitated playgroups (toddler program, ages 12-36 months). Outcomes were assessed by parent report and direct observation at baseline (0 weeks), post-intervention (12 weeks) and follow-up (32 weeks). Primary outcomes were parent verbal responsivity and home activities with child at 32 weeks. Secondary outcomes included parenting confidence, parent wellbeing and children's communication, socio-emotional and general development skills. Analyses will use intention-to-treat random effects ("multilevel") models to account for clustering. RECRUITMENT AND BASELINE DATA: Across the 20 LGAs, 986 parents of infants and 1200 parents of toddlers enrolled and completed baseline measures. Eighty four percent of families demonstrated one or more of the targeted risk factors for poor child development (low income; receives government benefits; single, socially isolated or young parent; culturally or linguistically diverse background). DISCUSSION: This study will provide unique data on the effectiveness of a brief group parenting intervention for enhancing the early home learning environment of young children from disadvantaged families. It will also provide evidence of the extent to which additional one-on-one support is required to achieve change and whether there are greater benefits when delivered in the 1st year of life or later. The program has been designed for scale-up across existing early childhood services if proven effective. TRIAL REGISTRATION: 8 September 2011; ACTRN12611000965909 .This research was commissioned and funded by the Victorian Government Department of Education and Early Childhood (now the Department of Education and Training, DET). JN, MT, SB, TH, VH, EW and NH were employees of the Parenting Research Centre when this study was designed and conducted. JN, SB, EW & NH are currently supported by the Australian Communities Foundation through the Roberta Holmes Transition to Contemporary Parenthood Program (Coronella sub-fund); EW was part-funded by the Centre for Research Excellence in Child Language at Murdoch Children’s Research Institute (NHMRC grant 1023493). OU is funded by the UK National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. The views expressed in this publication are those of the authors and not necessarily those of the funding bodies

Impact of a brief group intervention to enhance parenting and the home learning environment for children aged 6-36 months: A cluster randomised controlled trial

This is the final version of the article. Available from the publisher via the DOI in this record.This study evaluated the effectiveness of a group parenting intervention designed to strengthen the home learning environment of children from disadvantaged families. Two cluster randomised controlled superiority trials were conducted in parallel and delivered within existing services: a 6-week parenting group (51 locations randomised; 986 parents) for parents of infants (aged 6-12 months), and a 10-week facilitated playgroup (58 locations randomised; 1200 parents) for parents of toddlers (aged 12-36 months). Each trial had three conditions: intervention (smalltalk group-only); enhanced intervention with home coaching (smalltalk plus); and 'standard'/usual practice controls. Parent-report and observational measures were collected at baseline, 12 and 32 weeks follow-up. Primary outcomes were parent verbal responsivity and home learning activities at 32 weeks. In the infant trial, there were no differences by trial arm for the primary outcomes at 32 weeks. In the toddler trial at 32-weeks, participants in the smalltalk group-only trial showed improvement compared to the standard program for parent verbal responsivity (effect size (ES) = 0.16; 95% CI 0.01, 0.36) and home learning activities (ES = 0.17; 95% CI 0.01, 0.38) but smalltalk plus did not. For the secondary outcomes in the infant trial, several initial differences favouring smalltalk plus were evident at 12 weeks, but not maintained to 32 weeks. For the toddler trial, differences in secondary outcomes favouring smalltalk plus were evident at 12 weeks and maintained to 32 weeks. These trials provide some evidence of the benefits of a parenting intervention focused on the home learning environment for parents of toddlers but not infants. TRIAL REGISTRATION: 8 September 2011; ACTRN12611000965909 .This research was commissioned and funded by the Victorian Government Department of Education and Early Childhood Development (DEECD), and designed and conducted at the Parenting Research Centre. NH, EW, SB, AS, MT, MY and JN were employees of the Parenting Research Centre when this study was conducted. EW was part-funded by the Centre for Research Excellence in Child Language at Murdoch Childrens Research Institute (NHMRC grant 1023493). NH, EW, SB and JN are funded by the Australian Communities Foundation (Coronella sub-fund) at La Trobe University. OU is supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. Views expressed are those of the authors and not necessarily those of DEECD, NIHR, NHS or the Department of Health

Comorbid health conditions and their impact on social isolation, loneliness, quality of life, and well-being in people with dementia: longitudinal findings from the IDEAL programme

\ua9 2024, The Author(s).Background: Most people with dementia have multiple health conditions. This study explores (1) number and type of health condition(s) in people with dementia overall and in relation to age, sex, dementia type, and cognition; (2) change in number of health conditions over two years; and (3) whether over time the number of health conditions at baseline is related to social isolation, loneliness, quality of life, and/or well-being. Methods: Longitudinal data from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort were used. Participants comprised people with dementia (n = 1490) living in the community (at baseline) in Great Britain. Health conditions using the Charlson Comorbidity Index, cognition, social isolation, loneliness, quality of life, and well-being were assessed over two years. Mixed effects modelling was used. Results: On average participants had 1.8 health conditions at baseline, excluding dementia; increasing to 2.5 conditions over two years. Those with vascular dementia or mixed (Alzheimer’s and vascular) dementia had more health conditions than those with Alzheimer’s disease. People aged ≥ 80 had more health conditions than those aged &lt; 65 years. At baseline having more health conditions was associated with increased loneliness, poorer quality of life, and poorer well-being, but was either minimally or not associated with cognition, sex, and social isolation. Number of health conditions had either minimal or no influence on these variables over time. Conclusions: People with dementia in IDEAL generally had multiple health conditions and those with more health conditions were lonelier, had poorer quality of life, and poorer well-being

Health conditions in spousal caregivers of people with dementia and their relationships with stress, caregiving experiences, and social networks: longitudinal findings from the IDEAL programme

\ua9 The Author(s) 2024.Objectives: Longitudinal evidence documenting health conditions in spousal caregivers of people with dementia and whether these influence caregivers’ outcomes is scarce. This study explores type and number of health conditions over two years in caregivers of people with dementia and subgroups based on age, sex, education, hours of care, informant-rated functional ability, neuropsychiatric symptoms, cognition of the person with dementia, and length of diagnosis in the person with dementia. It also explores whether over time the number of health conditions is associated with caregivers’ stress, positive experiences of caregiving, and social networks Methods: Longitudinal data from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort were used. Participants comprised spousal caregivers (n = 977) of people with dementia. Self-reported health conditions using the Charlson Comorbidity Index, stress, positive experiences of caregiving, and social network were assessed over two years. Mixed effect models were used Results: On average participants had 1.5 health conditions at baseline; increasing to 2.1 conditions over two years. More health conditions were reported by caregivers who were older, had no formal education, provided 10 + hours of care per day, and/or cared for a person with more neuropsychiatric symptoms at baseline. More baseline health conditions were associated with greater stress at baseline but not with stress over time. Over two years, when caregivers’ health conditions increased, their stress increased whereas their social network diminished Discussion: Findings highlight that most caregivers have their own health problems which require management to avoid increased stress and shrinking of social network