Association of attrition with mortality: findings from 11 waves over three decades of the Whitehall II study

BACKGROUND: Attrition, the loss of participants as a study progresses, is a considerable challenge in longitudinal studies. This study examined whether two forms of attrition, ‘withdrawal’ (formal discontinued participation) and ‘non-response’ (non-response among participants continuing in the study), have different associations with mortality and whether these associations differed across time in a multi-wave longitudinal study. METHODS: Participants were 10 012 civil servants who participated at the baseline of the Whitehall II cohort study with 11 data waves over an average follow-up of 28 years. We performed competing-risks analyses to estimate sub-distribution HRs and 95% CIs, and likelihood ratio tests to examine whether hazards differed between the two forms of attrition. We then applied linear regression to examine any trend of hazards against time. RESULTS: Attrition rate at data collections ranged between 13% and 34%. There were 495 deaths recorded from cardiovascular disease and 1367 deaths from other causes. Study participants lost due to attrition had 1.55 (95% CI 1.26 to 1.89) and 1.56 (1.39 to 1.76) times higher hazard of cardiovascular and non-cardiovascular mortality than responders, respectively. Hazards for withdrawal and non-response did not differ for either cardiovascular (p value =0.28) or non-cardiovascular mortality (p value =0.38). There was no linear trend in hazards over the 11 waves (cardiovascular mortality p value =0.11, non-cardiovascular mortality p value =0.61). CONCLUSION: Attrition can be a problem in longitudinal studies resulting in selection bias. Researchers should examine the possibility of selection bias and consider applying statistical approaches that minimise this bias

High blood pressure predicts hippocampal atrophy rate in cognitively impaired elders

INTRODUCTION: Understanding relationships among blood pressure (BP), cognition, and brain volume could inform Alzheimer's disease (AD) management. METHODS: We investigated Alzheimer's Disease Neuroimaging Initiative (ADNI) participants: 200 controls, 346 mild cognitive impairment (MCI), and 154 AD. National Alzheimer's Co‐ordinating Center (NACC) participants were separately analyzed: 1098 controls, 2297 MCI, and 4845 AD. Relationships between cognition and BP were assessed in both cohorts and BP and atrophy rates in ADNI. Multivariate mixed linear‐regression models were fitted with joint outcomes of BP (systolic, diastolic, and pulse pressure), cognition (Mini‐Mental State Examination, Logical Memory, and Digit Symbol) and atrophy rate (whole‐brain, hippocampus). RESULTS: ADNI MCI and AD patients with greater baseline systolic BP had higher hippocampal atrophy rates ([r, P value]; 0.2, 0.005 and 0.2, 0.04, respectively). NACC AD patients with lower systolic BP had lower cognitive scores (0.1, 0.0003). DISCUSSION: Higher late‐life BP may be associated with faster decline in cognitively impaired elders

A Comparison of Accelerated and Non-accelerated MRI Scans for Brain Volume and Boundary Shift Integral Measures of Volume Change: Evidence from the ADNI Dataset

The aim of this study was to assess whether the use of accelerated MRI scans in place of non-accelerated scans influenced brain volume and atrophy rate measures in controls and subjects with mild cognitive impairment and Alzheimer’s disease. We used data from 861 subjects at baseline, 573 subjects at 6 months and 384 subjects at 12 months from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We calculated whole-brain, ventricular and hippocampal atrophy rates using the k-means boundary shift integral (BSI). Scan quality was visually assessed and the proportion of good quality accelerated and non-accelerated scans compared. We also compared MMSE scores, vascular burden and age between subjects with poor quality scans with those with good quality scans. Finally, we estimated sample size requirements for a hypothetical clinical trial when using atrophy rates from accelerated scans and non-accelerated scans. No significant differences in whole-brain, ventricular and hippocampal volumes and atrophy rates were found between accelerated and non-accelerated scans. Twice as many non-accelerated scan pairs suffered from at least some motion artefacts compared with accelerated scan pairs (p ≤ 0.001), which may influence the BSI. Subjects whose accelerated scans had significant motion had a higher mean vascular burden and age (p ≤ 0.05) whilst subjects whose non-accelerated scans had significant motion had poorer MMSE scores (p ≤ 0.05). No difference in estimated sample size requirements was found when using accelerated vs. non-accelerated scans. Accelerated scans reduce scan time and are better tolerated. Therefore it may be advantageous to use accelerated over non-accelerated scans in clinical trials that use ADNI-type protocols, especially in more cognitively impaired subjects

NADPH oxidases regulate septin-mediated cytoskeletal remodeling during plant infection by the rice blast fungus

notes: PMCID: PMC3581893types: Journal Article; Research Support, Non-U.S. Gov'tThe rice blast fungus Magnaporthe oryzae infects plants with a specialized cell called an appressorium, which uses turgor to drive a rigid penetration peg through the rice leaf cuticle. Here, we show that NADPH oxidases (Nox) are necessary for septin-mediated reorientation of the F-actin cytoskeleton to facilitate cuticle rupture and plant cell invasion. We report that the Nox2-NoxR complex spatially organizes a heteroligomeric septin ring at the appressorium pore, required for assembly of a toroidal F-actin network at the point of penetration peg emergence. Maintenance of the cortical F-actin network during plant infection independently requires Nox1, a second NADPH oxidase, which is necessary for penetration hypha elongation. Organization of F-actin in appressoria is disrupted by application of antioxidants, whereas latrunculin-mediated depolymerization of appressorial F-actin is competitively inhibited by reactive oxygen species, providing evidence that regulated synthesis of reactive oxygen species by fungal NADPH oxidases directly controls septin and F-actin dynamics.Biotechnology and Biological Sciences Research Council (BBSRC)National Natural Science Foundation of ChinaHalpin ScholarshipEuropean Research Council Advanced Investigator Awar

Memory deficits in APP23/Abca1+/− mice correlate with the level of Aβ oligomers

ABCA1, a member of the ATP-binding cassette family of transporters, lipidates ApoE (apolipoprotein A) and is essential for the generation of HDL (high-density lipoprotein)-like particles in the CNS (central nervous system). Lack of Abca1 increases amyloid deposition in several AD (Alzheimer's disease) mouse models. We hypothesized that deletion of only one copy of Abca1 in APP23 (where APP is amyloid precursor protein) AD model mice will aggravate memory deficits in these mice. Using the Morris Water Maze, we demonstrate that 2-year-old Abca1 heterozygous APP23 mice (referred to as APP23/het) have impaired learning during acquisition, and impaired memory retention during the probe trial when compared with age-matched wild-type mice (referred to as APP23/wt). As in our previous studies, the levels of ApoE in APP23/het mice were decreased, but the differences in the levels of Aβ and thioflavin-S-positive plaques between both groups were insignificant. Importantly, dot blot analysis demonstrated that APP23/het mice have a significantly higher level of soluble A11-positive Aβ (amyloid β protein) oligomers compared with APP23/wt which correlated negatively with cognitive performance. To confirm this finding, we performed immunohistochemistry with the A11 antibody, which revealed a significant increase of A11-positive oligomer structures in the CA1 region of hippocampi of APP23/het. This characteristic region-specific pattern of A11 staining was age-dependent and was missing in younger APP23 mice lacking Abca1. In contrast, the levels of Aβ*56, as well as other low-molecular-mass Aβ oligomers, were unchanged among the groups. Overall, the results of the present study demonstrate that in aged APP23 mice memory deficits depend on Abca1 and are likely to be mediated by the amount of Aβ oligomers deposited in the hippocampus

One-year molecular survey of astrovirus infection in turkeys in Poland

The presence of turkey astrovirus (TAstV) was monitored in meat-type turkey flocks in Poland in 2008. Clinical samples (10 individual faecal swabs/flock) from 77 flocks aged 1-19 weeks were collected from different regions of the country. RT-PCR experiments were performed for detection and molecular characterization of TAstV using four sets of primers within the RdRp gene (ORF1b). The prevalence of astrovirus was 34/77 (44.15%) in the flocks tested. TAstV type 2 was associated with 30 of 77 infections (38.9%), either alone or in mixed infections; TAstV type 1 was detected in 9 of 77 flocks (11.6%), either alone or in mixed infections; ANV was detected only in one flock (1.29%) by sequence analysis during this study. Phylogenetic analysis revealed genetic variability in the TAstV strains that were isolated. Some of Polish TAstV-2 strains were genetically related to the North American isolates; however, most of them formed a distinct subgroup of “European” isolates, suggesting their separate origin or evolution. Additionally, due to the high variability of the TAstV sequences, the most suitable method for TAstV typing seems to be sequencing

Understanding Multi-Device Usage Patterns: Physical Device Configurations and Fragmented Workflows

To better ground technical (systems) investigation and interaction design of cross-device experiences, we contribute an in-depth survey of existing multi-device practices, including fragmented workflows across devices and the way people physically organize and configure their workspaces to support such activity. Further, this survey documents a historically significant moment of transition to a new future of remote work, an existing trend dramatically accelerated by the abrupt switch to work-from-home (and having to contend with the demands of home-at-work) during the COVID-19 pandemic. We surveyed 97 participants, and collected photographs of home setups and open-ended answers to 50 questions categorized in 5 themes. We characterize the wide range of multi-device physical configurations and identify five usage patterns, including: partitioning tasks, integrating multi-device usage, cloning tasks to other devices, expanding tasks and inputs to multiple devices, and migrating between devices. Our analysis also sheds light on the benefits and challenges people face when their workflow is fragmented across multiple devices. These insights have implications for the design of multi-device experiences that support people's fragmented workflows

A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours

Background:The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we developed a robust technical pipeline to quantify these miRNAs in the serum and cerebrospinal fluid (CSF). The pipeline was used in samples from a cohort of exclusively paediatric patients with gonadal and extragonadal malignant GCTs, compared with appropriate tumour and non-tumour control groups.Methods:We developed a method for miRNA quantification that enabled sample adequacy assessment and reliable data normalisation. We performed qRT-PCR profiling for miR-371-373 and miR-302/367 cluster miRNAs in a total of 45 serum and CSF samples, obtained from 25 paediatric patients.Results:The exogenous non-human spike-in cel-miR-39-3p and the endogenous housekeeper miR-30b-5p were optimal for obtaining robust serum and CSF qRT-PCR quantification. A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early detection of relapse of a testicular mixed malignant GCT; and (iii) distinguished intracranial malignant GCT from intracranial non-GCT tumours at diagnosis, using CSF and serum samples.Conclusions:The pipeline we have developed is robust, scalable and transferable. It potentially promises to improve clinical management of paediatric (and adult) malignant GCTs