One-year regional brain volume changes as potential predictors of cognitive function in multiple sclerosis: a pilot study

BackgroundThe most reliable magnetic resonance imaging (MRI) marker of cognitive dysfunction in multiple sclerosis (MS) is brain atrophy. However, 1-year volumetric changes prior to cognitive assessment were never studied as potential predictors of cognition, which we aim to assess with this pilot work.MethodsTwenty-two MS patients were submitted to a baseline measure of 83 regional brain volumes with MRI and re-evaluated 1 year later; they were also tested with the Brief International Cognitive Assessment for MS (BICAMS): sustained attention and processing speed were examined with the Symbol Digit Modalities Test (SDMT), verbal and visuo-spatial learning and memory with the learning trials from the California Verbal Learning Test-II (CVLT) and the Brief Visuo-spatial Memory Test-revised (BVMT), respectively. Controlling for age, sex, and years of education, a multivariate linear regression model was created for each cognitive score at 1-year follow-up in a backward elimination manner, considering cross-sectional regional volumes and 1-year volume changes as potential predictors.ResultsDecreases in the volumes of the left amygdala and the right lateral orbitofrontal cortex in the year prior to assessment were identified as possible predictors of worse performance in verbal memory (P = 0.009) and visuo-spatial memory (P = 0.001), respectively, independently of cross-sectional brain regional volumes at time of testing.ConclusionOur work reveals novel 1-year regional brain volume changes as potential predictors of cognitive deficits in MS. This suggests a possible role of these regions in such deficits and might contribute to uncover cognitively deteriorating patients, whose detection is still unsatisfying in clinical practice.Open access funding provided by FCT|FCCN (b-on). Biogen, Fundacao para a Ciencia e Tecnologia, UIDB/50026/2020, Fundacao para a ciencia e tecnologia, UIDP/50026/2020, Fundacao para a Ciencia e a Tecnologia, EXPL/MEC-NEU/0888/2021, Torcato Meira

Ultraprecise single-molecule localization microscopy enables in situ distance measurements in intact cells

Single-molecule localization microscopy (SMLM) has the potential to quantify the diversity in spatial arrangements of molecules in intact cells. However, this requires that the single-molecule emitters are localized with ultrahigh precision irrespective of the sample format and the length of the data acquisition. We advance SMLM to enable direct distance measurements between molecules in intact cells on the scale between 1 and 20 nm. Our actively stabilized microscope combines three-dimensional real-time drift corrections and achieves a stabilization of <1 nm and localization precision of ∼1 nm. To demonstrate the biological applicability of the new microscope, we show a 4- to 7-nm difference in spatial separations between signaling T cell receptors and phosphatases (CD45) in active and resting T cells. In summary, by overcoming the major bottlenecks in SMLM imaging, it is possible to generate molecular images with nanometer accuracy and conduct distance measurements on the biological relevant length scales

Enabling binary neural network training on the edge

The ever-growing computational demands of increasingly complex machine learning models frequently necessitate the use of powerful cloud-based infrastructure for their training. Binary neural networks are known to be promising candidates for on-device inference due to their extreme compute and memory savings over higher-precision alternatives. In this paper, we demonstrate that they are also strongly robust to gradient quantization, thereby making the training of modern models on the edge a practical reality. We introduce a low-cost binary neural network training strategy exhibiting sizable memory footprint reductions and energy savings vs Courbariaux & Bengio's standard approach. Against the latter, we see coincident memory requirement and energy consumption drops of 2--6x, while reaching similar test accuracy in comparable time, across a range of small-scale models trained to classify popular datasets. We also showcase ImageNet training of ResNetE-18, achieving a 3.12x memory reduction over the aforementioned standard. Such savings will allow for unnecessary cloud offloading to be avoided, reducing latency, increasing energy efficiency and safeguarding privacy

Multidimensional Frailty and Pain in Community Dwelling Elderly

Artigo científico disponível actualmente em Early View (Online Version of Record published before inclusion in an issue)Objective_To examine the relationship between frailty and pain, particularly to analyze whether pain predicts physical, psychological and social frailty, after controlling for the effects of life-course determinants and comorbidity. Design: Cross-sectional. Methods: A nonprobabilistic sample of 252 community dwelling elderly was recruited. Frailty and determinants of frailty were assessed with the Tilburg Frailty Indicator and pain was measured with the Pain Impact Questionnaire. Hierarchical and logistic regression analyses were conducted. Results: In this study, 52.4% of the participants were aged 80 years and over, and 75.8% were women. Pain and frailty were higher in women, and physical frailty was higher in those aged ≥80 years. After controlling for the effects of the determinants and comorbidity, pain predicted 5.8% of the variance of frailty, 5.9% of the variance of physical frailty, and 4.0% of the variance of psychological frailty, while the prediction of social frailty was nonsignificant. Overall, a greater pain impact score was associated with the presence of frailty (odds ratio 1.06; 95% CI 1.03–1.10; P < 0.001). Conclusion: Frailty was independently predicted by pain, emphasizing the importance of its treatment, potentially contributing to the prevention of vulnerability, dependency, and mortality. Nonetheless, longitudinal studies are required to better understand the possible association between pain and frailty

Freezing and water availability structure the evolutionary diversity of trees across the Americas

The historical course of evolutionary diversification shapes the current distribution of biodiversity, but the main forces constraining diversification are still a subject of debate. We unveil the evolutionary structure of tree species assemblages across the Americas to assess whether an inability to move or an inability to evolve is the predominant constraint in plant diversification and biogeography. We find a fundamental divide in tree lineage composition between tropical and extratropical environments, defined by the absence versus presence of freezing temperatures. Within the Neotropics, we uncover a further evolutionary split between moist and dry forests. Our results demonstrate that American tree lineages tend to retain their ancestral environmental relationships and that phylogenetic niche conservatism is the primary force structuring the distribution of tree biodiversity. Our study establishes the pervasive importance of niche conservatism to community assembly even at intercontinental scales

Behaviour change techniques to optimise participation in physical activity or exercise in adolescents and young adults with chronic cardiorespiratory conditions: a systematic review

Participation in regular physical activity decreases the risk of developing cardiometabolic disease. However, the proportion of people who participate in the recommended amount of physical activity is low, with common barriers including competing interests and inclement weather. In people with chronic cardiorespiratory conditions, participation in physical activity is reduced further by disease-specific barriers; time-burden of treatment and unpleasant symptoms during physical activity. Addressing these barriers during adolescence and early adulthood may promote greater physical activity participation into older age. The aim of this review was, in people aged 15 to 45 years with chronic cardiorespiratory conditions, to classify interventions aimed at optimising participation in physical activity as 'promising' or 'not promising', and categorise the behaviour change techniques (BCTs) within these interventions. Nine databases and registries were searched (October 2017) for studies that reported objective measures of physical activity before and after an intervention period. Interventions were classified as 'promising' if a between-group difference in physical activity was demonstrated. Michie et al.'s (2013) v1 Taxonomy was used to unpack the BCTs within interventions. Across the six included studies (n = 396 participants), 19 (20%) of 93 BCTs were described. The interventions of three studies were classified as 'promising'. The most commonly used BCTs comprised goal setting, action planning and social support. Five BCTs were solely used in 'promising' interventions. Our review demonstrated that only 20% of BCTs have been utilised and isolated those BCTs that were used only in 'promising' physical activity interventions in adolescents and adults with chronic cardiorespiratory conditions. This article is protected by copyright. All rights reserved

Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes

Characteristics of Patients with Late-Stage Parkinsonism who are Nursing Home Residents Compared with those Living at Home

OBJECTIVES: To determine clinical characteristics and treatment complications of patients with late-stage Parkinsonism living in nursing homes compared with those living at home. DESIGN: Cross-sectional analysis. SETTING AND PARTICIPANTS: This study is an analysis of 692 patients with late stage Parkinsonism recruited to an in-depth international study, Care of Late-Stage Parkinsonism (CLaSP). MEASURES: Sociodemographic characteristics were compared between patients who were living in a nursing home (n = 194) and those living at home (n = 498). Clinical assessments included the Unified Parkinson's Disease Rating Scale (UPDRS), the nonmotor symptom scale, the neuropsychiatric inventory, and a structured interview of patients and carers. Predictors of nursing home status were determined in a multivariate analysis. RESULTS: Nursing home placement was strongly associated with more severe cognitive impairment, worse UPDRS motor scores and disability, and with being unmarried and older. Although nursing home residents had significantly higher axial scores, falls were less common. Despite similar levodopa equivalence doses, they had less dyskinesia. Nonmotor symptom burden, particularly delusion, hallucination, and depression scores were higher in nursing home residents, and they were more frequently on psychotropic medication. They had lower rates of dopamine agonist use and lower rates of impulse control disorders. In multivariate analysis, being unmarried, presence of cognitive impairment, worse disease severity as assessed on the UPDRS parts II and III, severity of delusions, and lower rate of dyskinesia were associated with nursing home placement. CONCLUSIONS AND IMPLICATIONS: These clinical characteristics suggest that in patients with Parkinsonsim who are nursing home residents, presence of cognitive impairment and delusions particularly add to the higher overall symptom burden, and more often require specific treatments, including clozapine. Despite similar levodopa equivalent daily dose, motor severity is higher, and dyskinesias, indicative of a response to levodopa, are less common. Falls, however, also occur less commonly, and dopamine agonists are less frequently used, with lower rates of impulse control disorder

Using technology to deliver cancer follow-up : a systematic review

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