The evolution of XY recombination: sexually antagonistic selection versus deleterious mutation load.

Recombination arrest between X and Y chromosomes, driven by sexually antagonistic genes, is expected to induce their progressive differentiation. However, in contrast to birds and mammals (which display the predicted pattern), most cold-blooded vertebrates have homomorphic sex chromosomes. Two main hypotheses have been proposed to account for this, namely high turnover rates of sex-determining systems and occasional XY recombination. Using individual-based simulations, we formalize the evolution of XY recombination (here mediated by sex reversal; the "fountain-of-youth" model) under the contrasting forces of sexually antagonistic selection and deleterious mutations. The shift between the domains of elimination and accumulation occurs at much lower selection coefficients for the Y than for the X. In the absence of dosage compensation, mildly deleterious mutations accumulating on the Y depress male fitness, thereby providing incentives for XY recombination. Under our settings, this occurs via "demasculinization" of the Y, allowing recombination in XY (sex-reversed) females. As we also show, this generates a conflict with the X, which coevolves to oppose sex reversal. The resulting rare events of XY sex reversal are enough to purge the Y from its load of deleterious mutations. Our results support the "fountain of youth" as a plausible mechanism to account for the maintenance of sex-chromosome homomorphy.

Identificació de marcadors biològics amb potencial per a l’optimització sensorial i tecnològica de la carn de porc i pernil curat

L’aplicació de tecnologies innovadores per a l’anàlisi de la qualitat (proteòmica) i per al processat de productes carnis (envasament actiu i altes pressions hidrostàtiques) amb la finalitat d’optimitzar la qualitat i la seguretat de productes carnis llestos per al consum fou evaluat. Els resultats obtinguts amb l’anàlisi proteòmic van permetre la detecció de pèptids/ proteïnes candidats a marcadors proteics de la qualitat dels lloms i dels pernils. La detecció d’aquests marcadors a la matèria primera (llom i pernil fresc) ajudaria a predir la qualitat final dels productes carnis processats (llom cuit i pernil curat), i proporcionaria una eina per al control de la qualitat de la carn de porc. No obstant, la validació del paper d’aquestes proteïnes a la qualitat final dels productes carnis és necessària abans de poder-los considerar marcadors proteics. Per altra banda, es va estudiar la possiblitat de millorar la seguretat alimentària de llonganissa sense sal afegida obtinguda amb el procés QDS® process a través l’ús de tecnologies innovadores (envasament actiu i altes pressions hidrostàtiques). La llonganissa sense sal afegida no va permetre el creixement de L. monocytogenes. No obstant, el patogen seria capaç de sobreviure durant la vida útil del producte en cas de recontaminació. L’envasament antimicrobià amb la inclusió de nisina com a antimicrobià natural es pot considerar un mètode efectiu per a millorar la seguretat de la llonganissa estudiada. L. monocytogenes va sobreviure al tractament d’alta pressió hidrostàtica (600 MPa, 5 min, 12ºC) gràcies a les característiques del producte de baixa activitat d’aigua i presència de lactat a la seva formulació. Per aquest motiu, la APH no es consideraria un tractament apropiat per a reduir la presència de L. monocytogenes en aquest tipus de producte.

Acidentes ocupacionais por exposição a material biológico entre a equipe multiprofissional do atendimento pré-hospitalar

Estudo transversal, tipo survey, realizado com a equipe multiprofissional de Atendimento Pré-hospitalar (APh) de Belo Horizonte, entre junho e dezembro de 2006. Objetivou-se determinar a incidência dos acidentes ocupacionais por exposição a material biológico, condutas pós-acidente, e fatores demográficos determinantes. Utilizou-se questionário estruturado, análise descritiva, cálculo de incidências e regressão logística. A incidência de acidentes com material biológico foi de 20,6%: 40,8% por pérfuro-cortantes e 49,0% por fluidos corporais; 35,3% entre médicos e 24,0% entre enfermeiros. Condutas pós-acidente: sem avaliação médica, 63,3%; subnotificação, 81,6%; nenhuma conduta, 55,0%; e, sem acompanhamento sorológico, 61,2%. Estiveram associados ao acidente: tempo na instituição (Odds ratio-OR 2,84; Intervalo de confiança-IC 95% 1,22-6,62), lotação na Unidade de Suporte Avançado (OR 4,18; IC 95% 1,64-10,64); interação: tempo na instituição e lotação na Unidade de Suporte Básico (OR 0,27; IC 95% 0,07-1,00). Sugere-se a implantação de protocolos pós-acidentes, visando a sua redução; a subnotificação e o aumento do acompanhamento pós-acidente.

General practitioners can evaluate the material, social and health dimensions of patient social status

OBJECTIVE: To identify which physician and patient characteristics are associated with physicians' estimation of their patient social status.DESIGN: Cross-sectional ulticentric survey. SETTING: Fourty-seven primary care private offices in Western Switzerland. PARTICIPANTS: Random sample of 2030 patients ≥ 16, who encountered a general practitioner (GP) between September 2010 and February 2011. MAIN MEASURES: PRIMARY OUTCOME: patient social status perceived by GPs, using the MacArthur Scale of Subjective Social Status, ranging from the bottom (0) to the top (10) of the social scale.Secondary outcome: Difference between GP's evaluation and patient's own evaluation of their social status. Potential patient correlates: material and social deprivation using the DiPCare-Q, health status using the EQ-5D, sources of income, and level of education. GP characteristics: opinion regarding patients' deprivation and its influence on health and care. RESULTS: To evaluate patient social status, GPs considered the material, social, and health aspects of deprivation, along with education level, and amount and type of income. GPs declaring a frequent reflexive consideration of their own prejudice towards deprived patients, gave a higher estimation of patients' social status (+1.0, p = 0.002). Choosing a less costly treatment for deprived patients was associated with a lower estimation (-0.7, p = 0.002). GP's evaluation of patient social status was 0.5 point higher than the patient's own estimate (p<0.0001). CONCLUSIONS: GPs can perceive the various dimensions of patient social status, although heterogeneously, according partly to their own characteristics. Compared to patients' own evaluation, GPs overestimate patient social status.

Validação de material informativo a pacientes em tratamento quimioterápico e aos seus familiares

O objetivo deste estudo foi a validação do conteúdo e a compreensibilidade do Material informativo a pacientes em tratamento quimioterápico e aos seus familiares. Para avaliar se as informações do material informativo sobre câncer, quimioterapia, cuidados com paciente, alimentação e medicação eram suficientemente esclarecedoras e claras, foram contatados 23 cuidadores principais de crianças com câncer. Os entrevistados responderam a um questionário contendo nove questões fechadas e uma aberta. A avaliação foi positiva e as informações foram consideradas esclarecedoras pela maioria dos participantes, dos quais alguns contribuíram com sugestões, que foram acrescentadas ao material. Após completa finalização, o material servirá como apoio aos pacientes com câncer e aos familiares. O intuito do material é melhorar a qualidade de assistência de enfermagem, pois acredita-se que, quando os responsáveis estão orientados sobre a maneira mais adequada de cuidar, a adesão do paciente ao tratamento aumenta, a informação os torna mais seguros, e colabora-se para o sucesso do tratamento.

Inter-rater agreement and reliability of the COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) Checklist

Background: The COSMIN checklist is a tool for evaluating the methodological quality of studies on measurement properties of health-related patient-reported outcomes. The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist (n = 114). Methods: 75 articles evaluating measurement properties were randomly selected from the bibliographic database compiled by the Patient-Reported Outcome Measurement Group, Oxford, UK. Raters were asked to assess the methodological quality of three articles, using the COSMIN checklist. In a one-way design, percentage agreement and intraclass kappa coefficients or quadratic-weighted kappa coefficients were calculated for each item. Results: 88 raters participated. Of the 75 selected articles, 26 articles were rated by four to six participants, and 49 by two or three participants. Overall, percentage agreement was appropriate (68% was above 80% agreement), and the kappa coefficients for the COSMIN items were low (61% was below 0.40, 6% was above 0.75). Reasons for low inter-rater agreement were need for subjective judgement, and accustom to different standards, terminology and definitions.Conclusions: Results indicated that raters often choose the same response option, but that it is difficult on item level to distinguish between articles. When using the COSMIN checklist in a systematic review, we recommend getting some training and experience, completing it by two independent raters, and reaching consensus on one final rating. Instructions for using the checklist are improved.

Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

Background: Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment andinnate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Results:Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection arefrequent on genes that are known to be at bifurcation points, and that are identified as beingin key position by a network-level analysis such as MGAT3 and GCS1.Conclusions: These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.

Influence of physico-chemical material characteristics on staphylococcal biofilm formation--a qualitative and quantitative in vitro analysis of five different calcium phosphate bone grafts.

Various compositions of synthetic calcium phosphates (CaP) have been proposed and their use has considerably increased over the past decades. Besides differences in physico-chemical properties, resorption and osseointegration, artificial CaP bone graft might differ in their resistance against biofilm formation. We investigated standardised cylinders of 5 different CaP bone grafts (cyclOS, chronOS (both β-TCP (tricalcium phosphate)), dicalcium phosphate (DCP), calcium-deficient hydroxyapatite (CDHA) and α-TCP). Various physico-chemical characterisations e.g., geometrical density, porosity, and specific surface area were investigated. Biofilm formation was carried out in tryptic soy broth (TSB) and human serum (SE) using Staphylococcus aureus (ATCC 29213) and S. epidermidis RP62A (ATCC 35984). The amount of biofilm was analysed by an established protocol using sonication and microcalorimetry. Physico-chemical characterisation showed marked differences concerning macro- and micropore size, specific surface area and porosity accessible to bacteria between the 5 scaffolds. Biofilm formation was found on all scaffolds and was comparable for α-TCP, chronOS, CDHA and DCP at corresponding time points when the scaffolds were incubated with the same germ and/or growth media, but much lower for cyclOS. This is peculiar because cyclOS had an intermediate porosity, mean pore size, specific surface area, and porosity accessible to bacteria. Our results suggest that biofilm formation is not influenced by a single physico-chemical parameter alone but is a multi-step process influenced by several factors in parallel. Transfer from in vitro data to clinical situations is difficult; thus, advocating the use of cyclOS scaffolds over the four other CaP bone grafts in clinical situations with a high risk of infection cannot be clearly supported based on our data.

Signatures of selection in the human olfactory receptor OR5I1 gene

The human olfactory receptor repertoire is reduced in comparison to other mammalsand to other non-human primates. Nonetheless, this olfactory decline opens an opportunity forevolutionary innovation and improvement. In the present study, we focus on an olfactoryreceptor gene, OR5I1, which had previously been shown to present an excess of amino acidreplacement substitutions between humans and chimpanzees. We analyze the geneticvariation in OR5I1 in a large worldwide human panel and find an excess of derived allelessegregating at relatively high frequencies in all populations. Additional evidence for selectionincludes departures from neutrality in allele frequency spectra tests but no unusually extendedhaplotype structure. Moreover, molecular structural inference suggests that one of thenonsynonymous polymorphisms defining the presumably adaptive protein form of OR5I1may alter the functional binding properties of the olfactory receptor. These results arecompatible with positive selection having modeled the pattern of variation found in the OR5I1gene and with a relatively ancient, mild selective sweep predating the “Out of Africa”expansion of modern humans.

Estimation of inelastic seismic material properties of a surgical sea-bed from multi-component marine seismic data

To date, state-of-the-art seismic material parameter estimates from multi-component sea-bed seismic data are based on the assumption that the sea-bed consists of a fully elastic half-space. In reality, however, the shallow sea-bed generally consists of soft, unconsolidated sediments that are characterized by strong to very strong seismic attenuation. To explore the potential implications, we apply a state-of-the-art elastic decomposition algorithm to synthetic data for a range of canonical sea-bed models consisting of a viscoelastic half-space of varying attenuation. We find that in the presence of strong seismic attenuation, as quantified by Q-values of 10 or less, significant errors arise in the conventional elastic estimation of seismic properties. Tests on synthetic data indicate that these errors can be largely avoided by accounting for the inherent attenuation of the seafloor when estimating the seismic parameters. This can be achieved by replacing the real-valued expressions for the elastic moduli in the governing equations in the parameter estimation by their complex-valued viscoelastic equivalents. The practical application of our parameter procedure yields realistic estimates of the elastic seismic material properties of the shallow sea-bed, while the corresponding Q-estimates seem to be biased towards too low values, particularly for S-waves. Given that the estimation of inelastic material parameters is notoriously difficult, particularly in the immediate vicinity of the sea-bed, this is expected to be of interest and importance for civil and ocean engineering purposes.

Acidente ocupacional por material perfurocortante entre profissionais de saúde de um Centro Cirúrgico

O acidente ocupacional por material perfurocortante constitui uma preocupação para instituições e trabalhadores de saúde, devido à elevada frequência de procedimentos invasivos, e a dinâmica do trabalho. Objetivou-se identificar a incidência dos acidentes, dos materiais envolvidos, dos fatores contribuintes e das condutas tomadas pós-acidente. Participaram de um estudo transversal 127 funcionários do centro cirúrgico. Registraram-se 23,6% (30/127) acidentes com envolvimento de agulha (73,3%), lâmina de bisturi (6,7%) e eletrocautério (6,7%). Os fatores contribuintes para o acidente foram: falta de atenção (36,7%), más condições de trabalho (20,0%), descuido (13,3%), pressa (10%) e acaso/azar (6,7%). Somente 15,4% dos acidentes foram registrados. A subnotificação deveu-se à irrelevância do acidente, desconhecimento do protocolo de rotina, displicência e sobrecarga de trabalho. Os resultados alertam para a importância de se implementar estratégias para adoção/revisão de protocolos pós-acidentes, visando a redução dos acidentes e de sua subnotificação.

Early maternal investment in mice: no evidence for compatible-genes sexual selection despite hybrid vigor.

Confronting a recently mated female with a strange male can induce a pregnancy block ('Bruce effect'). The physiology of this effect is well studied, but its functional significance is still not fully understood. The 'anticipated infanticide hypothesis' suggests that the pregnancy block serves to avoid the cost of embryogenesis and giving birth to offspring that are likely to be killed by a new territory holder. Some 'compatible-genes sexual selection hypotheses' suggest that the likelihood of a pregnancy block is also dependent on the female's perception of the stud's and the stimulus male's genetic quality. We used two inbred strains of mice (C57BL/6 and BALB/c) to test all possible combinations of female strain, stud strain, and stimulus strain under experimental conditions (N(total) = 241 mated females). As predicted from previous studies, we found increased rates of pregnancy blocks if stud and stimulus strains differed, and we found evidence for hybrid vigour in offspring of between-strain mating. Despite the observed heterosis, pregnancies of within-strain matings were not more likely to be blocked than pregnancies of between-strain matings. A power analysis revealed that if we missed an existing effect (type-II error), the effect must be very small. If a female gave birth, the number and weight of newborns were not significantly influenced by the stimulus males. In conclusion, we found no support for the 'compatible-genes sexual selection hypotheses'.

Gerenciamento de custos: aplicação do método de Custeio Baseado em Atividades em Centro de Material Esterilizado

Esta pesquisa exploratória descritiva, na modalidade de estudo de caso, teve por objetivo a aplicação do Custeio Baseado em Atividades (ABC) em Centro de Material e Esterilização (CME) de um hospital de ensino de capacidade extra. A coleta de dados ocorreu durante o ano de 2006, utilizando-se as técnicas de análise documental e observação direta não participante. A análise de processos possibilitou o conhecimento dos custos do ciclo/carga de desinfecção química ($9.95) e física ($12.63), e esterilização por vapor saturado sob pressão ($31.37) e por vapor de Baixa Temperatura e Formaldeído Gasoso ($255.28). As informações geradas pelo ABC resultaram na compreensão do processo gerador de custos e forneceram base para a mensuração de desempenho e melhorias de processos do CME.

Deciphering 3'ss selection in the yeast genome reveals an RNA thermosensor that mediates alternative splicing

Poor understanding of the spliceosomal mechanisms to select intronic 3' ends (3'ss) is a major obstacle to deciphering eukaryotic genomes. Here, we discern the rules for global 3'ss selection in yeast. We show that, in contrast to the uniformity of yeast splicing, the spliceosome uses all available 3'ss within a distance window from the intronic branch site (BS), and that in 70% of all possible 3'ss this is likely to be mediated by pre-mRNA structures. Our results reveal that one of these RNA folds acts as an RNA thermosensor, modulating alternative splicing in response to heat shock by controlling alternate 3'ss availability. Thus, our data point to a deeper role for the pre-mRNA in the control of its own fate, and to a simple mechanism for some alternative splicing.

African signatures of recent positive selection in human FOXI1

Background: The human FOXI1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene underhuman-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences.Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans,20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39worldwide human populations from the HGDP-CEPH diversity panel.Results: The genome sequences recently available from other primate and non-primate species showed that FOXI1divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant inEuropeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsbstatistics revealed significantly extended tracks of homozygosity around FOXI1 in Africa, suggesting a recentepisode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on theputatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies stronglycorrelated with the absolute geographical latitude of the populations sampled.Conclusions: We present evidence for recent positive selection in the FOXI1 gene region in Africa. Climate mightbe related to this recent adaptive event in humans. Of the multiple functions of FOXI1, its role in kidney-mediatedwater-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.