A comparison of health expectancies over two decades in England: results of the Cognitive Function and Ageing Study I and II.

BACKGROUND: Whether rises in life expectancy are increases in good-quality years is of profound importance worldwide, with population ageing. We investigate how various health expectancies have changed in England between 1991 and 2011, with identical study design and methods in each decade. METHODS: Baseline data from the Cognitive Function and Ageing Studies in populations aged 65 years or older in three geographically defined centres in England (Cambridgeshire, Newcastle, and Nottingham) provided prevalence estimates for three health measures: self-perceived health (defined as excellent-good, fair, or poor); cognitive impairment (defined as moderate-severe, mild, or none, as assessed by Mini-Mental State Examination score); and disability in activities of daily living (defined as none, mild, or moderate-severe). Health expectancies for the three regions combined were calculated by the Sullivan method, which applies the age-specific and sex-specific prevalence of the health measure to a standard life table for the same period. FINDINGS: Between 1991 and 2011, gains in life expectancy at age 65 years (4·5 years for men and 3·6 years for women) were accompanied by equivalent gains in years free of any cognitive impairment (4·2 years [95% CI 4·2-4·3] for men and 4·4 years [4·3-4·5] for women) and decreased years with mild or moderate-severe cognitive impairment. Gains were also identified in years in excellent or good self-perceived health (3·8 years [95% CI 3·5-4·1] for men and 3·1 years [2·7-3·4] for women). Gains in disability-free years were much smaller than those in excellent-good self-perceived health or those free from cognitive impairment, especially for women (0·5 years [0·2-0·9] compared with 2·6 years [2·3-2·9] for men), mostly because of increased mild disability. INTERPRETATION: During the past two decades in England, we report an absolute compression (ie, reduction) of cognitive impairment, a relative compression of self-perceived health (ie, proportion of life spent healthy is increasing), and dynamic equilibrium of disability (ie, less severe disability is increasing but more severe disability is not). Reasons for these patterns are unknown but might include increasing obesity during previous decades. Our findings have wide-ranging implications for health services and for extension of working life. FUNDING: UK Medical Research Council

Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells

RNA polymerase II transcribes the physical ends of linear eukaryotic chromosomes into a variety of long non-coding RNA molecules including telomeric repeat-containing RNA (TERRA). Since TERRA discovery, advances have been made in the characterization of TERRA biogenesis and regulation; on the contrary its associated functions remain elusive. Most of the biological roles so far proposed for TERRA are indeed based on in vitro experiments carried out using short TERRA-like RNA oligonucleotides. In particular, it has been suggested that TERRA inhibits telomerase activity. We have exploited two alternative cellular systems to test whether TERRA and/or telomere transcription influence telomerase-mediated telomere elongation in human cancer cells. In cells lacking the two DNA methyltransferases DNMT1 and DNMT3b, TERRA transcription and steady-state levels are greatly increased while telomerase is able to elongate telomeres normally. Similarly, telomerase can efficiently elongate transgenic inducible telomeres whose transcription has been experimentally augmented. Our data challenge the current hypothesis that TERRA functions as a general inhibitor of telomerase and suggest that telomere length homeostasis is maintained independently of TERRA and telomere transcription

The Cosmic Microwave Background and Particle Physics

In forthcoming years, connections between cosmology and particle physics will be made increasingly important with the advent of a new generation of cosmic microwave background (CMB) experiments. Here, we review a number of these links. Our primary focus is on new CMB tests of inflation. We explain how the inflationary predictions for the geometry of the Universe and primordial density perturbations will be tested by CMB temperature fluctuations, and how the gravitational waves predicted by inflation can be pursued with the CMB polarization. The CMB signatures of topological defects and primordial magnetic fields from cosmological phase transitions are also discussed. Furthermore, we review current and future CMB constraints on various types of dark matter (e.g. massive neutrinos, weakly interacting massive particles, axions, vacuum energy), decaying particles, the baryon asymmetry of the Universe, ultra-high-energy cosmic rays, exotic cosmological topologies, and other new physics.Comment: 43 pages. To appear in Annual Reviews of Nuclear and Particle Scienc

Revealing natural relationships among arbuscular mycorrhizal fungi: culture line BEG47 represents Diversispora epigaea, not Glomus versiforme

Background: Understanding the mechanisms underlying biological phenomena, such as evolutionarily conservative trait inheritance, is predicated on knowledge of the natural relationships among organisms. However, despite their enormous ecological significance, many of the ubiquitous soil inhabiting and plant symbiotic arbuscular mycorrhizal fungi (AMF, phylum Glomeromycota) are incorrectly classified. Methodology/Principal Findings: Here, we focused on a frequently used model AMF registered as culture BEG47. This fungus is a descendent of the ex-type culture-lineage of Glomus epigaeum, which in 1983 was synonymised with Glomus versiforme. It has since then been used as ‘G. versiforme BEG47’. We show by morphological comparisons, based on type material, collected 1860–61, of G. versiforme and on type material and living ex-type cultures of G. epigaeum, that these two AMF species cannot be conspecific, and by molecular phylogenetics that BEG47 is a member of the genus Diversispora. Conclusions: This study highlights that experimental works published during the last >25 years on an AMF named ‘G. versiforme’ or ‘BEG47’ refer to D. epigaea, a species that is actually evolutionarily separated by hundreds of millions of years from all members of the genera in the Glomerales and thus from most other commonly used AMF ‘laboratory strains’. Detailed redescriptions substantiate the renaming of G. epigaeum (BEG47) as D. epigaea, positioning it systematically in the order Diversisporales, thus enabling an evolutionary understanding of genetical, physiological, and ecological traits, relative to those of other AMF. Diversispora epigaea is widely cultured as a laboratory strain of AMF, whereas G. versiforme appears not to have been cultured nor found in the field since its original description

Standard psychological consultations and follow up for women at increased risk of hereditary breast cancer considering prophylactic mastectomy

__Background:__ Women at increased (genetic) risk of breast cancer have to weigh the personal pros and cons of prophylactic mastectomy (PM) as an option to reduce their cancer risk. So far, no routine referral to a psychologist has been investigated for women considering PM. Aim of this study was to asses: 1) the acceptance of the offer of a standard psychological consultation as part of pre-surgical decision-making in high-risk women, 2) reasons for PM and reasons for postponing it, 3) the need for additional psychological interventions, and factors associated, and 4) the frequency of psychiatric/psychological treatment history. __Methods:__ During a 30 months period, women at high risk considering PM were offered a psychological consultation. The content of these, and follow-up, consultations were analyzed. __Results:__ Most women (70 out of 73) accepted the psychological consultation, and 81% proceeded with PM. Main reasons for undergoing PM were to reduce anxiety about cancer, and to reduce the cancer risk. Uncertainty about surgery and the need for further information were the reasons given most frequently for postponing PM. Additional psychological support was given to 31% before and 14% after PM. The uptake of additional support was significantly higher in women with a BRCA1/2 mutation. A history of psychiatric/psychological treatment was present in 36%, mainly consisting of depression and grief after death of a mother. __Conclusion:__ The uptake-rate of the standard psychological consultation indicates a high level of acceptability of this service for women deciding about PM. Since anxiety is one of the main reasons for considering PM, and depression and grief were present in a third, a standard consultation with a psychologist for high-risk women considering PM may be indicated. This may help them arrive at an informed decision, to detect and manage psychological distress, and to plan psychological support services

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

How many crowdsourced workers should a requester hire?

Recent years have seen an increased interest in crowdsourcing as a way of obtaining information from a potentially large group of workers at a reduced cost. The crowdsourcing process, as we consider in this paper, is as follows: a requester hires a number of workers to work on a set of similar tasks. After completing the tasks, each worker reports back outputs. The requester then aggregates the reported outputs to obtain aggregate outputs. A crucial question that arises during this process is: how many crowd workers should a requester hire? In this paper, we investigate from an empirical perspective the optimal number of workers a requester should hire when crowdsourcing tasks, with a particular focus on the crowdsourcing platform Amazon Mechanical Turk. Specifically, we report the results of three studies involving different tasks and payment schemes. We find that both the expected error in the aggregate outputs as well as the risk of a poor combination of workers decrease as the number of workers increases. Surprisingly, we find that the optimal number of workers a requester should hire for each task is around 10 to 11, no matter the underlying task and payment scheme. To derive such a result, we employ a principled analysis based on bootstrapping and segmented linear regression. Besides the above result, we also find that overall top-performing workers are more consistent across multiple tasks than other workers. Our results thus contribute to a better understanding of, and provide new insights into, how to design more effective crowdsourcing processes

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths