Detecting Linkage between a Trait and a Marker in a Random Mating Population without Pedigree Record

Modern linkage-based approaches employing extended pedigrees are becoming powerful tools for localizing complex quantitative trait loci. For these linkage mapping methods, it is necessary to reconstruct extended pedigrees which include living individuals, using extensive pedigree records. Unfortunately, such records are not always easy to obtain and application of the linkage-based approaches has been restricted. Within a finite population under random mating, latent inbreeding rather than non-random inbreeding by consanguineous marriages is expected to occur and is attributable to coalescence in a finite population. Interestingly, it has been revealed that significant random inbreeding exists even in general human populations. Random inbreeding should be used to detect the hidden coancestry between individuals for a particular chromosomal position and it could also have application in linkage mapping methods. Here we present a novel method, named finite population based linkage mapping (FPL) method, to detect linkage between a quantitative trait and a marker via random inbreeding in a finite population without pedigree records. We show how to estimate coancestry for a chromosomal position between individuals by using multipoint Bayesian estimation. Subsequently, we describe the FPL method for detecting linkage via interval mapping method using a nonparametric test. We show that the FPL method does work via simulated data. For a random sample from a finite population, the FPL method is more powerful than a standard pedigree-based linkage mapping method with using genotypes of all parents of the sample. In addition, the FPL method was demonstrated by actual microsatellite genotype data of 750 Japanese individuals that are unrelated according to pedigree records to map a known Psoriasis susceptible locus. For samples without pedigree records, it was suggested that the FPL method require limited number of individuals, therefore would be better than other methods using thousands of individuals

Incentive motivation in first-episode psychosis: A behavioural study

<p>Abstract</p> <p>Background:</p> <p>It has been proposed that there are abnormalities in incentive motivational processing in psychosis, possibly secondary to subcortical dopamine abnormalities, but few empirical studies have addressed this issue.</p> <p>Methods:</p> <p>We studied incentive motivation in 18 first-episode psychosis patients from the Cambridge early psychosis service CAMEO and 19 control participants using the Cued Reinforcement Reaction Time Task, which measures motivationally driven behaviour. We also gathered information on participants' attentional, executive and spatial working memory function in order to determine whether any incentive motivation deficits were secondary to generalised cognitive impairment.</p> <p>Results:</p> <p>We demonstrated the anticipated "reinforcement-related speeding" effect in controls (17 out of 19 control participants responded faster during an "odd-one-out" task in response to a cue that indicated a high likelihood of a large points reward). Only 4 out of 18 patients showed this effect and there was a significant interaction effect between reinforcement probability and diagnosis on reaction time (F_1,35= 14.2, p = 0.001). This deficit was present in spite of preserved executive and attentional function in patients, and persisted even in antipsychotic medication free patients.</p> <p>Conclusion:</p> <p>There are incentive motivation processing abnormalities in first-episode psychosis; these may be secondary to dopamine dysfunction and are not attributable to generalised cognitive impairment.</p

Impact of HPV vaccination : health gains in the Italian female population

Abstract Background Human papillomavirus (HPV) is the leading cause of cervical cancer and other malignant and benign neoplastic lesions. HPV vaccination has three potential goals: to prevent transmission, infection, and disease. At present, there are no available data about health consequences of HPV immunization in Italy. The aim of this study is to evaluate the effect of current HPV vaccination strategy in Italy. Methods A multistate morbidity-mortality model was developed to estimate the infection process in a theoretical cohort of Italian women. The Markov process considered nine health states (health, anogenital warts, grade 1 and grade 2/3 cervical intraepithelial neoplasia, cervical cancer, anal cancer, death due to cervical cancer, anal cancer and other causes), and 26 transition probabilities for each age group. The model was informed with the available data in national and international literature. Effectiveness of immunization was assumed considering a literature review pertaining to models and vaccination coverage rates observed in Italy. Life expectancy (ex), Quality-Adjusted Life Years (QALYs), Disability-Adjusted Life Years (DALYs), and attributable risk (AR) were estimated for no intervention (cervical cancer screening) and vaccination strategies scenarios. Results The model showed that in a cohort of 100,000 Italian women the e0 is equal to 83.1 years. With current HPV vaccination strategy the e0 achieves 83.2 (+0.1) years. When HPV-related diseases are considered altogether, the QALYs increase from 82.7 to 82.9 (+0.2 QALYs) with no intervention and vaccination strategies respectively. DALYs decrease by 0.6 due to vaccination. Finally, AR is equal to 93 and 265 cases per 100,000 women in population and not vaccinated, respectively. Conclusion When mortality due to cervical cancer is considered, HPV vaccination seems to have a low impact on health unit gains in the Italian female population. Conversely, when several HPV-related and cancer morbidity conditions are included, the effect of vaccination becomes quite remarkable

Orally available Mn porphyrins with superoxide dismutase and catalase activities

Superoxide dismutase/catalase mimetics, such as salen Mn complexes and certain metalloporphyrins, catalytically neutralize reactive oxygen and nitrogen species, which have been implicated in the pathogenesis of many serious diseases. Both classes of mimetic are protective in animal models of oxidative stress. However, only AEOL11207 and EUK-418, two uncharged Mn porphyrins, have been shown to be orally bioavailable. In this study, EUK-418 and several new analogs (the EUK-400 series) were synthesized and shown to exhibit superoxide dismutase, catalase, and peroxidase activities in vitro. Some also protected PC12 cells against staurosporine-induced cell death. All EUK-400 compounds were stable in simulated gastric fluid, and most were substantially more lipophilic than the salen Mn complexes EUK-189 and EUK-207, which lack oral activity. Pharmacokinetics studies demonstrate the presence of all EUK-400 series compounds in the plasma of rats after oral administration. These EUK-400 series compounds are potential oral therapeutic agents for cellular damage caused by oxidative stress

Characteristics of Suicide Attempts in Anorexia and Bulimia Nervosa: A Case–Control Study

Objective: Compared to other eating disorders, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an eating disorders (ED). Method: Case-control study in a cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity. Results: AN patients were more likely to have made a serious attempt (OR = 3.4, 95 % CI 1.4–7.9), with a higher expectation of dying (OR = 3.7,95 % CI 1.1–13.5), and an increased risk of severity (OR = 3.4,95 % CI 1.2–9.6). BN patients did not differ from the control group. Clinical markers of the severity of ED were associated with the seriousness of the attempt. Conclusion: There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Higher completed suicide rates in AN may be partially explained by AN patients ’ higher desire to die and their more severe and lethal attempts

Public health and valorization of genome-based technologies: a new model

<p>Abstract</p> <p>Background</p> <p>The success rate of timely translation of genome-based technologies to commercially feasible products/services with applicability in health care systems is significantly low. We identified both industry and scientists neglect health policy aspects when commercializing their technology, more specifically, Public Health Assessment Tools (PHAT) and early on involvement of decision makers through which market authorization and reimbursements are dependent. While Technology Transfer (TT) aims to facilitate translation of ideas into products, Health Technology Assessment, one component of PHAT, for example, facilitates translation of products/processes into healthcare services and eventually comes up with recommendations for decision makers. We aim to propose a new model of valorization to optimize integration of genome-based technologies into the healthcare system.</p> <p>Methods</p> <p>The method used to develop our model is an adapted version of the Fish Trap Model and the Basic Design Cycle.</p> <p>Results</p> <p>We found although different, similarities exist between TT and PHAT. Realizing the potential of being mutually beneficial justified our proposal of their relative parallel initiation. We observed that the Public Health Genomics Wheel should be included in this relative parallel activity to ensure all societal/policy aspects are dealt with preemptively by both stakeholders. On further analysis, we found out this whole process is dependent on the Value of Information. As a result, we present our LAL (Learning Adapting Leveling) model which proposes, based on market demand; TT and PHAT by consultation/bi-lateral communication should advocate for relevant technologies. This can be achieved by public-private partnerships (PPPs). These widely defined PPPs create the innovation network which is a developing, consultative/collaborative-networking platform between TT and PHAT. This network has iterations and requires learning, assimilating and using knowledge developed and is called absorption capacity. We hypothesize that the higher absorption capacity, higher success possibility. Our model however does not address the phasing out of technology although we believe the same model can be used to simultaneously phase out a technology.</p> <p>Conclusions</p> <p>This model proposes to facilitate optimization/decrease the timeframe of integration in healthcare. It also helps industry and researchers to come to a strategic decision at an early stage, about technology being developed thus, saving on resources, hence minimizing failures.</p

Patient satisfaction in an acute medicine department in Morocco

<p>Abstract</p> <p>Background</p> <p>Patients' satisfaction is an important indicator for quality of care. Measuring healthcare quality and improving patient satisfaction have become increasingly prevalent, especially among healthcare providers and purchasers of healthcare. This is mainly due to the fact that consumers are becoming increasingly more knowledgeable about healthcare. No studies of inpatients' satisfaction with hospital care have been conducted in Morocco. The first objective of the present study was to confirm the reliability and validity of the Arabic version of the EQS-H (Echelle de Qualité des Soins en Hospitalisation). The second objective was to evaluate patient satisfaction in an acute medicine department in Morocco by using the EQS-H questionnaire; and also to assess the influence of certain demographics, socioeconomics, and health characteristics in patient satisfaction.</p> <p>Methods</p> <p>it was a patient survey conducted in an acute medicine department of a Moroccan University Hospital. We surveyed their socio demographic status, and health characteristics at admission. We performed structured face to face interviews with patients who were discharged from hospital. The core of the EQS-H questionnaire was translated to Arabic, adapted to the present setting, and then used to measure patient satisfaction with quality of care. The internal consistency of the EQS-H scale was assessed by Chronbach's coefficient alpha. Validity was assessed by factor analysis. Factors influencing inpatients' satisfaction were identified using multiple linear regression.</p> <p>Results</p> <p>The Arabic version of EQS-H demonstrated an excellent internal consistency for the two dimensions studied (0.889 for 'quality of medical information' (MI) and 0.906 for 'Relationship with staff and daily routine' (RS)). The principal component analysis confirmed the bidimensional structure of the questionnaire and explained 60% of the total variance. In the univariate analysis, urban residence, higher income, better perceived health status compared to admission, better perceived health status compared to people of the same age, and satisfaction with life in general were related to MI dimension; Otherwise, mal gender, urban residence, higher income, staying in double room, better perceived health status compared to admission, and satisfaction with life in general were related to RS dimension. The multiple linear regression showed that four independent variables were associated with higher satisfaction in MI: More than 2 prior hospitalizations, a longer length of stay (10-14 days) (<it>P </it>= 0.002), staying in double room (<it>P </it>= 0.022), and better perceived health status compared to admission (<it>P </it>= 0.036). Three independent variables were associated with higher satisfaction in RS: a longer length of stay (10-14 days) (<it>P </it>= 0.017), better perceived health status compared to admission day (<it>P </it>= 0.013), and satisfaction with life in general (<it>P </it>= 0.006).</p> <p>Conclusions</p> <p>Our current data assessing patient satisfaction with acute health care by the Arabic version of the EQS-H showed that the satisfaction rate was average on MI dimension; and good on RS dimension of the questionnaire. The majority of participants were satisfied with the overall care. Demographic, socioeconomic, and health characteristics may influence in-patients satisfaction in Morocco, a low/middle income country. An appreciation and understanding of these factors is essential to develop socio culturally appropriate interventions in order to improve satisfaction of patients.</p

Light and Heavy Fractions of Soil Organic Matter in Response to Climate Warming and Increased Precipitation in a Temperate Steppe

Soil is one of the most important carbon (C) and nitrogen (N) pools and plays a crucial role in ecosystem C and N cycling. Climate change profoundly affects soil C and N storage via changing C and N inputs and outputs. However, the influences of climate warming and changing precipitation regime on labile and recalcitrant fractions of soil organic C and N remain unclear. Here, we investigated soil labile and recalcitrant C and N under 6 years' treatments of experimental warming and increased precipitation in a temperate steppe in Northern China. We measured soil light fraction C (LFC) and N (LFN), microbial biomass C (MBC) and N (MBN), dissolved organic C (DOC) and heavy fraction C (HFC) and N (HFN). The results showed that increased precipitation significantly stimulated soil LFC and LFN by 16.1% and 18.5%, respectively, and increased LFC∶HFC ratio and LFN∶HFN ratio, suggesting that increased precipitation transferred more soil organic carbon into the quick-decayed carbon pool. Experimental warming reduced soil labile C (LFC, MBC, and DOC). In contrast, soil heavy fraction C and N, and total C and N were not significantly impacted by increased precipitation or warming. Soil labile C significantly correlated with gross ecosystem productivity, ecosystem respiration and soil respiration, but not with soil moisture and temperature, suggesting that biotic processes rather than abiotic factors determine variations in soil labile C. Our results indicate that certain soil carbon fraction is sensitive to climate change in the temperate steppe, which may in turn impact ecosystem carbon fluxes in response and feedback to climate change

Duplication and Gene Conversion in the Drosophila melanogaster Genome

Using the genomic sequences of Drosophila melanogaster subgroup, the pattern of gene duplications was investigated with special attention to interlocus gene conversion. Our fine-scale analysis with careful visual inspections enabled accurate identification of a number of duplicated blocks (genomic regions). The orthologous parts of those duplicated blocks were also identified in the D. simulans and D. sechellia genomes, by which we were able to clearly classify the duplicated blocks into post- and pre-speciation blocks. We found 31 post-speciation duplicated genes, from which the rate of gene duplication (from one copy to two copies) is estimated to be 1.0×10−9 per single-copy gene per year. The role of interlocus gene conversion was observed in several respects in our data: (1) synonymous divergence between a duplicated pair is overall very low. Consequently, the gene duplication rate would be seriously overestimated by counting duplicated genes with low divergence; (2) the sizes of young duplicated blocks are generally large. We postulate that the degeneration of gene conversion around the edges could explain the shrinkage of “identifiable” duplicated regions; and (3) elevated paralogous divergence is observed around the edges in many duplicated blocks, supporting our gene conversion–degeneration model. Our analysis demonstrated that gene conversion between duplicated regions is a common and genome-wide phenomenon in the Drosophila genomes, and that its role should be especially significant in the early stages of duplicated genes. Based on a population genetic prediction, we applied a new genome-scan method to test for signatures of selection for neofunctionalization and found a strong signature in a pair of transporter genes