930 research outputs found

    Evidence for physiological niche expansion of an intertidal flatworm: evolutionary rescue in the wild

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    Microevolution may enable populations to adapt physiologically to rapid climate change. Where it exists, historical data could provide a rare opportunity to document such adaptation. The intertidal flatworm Procerodes littoralis experiences large changes in salinity throughout the tidal cycle. We investigated whether regeneration performance of P. littoralis has changed over the last century. We repeated identical experiments to those published in 1914 on the same species and from the same location. In the modern experiment, when tested across a range of different salinities (S = 3, 6, 28, 44 and 53), P. littoralis could regenerate at lower salinities (S = 3) than reported previously. Also in the modern study, no significant optimum salinity could be identified, whereas in 1914 the optimum salinity (S = 28.5) was clear. The possibility of differences resulting from acclimation or oxygen availability instead of adaptation was investigated and discounted. It would appear that individuals from this population have extended their tolerance performance range further into hyposaline waters in the intervening 104 yr since the previous study. Local climate change is suggested to be the microevolution driver, as mean daily precipitation has increased and the number of days per year with no/trace precipitation has decreased in Plymouth, UK. Climate change is often considered a global phenomenon, but it drives local regime shifts. Here, we suggest an evolutionary shift attributable to a century-long local change in precipitation.</jats:p

    How couples with dementia experience healthcare, lifestyle, and everyday decision-making

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    Copyright © International Psychogeriatric Association 2018. Objectives: Recent research has demonstrated the challenges to self-identity associated with dementia, and the importance of maintaining involvement in decision-making while adjusting to changes in role and lifestyle. This study aimed to understand the lived experiences of couples living with dementia, with respect to healthcare, lifestyle, and everyday decision-making.Design: Semi-structured qualitative interviews using Interpretative Phenomenological Analysis as the methodological approach.Setting: Community and residential care settings in Australia.Participants: Twenty eight participants who self-identified as being in a close and continuing relationship (N = 13 people with dementia, N = 15 spouse partners). Nine couples were interviewed together.Results: Participants described a spectrum of decision-making approaches (independent, joint, supported, and substituted), with these approaches often intertwining in everyday life. Couples' approaches to decision-making were influenced by decisional, individual, relational, and external factors. The overarching themes of knowing and being known, maintaining and re-defining couplehood and relational decision-making, are used to interpret these experiences. The spousal relationship provided an important context for decision-making, with couples expressing a history and ongoing preference for joint decision-making, as an integral part of their experience of couplehood. However, the progressive impairments associated with dementia presented challenges to maintaining joint decision-making and mutuality in the relationship.Conclusions: This study illustrates relational perspectives on decision-making in couples with dementia. Post-diagnostic support, education resources, proactive dyadic interventions, and assistance for spouse care partners may facilitate more productive attempts at joint decision-making by couples living with dementia

    No effect of 24 h severe energy restriction on appetite regulation and ad libitum energy intake in overweight and obese males

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    Background/Objectives: Long-term success of weight loss diets might depend on how the appetite regulatory system responds to energy restriction (ER). This study determined the effect of 24 h severe ER on subjective and hormonal appetite regulation, subsequent ad libitum energy intake and metabolism. Subjects/Methods: In randomised order, eight overweight or obese males consumed a 24 h diet containing either 100% (12105 (1174 kJ; energy balance; EB) or 25% (3039 (295) kJ; ER) of estimated daily energy requirements (EER). An individualised standard breakfast containing 25% of EER (3216 (341) kJ) was consumed the following morning and resting energy expenditure, substrate utilisation and plasma concentrations of acylated ghrelin, glucagon-like peptide-1 (GLP-17–36), glucose-dependant insulinotropic peptide (GIP1–42), glucose, insulin and non-esterified fatty acid (NEFA) were determined for 4 h after breakfast. Ad libitum energy intake was assessed in the laboratory on day 2 and via food records on day 3. Subjective appetite was assessed throughout. Results: Energy intake was not different between trials for day 2 (EB: 14946 (1272) kJ; ER: 15251 (2114) kJ; P=0.623), day 3 (EB: 10580 (2457) kJ; 10812 (4357) kJ; P=0.832) or day 2 and 3 combined (P=0.693). Subjective appetite was increased during ER on day 1 (P0.381). Acylated ghrelin, GLP-17–36 and insulin were not different between trials (P>0.104). Post-breakfast area under the curve (AUC) for NEFA (P<0.05) and GIP1–42 (P<0.01) were greater during ER compared with EB. Fat oxidation was greater (P<0.01) and carbohydrate oxidation was lower (P<0.01) during ER, but energy expenditure was not different between trials (P=0.158). Conclusions: These results suggest that 24 h severe ER does not affect appetite regulation or energy intake in the subsequent 48 h. This style of dieting may be conducive to maintenance of a negative EB by limiting compensatory eating behaviour, and therefore may assist with weight loss

    A poisson regression approach for modelling spatial autocorrelation between geographically referenced observations

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    Abstract Background Analytic methods commonly used in epidemiology do not account for spatial correlation between observations. In regression analyses, omission of that autocorrelation can bias parameter estimates and yield incorrect standard error estimates. Methods We used age standardised incidence ratios (SIRs) of esophageal cancer (EC) from the Babol cancer registry from 2001 to 2005, and extracted socioeconomic indices from the Statistical Centre of Iran. The following models for SIR were used: (1) Poisson regression with agglomeration-specific nonspatial random effects; (2) Poisson regression with agglomeration-specific spatial random effects. Distance-based and neighbourhood-based autocorrelation structures were used for defining the spatial random effects and a pseudolikelihood approach was applied to estimate model parameters. The Bayesian information criterion (BIC), Akaike's information criterion (AIC) and adjusted pseudo R2, were used for model comparison. Results A Gaussian semivariogram with an effective range of 225 km best fit spatial autocorrelation in agglomeration-level EC incidence. The Moran's I index was greater than its expected value indicating systematic geographical clustering of EC. The distance-based and neighbourhood-based Poisson regression estimates were generally similar. When residual spatial dependence was modelled, point and interval estimates of covariate effects were different to those obtained from the nonspatial Poisson model. Conclusions The spatial pattern evident in the EC SIR and the observation that point estimates and standard errors differed depending on the modelling approach indicate the importance of accounting for residual spatial correlation in analyses of EC incidence in the Caspian region of Iran. Our results also illustrate that spatial smoothing must be applied with care.</p

    Mitochondrial phylogeography and demographic history of the Vicuña: implications for conservation

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    The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275 000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22°S) dry Andes 14–12 000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29°S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts

    A recurrent mosaic mutation of SMO, encoding the hedgehog signal transducer smoothened, is the major cause of Curry-Jones syndrome

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    Curry-Jones syndrome (CJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. Cerebellar medulloblastoma has been described in a single affected individual; in another, biopsy of skin lesions showed features of trichoblastoma. The combination of asymmetric clinical features, patchy skin manifestations, and neoplastic association previously led to the suggestion that this could be a mosaic condition, possibly involving hedgehog (Hh) signaling. Here, we show that CJS is caused by recurrent somatic mosaicism for a nonsynonymous variant in SMO (c.1234C&gt;T [p.Leu412Phe]), encoding smoothened (SMO), a G-protein-coupled receptor that transduces Hh signaling. We identified eight mutation-positive individuals (two of whom had not been reported previously) with highly similar phenotypes and demonstrated varying amounts of the mutant allele in different tissues. We present detailed findings from brain MRI in three mutation-positive individuals. Somatic SMO mutations that result in constitutive activation have been described in several tumors, including medulloblastoma, ameloblastoma, and basal cell carcinoma. Strikingly, the most common of these mutations is the identical nonsynonymous variant encoding p.Leu412Phe. Furthermore, this substitution has been shown to activate SMO in the absence of Hh signaling, providing an explanation for tumor development in CJS. This raises therapeutic possibilities for using recently generated Hh-pathway inhibitors. In summary, our work uncovers the major genetic cause of CJS and illustrates strategies for gene discovery in the context of low-level tissue-specific somatic mosaicism

    Routes for breaching and protecting genetic privacy

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    We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

    Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention

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    The isothiocyanate (ITC) sulforaphane (SFN) was shown at low levels (1-5 µM) to promote cell proliferation to 120-143% of the controls in a number of human cell lines, whilst at high levels (10-40 µM) it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control), whereas at 10-20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint

    Breast cancer incidence and mortality in Tyrol/Austria after fifteen years of opportunistic mammography screening

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    <p>Abstract</p> <p>Background</p> <p>The aim of this study was to analyse breast cancer incidence and mortality in Tyrol from 1970 to 2006, namely after performing more than a decade of opportunistic mammography screening and just before piloting an organised screening programme. Our investigation was conducted on a population level.</p> <p>Methods</p> <p>To study time trends in breast cancer incidence and mortality, we applied the age-period-cohort model by Poisson regression to the official mortality data covering more than three decades from 1970 to 2006 and to the incidence data ranging from 1988 to 2006. In addition, for incidence data we analysed data on breast cancer staging and compared these with EU guidelines.</p> <p>Results</p> <p>For the analysis of time trend in breast cancer mortality in age groups 40-79, an age-period-cohort model fits well and shows for years 2002-2006 a statistically significant reduction of 26% (95% CI 13%-36%) in breast cancer mortality as compared to 1992-1996.</p> <p>We see only slight non-significant increases in breast cancer incidence. For the past five years, incidence data show a 10% proportion of in situ cases, and of 50% for cases in stages II+.</p> <p>Conclusions</p> <p>The opportunistic breast cancer screening programme in Tyrol has only in part exploited the mortality reduction known for organised screening programmes. There seems to be potential for further improvement, and we recommend that an organised screening programme and a detailed screening database be introduced to collect all information needed to analyse the quality indicators suggested by the EU guidelines.</p
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