6,868 research outputs found

    Evolutionary selection of alleles in the melanophilin gene that impacts on prostate organ function and cancer risk.

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    BACKGROUND AND OBJECTIVES: Several hundred inherited genetic variants or SNPs that alter the risk of cancer have been identified through genome-wide association studies. In populations of European ancestry, these variants are mostly present at relatively high frequencies. To gain insight into evolutionary origins, we screened a series of genes and SNPs linked to breast or prostate cancer for signatures of historical positive selection. METHODOLOGY: We took advantage of the availability of the 1000 genome data and we performed genomic scans for positive selection in five different Caucasian populations as well as one African reference population. We then used prostate organoid cultures to provide a possible functional explanation for the interplay between the action of evolutionary forces and the disease risk association. RESULTS: Variants in only one gene showed genomic signatures of positive, evolutionary selection within Caucasian populations melanophilin (MLPH). Functional depletion of MLPH in prostate organoids, by CRISPR/Cas9 mutation, impacted lineage commitment of progenitor cells promoting luminal versus basal cell differentiation and on resistance to androgen deprivation. CONCLUSIONS AND IMPLICATIONS: The MLPH variants influencing prostate cancer risk may have been historically selected for their adaptive benefit on skin pigmentation but MLPH is highly expressed in the prostate and the derivative, positively selected, alleles decrease the risk of prostate cancer. Our study suggests a potential functional mechanism via which MLPH and its genetic variants could influence risk of prostate cancer, as a serendipitous consequence of prior evolutionary benefits to another tissue. LAY SUMMARY: We screened a limited series of genomic variants associated with breast and prostate cancer risk for signatures of historical positive selection. Variants within the melanophilin (MLPH) gene fell into this category. Depletion of MLPH in prostate organoid cultures, suggested a potential functional mechanism for impacting on cancer risk, as a serendipitous consequence of prior evolutionary benefits to another tissue

    Insights into the Value of Inclusive Education to Both Children with and without Diasabilities at Kabulonga Boys Secondary School in Lusaka, Zambia

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    The study was undertaken to analyze the benefits of inclusive education to children both with and without special education needs. A descriptive survey design was used. The study sample comprised 20 participants: one head teacher, one deputy head teacher, nine special education teachers and nine regular teachers. Simple random sampling and purposive sampling techniques were used to select these participants. Data was collected using questionnaires and interview guides while analysis of data was done by SPSS (descriptive statistics) and themes (thematic analysis). The study revealed that the benefits of inclusive education are many; inclusive education can be an important and a meaningful thing or program to implement if all the materials needed are available, and if specially trained teachers are available to work with regular teachers and other stakeholders that may be needed for it to work. The study also established that regular teachers face many challenges in curriculum modification and adaptation. The study suggests that CPD activities be done so as to train regular teacher on how to modify and adapt the curriculum in inclusive classes; more sensitization of the benefits of inclusive education be done via different media platforms, and schools to strictly follow the stipulated guidelines on inclusive education and special education. This study concludes that there many benefits of inclusive education to both CSENs and those without special educational needs. On the other hand, curriculum adaptation and modification is very vital for inclusion to come to fruition. However, regular teachers face many challenges in this area. Keywords: Inclusive education, curriculum modification and adaptation, children with and without special education needs. DOI: 10.7176/JEP/13-35-01 Publication date: December 31st 202

    A cohort study of post-weaning multisystemic wasting syndrome and PCV2 in 178 pigs from birth to 14 weeks on a single farm in England

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    Our hypothesis was that pigs that develop post-weaning multisystemic wasting syndrome (PMWS) are detectable from an early age with signs of weight loss and other clinical and serological abnormalities. Therefore, the objective of this study was to investigate the temporally varying and fixed events linked with the clinical incidence of PMWS by comparing affected and unaffected pigs in a cohort of 178 male piglets. Piglets were enrolled at birth and examined each week. Samples of blood were collected at regular intervals. The exposures measured were porcine circovirus type 2 (PCV2) antibody titres in all 178 and PCV2 antigen in a subset of 75 piglets. We also observed piglet health and measured their weight, and a post-mortem examination was performed by an external laboratory on all pigs between 6 and 14 weeks of age that died. From the cohort, 14 (8%) pigs died from PMWS and 4% from other causes. A further 37 pigs between 6 and 14 weeks of age died from PMWS (30) and ileitis and other causes (7). PMWS was only apparent in pigs from 1 to 2 weeks before death when they wasted rapidly. There were no other characteristic clinical signs and no obvious gross clinical lesions post-mortem. There was no strong link with PCV2 antibody throughout life but PCV2 antigen level was higher from 4 to 6 weeks of age in pigs that died from PMWS compared with pigs that died from other causes

    Histology Verification Demonstrates That Biospectroscopy Analysis of Cervical Cytology Identifies Underlying Disease More Accurately than Conventional Screening:Removing the Confounder of Discordance

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    Background Subjective visual assessment of cervical cytology is flawed, and this can manifest itself by inter- and intra-observer variability resulting ultimately in the degree of discordance in the grading categorisation of samples in screening vs. representative histology. Biospectroscopy methods have been suggested as sensor-based tools that can deliver objective assessments of cytology. However, studies to date have been apparently flawed by a corresponding lack of diagnostic efficiency when samples have previously been classed using cytology screening. This raises the question as to whether categorisation of cervical cytology based on imperfect conventional screening reduces the diagnostic accuracy of biospectroscopy approaches; are these latter methods more accurate and diagnose underlying disease? The purpose of this study was to compare the objective accuracy of infrared (IR) spectroscopy of cervical cytology samples using conventional cytology vs. histology-based categorisation. Methods Within a typical clinical setting, a total of n = 322 liquid-based cytology samples were collected immediately before biopsy. Of these, it was possible to acquire subsequent histology for n = 154. Cytology samples were categorised according to conventional screening methods and subsequently interrogated employing attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. IR spectra were pre-processed and analysed using linear discriminant analysis. Dunn?s test was applied to identify the differences in spectra. Within the diagnostic categories, histology allowed us to determine the comparative efficiency of conventional screening vs. biospectroscopy to correctly identify either true atypia or underlying disease. Results Conventional cytology-based screening results in poor sensitivity and specificity. IR spectra derived from cervical cytology do not appear to discriminate in a diagnostic fashion when categories were based on conventional screening. Scores plots of IR spectra exhibit marked crossover of spectral points between different cytological categories. Although, significant differences between spectral bands in different categories are noted, crossover samples point to the potential for poor specificity and hampers the development of biospectroscopy as a diagnostic tool. However, when histology-based categories are used to conduct analyses, the scores plot of IR spectra exhibit markedly better segregation. Conclusions Histology demonstrates that ATR-FTIR spectroscopy of liquid-based cytology identifies the presence of underlying atypia or disease missed in conventional cytology screening. This study points to an urgent need for a future biospectroscopy study where categories are based on such histology. It will allow for the validation of this approach as a screening tool

    Non-smooth developable geometry for interactively animating paper crumpling

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    International audienceWe present the first method to animate sheets of paper at interactive rates, while automatically generating a plausible set of sharp features when the sheet is crumpled. The key idea is to interleave standard physically-based simulation steps with procedural generation of a piecewise continuous developable surface. The resulting hybrid surface model captures new singular points dynamically appearing during the crumpling process, mimicking the effect of paper fiber fracture. Although the model evolves over time to take these irreversible damages into account, the mesh used for simulation is kept coarse throughout the animation, leading to efficient computations. Meanwhile, the geometric layer ensures that the surface stays almost isometric to its original 2D pattern. We validate our model through measurements and visual comparison with real paper manipulation, and show results on a variety of crumpled paper configurations

    Political Discourse in the Hospital Heterotopia

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    To what extent do we pay attention to the text and images that cover our hospital walls and do we offer any critique either as professionals or service users? In the past we might have expected to see functional or helpful instructions about where to go (or not to go) and in more well‐endowed buildings, perhaps we would see some works of art, sculpture, stained glass even, with the intention to encourage, distract or even forewarn us. However, it is now common in UK hospitals, for wall space to be used as a portal for a range of institutional political messages, that convey information about everything from its own values, behaviours to advertisements for products and services to requirements for rule following. Michel Foucault's ideas about Heterotopic space can help us to see that hospitals tend to fall (awkwardly) between being a public and personal health care space, and this is a possible explanation for the confused material culture and messages that are shared there. This paper draws on ethnographic methods to reflect on personal experience in order to offer a critique of the contemporary political discourse which has become 'literally' written onto our hospital walls

    The tropical rain belts with an annual cycle and a continent model intercomparison project: TRACMIP

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    This paper introduces the Tropical Rain belts with an Annual cycle and a Continent Model Intercomparison Project (TRACMIP). TRACMIP studies the dynamics of tropical rain belts and their response to past and future radiative forcings through simulations with 13 comprehensive and one simplified atmosphere models coupled to a slab ocean and driven by seasonally-varying insolation. Five idealised experiments, two with an aquaplanet setup and three with a setup with an idealized tropical continent, fill the space between prescribed-SST aquaplanet simulations and realistic simulations provided by CMIP5/6. The simulations reproduce key features of present-day climate and expected future climate change, including an annual-mean intertropical convergence zone (ITCZ) that is located north of the equator and Hadley cells and eddy-driven jets that are similar to present-day climate. Quadrupling CO2 leads to a northward ITCZ shift and preferential warming in Northern high-latitudes. The simulations show interesting CO2-induced changes in the seasonal excursion of the ITCZ and indicate a possible state-dependence of climate sensitivity. The inclusion of an idealized continent modulates both the control climate and the response to increased CO2; for example, it reduces the northward ITCZ shift associated with warming and, in some models, climate sensitivity. In response to eccentricity-driven orbital seasonal insolation changes, seasonal changes in oceanic rainfall are best characterized as a meridional dipole, while seasonal continental rainfall changes tend to be symmetric about the equator. This survey illustrates TRACMIP's potential to engender a deeper understanding of global and regional climate and to address questions on past and future climate
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