Human sperm accumulation near surfaces: a simulation study

A hybrid boundary integral/slender body algorithm for modelling flagellar cell motility is presented. The algorithm uses the boundary element method to represent the ‘wedge-shaped’ head of the human sperm cell and a slender body theory representation of the flagellum. The head morphology is specified carefully due to its significant effect on the force and torque balance and hence movement of the free-swimming cell. The technique is used to investigate the mechanisms for the accumulation of human spermatozoa near surfaces. Sperm swimming in an infinite fluid, and near a plane boundary, with prescribed planar and three-dimensional flagellar waveforms are simulated. Both planar and ‘elliptical helicoid’ beating cells are predicted to accumulate at distances of approximately 8.5–22 μm from surfaces, for flagellar beating with angular wavenumber of 3π to 4π. Planar beating cells with wavenumber of approximately 2.4π or greater are predicted to accumulate at a finite distance, while cells with wavenumber of approximately 2π or less are predicted to escape from the surface, likely due to the breakdown of the stable swimming configuration. In the stable swimming trajectory the cell has a small angle of inclination away from the surface, no greater than approximately 0.5°. The trapping effect need not depend on specialized non-planar components of the flagellar beat but rather is a consequence of force and torque balance and the physical effect of the image systems in a no-slip plane boundary. The effect is relatively weak, so that a cell initially one body length from the surface and inclined at an angle of 4°–6° towards the surface will not be trapped but will rather be deflected from the surface. Cells performing rolling motility, where the flagellum sweeps out a ‘conical envelope’, are predicted to align with the surface provided that they approach with sufficiently steep angle. However simulation of cells swimming against a surface in such a configuration is not possible in the present framework. Simulated human sperm cells performing a planar beat with inclination between the beat plane and the plane-of-flattening of the head were not predicted to glide along surfaces, as has been observed in mouse sperm. Instead, cells initially with the head approximately 1.5–3 μm from the surface were predicted to turn away and escape. The simulation model was also used to examine rolling motility due to elliptical helicoid flagellar beating. The head was found to rotate by approximately 240° over one beat cycle and due to the time-varying torques associated with the flagellar beat was found to exhibit ‘looping’ as has been observed in cells swimming against coverslips

Weak associations between pubertal development and psychiatric and behavioral problems

Pubertal development has been associated with adverse outcomes throughout adolescence and adulthood. However, much of the previous literature has categorized outcome variables and pubertal timing measures for ease of mean difference or odds ratio interpretation. We use a UK-representative sample of over 5000 individuals drawn from the Twins Early Development Study to extend this literature by adopting an individual differences approach and emphasizing effect sizes. We investigate a variety of psychiatric and behavioral measures collected longitudinally at ages 11, 14 and 16, for multiple raters and for males and females separately. In addition, we use two measures of pubertal development: the Pubertal Development Scale at each age, as well as the age of menarche for girls. We found that pubertal development, however assessed, was linearly associated with a range of psychiatric and behavioral outcomes; however, the effect sizes of these associations were modest for both males and females with most correlations between −0.10 and 0.10. Our systematic analysis of associations between pubertal development, and psychiatric and behavioral problems is the most comprehensive to date. The results showing linearity of the effects of pubertal development support an individual differences approach, treating both pubertal development and associated outcomes as continuous rather than categorical variables. We conclude that pubertal development explains little variance in psychiatric and behavioral outcomes (<1% on average). The small effect sizes indicate that the associations are weak and should not warrant major concern at least in non-clinical populations

The winding roads to adulthood: A twin study.

AIMS: Here we report the results of the first systematic investigation of genetic and environmental influences on 57 psychological traits covering major issues in emerging adulthood such as aspirations, thoughts and attitudes, relationships and personality. We also investigate how these traits relate to physical and mental health, educational attainment and wellbeing. MATERIALS & METHODS: We use a sample of nearly 5000 pairs of UK twins aged 21-25 from the Twins Early Development Study. We included 57 measures of traits selected to represent issues in emerging adulthood (EA) such as aspirations, thoughts and attitudes, life events, relationships, sexual and health behaviour and personality. We also included measures related to what are often considered to be the core functional outcomes even though here we refer to the data collected at the same time: adverse physical health, adverse mental health, wellbeing, and education. RESULTS: All 57 traits showed significant genetic influence, with an average heritability of 34% (SNP heritability ~10%). Most of the variance (59% on average) was explained by non-shared environmental influences. These diverse traits were associated with mental health (average correlation 0.20), wellbeing (0.16), physical health (0.12) and educational attainment (0.06). Shared genetic factors explained the majority of these correlations (~50%). Together, these emerging adulthood traits explained on average 30% of variance in the outcomes (range = 8% to 69%), suggesting that these traits relate to the outcomes additively. DISCUSSION & CONCLUSIONS: We conclude that even as the majority of individual differences in EA traits is explained by non-shared environmental factors, genetic influence on these traits is still substantial; the environmental uncertainties of emerging adulthood in the 21st century do not diminish the importance of genetics. As adolescents travel down long and winding roads to adulthood, their trip is substantially influenced by genetic proclivities that nudge them down different paths leading to different destinations

Rating the intelligibility of dysarthic speech amongst people with Parkinson’s Disease: a comparison of trained and untrained listeners

Intelligibility of speech is a key outcome in speech and language therapy (SLT) and research. SLT students frequently participate as raters of intelligibility but we lack information about whether they rate intelligibility in the same way as the general public. This paper aims to determine if there is a difference in the intelligibility ratings made by SLT students (trained in speech related topics) compared to individuals from the general public (untrained). The SLT students were in year 2 of a BSc programme or the first 6 months of a MSc programme. We recorded 10 speakers with Parkinson’s disease (PD) related speech reading aloud the words and sentences from the Assessment of Intelligibility of Dysarthric Speech. These speech recordings were rated for intelligibility by ‘trained’ raters and ‘untrained’ raters. The effort required to understand the speech was also reported. There were no significant differences in the measures of intelligibility from the trained and untrained raters for words or sentences after adjusting for speaker by including them as a covariate in the model. There was a slight increase in effort reported by the untrained raters for the sentences. This difference in reported effort was not evident with the words. SLT students can be recruited alongside individuals from the general public as naïve raters for evaluating intelligibility in people with speech disorders

Lee Silverman Voice Treatment versus NHS Speech and Language Therapy versus control for dysarthria in Parkinson’s disease (PD COMM):a UK, multicentre, pragmatic, randomised controlled trial

Objectives: We aimed to assess the clinical effectiveness of two speech and language therapy (SLT) approaches versus no speech and language therapy for dysarthria in people with Parkinson’s disease. Design: This was a pragmatic, UK-wide, multicentre, three-arm, parallel group, unblinded, randomised controlled trial. Participants were randomly assigned using minimisation in a 1:1:1 ratio to Lee Silverman Voice Treatment (LSVT LOUD®), NHS SLT, or no SLT. Analyses were based on the intention to treat principle.Setting: The speech and language therapy interventions were delivered in outpatient or home settings.Participants: Between September 2016 and March 2020, 388 people with Parkinson’s disease and dysarthria were randomised into the trial: 130 to LSVT LOUD®, 129 to NHS SLT, and 129 to no SLT.Interventions: Lee Silverman Voice Treatment (LSVT LOUD®) consisted of four, face-to-face or remote, 50-minute sessions each week delivered over 4 weeks. Home-based practice activities were set for up to 5 to 10 minutes daily on treatment days and 15 minutes twice daily on non-treatment days. NHS Speech and language therapy (NHS SLT) dosage was determined by the local therapist in response to individual participants’ needs. Prior research suggested that NHS SLT participants would receive an average of one session per week over 6 to 8 weeks. Local practices for NHS SLT were accepted, except for those within the LSVT LOUD® protocol. Main outcome measures: The primary outcome was the self-reported Voice Handicap Index (VHI) total score at 3 months.Results: People randomised to LSVT LOUD® reported lower VHI scores at 3 months post-randomisation than those who were randomised to no SLT (-8·0 points (99%CI: -13·3 to -2·6); p = 0·0001). There was no evidence of a difference in VHI scores between NHS SLT and no SLT (1·7 points; (99%Cl: -3·8 to 7·1); p = 0·43). Patients randomised to LSVT LOUD® also reported lower VHI scores than those randomised to NHS SLT (-9·6 points; (99%CI: -14·9 to -4·4); p &lt; 0.0001). There were 93 adverse events (predominately vocal strain) in the LSVT LOUD® group, 46 in the NHS SLT group, and none in the no SLT group. There were no serious adverse events. Conclusions: LSVT LOUD® was more effective at reducing the participant reported impact of voice problems than no SLT and NHS SLT. NHS SLT showed no evidence of benefit compared to no SLT. Trial registration: The completed trial registration is ISRCTN12421382. Funding: NIHR HTA Programme, project number HTA 10/135/02. <br/

Aggressive behaviour in childhood and adolescence : the role of smoking during pregnancy, evidence from four twin cohorts in the EU-ACTION consortium

Background Maternal smoking during pregnancy (MSDP) has been linked to offspring's externalizing problems. It has been argued that socio-demographic factors (e.g. maternal age and education), co-occurring environmental risk factors, or pleiotropic genetic effects may account for the association between MSDP and later outcomes. This study provides a comprehensive investigation of the association between MSDP and a single harmonized component of externalizing: aggressive behaviour, measured throughout childhood and adolescence. Methods Data came from four prospective twin cohorts - Twins Early Development Study, Netherlands Twin Register, Childhood and Adolescent Twin Study of Sweden, and FinnTwin12 study - who collaborate in the EU-ACTION consortium. Data from 30 708 unrelated individuals were analysed. Based on item level data, a harmonized measure of aggression was created at ages 9-10; 12; 14-15 and 16-18. Results MSDP predicted aggression in childhood and adolescence. A meta-analysis across the four samples found the independent effect of MSDP to be 0.4% (r = 0.066), this remained consistent when analyses were performed separately by sex. All other perinatal factors combined explained 1.1% of the variance in aggression across all ages and samples (r = 0.112). Paternal smoking and aggressive parenting strategies did not account for the MSDP-aggression association, consistent with the hypothesis of a small direct link between MSDP and aggression. Conclusions Perinatal factors, including MSDP, account for a small portion of the variance in aggression in childhood and adolescence. Later experiences may play a greater role in shaping adolescents' aggressive behaviour.Peer reviewe

Lee Silverman Voice Treatment versus NHS Speech and Language Therapy versus control for dysarthria in Parkinson’s disease (PD COMM):a UK, multicentre, pragmatic, randomised controlled trial

Objectives: We aimed to assess the clinical effectiveness of two speech and language therapy (SLT) approaches versus no speech and language therapy for dysarthria in people with Parkinson’s disease. Design: This was a pragmatic, UK-wide, multicentre, three-arm, parallel group, unblinded, randomised controlled trial. Participants were randomly assigned using minimisation in a 1:1:1 ratio to Lee Silverman Voice Treatment (LSVT LOUD®), NHS SLT, or no SLT. Analyses were based on the intention to treat principle.Setting: The speech and language therapy interventions were delivered in outpatient or home settings.Participants: Between September 2016 and March 2020, 388 people with Parkinson’s disease and dysarthria were randomised into the trial: 130 to LSVT LOUD®, 129 to NHS SLT, and 129 to no SLT.Interventions: Lee Silverman Voice Treatment (LSVT LOUD®) consisted of four, face-to-face or remote, 50-minute sessions each week delivered over 4 weeks. Home-based practice activities were set for up to 5 to 10 minutes daily on treatment days and 15 minutes twice daily on non-treatment days. NHS Speech and language therapy (NHS SLT) dosage was determined by the local therapist in response to individual participants’ needs. Prior research suggested that NHS SLT participants would receive an average of one session per week over 6 to 8 weeks. Local practices for NHS SLT were accepted, except for those within the LSVT LOUD® protocol. Main outcome measures: The primary outcome was the self-reported Voice Handicap Index (VHI) total score at 3 months.Results: People randomised to LSVT LOUD® reported lower VHI scores at 3 months post-randomisation than those who were randomised to no SLT (-8·0 points (99%CI: -13·3 to -2·6); p = 0·0001). There was no evidence of a difference in VHI scores between NHS SLT and no SLT (1·7 points; (99%Cl: -3·8 to 7·1); p = 0·43). Patients randomised to LSVT LOUD® also reported lower VHI scores than those randomised to NHS SLT (-9·6 points; (99%CI: -14·9 to -4·4); p &lt; 0.0001). There were 93 adverse events (predominately vocal strain) in the LSVT LOUD® group, 46 in the NHS SLT group, and none in the no SLT group. There were no serious adverse events. Conclusions: LSVT LOUD® was more effective at reducing the participant reported impact of voice problems than no SLT and NHS SLT. NHS SLT showed no evidence of benefit compared to no SLT. Trial registration: The completed trial registration is ISRCTN12421382. Funding: NIHR HTA Programme, project number HTA 10/135/02. <br/

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

Background: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. Animals: Three hundred and fifty-four dogs with MMVD and cardiomegaly. Materials and Methods: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. Results: At day 35, heart size had reduced in the pimobendan group:median change in (Delta) LVIDDN -0.06 (IQR:-0.15 to + 0.02), P < 0.0001, and LA:Ao -0.08 (IQR:-0.23 to + 0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in Delta LVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in Delta LA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. Conclusions and Clinical Importance: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo