How to classify the Oldest Old according to Health Status: A study of 1160 subjects belonging to 552 90+ Italian sibships characterised by familial longevity recruited within the GeHA EU project

The health status of the oldest old, the fastest increasing population segment worldwide, progressively becomes more heterogeneous, and this peculiarity represents a major obstacle to their classification. We compared the effectiveness of four previously proposed criteria (Franceschi et al., 2000; Evert et al., 2003; Gondo et al., 2006; Andersen-Ranberg et al., 2001) in 1160 phenotypically fully characterized Italian siblings of 90 years of age and older (90+, mean age: 93 years; age range: 90–106 years) belonging to 552 sib-ships, recruited in Northern, Central and Southern Italy within the EU-funded project GEHA, followed for a six-year-survival. Main findings were: (i) ‘‘healthy’’ subjects varied within a large range, i.e. 5.2% (Gondo), 8.7% (Evert), 17.7% (Franceschi), and 28.5% (Andersen-Ranberg); (ii) Central Italy subjects showed better health than those from Northern and Southern Italy; (iii) mortality risk was correlated with health status independently of geographical areas; and (iv) 90+ males, although fewer in number, were healthier than females, but with no survival advantage. In conclusion, we identified a modified version of Andersen-Ranberg criteria, based on the concomitant assessment of two basic domains (cognitive, SMMSE; physical, ADL), called ‘‘Simple Model of Functional Status’’ (SMFS), as the most effective proxy to distinguish healthy from not-healthy subjects. This model showed that health status was correlated within sib-ships, suggesting a familial/genetic component.

Retinal Pigment Epithelial Cell DNA is Damaged by Exposure to Benzo[a]pyrene, a Constituent of Cigarette Smoke.

This study examined the effect of exogenous benzo[ a ]pyrene (BaP), an important constituent of cigarette smoke, on cultured bovine retinal pigment epithelial (RPE) cells. Evidence is presented for its metabolic conversion into benzo[ a ]pyrene diol epoxide (BPDE) and the consequent formation of potentially cytotoxic nucleobase adducts in DNA. Cultured RPE cells were treated with BaP at concentrations in the range of 0–100 µm. The presence of BaP was found to cause inhibition of cell growth and replication. BaP induced the expression of a phase I drug metabolizing enzyme which was identified as cytochrome P450 1A1 (CYP 1A1) by RT–PCR and by Western blotting. Coincident with the increased expression of CYP 1A1, covalent adducts between the mutagenic metabolite BPDE and DNA could be detected within RPE cells by immunocytochemical staining. Additional support for their formation was afforded by nuclease P1 enhanced 32P-postlabelling assays on cellular DNA. Single-cell gel electrophoresis (comet) assays showed that exposure of RPE cells to BaP rendered them markedly more susceptible to DNA damage induced by broad band UVB or blue light laser irradiation. In the case of UVB, this is consistent with the photosensitization of DNA cleavage by nucleobase adducts of BPDE. Collectively, these findings imply that BaP has a significant impact on RPE cell pathophysiology and suggest mechanisms whereby exposure to cigarette smoke might cause RPE dysfunction and cell death, thus possibly contributing to degenerative disorders of the retina.

Design of quantum-dot cellular automata circuits using cut-set retiming

As a potential alternative to CMOS technology, QCA provides an interesting paradigm in both communication and computation. However, QCAs unique four-phase clocking scheme and timing constraints present serious timing issues for interconnection and feedback. In this work, a cut-set retiming design procedure is proposed to resolve these QCA timing issues. The proposed design procedure can accommodate QCAs unique characteristics by performing delay-transfer and time-scaling to reallocate the existing delays so as to achieve efficient clocking zone assignment. Cut-set retiming makes it possible to effectively design relatively complex QCA circuits that include feedback. It utilizes the similar characteristics of synchronization, deep pipelines and local interconnections common to both QCA and systolic architectures. As a case study, a systolic Montgomery modular multiplier is designed to illustrate the procedure. Furthermore, a nonsystolic architecture, an S27 benchmark circuit, is designed and compared with previous designs. The comparison shows that the cut-set retiming method achieves a more efficient design, with a reduction of 22%, 44%, and 46% in terms of cell count, area, and latency, respectively.

Is dieting behaviour decreasing in young adolescents?

Abstract Objective: To report trends in underweight, overweight and obesity in 12–15-year-old adolescents and examine changes in dieting behaviour, which have been less well documented. Design: Comparison of two independent representative cross-sectional surveys. Setting: Northern Ireland. Subjects: Weight and height were objectively measured in 1324 boys and 1160 girls in 1996 and 1274 boys and 1374 girls in 2007. Participants reported whether they were following any particular diet including a self-proposed or prescribed weight-reduction diet. Results: Overweight and obesity increased in girls from 15% to 23% and 2% to 6%, respectively. Increases were more modest in boys with overweight increasing from 13% to 18% and obesity from 3% to 6%. The proportion of underweight adolescents decreased from 9% to 6% in girls and 8% to 5% in boys. Evidence of social disparity was observed in girls from a manual socio-economic background, with overweight/obesity prevalence rates increasing from 21% to 36% compared with 15% to 26% in girls from a non-manual background. Despite these trends fewer adolescents, in particular girls, reported following weight-reduction diets (14% of overweight/obese girls in 2007 v. 21% in 1996; 8% of boys in 2007 v. 13% in 1996). Of these girls, the proportion from a manual background following weight-reduction diets decreased from 25% to 11%. Conclusions: Overweight and obesity are continuing to increase in adolescents despite government and media awareness strategies. There also appears to be reduced dieting behaviour, despite increasing body weight, particularly in girls from manual socio-economic backgrounds.

Evaluating periocidities in peat-based climate proxy records.

Proxy records derived from ombrotrophic peatlands provide important insights into climate change over decadal to millennial timescales. We present mid- to late- Holocene humification data and testate amoebae-derived water table records from two peatlands in Northern Ireland. We examine the repli- cation of periodicities in these proxy climate records, which have been precisely linked through teph- rochronology. Age-depth models are constructed using a Bayesian piece-wise linear accumulation model and chronological errors are calculated for each profile. A Lomb-Scargle Fourier transform-based spectral analysis is used to test for statistically significant periodicities in the data. Periodicities of c. 130, 180, 260, 540 and 1160 years are present in at least one proxy record at each site. The replication of these peri- odicities provides persuasive evidence that they are a product of allogenic climate controls, rather than internal peatland dynamics. A technique to estimate the possible level of red-noise in the data is applied and demonstrates that the observed periodicities cannot be explained by a first-order autoregressive model. We review the periodicities in the light of those reported previously from other marine and terrestrial climate proxy archives to consider climate forcing parameters. © 2012 Elsevier Ltd. All rights reserved.

Modelling the response of fresh groundwater to climate and vegetation changes in coral islands

In coral islands, groundwater is a crucial freshwater resource for terrestrial life, including human water supply. Response of the freshwater lens to expected climate changes and subsequent vegetation alterations is quantified for Grande Glorieuse, a low-lying coral island in the Western Indian Ocean. Distributed models of recharge, evapotranspiration and saltwater phytotoxicity are integrated into a variable-density groundwater model to simulate the evolution of groundwater salinity. Model results are assessed against field observations including groundwater and geophysical measurements. Simulations show the major control currently exerted by the vegetation with regards to the lens morphology and the high sensitivity of the lens to climate alterations, impacting both quantity and salinity. Long-term changes in mean sea level and climatic conditions (rainfall and evapotranspiration) are predicted to be responsible for an average increase in salinity approaching 140 % (+8 kg m-3) when combined. In low-lying areas with high vegetation density, these changes top +300 % (+10 kg m-3). However, due to salinity increase and its phytotoxicity, it is shown that a corollary drop in vegetation activity can buffer the alteration of fresh groundwater. This illustrates the importance of accounting for vegetation dynamics to study groundwater in coral islands.

Characterisation of a secretory serine protease inhibitor (SjB6) from Schistosoma japonicum

BACKGROUND: Proteins belonging to the serine protease inhibitor (serpin) superfamily play essential physiological roles in many organisms. In pathogens, serpins are thought to have evolved specifically to limit host immune responses by interfering with the host immune-stimulatory signals. Serpins are less well characterised in parasitic helminths, although some are thought to be involved in mechanisms associated with host immune modulation. In this study, we cloned and partially characterised a secretory serpin from Schistosoma japonicum termed SjB6, these findings provide the basis for possible functional roles.

METHODS: SjB6 gene was identified through database mining of our previously published microarray data, cloned and detailed sequence and structural analysis and comparative modelling carried out using various bioinformatics and proteomics tools. Gene transcriptional profiling was determined by real-time PCR and the expression of native protein determined by immunoblotting. An immunological profile of the recombinant protein produced in insect cells was determined by ELISA.

RESULTS: SjB6 contains an open reading frame of 1160 base pairs that encodes a protein of 387 amino acid residues. Detailed sequence analysis, comparative modelling and structural-based alignment revealed that SjB6 contains the essential structural motifs and consensus secondary structures typical of inhibitory serpins. The presence of an N-terminal signal sequence indicated that SjB6 is a secretory protein. Real-time data indicated that SjB6 is expressed exclusively in the intra-mammalian stage of the parasite life cycle with its highest expression levels in the egg stage (p < 0.0001). The native protein is approximately 60 kDa in size and recombinant SjB6 (rSjB6) was recognised strongly by sera from rats experimentally infected with S. japonicum.

CONCLUSIONS: The significantly high expression of SjB6 in schistosome eggs, when compared to other life cycle stages, suggests a possible association with disease pathology, while the strong reactivity of sera from experimentally infected rats against rSjB6 suggests that native SjB6 is released into host tissue and induces an immune response. This study presents a comprehensive demonstration of sequence and structural-based analysis of a secretory serpin from a trematode and suggests SjB6 may be associated with important functional roles in S. japonicum, particularly in parasite modulation of the host microenvironment.

The epidemiology, healthcare and societal burden and costs of asthma in the UK and its member nations: analyses of standalone and linked national databases

Background: There are a lack of reliable data on the epidemiology and associated burden and costs of asthma. We sought to provide the first UK-wide estimates of the epidemiology, healthcare utilisation and costs of asthma. 

Methods: We obtained and analysed asthma-relevant data from 27 datasets: these comprised national health surveys for 2010-11, and routine administrative, health and social care datasets for 2011-12; 2011-12 costs were estimated in pounds sterling using economic modelling. 

Results: The prevalence of asthma depended on the definition and data source used. The UK lifetime prevalence of patient-reported symptoms suggestive of asthma was 29.5 % (95 % CI, 27.7-31.3; n = 18.5 million (m) people) and 15.6 % (14.3-16.9, n = 9.8 m) for patient-reported clinician-diagnosed asthma. The annual prevalence of patient-reported clinician-diagnosed-and-treated asthma was 9.6 % (8.9-10.3, n = 6.0 m) and of clinician-reported, diagnosed-and-treated asthma 5.7 % (5.7-5.7; n = 3.6 m). Asthma resulted in at least 6.3 m primary care consultations, 93,000 hospital in-patient episodes, 1800 intensive-care unit episodes and 36,800 disability living allowance claims. The costs of asthma were estimated at least £1.1 billion: 74 % of these costs were for provision of primary care services (60 % prescribing, 14 % consultations), 13 % for disability claims, and 12 % for hospital care. There were 1160 asthma deaths. 

Conclusions: Asthma is very common and is responsible for considerable morbidity, healthcare utilisation and financial costs to the UK public sector. Greater policy focus on primary care provision is needed to reduce the risk of asthma exacerbations, hospitalisations and deaths, and reduce costs.