Clinical presentation and outcome in a series of 88 patients with the cblC defect.

The cblC defect is the most common inborn error of vitamin B12 metabolism. Despite therapeutic measures, the long-term outcome is often unsatisfactory. This retrospective multicentre study evaluates clinical, biochemical and genetic findings in 88 cblC patients. The questionnaire designed for the study evaluates clinical and biochemical features at both initial presentation and during follow up. Also the development of severity scores allows investigation of individual disease load, statistical evaluation of parameters between the different age of presentation groups, as well as a search for correlations between clinical endpoints and potential modifying factors. RESULTS: No major differences were found between neonatal and early onset patients so that these groups were combined as an infantile-onset group representing 88 % of all cases. Hypotonia, lethargy, feeding problems and developmental delay were predominant in this group, while late-onset patients frequently presented with psychiatric/behaviour problems and myelopathy. Plasma total homocysteine was higher and methionine lower in infantile-onset patients. Plasma methionine levels correlated with "overall impression" as judged by treating physicians. Physician's impression of patient's well-being correlated with assessed disease load. We confirmed the association between homozygosity for the c.271dupA mutation and infantile-onset but not between homozygosity for c.394C>T and late-onset. Patients were treated with parenteral hydroxocobalamin, betaine, folate/folinic acid and carnitine resulting in improvement of biochemical abnormalities, non-neurological signs and mortality. However the long-term neurological and ophthalmological outcome is not significantly influenced. In summary the survey points to the need for prospective studies in a large cohort using agreed treatment modalities and monitoring criteria.

The genome sequence of taurine cattle: a window to ruminant biology and evolution.

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis.

IMPORTANCE: There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). OBJECTIVE: To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. INTERVENTIONS: Valve replacement during index hospitalization (early surgery) vs medical therapy. MAIN OUTCOMES AND MEASURES: In-hospital and 1-year mortality. RESULTS: Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity. CONCLUSIONS AND RELEVANCE: Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.

A novel TMPRSS3 missense mutation in a DFNB8/10 family prevents proteolytic activation of the protein.

Pathogenic mutations in TMPRSS3, which encodes a transmembrane serine protease, cause non-syndromic deafness DFNB8/10. Missense mutations map in the low density-lipoprotein receptor A (LDLRA), scavenger-receptor cysteine-rich (SRCR), and protease domains of the protein, indicating that all domains are important for its function. TMPRSS3 undergoes proteolytic cleavage and activates the ENaC sodium channel in a Xenopus oocyte model system. To assess the importance of this gene in non-syndromic childhood or congenital deafness in Turkey, we screened for mutations affected members of 25 unrelated Turkish families. The three families with the highest LOD score for linkage to chromosome 21q22.3 were shown to harbor P404L, R216L, or Q398X mutations, suggesting that mutations in TMPRSS3 are a considerable contributor to non-syndromic deafness in the Turkish population. The mutant TMPRSS3 harboring the novel R216L missense mutation within the predicted cleavage site of the protein fails to undergo proteolytic cleavage and is unable to activate ENaC, thus providing evidence that pre-cleavage of TMPRSS3 is mandatory for normal function.

Invisible Environments: Old Age and its spaces

Despite the progressive ageing of a worldwide population, negative attitudes towards old age have proliferated thanks to cultural constructs and myths that, for decades, have presented old age as a synonym of decay, deterioration and loss. Moreover, even though every human being knows he/she will age and that ageing is a process that cannot be stopped, it always seems distant, far off in the future and, therefore, remains invisible. In this paper, I aim to analyse the invisibility of old age and its spaces through two contemporary novels and their ageing females protagonists –Maudie Fowler in Doris Lessing ’s The Diary of a Good Neighbour and Erica March in Rose Tremain ’s The Cupboard. Although invisible to the rest of society, these elderly characters succeed in becoming significant in the lives of younger protagonists who, immersed in their active lives, become aware of the need to enlarge our vision of old age.

External urethral sphincter electromyography in asymptomatic women and the influence of the menstrual cycle.

OBJECTIVE: To investigate by electromyography (EMG), the presence of complex repetitive discharges (CRDs) and decelerating bursts (DBs) in the striated external urethral sphincter during the menstrual cycle in female volunteers with no urinary symptoms and complete bladder emptying. SUBJECTS AND METHODS: Healthy female volunteers aged 20-40 years, with regular menstrual cycles and no urinary symptoms were recruited. Volunteers completed a menstruation chart, urinary symptom questionnaires, pregnancy test, urine dipstick, urinary free flow and post-void ultrasound bladder scan. Exclusion criteria included current pregnancy, use of hormonal medication or contraception, body mass index of >35 kg/m(2) , incomplete voiding and a history of pelvic surgery. Eligible participants underwent an external urethral sphincter EMG, using a needle electrode in the early follicular phase and the mid-luteal phase of their menstrual cycles. Serum oestradiol and progesterone were measured at each EMG test. RESULTS: In all, 119 women enquired about the research and following screening, 18 were eligible to enter the study phase. Complete results were obtained in 15 women. In all, 30 EMG tests were undertaken in the 15 asymptomatic women. Sphincter EMG was positive for CRDs and DBs at one or both phases of the menstrual cycle in eight (53%) of the women. Three had CRDs and DBs in both early follicular and mid-luteal phases. Five had normal EMG activity in the early follicular phase and CRDs and DBs in the mid-luteal phase. No woman had abnormal EMG activity in the early follicular phase and normal activity in the luteal phase. There was no relationship between EMG activity and age, parity or serum levels of oestradiol and progesterone. CONCLUSIONS: CRDs and DB activity in the external striated urethral sphincter is present in a high proportion of asymptomatic young women. This abnormal EMG activity has been shown for the first time to change during the menstrual cycle in individual women. CRDs and DBs are more commonly found in the luteal phase of the menstrual cycle. The importance of CRDs and DBs in the aetiology of urinary retention in young women remains uncertain. The distribution and or quantity of abnormal EMG activity in the external urethral sphincter may be important. In a woman with urinary retention the finding of CRDs and DBs by needle EMG does not automatically establish Fowler's syndrome as the explanation for the bladder dysfunction. Urethral pressure profilometry may be helpful in establishing a diagnosis. Opiate use and psychological stress should be considered in young women with urinary retention.

IL-27 Induces Th17 Differentiation in the Absence of STAT1 Signaling.

It is known that differentiation of Th17 cells is promoted by activation of STAT3 and inhibited by activation of STAT1. Although both transcription factors are activated by several cytokines, including IL-6, IL-21, and IL-27, each of these cytokines has a very different effect on Th17 differentiation, ranging from strong induction (IL-6) to strong inhibition (IL-27). To determine the molecular basis for these differences, we measured STAT3 and STAT1 activation profiles for IL-6, IL-21, and IL-27, as well as for cytokine pairs over time. We found that the ratio of activated STAT3/activated STAT1 is crucial in determining whether cytokines promote or inhibit Th17 differentiation. IL-6 and IL-21 induced p-STAT3/p-STAT1 ratios > 1, leading to the promotion of Th17 differentiation, whereas IL-27 or IL-6+IL-27 induced p-STAT3/p-STAT1 ratios < 1, resulting in inhibition of Th17 differentiation. Consistent with these findings, we show that IL-27 induces sufficient p-STAT3 to promote Th17 differentiation in the absence of STAT1. Furthermore, IL-27-induced STAT1-deficient T cells were indistinguishable from bona fide highly proinflammatory Th17 cells because they induced severe experimental autoimmune encephalomyelitis upon adoptive transfer. Our results suggest that the ratio of p-STAT3/p-STAT1 induced by a cytokine or cytokine pairs can be used to predict whether they induce a competent Th17-differentiation program.

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the International Collaboration of Endocarditis-Prospective Cohort Study.

BACKGROUND: The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. METHODS: Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. RESULTS: EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). CONCLUSIONS: In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

'A pilot study to investigate external urethral sphincter electromyographic activity and the influence of hormonal changes in the menstrual cycle'

But de l'étude Un enregistrement spécifique EMG du sphincter strié urétral avec décharges répétitives et complexes ainsi que salves de décélération a été décrit comme pathognomonique du syndrome de Fowler, un trouble de la relaxation du sphincter strié urétral chez la femme jeune responsable d'une retention urinaire. Nous avons souhaité étudier la présence de cet enregistrement EMG spécifique chez la femme asymptomatique, ceci à différents moments du cycle menstruel. Matériel et Méthode Nous avons recruté des femmes volontaires saines âgées entre 20 et 40 ans, ayant un cycle hormonal régulier, et ne présentant aucun symptôme urinaire. Les critères d'exclusion étaient la presence d'une dysfonction mictionnelle, d'une infection urinaire, la grossesse, la prise d'une thérapie hormonale ou d'hormone contraceptive, une obésité et des antécédants d'intervention pelvienne. Nous avons procédé à deux enregistrements EMG du sphincter strié urétral des participantes éligibles, utilisant une aiguille concentrique, ceci dans la première phase du cycle (phase folliculaire) et dans la dernière phase du cycle (phase lutéale). Les taux sériques de progestérone et d'oestrogène étaient mesurés à chaque enregistrement. Résultats 15 participantes ont complété l'étude. L' enregistrement EMG du sphincter a été positif avec présence de décharges répétitives et de salves de décélération lors d'une ou des deux phases du cycle menstruel chez 8 participantes (53%). Trois participantes présentaient cet enregistrement spécifique lors des deux phases du cycle et cinq participantes présentaient cet enregistrement spécifique lors de la phase lutéale uniquement. Aucune femme ne présentait cet enregistrement spécifique en début de cycle uniquement. Il n'y avait pas de relation avec l'âge, la parité ou les taux hormonaux. Conclusions L'enregistrement EMG spécifique du sphincter strié urétral, avec décharges répétitives et salves de décélération, se retrouve chez une proportion élevée de femmes asymptomatiques. Il a été montré que ce tracé change lors du cycle menstruel, en étant retrouvé plus fréquemment dans la dernière phase du cycle. L'importance de cet enregistrement EMG dans l'étiologie de la retention urinaire de la femme jeune reste à éclaircir. Nous devons considérer que sa présence ne pose pas automatiquement un diagnostic de syndrome de Fowler chez la femme en rétention urinaire.

The Brazilian and patagonian fishes of the wilkes expedition: 1838-1842

Na viagem efetuada à volta do mundo pela U. S. Exploring Expedition mais conhecida pelo nome de Expedição Wilkes e durante o período em que a mesma operava no Atlântico Ocidental, foram visitadas as regiões do Rio de Janeiro e da Patagônia. Por ocasião da festa comemorativa do centenário da The American Philosophical Society, de Filadélfia, ocorrida a 23 de Fevereiro de 1930, o autor teve a oportunidade de apresentar uma nota prévia da qual constava uma lista de peixes capturados durante o cruzeiro da Expedição. Teve, então, o ensejo de examinar o diário redigido pelo Dr. Charles Pickering, botânico da Expedição, nele encontrando anotações valiosas para a História Natural, considerada em seu sentido amplo, detalhes a respeito das localidades percorridas e relações extensas de animais e plantas, além de diversos representantes pertencentes a outros grupos. Sob o ponto de vista histórico, os comentários aí constantes são de importância significativa. Em muitos casos, essas apreciações fornecem base sólida para a efetivação de estudos faunísticos, de caráter comparativo, muito instrutivos e úteis. O autor examinou a coleção de peixes da Expedição Wilkes que se encontra no Museu Nacional dos Estados Unidos, em Washington, acervo esse gentilmente posto à sua disposição para estudo. Dessa maneira, no presente trabalho, fornece matéria de amplo interesse histórico, visando com isso lançar alguma luz sobre a imensa fauna do Brasil e da Argentina. Baseando-se nos dados fornecidos por Pickering, o autor divulga dados curiosos a respeito da baía do Rio de Janeiro e adjacências, no ano de 1838. Segue-se uma lista contendo a diagnose de 82 espécimes de água doce, salobra e salgada, estudados e comparados com outros de várias procedências. Referindo-se ao Rio Negro, descreve o autor o aspeto da região patagônica, durante certo período de 1839, fazendo comentários a respeito de 7 espécies de peixes nela, encontradas.

Efeito do sulfato de magnésio sobre o índice de pulsatilidade das artérias uterinas, umbilical e cerebral média fetal de acordo com a persistência da incisura protodiastólica da artéria uterina na pré-eclâmpsia grave

OBJETIVO: avaliar o efeito do sulfato de magnésio sobre o índice de pulsatilidade (IP) das artérias uterinas, umbilicais e cerebral média fetal, de acordo com a persistência ou não da incisura protodiastólica bilateral das artérias uterinas na pré-eclâmpsia grave. MÉTODOS: foi desenvolvido um estudo do tipo coorte, incluindo 40 gestantes com pré-eclâmpsia grave, das quais 23 apresentavam incisura protodiastólica bilateral e 17, incisura ausente/unilateral. As pacientes foram submetidas a doplervelocimetria antes e depois de 20 minutos da administração intravenosa de 6 g do sulfato de magnésio. O exame foi realizado com a paciente em posição semi-Fowler, obtendo-se os sonogramas durante a inatividade fetal, em períodos de apneia e ausência de contrações uterinas. Todos os exames foram realizados por dois pesquisadores, considerando a média como resultado final. A comparação dos IP antes e depois do sulfato de magnésio em cada grupo foi realizada pelo teste de Wilcoxon. A diferença das duas medidas (antes e depois do sulfato de magnésio) foi comparada entre os grupos (incisura bilateral e incisura ausente/unilateral) utilizando-se o teste de Mann-Whitney. RESULTADOS: houve um aumento significativo da frequência cardíaca materna e uma diminuição da pressão arterial materna e da mediana dos IP das duas artérias uterinas e da artéria cerebral média fetal depois da utilização do sulfato de magnésio em ambos os grupos. Houve redução significativa do IP da artéria uterina esquerda e da artéria umbilical apenas no grupo com incisura protodiastólica unilateral/ausente. No entanto, não foram encontradas diferenças significativas em relação ao IP da artéria uterina direita e relação umbilical/cerebral antes e depois do sulfato de magnésio em cada grupo. Não se encontrou diferença entre os grupos, antes e depois do sulfato de magnésio, para nenhum dos desfechos estudados. CONCLUSÕES: após a administração intravenosa de 6 g do sulfato de magnésio nas pacientes com pré-eclâmpsia grave, ocorre uma diminuição da pressão arterial e do IP das artérias uterinas, umbilicais e cerebral média fetal, além de aumento da frequência cardíaca materna, não influenciada pela presença de incisura protodiastólica bilateral nas artérias uterinas.

A crisis of social democracy : organized labour and the NDP in an era of neoliberalism

The NDP was founded out of the ashes of the Co-Operative Commonwealth Federation to cooperate with the Canadian Labour Congress to become the 'political arm of organized labour' in Canada. The NDP has long claimed they are the party which represents the policy goals of organized labour in Canada: that the NDP alone will fight for trade union rights, and will fight for Canadian workers. Divergent Paths is an examination of the links between the labour movement and the ND P in an era ofneo-liberalism. Provincial NDP governments have become increasingly neoliberal in their ideological orientation, and have often proved to be no friend to the labour movement when they hold office. The Federal party has never held power, nor have they ever formed the Official Opposition. This thesis charts the progress of the federal NDP as they become more neoliberal from 1988 to 2006, and shows how this trend effects the links between the NDP and labour. Divergent Paths studies each federal election from 1988 to 2006, looking at the interactions between Labour and the NDP during these elections. Elections provide critical junctions to study discourse - party platforms, speeches, and other official documents can be used to examine discourse. Extensive newspaper searches were used to follow campaign events and policy speeches. Studying the party's discourse can be used to determine the ideological orientation of the party itself: the fact that the party's discourse has become neoliberal is a sure sign that the party itself is neoliberal. The NDP continues to drive towards the centre of the political spectrum in an attempt to gain multi-class support. The NDP seems more interested in gaining seats at any cost, rather then promoting the agenda of Labour. As the party attempts to open up to more multi-class support, Labour becomes increasingly marginalised in the party. A rift which arguably started well before the 1988 election was exacerbated during that election; labour encouraged the NDP to campaign solely on the issue of Free Trade, and the NDP did not. The 1993 election saw the rift between the two grow even further as the Federal NDP suffered major blowbacks from the actions of the Ontario NDP. The 1997 and 2000 elections saw the NDP make a deliberate move to the centre of the political spectrum which increasingly marginalised labour. In the 2004 election, Jack Layton made no attempt to move the party back to the left; and in 2006 the link between labour and the NDP was perhaps irreparably damaged when the CAW endorsed the Liberal party in a strategic voting strategy, and the CLC did not endorse the NDP. The NDP is no longer a reliable ally of organized labour. The Canadian labour movement must decide wether the NDP can be 'salvaged' or if the labour movement should end their alliance with the NDP and engage in a new political project.

Revision of the Niagara Railway Arch Bridge (1920)

From American Society of Civil Engineers.

The Digital Dream Team - Digital Divide (Group 4)

This vessel contains the poster and artefact link for The Digital Dream Teams' project

El modelo integral y su aplicación en terapia

La presente monografía es una revisión de la literatura frente a los postulados fundamentales del modelo integral propuesto por Ken Wilber y la aplicación de dicho modelo a la psicoterapia. Se presentan cada una de los elementos que sostienen esta meta-perspectiva tales como cuadrantes, niveles, líneas, y estados, y la forma en que cada uno de ellos se relaciona con la psicoterapia integral. Se abordan a continuación temas como los diferentes niveles de terapia, las etapas del desarrollo de la identidad, las patologías típicas en cada una de ellas y las posibles intervenciones para manejarlas, el rol que posee el terapeuta y algunos otros campos de aplicación del modelo integral a terapias grupales y al asesoramiento.