Executive function in Williams and Down syndromes

Williams (WS) and Down (DS) syndromes are characterised by roughly opposing ability profiles. Relative verbal strengths and visuospatial difficulties have been reported in those with WS, while expressive language difficulties have been observed in individuals with DS. Few investigations into the executive function (EF) skills of these groups have examined the effect of verbal/visuospatial task type on performance. Analogous verbal and visuospatial measures were administered to these populations within four EF domains: executive-loaded working memory (ELWM), inhibition, fluency and set-shifting. Performance in both groups was compared to that of typically developing (TD) children using regression techniques controlling for potentially influential cognitive/developmental factors. Individuals with WS showed the expected relative visuospatial difficulties, as indicated by poorer performance than TD individuals, on tests of ELWM and fluency. Individuals with DS displayed the expected relative verbal difficulty in the domain of set-shifting. In addition, each population showed pervasive deficits across modality in one domain; ELWM for individuals with DS, and inhibition for individuals with WS. Individuals with WS and DS showed EF difficulties in comparison to a TD group, but, their executive performance was affected by EF task type (verbal/visuospatial) and EF domain in different ways. While the findings indicated that EF in these populations is characterised by a range of specific strengths and weaknesses, it was also suggested that the relative verbal/visuospatial strengths associated with each population do not consistently manifest across EF domains. Lastly, syndrome specificity was indicated by the differences in groups’ performance patterns

Using developmental trajectories to examine verbal and visuospatial short-term memory development in children and adolescents with Williams and Down syndromes

Williams (WS) and Down (DS) syndromes have been associated with specifically compromised short-term memory (STM) subsystems. Individuals with WS have shown impairments in visuospatial STM, while individuals with DS have often shown problems with the recall of verbal material. However, studies have not usually compared the development of STM skills in these domains, in these populations. The present study employed a cross sectional developmental trajectories approach, plotting verbal and visuospatial STM performance against more general cognitive and chronological development, to investigate how the domain-specific skills of individuals with WS and DS may change as development progresses, as well as whether the difference between STM skill domains increases, in either group, as development progresses. Typically developing children, of broadly similar cognitive ability to the clinical groups, were also included. Planned between- and within group comparisons were carried out. Individuals with WS and DS both showed the domain specific STM weaknesses in overall performance that were expected based on the respective cognitive profiles. However, skills in both groups developed, according to general cognitive development, at similar rates to those of the TD group. In addition, no significant developmental divergence between STM domains was observed in either clinical group according to mental age or chronological age, although the general pattern of findings indicated that the influence of the latter variable across STM domains, particularly in WS, might merit further investigation

Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome

IMPORTANCE: Patients with atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson’s disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes, but have not been prospectively studied. OBJECTIVE: To define the distinguishing features of PSP and CBS, and to assess their usefulness in facilitating early diagnosis and separation from PD. DESIGN, SETTING, PARTICIPANTS: Cohort study which recruited APS and PD patients from movement disorder clinics across the UK from September 2015 to December 2018, and will follow up patients over 5 years. APS patients were stratified into PSP-Richardson syndrome, PSP-subcortical (including PSP-parkinsonism and PSP-progressive gait freezing cases), PSP-cortical (including PSP-frontal and PSP/CBS overlap cases), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer’s and CBS-non-Alzheimer’s groups. MAIN OUTCOME MEASURES: Baseline group comparisons were conducted using: 1) Clinical trajectory; 2) Cognitive screening scales; 3) Serum neurofilament light chain (NF-L); 4) TRIM11, ApoE and MAPT genotypes; 5) Volumetric MRI. RESULTS: 222 APS cases (101 PSP, 55 MSA, 40 CBS and 26 indeterminate) were recruited (58% male; mean age at recruitment, 68.3 years). Age-matched controls (n=76) and PD cases (n=1967) were also included. Concordance between the ante-mortem clinical diagnosis and pathological diagnosis was achieved in 12/13 (92%) of PSP and CBS cases coming to post-mortem. Applying the MDS PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP. 49/101 (49%) of reclassified PSP patients did not have classical PSP-Richardson syndrome. PSP-subcortical patients had a longer diagnostic latency and a more benign clinical trajectory than PSP-Richardson syndrome and PSP-cortical (p<0.05). PSP-subcortical was distinguished from PSP-cortical and PSP-Richardson syndrome by cortical volumetric MRI measures (AUC 0.84-0.89), cognitive profile (AUC 0.80-0.83), serum NF-L (AUC 0.75-0.83) and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP subtypes. 8/17 (47%) of CBS patients with CSF analysis were identified as having CBS-Alzheimer’s. CBS-Alzheimer’s patients had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment and higher APOE-ε4 allele frequency than CBS-non-Alzheimer’s (p<0.05, AUC 0.80-0.87). Serum NF-L levels distinguished PD from PSP and CBS (p<0.05, AUC 0.80). CONCLUSIONS AND RELEVANCE: Clinical, therapeutic and epidemiological studies focusing on PSP-Richardson syndrome are likely to miss a large number of patients with underlying PSP-tau pathology. CSF analysis defines a distinct CBS-Alzheimer’s subgroup. PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis

Recording behaviour of indoor-housed farm animals automatically using machine vision technology: a systematic review

Large-scale phenotyping of animal behaviour traits is time consuming and has led to increased demand for technologies that can automate these procedures. Automated tracking of animals has been successful in controlled laboratory settings, but recording from animals in large groups in highly variable farm settings presents challenges. The aim of this review is to provide a systematic overview of the advances that have occurred in automated, high throughput image detection of farm animal behavioural traits with welfare and production implications. Peer-reviewed publications written in English were reviewed systematically following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After identification, screening, and assessment for eligibility, 108 publications met these specifications and were included for qualitative synthesis. Data collected from the papers included camera specifications, housing conditions, group size, algorithm details, procedures, and results. Most studies utilized standard digital colour video cameras for data collection, with increasing use of 3D cameras in papers published after 2013. Papers including pigs (across production stages) were the most common (n = 63). The most common behaviours recorded included activity level, area occupancy, aggression, gait scores, resource use, and posture. Our review revealed many overlaps in methods applied to analysing behaviour, and most studies started from scratch instead of building upon previous work. Training and validation sample sizes were generally small (mean±s.d. groups = 3.8±5.8) and in data collection and testing took place in relatively controlled environments. To advance our ability to automatically phenotype behaviour, future research should build upon existing knowledge and validate technology under commercial settings and publications should explicitly describe recording conditions in detail to allow studies to be reproduced

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society