A Scoping Survey to Inform Design of Digital Dementia Risk Reduction Interventions for Adults Concerned about their Cognitive Health

Background: Digital dementia risk reduction interventions are cost-effective and scalable. However, it is unknown how they are perceived by people already experiencing cognitive concerns or decline. Objective: To understand the current use, interest, and preferences for online learning courses and interest in learning about factors influencing brain health and dementia risk among adults ≥45. To explore potential differences between individuals experiencing cognitive concerns and those without. Methods: Adults aged 45 and older completed a survey on technology use and healthy ageing (n = 249, Mean age = 65.6, 76.3% female). The Memory Assessment Clinic-Questionnaire was used to assess subjective memory decline, and 153 participants met the study criteria for cognitive concerns (≥25). Results: Almost all participants (98.4%) reported using two or more digital devices, and 51.8% reported increasing device usage following COVID-19. Most (92.1%) were interested in learning about healthy living and memory within an online course, and over 80% indicated a high interest in learning about dementia risk factors. People with cognitive concerns were more likely to report using a 'routine or system' to aid memory than people without (82.4% versus 62.9%, p = 0.001). However, no significant difference was found in technology use, course preferences, or interest in learning about different risk factors. Conclusions: We conclude that adults 45 years and over are interested in online methods for learning about brain health and offer unique insights into adapting dementia prevention programs for cognitive concerns

MyCOACH (COnnected Advice for Cognitive Health): a digitally delivered multidomain intervention for cognitive decline and risk of dementia in adults with mild cognitive impairment or subjective cognitive decline–study protocol for a randomised controlled trial

Introduction Digital health interventions are cost-effective and easily accessible, but there is currently a lack of effective online options for dementia prevention especially for people at risk due to mild cognitive impairment (MCI) or subjective cognitive decline (SCD). Methods and analysis MyCOACH (COnnected Advice for Cognitive Health) is a tailored online dementia risk reduction programme for adults aged ≥65 living with MCI or SCD. The MyCOACH trial aims to evaluate the programme’s effectiveness in reducing dementia risk compared with an active control over a 64-week period (N=326). Eligible participants are randomly allocated to one of two intervention arms for 12 weeks: (1) the MyCOACH intervention programme or (2) email bulletins with general healthy ageing information (active control). The MyCOACH intervention programme provides participants with information about memory impairments and dementia, memory strategies and different lifestyle factors associated with brain ageing as well as practical support including goal setting, motivational interviewing, brain training, dietary and exercise consultations, and a 26-week post-intervention booster session. Follow-up assessments are conducted for all participants at 13, 39 and 65 weeks from baseline, with the primary outcome being exposure to dementia risk factors measured using the Australian National University-Alzheimer’s Disease Risk Index. Secondary measures include cognitive function, quality of life, functional impairment, motivation to change behaviour, self-efficacy, morale and dementia literacy. Ethics and dissemination Ethical approval was obtained from the University of New South Wales Human Research Ethics Committee (HC210012, 19 February 2021). The results of the study will be disseminated in peer-reviewed journals and research conferences

Recent changes of water discharge and sediment load in the Yellow River basin, China

The Yellow River basin contributes approximately 6% of the sediment load from all river systems globally, and the annual runoff directly supports 12% of the Chinese population. As a result, describing and understanding recent variations of water discharge and sediment load under global change scenarios are of considerable importance. The present study considers the annual hydrologic series of the water discharge and sediment load of the Yellow River basin obtained from 15 gauging stations (10 mainstream, 5 tributaries). The Mann-Kendall test method was adopted to detect both gradual and abrupt change of hydrological series since the 1950s. With the exception of the area draining to the Upper Tangnaihai station, results indicate that both water discharge and sediment load have decreased significantly (p<0.05). The declining trend is greater with distance downstream, and drainage area has a significant positive effect on the rate of decline. It is suggested that the abrupt change of the water discharge from the late 1980s to the early 1990s arose from human extraction, and that the abrupt change in sediment load was linked to disturbance from reservoir construction.Geography, PhysicalGeosciences, MultidisciplinarySCI(E)43ARTICLE4541-5613

Extreme Clonality in Lymphoblastoid Cell Lines with Implications for Allele Specific Expression Analyses

Lymphoblastoid cell lines (LCL) are being actively and extensively used to examine the expression of specific genes and genome-wide expression profiles, including allele specific expression assays. However, it has recently been shown that approximately 10% of human genes exhibit random patterns of monoallelic expression within single clones of LCLs. Consequently allelic imbalance studies could be significantly compromised if bulk populations of donor cells are clonal, or near clonal. Here, using X chromosome inactivation as a readout, we confirm and quantify widespread near monoclonality in two independent sets of cell lines. Consequently, we recommend where possible the use of bulk, non cell line, ex vivo cells for allele specific expression assays

Survey of CF mutations in the clinical laboratory

BACKGROUND: Since it is impossible to sequence the complete CFTR gene routinely, clinical laboratories must rely on test systems that screen for a panel of the most frequent mutations causing disease in a high percentage of patients. Thus, in a cohort of 257 persons that were referred to our laboratory for analysis of CF gene mutations, reverse line probe assays for the most common CF mutations were performed. These techniques were evaluated as routine first-line analyses of the CFTR gene status. METHODS: DNA from whole blood specimens was extracted and subjected to PCR amplification of 9 exons and 6 introns of the CFTR gene. The resulting amplicons were hybridised to probes for CF mutations and polymorphisms, immobilised on membranes supplied by Roche Molecular Systems, Inc. and Innogenetics, Inc.. Denaturing gradient gel electrophoresis and sequencing of suspicious fragments indicating mutations were done with CF exon and intron specific primers. RESULTS: Of the 257 persons tested over the last three years (referrals based on 1) clinical symptoms typical for/indicative of CF, 2) indication for in vitro fertilisation, and 3) gene status determination because of anticipated parenthood and partners or relatives affected by CF), the reverse line blots detected heterozygote or homozygote mutations in the CFTR gene in 68 persons (26%). Eighty-three percent of those affected were heterozygous (47 persons) or homozygous (10 persons) for the ΔF508 allele. The only other CF-alleles that we found with these tests were the G542X allele (3 persons), the G551D allele (3 persons), the 3849+10kb C-T allele (2 persons) the R117H allele (2 persons) and the 621+1G-T allele (1 person). Of the fifteen IVS8-5T-polymorphisms detected in intron 8, seven (47%) were found in males referred to us from IVF clinics. These seven 5T-alleles were all coupled with a heterozygous ΔF508 allele, they make up 35% of the males with fertility problems (20 men) referred to us. CONCLUSIONS: In summary, the frequency of CF chromosomes in the cohort examined with these tests was 26%, with the ΔF508 allele affecting 83% of the CF chromosomes. It is a substantial improvement for routine CF diagnostics to have available a test system for 30 mutations plus the polypyrimidine length variants in intron 8. Our results show that this test system allows a routine first-line analyses of the CFTR gene status

A vibrational circular dichroism implementation within a Slater-type-orbital based density functional framework and its application to hexa- and hepta-helicenes

We describe the implementation of the rotational strengths for vibrational circular dichroism (VCD) in the Slater-type orbital based Amsterdam Density Functional (ADF) package. We show that our implementation, which makes use of analytical derivative techniques and London atomic orbitals, yields origin independent rotational strengths. The basis set dependence in the particular case of Slater-type basis functions is also discussed. It turns out that the triple zeta STO basis sets with one set of polarization functions (TZP) are adequate for VCD calculations. The origin- dependence of the atomic axial tensors is checked by a distributed origin gauge implementation. The distributed and common origin gauge implementations yield virtually identical atomic axial tensors with the Slater-type basis sets employed here, proving that our implementation yields origin independent rotational strengths. We verify the implementation for a set of benchmark molecules, for which the dependence of the VCD spectra on the particular choice of the exchange–correlation functional is studied. The pure functionals BP86 and OLYP show a particularly good performance. Then, we apply this approach to study the VCD spectra of hexa- and hepta- helicenes. In particular we focus on relationships between the sign of the rotational strengths of the two helicenes

Widespread Translocation from Autosomes to Sex Chromosomes Preserves Genetic Variability in an Endangered Lark

Species that pass repeatedly through narrow population bottlenecks (<100 individuals) are likely to have lost a large proportion of their genetic variation. Having genotyped 92 Raso larks Alauda razae, a Critically Endangered single-island endemic whose world population in the Cape Verdes over the last 100 years has fluctuated between about 15 and 130 pairs, we found variation at 7 of 21 microsatellite loci that successfully amplified, the remaining loci being monomorphic. At 6 of the polymorphic loci variation was sex-linked, despite the fact that these microsatellites were not sex-linked in the other passerine birds where they were developed. Comparative analysis strongly suggests that material from several different autosomes has been recently transferred to the sex chromosomes in larks. Sex-linkage might plausibly allow some level of heterozygosity to be maintained, even in the face of persistently small population sizes

The Pap smear screening as an occasion for smoking cessation and physical activity counselling: baseline characteristics of women involved in the SPRINT randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Gender-specific smoking cessation strategies have rarely been developed. Evidence of effectiveness of physical activity (PA) promotion and intervention in adjunct to smoking cessation programs is not strong. SPRINT study is a randomized controlled trial (RCT) designed to evaluate a counselling intervention on smoking cessation and PA delivered to women attending the Italian National Health System Cervical Cancer Screening Program. This paper presents study design and baseline characteristics of the study population.</p> <p>Methods/Design</p> <p>Among women undergoing the Pap examination in three study centres (Florence, Turin, Mantua), participants were randomized to the smoking cessation counselling [S], the smoking cessation + PA counselling [S + PA], or the control [C] groups. The program under evaluation is a standard brief counselling on smoking cessation combined with a brief counselling on increasing PA, and was delivered in 2010. A questionnaire, administered before, after 6 months and 1 year from the intervention, was used to track behavioural changes in tobacco use and PA, and to record cessation rates in participants.</p> <p>Discussion</p> <p>Out of the 5,657 women undergoing the Pap examination, 1,100 participants (55% of smokers) were randomized in 1 of the 3 study groups (363 in the S, 366 in the S + PA and 371 in the C groups). The three arms did not differ on any demographic, PA, or tobacco-use characteristics. Recruited smokers were older, less educated than non-participant women, more motivated to quit (33% vs.9% in the Preparation stage, <it>p </it>< 0.001), smoked more cigarettes per day (12 vs.9, <it>p </it>< 0.001), and were more likely to have already done 1 or more quit attempts (64% vs.50%, <it>p </it>< 0.001). The approach of SPRINT study appeared suitable to enrol less educated women who usually smoke more and have more difficulties to quit.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN52660565">ISRCTN52660565</a></p

Fluvial sediment supply to a mega-delta reduced by shifting tropical-cyclone activity

© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. The world's rivers deliver 19 billion tonnes of sediment to the coastal zone annually, with a considerable fraction being sequestered in large deltas, home to over 500 million people. Most (more than 70 per cent) large deltas are under threat from a combination of rising sea levels, ground surface subsidence and anthropogenic sediment trapping, and a sustainable supply of fluvial sediment is therefore critical to prevent deltas being 'drowned' by rising relative sea levels. Here we combine suspended sediment load data from the Mekong River with hydrological model simulations to isolate the role of tropical cyclones in transmitting suspended sediment to one of the world's great deltas. We demonstrate that spatial variations in the Mekong's suspended sediment load are correlated (r = 0.765, P < 0.1) with observed variations in tropical-cyclone climatology, and that a substantial portion (32 per cent) of the suspended sediment load reaching the delta is delivered by runoff generated by rainfall associated with tropical cyclones. Furthermore, we estimate that the suspended load to the delta has declined by 52.6 ± 10.2 megatonnes over recent years (1981-2005), of which 33.0 ± 7.1 megatonnes is due to a shift in tropical-cyclone climatology. Consequently, tropical cyclones have a key role in controlling the magnitude of, and variability in, transmission of suspended sediment to the coast. It is likely that anthropogenic sediment trapping in upstream reservoirs is a dominant factor in explaining past, and anticipating future, declines in suspended sediment loads reaching the world's major deltas. However, our study shows that changes in tropical-cyclone climatology affect trends in fluvial suspended sediment loads and thus are also key to fully assessing the risk posed to vulnerable coastal systems

High prevalence of germline STK11 mutations in Hungarian Peutz-Jeghers Syndrome patients

<p>Abstract</p> <p>Background</p> <p>Peutz-Jeghers syndrome (PJS) is a rare autosomal dominantly inherited disease characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. The genetic predisposition for PJS has been shown to be associated with germline mutations in the <it>STK11</it>/<it>LKB1 </it>tumor suppressor gene. The aim of the present study was to characterize Hungarian PJS patients with respect to germline mutation in <it>STK11</it>/<it>LKB1 </it>and their association to disease phenotype.</p> <p>Methods</p> <p>Mutation screening of 21 patients from 13 PJS families were performed using direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). Comparative semi-quantitative sequencing was applied to investigate the mRNA-level effects of nonsense and splice-affecting mutations.</p> <p>Results</p> <p>Thirteen different pathogenic mutations in <it>STK11</it>, including a high frequency of large genomic deletions (38%, 5/13), were identified in the 13 unrelated families studied. One of these deletions also affects two neighboring genes (<it>SBNO2 </it>and <it>GPX4</it>), located upstream of <it>STK11</it>, with a possible modifier effect. The majority of the point mutations (88%, 7/8) can be considered novel. Quantification of the <it>STK11 </it>transcript at the mRNA-level revealed that the expression of alleles carrying a nonsense or frameshift mutation was reduced to 30-70% of that of the wild type allele. Mutations affecting splice-sites around exon 2 displayed an mRNA processing pattern indicative of co-regulated splicing of exons 2 and 3.</p> <p>Conclusions</p> <p>A combination of sensitive techniques may assure a high (100%) <it>STK11 </it>mutation detection frequency in PJS families. Characterization of mutations at mRNA level may give a deeper insight into the molecular consequences of the pathogenic mutations than predictions made solely at the genomic level.</p