Posterior cortical atrophy : impact on daily living activities and exploration of a cognitive rehabilitation approach

Posterior cortical atrophy (PCA) is a neurodegenerative disease affecting the posterior region of the brain. Little is known about both the impact of PCA on functioning and how to support patients on a daily basis. The purpose of this study was to describe the functional profile of DD, a woman diagnosed with PCA, as well as to explore a pilot cognitive rehabilitation program designed to optimize functioning in daily living. The ADL Profile was used to assess the daily tasks that DD chose to undertake. Four operations, i.e. formulate a goal, plan, carry out and verify goal attainment, were scored for each task. Difficulties were observed during the execution of all tasks, as she struggled to find items or showed unsafe behaviors. Impairments were also seen in formulating a goal and planning, especially for less routine tasks. DD identified two tasks to be addressed in rehabilitation: setting the table and dealing cards. Learning was optimized using errorless learning and compensatory aids when setting the table, while dealing cards received no intervention. Only setting the table improved significantly with time. Further studies should be conducted to portray a wider functional profile of people living with PCA and develop effective rehabilitation programs

Larval exposure to predator cues alters immune function and response to a fungal pathogen in post-metamorphic wood frogs

For the past several decades, amphibian populations have been decreasing around the globe at an unprecedented rate. Batrachochytrium dendrobatidis (Bd), the fungal pathogen that causes chytridiomycosis in amphibians, is contributing to amphibian declines. Natural and anthropogenic environmental factors are hypothesized to contribute to these declines by reducing the immunocompetence of amphibian hosts, making them more susceptible to infection. Antimicrobial peptides (AMPs) produced in the granular glands of a frog’s skin are thought to be a key defense against Bd infection. These peptides may be a critical immune defense during metamorphosis because many acquired immune functions are suppressed during this time. To test if stressors alter AMP production and survival of frogs exposed to Bd, we exposed wood frog (Lithobates sylvaticus) tadpoles to the presence or absence of dragonfly predator cues crossed with a single exposure to three nominal concentrations of the insecticide malathion (0, 10, or 100 parts per billion [ppb]). We then exposed a subset of post-metamorphic frogs to the presence or absence of Bd zoospores and measured frog survival. Although predator cues and malathion had no effect on survival or size at metamorphosis, predator cues increased the time to metamorphosis by 1.5 days and caused a trend of a 20% decrease in hydrophobic skin peptides. Despite this decrease in peptides determined shortly after metamorphosis, previous exposure to predator cues increased survival in both Bd-exposed and unexposed frogs several weeks after metamorphosis. These results suggest that exposing tadpoles to predator cues confers fitness benefits later in life.Keywords: immunosuppression, AchE inhibitor, chytridiomycosis, disease ecology, brevinin, emerging infectious disease, Batrachochytrium dendrobatidis, temporin, Lithobates sylvaticus, indirect effect

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt beta II-spectrin function and disturb cytoskeletal organization and dynamics. SPTBN1 encodes beta II-spectrin, the ubiquitously expressed beta-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal beta II-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays;mild to severe intellectual disability;autistic features;seizures;behavioral and movement abnormalities;hypotonia;and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect beta II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of beta II-spectrin in the central nervous system

Evaluation of the cost and effectiveness of diverse recruitment methods for a genetic screening study

Purpose: Recruitment of participants from diverse backgrounds is crucial to the generalizability of genetic research, but has proven challenging. We retrospectively evaluated recruitment methods used for a study on return of genetic results. Methods: The costs of study design, development, and participant enrollment were calculated, and the characteristics of the participants enrolled through the seven recruitment methods were examined. Results: A total of 1118 participants provided consent, a blood sample, and questionnaire data. The estimated cost across recruitment methods ranged from $579 to$1666 per participant and required a large recruitment team. Recruitment methods using flyers and staff networks were the most cost-efficient and resulted in the highest completion rate. Targeted sampling that emphasized the importance of Latino/a participation, utilization of translated materials, and in-person recruitments contributed to enrolling a demographically diverse sample. Conclusions: Although all methods were deployed in the same hospital or neighborhood and shared the same staff, each recruitment method was different in terms of cost and characteristics of the enrolled participants, suggesting the importance of carefully choosing the recruitment methods based on the desired composition of the final study sample. This analysis provides information about the effectiveness and cost of different methods to recruit adults for genetic research

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

India in Situ: Textile History and Practice, a Team Approach

Five textile specialists from various backgrounds came together to explore shared interests in Indian fabrics, histories, and architectural patterns. Guided by Rahul Jain’s extraordinary scholarship and generosity, we visited weaving workshops producing exquisite fabric and metallic yarn in our quest to understand the naqsha system for drawloom patterning. In Cholapur and Varanasi, we studied drawlooms set up to weave velvet, lampas, and samite, and a distinguished naqshaband demonstrated the making of a naqsha that provides the design for drawloom lifts. We examined rare historic textiles in New Delhi’s National Museum, Ahmedabad’s Calico Museum of Textiles, Varanasi’s Bharat Kala Bhavan Museum, and private collections. In Jaipur, we visited the Indian Institute of Crafts and Design, Nila House, Anokhi Farm, City Palace Museum, and Prince Albert Hall Museum, and in Ahmedabad, the National Institute of Design and the Kasturbhai Lalbhai Indigo Museum. At Patola House in Patan, we observed the preparation and weaving of double ikat. Our diverse perspectives resulted in a most enjoyable interdisciplinary traveling seminar. Come with us as we share our adventure in collaborative textile research. Themes of inquiry:• Understanding the naqsha harness for the Indian drawloom • Examining relations between textiles and architecture • Using symmetry analysis to recognize pattern repeats • Considering fashion in India, an evolving tradition • Learning about the revival of natural indigo in India • Observing craft traditions preserved through development and sustainability Our team: • Annin Barrett—textile artist and designer; instructor, fashion history and sustainable design • Carol Bier—curator, The Textile Museum (1984-2001); research associate (2001-2020); research scholar, Center for Islamic Studies, Graduate Theological Union • Anna Jolly—curator of textiles 1500-1800, Abegg-Stiftung, Riggisberg, Switzerland • Louise Mackie—curator emerita, Textiles & Islamic Art, the Cleveland Museum of Art, Royal Ontario Museum, and The Textile Museum • Barbara Setsu Pickett—associate professor emerita, Department of Art, University of Orego

Association between cognitive function and life-space mobility in older adults: results from the FRéLE longitudinal study

Abstract Background Cross-sectional and longitudinal studies show conflicting results regarding the association between cognition and life-space mobility, and little is known regarding the mediators and moderators of the association. The aim of this study was to investigate the association between cognition and life-space mobility in older adults, as well as the intervening variables modifying the relationship. Methods Community-dwelling older adults aged 65 years and older (N = 1643) were assessed at three time points over a period of 2 years. Growth mixture models with mediation and moderation analysis were utilised to investigate association between cognitive function and life-space mobility. The potential mediators and moderators were depressive symptoms, locus of control, gait speed and grip strength. Analysis was controlled for age, sex, education, annual income, number of chronic illnesses, and living site. Results The direct association between initial scores of cognitive function and life-space was mediated by initial scores of depressive symptoms and gait speed, and moderated by initial scores of grip strength. No direct association between change in cognitive function and change in life-space mobility was found; the scores were mediated by change in depressive symptoms. Conclusions We conclude that the relationship between change in cognitive function and life-space mobility in older adults is not well-defined over an observation period of 2 years