Toward Increased Utilization of Historical Hurricane Chronologies

The record of past tropical cyclones provides an important means to evaluate the hurricane hazard. Historical chronologies are a source of information about tropical cyclones prior to the modern era. Chenoweth (2006) describes an archive of 383 tropical cyclones occurring during the eighteenth and nineteenth centuries, largely before the official hurricane record. The present study demonstrates a novel way this archive can be used to articulate historical tropical cyclone activity across space. First, an event in the archive is assigned a series of latitude/longitude coordinates approximating the descriptive locations of the cyclone’s affect. Second, tropical cyclones from the modern record that approach these locations (modern analogs) are mapped. Third, a probable pathway and a realistic track of the archived event is created by averaging the modern analog tracks. As an example, the procedure is used to generate a map showing the tracks of the Atlantic tropical cyclones of 1766. Sensitivity of the methodology to changes in event location and event timing are considered. The study shows that historical hurricane chronologies when combined with a history of cyclone tracks can provide useful information about the older events that is not directly related to where the original information was gathered. When this information is available for all cyclones it should help climatologists better understand long-term variations in tropical cyclone activity

Gamma-ray bursts and terrestrial planetary atmospheres

We describe results of modeling the effects on Earth-like planets of long-duration gamma-ray bursts (GRBs) within a few kiloparsecs. A primary effect is generation of nitrogen oxide compounds which deplete ozone. Ozone depletion leads to an increase in solar UVB radiation at the surface, enhancing DNA damage, particularly in marine microorganisms such as phytoplankton. In addition, we expect increased atmospheric opacity due to buildup of nitrogen dioxide produced by the burst and enhanced precipitation of nitric acid. We review here previous work on this subject and discuss recent developments, including further discussion of our estimates of the rates of impacting GRBs and the possible role of short-duration bursts.Comment: 12 pages including 5 figures (4 in color). Added discussion of GRB rates and biological effects. Accepted for publication in New Journal of Physics, for special issue "Focus on Gamma-Ray Bursts

Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS)

Background: Little is known about how the proportions of dependency states have changed between generational cohorts of older people. We aimed to estimate years lived in different dependency states at age 65 years in 1991 and 2011, and new projections of future demand for care. Methods: In this population-based study, we compared two Cognitive Function and Ageing Studies (CFAS I and CFAS II) of older people (aged ≥65 years) who were permanently registered with a general practice in three defined geographical areas (Cambridgeshire, Newcastle, and Nottingham; UK). These studies were done two decades apart (1991 and 2011). General practices provided lists of individuals to be contacted and were asked to exclude those who had died or might die over the next month. Baseline interviews were done in the community and care homes. Participants were stratified by age, and interviews occurred only after written informed consent was obtained. Information collected included basic sociodemographics, cognitive status, urinary incontinence, and self-reported ability to do activities of daily living. CFAS I was assigned as the 1991 cohort and CFAS II as the 2011 cohort, and both studies provided prevalence estimates of dependency in four states: high dependency (24-h care), medium dependency (daily care), low dependency (less than daily), and independent. Years in each dependency state were calculated by Sullivan's method. To project future demands for social care, the proportions in each dependency state (by age group and sex) were applied to the 2014 England population projections. Findings: Between 1991 and 2011, there were significant increases in years lived from age 65 years with low dependency (1·7 years [95% CI 1·0-2·4] for men and 2·4 years [1·8-3·1] for women) and increases with high dependency (0·9 years [0·2-1·7] for men and 1·3 years [0·5-2·1] for women). The majority of men's extra years of life were spent independent (36·3%) or with low dependency (36·3%) whereas for women the majority were spent with low dependency (58·0%), and only 4·8% were independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71 215 care home places by 2025. Interpretation: On average older men now spend 2·4 years and women 3·0 years with substantial care needs, and most will live in the community. These findings have considerable implications for families of older people who provide the majority of unpaid care, but the findings also provide valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations. Funding: Medical Research Council (G9901400) and (G06010220), with support from the National Institute for Health Research Comprehensive Local research networks in West Anglia and Trent, UK, and Neurodegenerative Disease Research Network in Newcastle, UK

The oldest old in England and Wales: a descriptive analysis based on the MRC Cognitive Function and Ageing Study

Objective: to describe the characteristics and survival of the oldest old in England and Wales

Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS)

Background: Little is known about how dependency levels have changed between generational cohorts of older people. We estimated years lived in different care states at age 65 in 1991 and 2011 and new projections of future demand for care. Methods: Two population-based studies of older people in defined geographical areas conducted two decades apart (the Cognitive Function and Ageing Studies) provided prevalence estimates of dependency in four states: high (24-hour care); medium (daily care); low (less than daily); independent. Years in each dependency state were calculated by Sullivan’s method. To project future demand, the proportions in each dependency state (by age group and sex) were applied to the 2014 England population projections. Findings: Between 1991 and 2011 there were significant increases in years lived from age 65 with low (men:1·7 years, 95%CI 1·0-2·4; women:2·4 years, 95%CI 1·8-3·1) and high dependency (men:0·9 years, 95%CI 0·2-1·7; women:1·3 years, 95%CI 0·5-2·1). The majority of men’s extra years of life were independent (36%) or with low dependency (36%) whilst for women the majority were spent with low dependency (58%), only 5% being independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71,000 care home places by 2025. Interpretation: On average older men now spend 2.4 years and women 3.0 years with substantial care needs (medium or high dependency), and most will live in the community. These findings have considerable implications for older people’s families who provide the majority of unpaid care, but the findings also supply valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations

Ribosomal frameshifting used in influenza A virus expression occurs within the sequence UCC_UUU_CGU and is in the +1 direction

Programmed ribosomal frameshifting is used in the expression of many virus genes and some cellular genes. In eukaryotic systems, the most well-characterized mechanism involves –1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast, the mechanisms involved in programmed +1 (or −2) slippage are more varied and often poorly characterized. Recently, a novel gene, PA-X, was discovered in influenza A virus and found to be expressed via a shift to the +1 reading frame. Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU) and direction (+1) of the frameshifting that is involved in PA-X expression. Related sites are identified in other virus genes that have previously been proposed to be expressed via +1 frameshifting. As these viruses infect insects (chronic bee paralysis virus), plants (fijiviruses and amalgamaviruses) and vertebrates (influenza A virus), such motifs may form a new class of +1 frameshift-inducing sequences that are active in diverse eukaryotes

The Impact of Education and Lifestyle Factors on Disability-Free Life Expectancy From Mid-Life to Older Age: A Multi-Cohort Study

Objectives: Low education and unhealthy lifestyle factors such as obesity, smoking, and no exercise are modifiable risk factors for disability and premature mortality. We aimed to estimate the individual and joint impact of these factors on disability-free life expectancy (DFLE) and total life expectancy (TLE). Methods: Data (n = 22,304) were from two birth cohorts (1921-26 and 1946-51) of the Australian Longitudinal Study on Women's Health and linked National Death Index between 1996 and 2016. Discrete-time multi-state Markov models were used to assess the impact on DFLE and TLE. Results: Compared to the most favourable combination of education and lifestyle factors, the least favourable combination (low education, obesity, current/past smoker, and no exercise) was associated with a loss of 5.0 years TLE, 95% confidence interval (95%CI): 3.2-6.8 and 6.4 years DFLE (95%CI: 4.8-7.8) at age 70 in the 1921-26 cohort. Corresponding losses in the 1946-51 cohort almost doubled (TLE: 11.0 years and DFLE: 13.0 years). Conclusion: Individual or co-ocurrance of lifestyle risk factors were associated with a significant loss of DFLE, with a greater loss in low-educated women and those in the 1946-51 cohort.Md. Mijanur Rahman, Carol Jagger, Lucy Leigh, Elizabeth Holliday, Emily Princehorn, Deb Loxton, Paul Kowal, John Beard, and Julie Byle

An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behaviour.

Serpins are important regulators of proteolytic pathways with an anti-protease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an inter-molecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of a number of pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks α1-antitrypsin (α1-AT) polymerisation in cells. Here we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39, and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered β-sheet A - on the opposite face of the molecule - more liable to adopt an 'open' state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of pre-formed serpin-enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the β-sheet A equilibrium towards the 'open' state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for rational design of ligands that is able to dynamically influence α1-AT polymerisation

The effect of smoking on the duration of life with and without disability, Belgium 1997-2011

Background: Smoking is the single most important health threat yet there is no consistency as to whether non-smokers experience a compression of years lived with disability compared to (ex-)smokers. The objectives of the manuscript are (1) to assess the effect of smoking on the average years lived without disability (Disability Free Life Expectancy (DFLE)) and with disability (Disability Life Expectancy (DLE)) and (2) to estimate the extent to which these effects are due to better survival or reduced disability in never smokers. Methods. Data on disability and mortality were provided by the Belgian Health Interview Survey 1997 and 2001 and a 10 years mortality follow-up of the survey participants. Disability was defined as difficulties in activities of daily living (ADL), in mobility, in continence or in sensory (vision, hearing) functions. Poisson and multinomial logistic regression models were fitted to estimate the probabilities of death and the prevalence of disability by age, gender and smoking status adjusted for socioeconomic position. The Sullivan method was used to estimate DFLE and DLE at age 30. The contribution of mortality and of disability to smoking related differences in DFLE and DLE was assessed using decomposition methods. Results: Compared to never smokers, ex-smokers have a shorter life expectancy (LE) and DFLE but the number of years lived with disability is somewhat larger. For both sexes, the higher disability prevalence is the main contributing factor to the difference in DFLE and DLE. Smokers have a shorter LE, DFLE and DLE compared to never smokers. Both higher mortality and higher disability prevalence contribute to the difference in DFLE, but mortality is more important among males. Although both male and female smokers experience higher disability prevalence, their higher mortality outweighs their disability disadvantage resulting in a shorter DLE. Conclusion: Smoking kills and shortens both life without and life with disability. Smoking related disability can however not be ignored, given its contribution to the excess years with disability especially in younger age groups