RAS mutations and cetuximab in locally advanced rectal cancer: results of the EXPERT-C trial.

Background: RAS mutations predict resistance to anti-epidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial.

Methods: Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type, and randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-directional Sanger sequencing. The effect of cetuximab on study end-points in the RAS wild-type population was analysed.

Results: Eleven (13%) of 84 patients initially classified as KRAS/BRAF wild-type were found to have a mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, 78/149 (52%) assessable patients were RAS wild-type (CAPOX, n = 40; CAPOX-C, n = 38). In this population, after a median follow-up of 63.8 months, in line with the initial analysis, the addition of cetuximab was associated with numerically higher, but not statistically significant, rates of complete response (15.8% versus 7.5%, p = 0.31), 5-year progression-free survival (75.5% versus 67.5%, hazard ratio (HR) 0.61, p = 0.25) and 5-year overall survival (83.8% versus 70%, HR 0.54, p = 0.20).

Conclusions: RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of locally advanced rectal cancer patients. Given the small sample size, no definitive conclusions on the effect of additional RAS mutations on cetuximab treatment in this setting can be drawn and further investigation of RAS in larger studies is warranted.

Analyzing Gene Centres with the Help of the Checklist Method – the Case of Syria

The present survey of species diversity of cultivated plants is the first for Syria. Some cultivated species will be added in the future, because due to the civil war in Syria, it was not possible to visit the country in the frame of the present work, as initially planned. Checklists proved to be a useful tool for overviewing the cultivated plants of selected areas and allow a characterization of the state of plant genetic resources of Syria. Syria has experienced several civilizations. Man settled in this productive land since ancient times and used its resources. However, such use has led to changes in vegetation and decline of wildlife through the country, in seashore areas, interior, mountains, and grassland. Plant domestication and growing started more than 10,000 years ago in West Asia. Since then, plentiful of economic plant species were present and used by man and his domesticated animals. Forming a part of the Fertile Crescent, where many of the world’s agricultural plants have evolved, Syria is extremely rich in agrobiodiversity. Wild progenitors of wheat and barley and wild relatives of many fruit trees such as almonds and pistachio as well as forage species are still found in marginal lands and less disturbed areas. These are threatened by a wide range of human activities, notably modern, extensive agriculture, overgrazing, overcutting and urban expansion. Syria is also considered as part of one of the main centres of origin, according to Vavilov, who had collected in Syria in 1926. The first expeditions to crop fields showed the exclusive nature of cultivated plants in Syria with a high number of endemic forms. Furthermore, Syria is a part of a biodiversity hotspot. Several studies have been performed to study agrobiodiversity in different parts of Syria, but usually on wild species. Many collections have been carried out; however, they focussed preferably on cereals and pulses, and particularly on wheat, like Vavilov’s expedition. Only 30 crops make up the major part of the conserved Syrian crop plant material in the genebank, indicating that most of the remaining 7,000 species of cultivated plants and many other valuable genetic resources species have only been included on a limited scale in the genebank collections. Although a small country (185,180 km2), Syria accommodates numerous ecosystems that allow for a large diversity of plant genetic resources for agriculture ranging from cold-requiring to subtropical crops to live and thrive. Only few references are available in this respect. The aim of the present study was to complete a checklist of Syria’s cultivated plants of agriculture and horticulture excluding plants only grown as ornamental or for forestry. Furthermore, plants taken for reforestation have not been included, if they do not have also agricultural or horticultural uses. Therefore, the inclusion of plants into the checklist follows the same principles as “Mansfeld’s Encyclopedia”. Main sources of information were published literature, floras of Syria, Lebanon and the Mediterranean, as well as Syrian printed sources in Arabic and/or English, reports from FAO on agricultural statistics in Syria, and data from ICARDA and Bioversity International. In addition, personal observations gathered during professional work in the General Commission for Scientific Agricultural Research (GCSAR) in Syria (since 1989) and participation in projects were taken into account. These were: (1) A project on “Conservation and Sustainable Use of Dry Land Agrobiodiversity in the Near East” with participation of Jordan, Lebanon, Syria, and the Palestinian Authority, focussing on landraces and wild relatives of barley, wheat, lentil, alliums, feed legumes, and fruit trees (1999–2005). (2) A project for vegetable landraces (1993–1995) in collaboration with the former International Plant Genetic Resources Institute and the UN Development Programme, in which 380 local vegetable accessions were evaluated. For medicinal plants and fruit trees I was in personal contact with departments of GCSAR and the Ministry of Agriculture and Agrarian Reform, as well as with private organizations. The resulting checklist was compared with the catalogues of crop plants of Italy and a checklist of cultivated plants of Iraq. The cultivated plant species are presented in alphabetical order according to their accepted scientific names. Each entry consists of a nomenclatural part, folk names, details of plant uses, the distribution in Syria (by provinces), a textual description, and references to literature. In total, 262 species belonging to 146 genera and 57 families were identified. Within-species (intraspecific) diversity is a significant measure of the biodiversity. Intraspecific diversity for wild plants has been and remains to be well studied, but for crop plants there are only few results. Mansfeld’s method is an actual logical contribution to such studies. Among the families, the following have the highest number of crop species: Leguminosae (34 spp.), Rosaceae (24), Gramineae (18), Labiatae (18), Compositae (14), Cruciferae (14), Cucurbitaceae (11), Rutaceae (10), Malvaceae (9), Alliaceae (7), and Anacardiaceae (7). The establishment of an effective programme for the maintenance of plant genetic resources in Syria started in the mid-1970s. This programme considered ex situ and in situ collection of the genetic resources of various field crops, fruit trees and vegetables. From a plant genetic resources viewpoint, it is clear that the homegarden is an important location for the cultivation of so-called neglected and underutilized species (neglected from a research side and underutilized from a larger economic side). Such species have so far not received much care from ecologists, botanists and agronomists, and they are considerably under-represented in genebanks.

Obésité abdominale et autres déterminants du risque cardiométabolique dans deux populations urbaines noires apparentées : Port-au-Prince (Haïti) et Cotonou (Bénin)

L’obésité est un problème de santé publique reconnu. Dans la dernière décennie l’obésité abdominale (OA) a été considérée comme une maladie métabolique qui contribue davantage au risque de diabète et de maladies cardiovasculaires que l’obésité générale définie par l’indice de masse corporelle. Toutefois, dans les populations d’origine africaine, la relation entre l’OA et les autres biomarqueurs de risque cardiométabolique (RCM) demeure obscure à cause du manque d’études chez ces populations et de l’absence de valeurs-seuils spécifiques pour juger d’une OA. Cette étude visait à comparer la prévalence des biomarqueurs de RCM (OA, hypertension artérielle, hyperglycémie, dyslipidémie, résistance à l'insuline et inflammation pré-clinique) chez les Béninois de Cotonou et les Haïtiens de Port-au-Prince (PAP), à étudier l’association de l’OA avec les autres biomarqueurs de RCM, à documenter le rôle du niveau socio-économique (NSE) et du mode de vie dans cette association et à ’identifier les indicateurs anthropométriques de l’OA -tour de taille (TT) et le ratio TT/hauteur (TT/H)- et les seuils qui prédisent le mieux le RCM à Cotonou et à PAP. Il s’est agi d’une analyse de données transversales chez 452 adultes (52 % hommes) apparemment en bonne santé, âgés de 25 à 60 ans, avec 200 sujets vivant à Cotonou (Bénin) et 252 sujets à PAP (Haïti). Les biomarqueurs de RCM considérés étaient : le syndrome métabolique (SMet) d’après les critères harmonisés de 2009 et ses composantes individuelles - une OA à partir d’un TT ≥ 94cm chez les hommes et ≥ 80cm chez les femmes, une hypertension, une dyslipidémie et une hyperglycémie; la résistance à l’insuline définie chez l’ensemble des sujets de l’étude à partir du 75e centile de l’Homeostasis Model Assessment (HOMA-IR); un ratio d’athérogénicité élevé (Cholestérol sérique total/HDL-Cholestérol); et l’inflammation pré-clinique mesurée à partir d’un niveau de protéine C-réactive ultrasensible (PCRus) entre 3 et 10 mg/l. Le ratio TT/H était aussi considéré pour définir l’OA à partir d’un seuil de 0,5. Les données sur les habitudes alimentaires, la consommation d’alcool, le tabagisme, les caractéristiques sociodémographiques et les conditions socio-économiques incluant le niveau d’éducation et un proxy du revenu (basé sur l’analyse par composante principale des biens et des possessions) ont été recueillies au moyen d’un questionnaire. Sur la base de données de fréquence de consommation d’aliments occidentaux, urbains et traditionnels, des schémas alimentaires des sujets de chaque ville ont été identifiés par analyse typologique. La validité et les valeurs-seuils de TT et du ratio TT/H prédictives du RCM ont été définies à partir des courbes ROC (Receiver Operating Characteristics). Le SMet était présent chez 21,5 % et 16,1 % des participants, respectivement à Cotonou et à PAP. La prévalence d’OA était élevée à Cotonou (52,5 %) qu’à PAP (36%), avec une prévalence plus élevée chez les femmes que chez les hommes. Le profil lipidique sérique était plus athérogène à PAP avec 89,3 % d’HDL-c bas à PAP contre 79,7 % à Cotonou et un ratio CT/HDL-c élevé de 73,4 % à PAP contre 42 % à Cotonou. Les valeurs-seuils spécifiques de TT et du TT/H étaient respectivement 94 cm et 0,59 chez les femmes et 80 cm et 0,50 chez les hommes. Les analyses multivariées de l’OA avec les biomarqueurs de RCM les plus fortement prévalents dans ces deux populations montraient que l’OA était associée à un risque accru de résistance à l’insuline, d’athérogénicité et de tension artérielle élevée et ceci, indépendamment des facteurs socio-économiques et du mode de vie. Deux schémas alimentaires ont émergé, transitionnel et traditionnel, dans chaque ville, mais ceux-ci ne se révélaient pas associés aux biomarqueurs de RCM bien qu’ils soient en lien avec les variables socio-économiques. La présente étude confirme la présence de plusieurs biomarqueurs de RCM chez des sujets apparemment sains. En outre, l’OA est un élément clé du RCM dans ces deux populations. Les seuils actuels de TT devraient être reconsidérés éventuellement à la lumière d’études de plus grande envergure, afin de mieux définir l’OA chez les Noirs africains ou d’origine africaine, ce qui permettra une surveillance épidémiologique plus adéquate des biomarqueurs de RCM.

Migration and Residence Patterns of Salmonids in Puget Sound, Washington

Thesis (Ph.D.)--University of Washington, 2016-08

Adaptation of the MacNew quality of life questionnaire after myocardial infarction in an Iranian population

BACKGROUND: Health-related quality of life (HRQL) assessment is an important measure of the impact of a wide range of disease process on an individual. To date, no HRQL tool has been evaluated in an Iranian population with cardiovascular disorders, specifically myocardial infarction, a major cause of mortality and morbidity. The MacNew Heart Disease Health-related Quality of Life instrument is a disease-specific HRQL questionnaire with satisfactory validity and reliability when applied cross-culturally. METHOD: A Persian version of MacNew was prepared by both forward and backward translation by bilinguals after which a feasibility test was performed. Consecutive patients (n = 51) admitted to a coronary care unit with acute myocardial infarction were recruited for measurement of their HRQL with retest one month after discharge in the follow-up clinic. Principal components analysis, intra-class correlation reliability, internal consistency, and test-retest reliability were assessed. RESULTS: Trivial rates of missing data confirmed the acceptability of the tool. Principal component analysis revealed that the three domains, emotional, social and physical, performed as well as in the original studies. Internal consistency was high and comparable to other studies, ranging from 0.92 for the emotional and physical domains, to 0.94 for the social domain, and to 0.95 for the Global score. Domain means of 5, 5.3 and 4.9 for emotional, physical and social respectively indicate that our Iranian population has similar emotional and physical but worse social HRQL scores. Test-retest analysis showed significant correlation in emotional and physical domains (P < 0.05). CONCLUSION: The Persian version of the MacNew questionnaire is comparable to the English version. It has high internal consistency and reasonable reproducibility, making it an appropriate specific quality of life tool for population-based studies and clinical practice in Iran in patients who have survived an acute myocardial infraction. Further studies are needed to confirm its validity in larger populations with cardiovascular disease

Medication reconciliation at patient admission: a randomized controlled trial

Objective: To measure length of hospital stay (LHS) in patients receiving medication reconciliation. Secondary characteristics included analysis of number of preadmission medications, medications prescribed at admission, number of discrepancies, and pharmacists interventions done and accepted by the attending physician. Methods: A 6 month, randomized, controlled trial conducted at a public teaching hospital in southern Brazil. Patients admitted to general wards were randomized to receive usual care or medication reconciliation, performed within the first 72 hours of hospital admission. Results: The randomization process assigned 68 patients to UC and 65 to MR. LHS was 10±15 days in usual care and 9±16 days in medication reconciliation (p=0.620). The total number of discrepancies was 327 in the medication reconciliation group, comprising 52.6% of unintentional discrepancies. Physicians accepted approximately 75.0% of the interventions. Conclusion: These results highlight weakness at patient transition care levels in a public teaching hospital. LHS, the primary outcome, should be further investigated in larger studies. Medication reconciliation was well accepted by physicians and it is a useful tool to find and correct discrepancies, minimizing the risk of adverse drug events and improving patient safety.

An evolutionary model explaining the Neolithic transition from egalitarianism to leadership and despotism.

The Neolithic was marked by a transition from small and relatively egalitarian groups, to much larger groups with increased stratification. But the dynamics of this remain poorly understood. It is hard to see how despotism can arise without coercion, yet coercion could not easily have occurred in an egalitarian setting. Using a quanti- tative model of evolution in a patch-structured population, we demonstrate that the interaction between demographic and ecological factors can overcome this conundrum. We model the co-evolution of individual preferences for hierarchy alongside the degree of despotism of leaders, and the dispersal preferences of followers. We show that voluntary leadership without coercion can evolve in small groups, when leaders help to solve coordination problems related to resource production. An example is coordinating construction of an irrigation system. Our model predicts that the transition to larger despotic groups will then occur when: 1. surplus resources lead to demographic expansion of groups, removing the viability of an acephalous niche in the same area and so locking individuals into hierarchy; 2. high dispersal costs limit followers' ability to escape a despot. Empirical evidence suggests that these conditions were likely met for the first time during the subsistence intensification of the Neolithic.

Estudo da prevalência e da gravidade da dermatite de contacto em 'frango do campo'

O sector avícola enfrenta atualmente dois desafios muito estimulantes. O primeiro decorre do aumento, que se prevê continuar a crescer, nos níveis de procura de carne de aves no mercado interno e internacional; o segundo decorre do facto da criação avícola ter adotado métodos de produção mais intensivos (kg peso vivo/m2/ano) e em maior escala, i.e. com maior concentração animal na mesma exploração. Este carácter vincadamente “industrial” tem merecido uma natural atenção das sociedades e das autoridades pecuárias no sentido desta economia de escala passar a ter num conjunto de instrumentos legais e técnicos o devido contrapeso para a salvaguarda das aves enquanto ser vivo. O presente trabalho tem como ponto de partida a Directiva 2007/43/CE do Conselho de 28 de Junho, relativa ao estabelecimento de regras mínimas para a proteção de frangos de carne. Em virtude de não existir ainda informação suficiente sobre a forma como a qualidade do maneio animal pode ser monitorizada, ao nível do abate, por médicos veterinários e auxiliares oficiais, em frangos de criação especial segundo os modelos definidos no Regulamento (CE) n.º 543/2008, urge realizar estudos neste domínio. O principal objetivo da realização do presente trabalho de campo foi o estudo da ocorrência das dermatites de contacto plantar (pododermatites) e da bolsa sinovial préesternal em frangos produzidos em sistemas de produção considerados “protetores” do bem-estar animal, designadamente os seguintes: i) ar livre; e, ii) extensivo de interior. O estudo foi efetuado num centro de abate de frangos do campo, em Oliveira de Frades, entre Maio de 20012 e Março de 2013. Os animais abatidos foram criados em explorações com contratos de integração situadas no Distrito de Viseu. Os dados foram recolhidos em 39 bandos diferentes da espécie Gallus domesticus, dos quais 1021 carcaças foram avaliadas após evisceração, o que correspondeu ao exame de uma a cada quinze aves da linha de abate. Para a avaliação da pododermatite foi utilizado o método adaptado pela DGAV, enquanto para a avaliação da bursite esternal foi efetuada tendo em conta o modelo aplicado em perus por Berk em 2002. Apesar do modelo estatístico desenvolvido para a análise dos resultados obtidos no presente trabalho exigir um maior número de observações, foi possível identificar com grande precisão alguns fatores de risco que devem ser realçados pela sua relevância no contexto dos sistemas produtivos escrutinados ou no mecanismo fisiopatológico da dermatite de contacto, nomeadamente os seguintes: (i) a idade das aves que, apesar de não ter sido identificada uma relação directa com os scores de pododermatite e bursite, verificou-se que a idade elevada que os animais tipicamente atingem nos sistemas de produção extensivos está associada a uma taxa superior de rejeições pela inspecção sanitária; (ii) o peso pré-abate que, independentemente da inconsistência defendida por diversos autores em relação à influência do peso vivo do frango industrial sobre a dermatite de contacto, nos animais produzidos em regime extensivo, esta variável pode desempenhar um fator chave para a ocorrência desta lesão. De facto, há que realçar que o peso destes animais tem uma importância fulcral na modelação da biomecânica da ave, incluindo na pressão exercida sobre a superfície plantar; (iii) o tipo de sistema de abeberamento, tendo ficado demonstrado que a selecção do tipo de bebedouro tem uma importância peculiar sobre a ocorrência de pododermatite em “frango de campo”, algo que está provavelmente relacionado com a influência exercida sobre o teor de humidade da cama. Globalmente, as frequências de pododermatite e bursite apuradas neste trabalho devem ser consideradas inquietantes. Esta preocupação eleva-se quando se toma consciência que as aves provieram de regimes considerados “amigáveis” e “sustentáveis”, pelo que urge monitorizar adequadamente aqueles sistemas produtivos, melhorar as suas condições e reanalisar os benefícios ao nível do bem-estar animal.

Recommended reporting standards for test accuracy studies of infectious diseases of finfish, amphibians, molluscs and crustaceans: the STRADAS-aquatic checklist

Complete and transparent reporting of key elements of diagnostic accuracy studies for infectious diseases in cultured and wild aquatic animals benefits end-users of these tests, enabling the rational design of surveillance programs, the assessment of test results from clinical cases and comparisons of diagnostic test performance. Based on deficiencies in the Standards for Reporting of Diagnostic Accuracy (STARD) guidelines identified in a prior finfish study (Gardner et al. 2014), we adapted the Standards for Reporting of Animal Diagnostic Accuracy Studies—paratuberculosis (STRADAS-paraTB) checklist of 25 reporting items to increase their relevance to finfish, amphibians, molluscs, and crustaceans and provided examples and explanations for each item. The checklist, known as STRADAS-aquatic, was developed and refined by an expert group of 14 transdisciplinary scientists with experience in test evaluation studies using field and experimental samples, in operation of reference laboratories for aquatic animal pathogens, and in development of international aquatic animal health policy. The main changes to the STRADAS-paraTB checklist were to nomenclature related to the species, the addition of guidelines for experimental challenge studies, and the designation of some items as relevant only to experimental studies and ante-mortem tests. We believe that adoption of these guidelines will improve reporting of primary studies of test accuracy for aquatic animal diseases and facilitate assessment of their fitness-for-purpose. Given the importance of diagnostic tests to underpin the Sanitary and Phytosanitary agreement of the World Trade Organization, the principles outlined in this paper should be applied to other World Organisation for Animal Health (OIE)-relevant species.

Evaluation and measurement of chromium in sea water in order to remove it with mineral absorbent kaolin for desalination

Today, the use of heavy metals and chemical products industry expanded. The presence of significant amounts of, pollutants in industrial waste water can lead to serious risks to the environment and human health have heavy metals like chromium is one example of the future of salmon knock pond environment. Chromium is an essential element in the diet, but high doses of this element is very dangerous. Hence the use of chemical methods as a tool for the removal of metals from waste water pond be used. The aim of this study was to investigate the mineral kaolin adsorbents for the removal of chromium is water. Thus, the effect of different concentrations of absorbent micro amounts of chromium absorption and variable temperature, pH and electrolytes were studied. During the investigation of spectroscopic instrument (Varian) UV-VIS are used. Comparison of the absorption mechanism of chromium adsorption by the adsorbent with nano-absorbent kaolin kaolin was investigated. According to the studies done in the same conditions of temperature, pH and shaking rate of chromium absorption by nano kaolin kaolin is much more attractive. Therefore, its use as an adsorbent abundant, cheap, accessible, efficient and effective is proposed.

Effect of remote ischaemic preconditioning in cardiac dysfunction and end-organ injury following cardiac surgery with cardiopulmonary bypass in children: A translational approach investigating clinical outcome and myocardial molecular biology

Congenital heart disease (CHD) is the most common birth defect, causing an important rate of morbidity and mortality. Treatment of CHD requires surgical correction in a significant percentage of cases which exposes patients to cardiac and end organ injury. Cardiac surgical procedures often require the utilisation of cardiopulmonary bypass (CPB), a system that replaces heart and lungs function by diverting circulation into an external circuit. The use of CPB can initiate potent inflammatory responses, in addition a proportion of procedures require a period of aortic cross clamp during which the heart is rendered ischaemic and is exposed to injury. High O2 concentrations are used during cardiac procedures and when circulation is re-established to the heart which had adjusted metabolically to ischaemia, further injury is caused in a process known as ischaemic reperfusion injury (IRI). Several strategies are in place in order to protect the heart during surgery, however injury is still caused, having detrimental effects in patients at short and long term. Remote ischaemic preconditioning (RIPC) is a technique proposed as a potential cardioprotective measure. It consists of exposing a remote tissue bed to brief episodes of ischaemia prior to surgery in order to activate protective pathways that would act during CPB, ischaemia and reperfusion. This study aimed to assess RIPC in paediatric patients requiring CHD surgical correction with a translational approach, integrating clinical outcome, marker analysis, cardiac function parameters and molecular mechanisms within the cardiac tissue. A prospective, single blinded, randomized, controlled trial was conducted applying a RIPC protocol to randomised patients through episodes of limb ischaemia on the day before surgery which was repeated right before the surgery started, after anaesthesia induction. Blood samples were obtained before surgery and at three post-operative time points from venous lines, additional pre and post-bypass blood samples were obtained from the right atrium. Myocardial tissue was resected during the ischaemic period of surgery. Echocardiographic images were obtained before the surgery started after anaesthetic induction and the day after surgery, images were stored for later off line analysis. PICU surveillance data was collected including ventilation parameters, inotrope use, standard laboratory analysis and six hourly blood gas analysis. Pre and post-operative quantitation of markers in blood specimens included cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP), inflammatory mediators including interleukins IL-6, IL-8, IL-10, tumour necrosis factor (TNF-α), and the adhesion molecules ICAM-1 and VCAM-1; the renal marker Cystatin C and the cardiovascular markers asymmetric dymethylarginine (ADMA) and symmetric dymethylarginine (SDMA). Nitric oxide (NO) metabolites and cyclic guanosine monophosphate (cGMP) were measured before and after bypass. Myocardial tissue was processed at baseline and after incubation at hyperoxic concentration during four hours in order to mimic surgical conditions. Expression of genes involved in IRI and RIPC pathways was analysed including heat shock proteins (HSPs), toll like receptors (TLRs), transcription factors nuclear factor κ-B (NF- κ-B) and hypoxia inducible factor 1 (HIF-1). The participation of hydrogen sulfide enzymatic genes, apelin and its receptor were explored. There was no significant difference according to group allocation in any of the echocardiographic parameters. There was a tendency for higher cTnI values and inotropic score in control patients post-operatively, however this was not statistically significant. BNP presented no significant difference according to group allocation. Inflammatory parameters tended to be higher in the control group, however only TNF- α was significantly higher. There was no difference in levels of Cystatin C, NO metabolites, cGMP, ADMA or SDMA. RIPC patients required shorter PICU stay, all other clinical and laboratory analysis presented no difference related to the intervention. Gene expression analysis revealed interesting patterns before and after incubation. HSP-60 presented a lower expression at baseline in tissue corresponding to RIPC patients, no other differences were found. This study provided with valuable descriptive information on previously known and newly explored parameters in the study population. Demographic characteristics and the presence of cyanosis before surgery influenced patterns of activity in several parameters, numerous indicators were linked to the degree of injury suffered by the myocardium. RIPC did not reduce markers of cardiac injury or improved echocardiographic parameters and it did not have an effect on end organ function; some effects were seen in inflammatory responses and gene expression analysis. Nevertheless, an important clinical outcome indicator, PICU length of stay was reduced suggesting benefit from the intervention. Larger studies with more statistical power could determine if the tendency of lower injury and inflammatory markers linked to RIPC is real. The present results mostly support findings of larger multicentre trials which have reported no cardiac benefit from RIPC in paediatric cardiac surgery.

Empirical evidence of bias in the design of experimental stroke studies: a metaepidemiologic approach

Background and Purpose: At least part of the failure in the transition from experimental to clinical studies in stroke has been attributed to the imprecision introduced by problems in the design of experimental stroke studies. Using a metaepidemiologic approach, we addressed the effect of randomization, blinding, and use of comorbid animals on the estimate of how effectively therapeutic interventions reduce infarct size. Methods: Electronic and manual searches were performed to identify meta-analyses that described interventions in experimental stroke. For each meta-analysis thus identified, a reanalysis was conducted to estimate the impact of various quality items on the estimate of efficacy, and these estimates were combined in a meta meta-analysis to obtain a summary measure of the impact of the various design characteristics. Results: Thirteen meta-analyses that described outcomes in 15 635 animals were included. Studies that included unblinded induction of ischemia reported effect sizes 13.1% (95% CI, 26.4% to 0.2%) greater than studies that included blinding, and studies that included healthy animals instead of animals with comorbidities overstated the effect size by 11.5% (95% CI, 21.2% to 1.8%). No significant effect was found for randomization, blinded outcome assessment, or high aggregate CAMARADES quality score. Conclusions: We provide empirical evidence of bias in the design of studies, with studies that included unblinded induction of ischemia or healthy animals overestimating the effectiveness of the intervention. This bias could account for the failure in the transition from bench to bedside of stroke therapies.

Obésité abdominale et autres déterminants du risque cardiométabolique dans deux populations urbaines noires apparentées : Port-au-Prince (Haïti) et Cotonou (Bénin)

L’obésité est un problème de santé publique reconnu. Dans la dernière décennie l’obésité abdominale (OA) a été considérée comme une maladie métabolique qui contribue davantage au risque de diabète et de maladies cardiovasculaires que l’obésité générale définie par l’indice de masse corporelle. Toutefois, dans les populations d’origine africaine, la relation entre l’OA et les autres biomarqueurs de risque cardiométabolique (RCM) demeure obscure à cause du manque d’études chez ces populations et de l’absence de valeurs-seuils spécifiques pour juger d’une OA. Cette étude visait à comparer la prévalence des biomarqueurs de RCM (OA, hypertension artérielle, hyperglycémie, dyslipidémie, résistance à l'insuline et inflammation pré-clinique) chez les Béninois de Cotonou et les Haïtiens de Port-au-Prince (PAP), à étudier l’association de l’OA avec les autres biomarqueurs de RCM, à documenter le rôle du niveau socio-économique (NSE) et du mode de vie dans cette association et à ’identifier les indicateurs anthropométriques de l’OA -tour de taille (TT) et le ratio TT/hauteur (TT/H)- et les seuils qui prédisent le mieux le RCM à Cotonou et à PAP. Il s’est agi d’une analyse de données transversales chez 452 adultes (52 % hommes) apparemment en bonne santé, âgés de 25 à 60 ans, avec 200 sujets vivant à Cotonou (Bénin) et 252 sujets à PAP (Haïti). Les biomarqueurs de RCM considérés étaient : le syndrome métabolique (SMet) d’après les critères harmonisés de 2009 et ses composantes individuelles - une OA à partir d’un TT ≥ 94cm chez les hommes et ≥ 80cm chez les femmes, une hypertension, une dyslipidémie et une hyperglycémie; la résistance à l’insuline définie chez l’ensemble des sujets de l’étude à partir du 75e centile de l’Homeostasis Model Assessment (HOMA-IR); un ratio d’athérogénicité élevé (Cholestérol sérique total/HDL-Cholestérol); et l’inflammation pré-clinique mesurée à partir d’un niveau de protéine C-réactive ultrasensible (PCRus) entre 3 et 10 mg/l. Le ratio TT/H était aussi considéré pour définir l’OA à partir d’un seuil de 0,5. Les données sur les habitudes alimentaires, la consommation d’alcool, le tabagisme, les caractéristiques sociodémographiques et les conditions socio-économiques incluant le niveau d’éducation et un proxy du revenu (basé sur l’analyse par composante principale des biens et des possessions) ont été recueillies au moyen d’un questionnaire. Sur la base de données de fréquence de consommation d’aliments occidentaux, urbains et traditionnels, des schémas alimentaires des sujets de chaque ville ont été identifiés par analyse typologique. La validité et les valeurs-seuils de TT et du ratio TT/H prédictives du RCM ont été définies à partir des courbes ROC (Receiver Operating Characteristics). Le SMet était présent chez 21,5 % et 16,1 % des participants, respectivement à Cotonou et à PAP. La prévalence d’OA était élevée à Cotonou (52,5 %) qu’à PAP (36%), avec une prévalence plus élevée chez les femmes que chez les hommes. Le profil lipidique sérique était plus athérogène à PAP avec 89,3 % d’HDL-c bas à PAP contre 79,7 % à Cotonou et un ratio CT/HDL-c élevé de 73,4 % à PAP contre 42 % à Cotonou. Les valeurs-seuils spécifiques de TT et du TT/H étaient respectivement 94 cm et 0,59 chez les femmes et 80 cm et 0,50 chez les hommes. Les analyses multivariées de l’OA avec les biomarqueurs de RCM les plus fortement prévalents dans ces deux populations montraient que l’OA était associée à un risque accru de résistance à l’insuline, d’athérogénicité et de tension artérielle élevée et ceci, indépendamment des facteurs socio-économiques et du mode de vie. Deux schémas alimentaires ont émergé, transitionnel et traditionnel, dans chaque ville, mais ceux-ci ne se révélaient pas associés aux biomarqueurs de RCM bien qu’ils soient en lien avec les variables socio-économiques. La présente étude confirme la présence de plusieurs biomarqueurs de RCM chez des sujets apparemment sains. En outre, l’OA est un élément clé du RCM dans ces deux populations. Les seuils actuels de TT devraient être reconsidérés éventuellement à la lumière d’études de plus grande envergure, afin de mieux définir l’OA chez les Noirs africains ou d’origine africaine, ce qui permettra une surveillance épidémiologique plus adéquate des biomarqueurs de RCM.

Interventions for dysphagia in acute stroke (Review)

Background It is unclear how dysphagic patients should be fed and treated after acute stroke. Objectives The objective of this review was to assess the effect of different management strategies for dysphagic stroke patients, in particular how and when to feed, whether to supplement nutritional intake, and how and whether to treat dysphagia. Search strategy We searched the Cochrane Stroke Group trials register, Medline, Embase, ISI, and existing review articles.We contacted researchers in the field and equipment manufacturers. Date of the most recent searches: March 1999. Selection criteria Unconfounded truly or quasi randomised controlled trials in dysphagic patients with acute/subacute (within 3 months) stroke. Data collection and analysis Three reviewers independently applied the trial inclusion criteria. Two reviewers assessed trial quality and extracted the data. Main results Percutaneous endoscopic gastrostomy (PEG) versus nasogastric tube (NGT) feeding: two trials (49 patients) suggest that PEG reduces end-of-trial case fatality (Peto Odds Ratio, OR 0.28, 95% CI 0.09 to 0.89) and treatment failures (OR 0.10, 95% CI 0.02 to 0.52), and improves nutritional status, assessed as weight (Weighted Men Difference, WMD +4.1 kg, 95% CI -4.3 to +12.5), mid-arm circumference (WMD +2.2 cm, 95% CI -0.5 to +4.9) or serum albumin (WMD + 7.0 g/l, 95% CI +4.9 to +9.1) as compared with NGT feeding; two larger studies are ongoing. Timing of feeding: no completed trials; one large study is ongoing. Swallowing therapy for dysphagia: two trials (85 patients) suggest that formal swallowing therapy does not significantly reduce end-of-trial dysphagia rates (OR 0.55, 95%CI 0.18 to 1.66). Drug therapy for dysphagia: one trial (17 patients); nifedipine did not alter end-of-trial case fatality or the frequency of dysphagia. Nutritional supplementation: one trial (42 patients) found a non-significant trend to a lower case fatality, and significantly increased energy and protein intake; one large trial is ongoing and data is awaited from two other studies. Fluid supplementation: one trial (20 patients) found that supplementation did not alter the time to resolution of dysphagia. Authors’ conclusions Too few studies have been performed, and these have involved too few patients. PEG feeding may improve outcome and nutrition as compared with NGT feeding. Further research is required to assess how and when patients are fed, and the effect of swallowing or drug therapy on dysphagia.

BOA for nurse scheduling

Our research has shown that schedules can be built mimicking a human scheduler by using a set of rules that involve domain knowledge. This chapter presents a Bayesian Optimization Algorithm (BOA)for the nurse scheduling problem that chooses such suitable scheduling rules from a set for each nurse’s assignment. Based on the idea of using probabilistic models, the BOA builds a Bayesian network for the set of promising solutions and samples these networks to generate new candidate solutions. Computational results from 52 real data instances demonstrate the success of this approach. It is also suggested that the learning mechanism in the proposed algorithm may be suitable for other scheduling problems.