Dose-adapted post-transplant cyclophosphamide for HLA-haploidentical transplantation in Fanconi anemia.

We developed a haploidentical transplantation protocol with post-transplant cyclophosphamide (CY) for in vivo T-cell depletion (TCD) using a novel adapted-dosing schedule (25 mg/kg on days +3 and +4) for Fanconi anemia (FA). With median follow-up of 3 years (range, 37 days to 6.2 years), all six patients engrafted. Two patients with multiple pre-transplant comorbidities died, one from sepsis and one from sepsis with associated chronic GVHD. Four patients without preexisting comorbidities and early transplant referrals are alive with 100% donor chimerism and excellent performance status. We conclude that adjusted-dosing post-transplant CY is effective in in vivo TCD to promote full donor engraftment in patients with FA

Prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries: a systematic review and meta-analysis

OBJECTIVE: To systematically review the research conducted on prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries (LMICs) and to estimate the pooled prevalence of frailty and prefrailty in community-dwelling older adults in LMICs. DESIGN: Systematic review and meta-analysis. PROSPERO registration number is CRD42016036083. DATA SOURCES: MEDLINE, EMBASE, AMED, Web of Science, CINAHL and WHO Global Health Library were searched from their inception to 12 September 2017. SETTING: Low-income and middle-income countries. PARTICIPANTS: Community-dwelling older adults aged ≥60 years. RESULTS: We screened 7057 citations and 56 studies were included. Forty-seven and 42 studies were included in the frailty and prefrailty meta-analysis, respectively. The majority of studies were from upper middle-income countries. One study was available from low-income countries. The prevalence of frailty varied from 3.9% (China) to 51.4% (Cuba) and prevalence of prefrailty ranged from 13.4% (Tanzania) to 71.6% (Brazil). The pooled prevalence of frailty was 17.4% (95% CI 14.4% to 20.7%, I²=99.2%) and prefrailty was 49.3% (95% CI 46.4% to 52.2%, I²=97.5%). The wide variation in prevalence rates across studies was largely explained by differences in frailty assessment method and the geographic region. These findings are for the studies with a minimum recruitment age 60, 65 and 70 years. CONCLUSION: The prevalence of frailty and prefrailty appears higher in community-dwelling older adults in upper middle-income countries compared with high-income countries, which has important implications for healthcare planning. There is limited evidence on frailty prevalence in lower middle-income and low-income countries

Association between frailty and disability among rural community-dwelling older adults in Sri Lanka: a cross-sectional study

OBJECTIVE: We examined the association between frailty and disability in rural community-dwelling older adults in Kegalle district of Sri Lanka. DESIGN: A population-based cross-sectional study. PARTICIPANTS: A total of 746 community-dwelling adults aged ≥60 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Frailty was assessed using the Fried phenotype. Disability was operationalised in terms of having one or more activity limitation/s in instrumental activities of daily living (IADL) and basic activities of daily living (BADL). RESULTS: The median age of the sample was (median 68; IQR 64-75) years and 56.7% were female. 15.2% were frail and 48.5% were prefrail. The prevalence of ≥1 IADL limitations was high, 84.4% among frail adults. 38.7% of frail adults reported ≥1 BADL limitations. Over half of frail older adults (58.3%) reported both ≥1 physical and cognitive IADL limitations. Being frail decreased the odds of having no IADL limitations, and was associated with a higher count of IADL limitations. No significant association was found between prefrailty and number of IADL limitations. CONCLUSIONS: The prevalence of ≥1 IADL limitations was high among rural community-dwelling frail older adults. Findings imply the greater support and care required for rural Sri Lankan frail older adults to live independently in the community

Structural crossover in a model fluid exhibiting two length scales: repercussions for quasicrystal formation

We investigate the liquid state structure of the two-dimensional model introduced by Barkan et al. [Phys. Rev. Lett. 113, 098304 (2014)], which exhibits quasicrystalline and other unusual solid phases, focusing on the radial distribution function g(r) and its asymptotic decay r→∞. For this particular model system, we find that as the density is increased there is a structural crossover from damped oscillatory asymptotic decay with one wavelength to damped oscillatory asymptotic decay with another distinct wavelength. The ratio of these wavelengths is ≈1.932. Following the locus in the phase diagram of this structural crossover leads directly to the region where quasicrystals are found. We argue that identifying and following such a crossover line in the phase diagram towards higher densities where the solid phase(s) occur is a good strategy for finding quasicrystals in a wide variety of systems. We also show how the pole analysis of the asymptotic decay of equilibrium fluid correlations is intimately connected with the nonequilibrium growth or decay of small-amplitude density fluctuations in a bulk fluid

Association of genetic liability for psychiatric disorders with accelerometer-assessed physical activity in the UK Biobank.

Levels of activity are often affected in psychiatric disorders and can be core symptoms of illness. Advances in technology now allow the accurate assessment of activity levels but it remains unclear whether alterations in activity arise from shared risk factors for developing psychiatric disorders, such as genetics, or are better explained as consequences of the disorders and their associated factors. We aimed to examine objectively-measured physical activity in individuals with psychiatric disorders, and assess the role of genetic liability for psychiatric disorders on physical activity. Accelerometer data were available on 95,529 UK Biobank participants, including measures of overall mean activity and minutes per day of moderate activity, walking, sedentary activity, and sleep. Linear regressions measured associations between psychiatric diagnosis and activity levels, and polygenic risk scores (PRS) for psychiatric disorders and activity levels. Genetic correlations were calculated between psychiatric disorders and different types of activity. Having a diagnosis of schizophrenia, bipolar disorder, depression, or autism spectrum disorders (ASD) was associated with reduced overall activity compared to unaffected controls. In individuals without a psychiatric disorder, reduced overall activity levels were associated with PRS for schizophrenia, depression, and ASD. ADHD PRS was associated with increased overall activity. Genetic correlations were consistent with PRS findings. Variation in physical activity is an important feature across psychiatric disorders. Whilst levels of activity are associated with genetic liability to psychiatric disorders to a very limited extent, the substantial differences in activity levels in those with psychiatric disorders most likely arise as a consequences of disorder-related factors

Examining the alcohol-related consequences of adult drinkers who self-report medicating low mood with alcohol: an analysis of the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions survey data.

The aim of this paper is to examine the alcohol-related consequences experienced by adults who experienced a two-week period of low mood and identify as a 'self-mediator' compared to those who do not. Our focus is on assessing whether the conceptualization of alcohol use disorder severity differs across adult drinkers who self-medicate with alcohol during a period of low mood, compared to those who do not. This study used secondary data from the NESARC survey. The analytic sample consisted of 5945 participants who answered questions from the alcohol abuse/dependence (alcohol experiences) section, in the last 12 months. The sample was split into four groups by whether they self-medicated with alcohol or not, and drank alcohol in the last year and their drinking class. The findings indicated that a one factor model was the best fit and all items were a strong indicator of alcohol use disorder. The two-parameter model had the best fit, indicating that the diagnostic criteria were placed as a good fit along a continuum of severity. It was revealed that the hazardous drinking group who self-medicated, experienced more consequences even at low levels of severity. As the self-medicating hazardous drinking group also showed the highest estimates for alcohol use disorder severity, this may indicate that this group are high functioning self-medicators who are trying to regulate their drinking, and may not be as clinically high risk as expected, due to their drinking patterns

Prevalence of frailty in rural community-dwelling older adults in Kegalle district of Sri Lanka: a population-based cross-sectional study

OBJECTIVE: Our main objective was to describe the prevalence and associated sociodemographic factors of frailty and pre-frailty in rural community-dwelling older adults in Kegalle district of Sri Lanka. DESIGN: Community-based cross-sectional study. SETTING: The study was conducted in rural areas of Kegalle district in Sri Lanka. PARTICIPANTS: A total of 746 community-dwelling older adults aged ≥60 years were included in the study. RESULTS: The prevalence of frailty and pre-frailty in rural Kegalle district was 15.2% (95% CI 12.3% to 18.6%) and 48.5% (95% CI 43.8% to 53.2%), respectively. We found a strong association between age and both frailty and pre-frailty. There were strong associations between longest-held occupation and frailty and education level and pre-frailty. CONCLUSIONS: The prevalence of frailty in this rural Sri Lankan older population was high compared with high-income and upper middle-income countries. The profile of health and social care services in Sri Lanka needs to address frailty and its consequences

Evolution of associative learning in chemical networks

Organisms that can learn about their environment and modify their behaviour appropriately during their lifetime are more likely to survive and reproduce than organisms that do not. While associative learning – the ability to detect correlated features of the environment – has been studied extensively in nervous systems, where the underlying mechanisms are reasonably well understood, mechanisms within single cells that could allow associative learning have received little attention. Here, using in silico evolution of chemical networks, we show that there exists a diversity of remarkably simple and plausible chemical solutions to the associative learning problem, the simplest of which uses only one core chemical reaction. We then asked to what extent a linear combination of chemical concentrations in the network could approximate the ideal Bayesian posterior of an environment given the stimulus history so far? This Bayesian analysis revealed the ’memory traces’ of the chemical network. The implication of this paper is that there is little reason to believe that a lack of suitable phenotypic variation would prevent associative learning from evolving in cell signalling, metabolic, gene regulatory, or a mixture of these networks in cells

Staphylococcus epidermidis glucose uptake in biofilm versus planktonic cells

The aim of this work was to compare the glucose uptake of biofilms formed by four different Staphylococcus epidermidis strains as well as to compare between sessile and planktonic cells of the same strain. Biofilm cells showed a lower level of glucose uptake compared to planktonic cells. Moreover, glucose uptake by cells in the sessile form was strongly influenced by biofilm composition. Therefore, this work helps to confirm the phenotypic variability of S. epidermidis strains and the different behaviour patterns between sessile and free cells.Fundação para a Ciência e a Tecnologia (FCT) - POCTI/ESP/42688/2001; SFRH/BD/19265/2004