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  • Open Access
    Authors: 
    Muriel Tabariés; Viviane Tchernonog;
    Publisher: CAIRN
    Countries: France, Canada

    Cet article analyse l’évolution de la participation des femmes aux structures dirigeantes des associations. Les femmes apparaissent largement en retrait des fonctions de président d’association et leur accession aux postes de dirigeants s’effectue principalement à partir des associations créées récemment et dans des types d’associations orientées vers des populations fragiles ou vulnérables. L’article montre que l’on peut imputer leur plus forte présence essentiellement aux évolutions sociétales en cours depuis les années 70 : activité croissante des femmes, hausse de leur qualification, démocratisation de la société et de la vie associative, ouverture plus grande des associations récentes aux plus jeunes et à des catégories sociales plus variées. This article examines the evolution of the participation of women in the governing bodies of nonprofit organizations. There appear to be very few women CEOs in nonprofit organizations, and women who have reached executive positions have mainly done so in recently created nonprofit organizations and those concerned with people at risk and vulnerable social groups. The article shows that the increase is essentially due to societal changes since the 1970s: growing female participation in the workforce, their higher level of education, democratization of society and nonprofit organizations, and recent nonprofit organizations more open to younger people and a broader cross-section of the population.

  • Publication . Conference object . Preprint . Article . Part of book or chapter of book . 2010
    Open Access English
    Authors: 
    Britt Reichborn-Kjennerud; Asad M. Aboobaker; Peter A. R. Ade; François Aubin; Carlo Baccigalupi; Chaoyun Bao; Julian Borrill; Christopher Cantalupo; Daniel Chapman; Joy Didier; +36 more
    Countries: United States, France, France, France, France

    EBEX is a NASA-funded balloon-borne experiment designed to measure the polarization of the cosmic microwave background (CMB). Observations will be made using 1432 transition edge sensor (TES) bolometric detectors read out with frequency multiplexed SQuIDs. EBEX will observe in three frequency bands centered at 150, 250, and 410 GHz, with 768, 384, and 280 detectors in each band, respectively. This broad frequency coverage is designed to provide valuable information about polarized foreground signals from dust. The polarized sky signals will be modulated with an achromatic half wave plate (AHWP) rotating on a superconducting magnetic bearing (SMB) and analyzed with a fixed wire grid polarizer. EBEX will observe a patch covering ~1% of the sky with 8' resolution, allowing for observation of the angular power spectrum from \ell = 20 to 1000. This will allow EBEX to search for both the primordial B-mode signal predicted by inflation and the anticipated lensing B-mode signal. Calculations to predict EBEX constraints on r using expected noise levels show that, for a likelihood centered around zero and with negligible foregrounds, 99% of the area falls below r = 0.035. This value increases by a factor of 1.6 after a process of foreground subtraction. This estimate does not include systematic uncertainties. An engineering flight was launched in June, 2009, from Ft. Sumner, NM, and the long duration science flight in Antarctica is planned for 2011. These proceedings describe the EBEX instrument and the North American engineering flight. 12 pages, 9 figures, Conference proceedings for SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010)

  • Open Access
    Authors: 
    Malgorzata Milkiewicz; Emilie Roudier; Jennifer L. Doyle; Anastassia Trifonova; Olivier Birot; Tara L. Haas;
    Publisher: Elsevier BV

    Chronic limb ischemia, a complication commonly observed in conjunction with cardiovascular disease, is characterized by insufficient neovascularization despite the up-regulation of pro-angiogenic mediators. One hypothesis is that ischemia induces inhibitory signals that circumvent the normal capillary growth response. FoxO transcription factors exert anti-proliferative and pro-apoptotic effects on many cell types. We studied the regulation of FoxO1 protein in ischemic rat skeletal muscle following iliac artery ligation and in cultured endothelial cells. We found that FoxO1 expression was increased in capillaries within ischemic muscles compared with those from rats that underwent a sham operation. This finding correlated with increased expression of p27(Kip1) and reduced expression of Cyclin D1. Phosphorylated Akt was reduced concurrently with the increase in FoxO1 protein. In skeletal muscle endothelial cells, nutrient stress as well as lack of shear stress stabilized FoxO1 protein, whereas shear stress induced FoxO1 degradation. Endogenous FoxO1 co-precipitated with the E3 ubiquitin ligase murine double minute-2 (Mdm2) in endothelial cells, and this interaction varied in direct relation to the extent of Akt and Mdm2 phosphorylation. Moreover, ischemic muscles had a decreased level of Mdm2 phosphorylation and a reduced interaction between Mdm2 and FoxO1. Our results provide novel evidence that the Akt-Mdm2 pathway acts to regulate endothelial cell FoxO1 expression and illustrate a potential mechanism underlying the pathophysiological up-regulation of FoxO1 under ischemic conditions.

  • Closed Access
    Authors: 
    R. Knystautas; John H.S. Lee; Joseph E. Shepherd; Andrzej Teodorczyk;
    Publisher: Elsevier BV

    Abstract We report results on flame acceleration and transition to detonation of benzene–air mixtures at room temperature. Flame acceleration experiments were carried out in a 150-mm-diameter, 3.6-m-long steel tube. The entire length of the tube is filled with circular orifice plates (blockage or obstructed area ratio of 0.43) spaced one diameter apart. The fuel concentration was varied between 1.7% and 5% by volume of benzene in the fuel–air mixture. Three regimes of propagation were observed: (1) a turbulent deflagration with typical flame speeds less than 100 m/s, (2) a “choking” regime with the flame speed corresponding to the speed of sound of the combustion products, 700 to 900 m/s, and (3) a quasi-detonation regime with a wave speed ranging from 50% to 100% of the Chapman-Jouguet value. Transition from turbulent deflagration to the choking regime occurs at an equivalence ratio of Φ = 0.65 (1.8% C6H6) and Φ = 1.8 (4.8% C6H6) on the lean and rich sides, respectively. Transition from the choking to the quasi-detonation regime is observed at Φ = 0.88 (2.4% C6H6) on the lean side and Φ = 1.6 (4.3% C6H6) on the rich side. Detonation cell widths were measured using a small charge (8 to 50 g) of solid explosive for direct initiation of the detonation in both the 150-mm-diameter tube and a larger 300-mm-diameter, 18-m-long, steel tube. Sooted foils are used for determining the cell size, which was 66 mm for a stoichiometric composition. A detailed chemical reaction scheme was used to carry out numerical solutions of the idealized Zel’dovich–von Neumann–Doring (ZND) model. The cell widths were approximately 20 times larger than the computed reaction zone lengths. The ZND model was used to examine the effects of initial temperature and dilution by steam and nitrogen, and the effects of adding hydrogen.

  • Authors: 
    Florence Loisel; Chantal Farmer; P. Ramaekers; Hélène Quesnel;
    Publisher: Oxford University Press (OUP)

    Dietary fiber given during pregnancy may influence sow endocrinology and increase piglet BW gain during early lactation. The aim of the current study was to determine whether dietary fiber given to sows during late pregnancy induces endocrine changes that could modulate sow colostrum production and, thus, piglet performance. From d 106 of pregnancy until parturition, 29 Landrace×Large White nulliparous sows were fed gestation diets containing 23.4 [high fiber (HF); n=15] or 13.3% total dietary fiber [low fiber (LF); n=14]. In the HF diet, wheat and barley were partly replaced by soybean hulls, wheat bran, sunflower meal (undecorticated), and sugar beet pulp. After parturition, sows were fed a standard lactation diet. Colostrum production was estimated during 24 h, starting at the onset of parturition (T0) and ending at 24 h after parturition (T24) based on piglet weight gains. Jugular blood samples were collected from sows on d 101 of pregnancy, daily from d 111 of gestation to d 3 of lactation, and then on d 7 and 21 of lactation (d 0 being the day of parturition). Postprandial kinetics of plasma glucose and insulin concentrations were determined on d 112 of pregnancy. The feeding treatment did not influence sow colostrum yield (3.9±0.2 kg) or piglet weight gain during the first day postpartum to d 21 of lactation. Colostrum intake of low birth weight piglets (<900 g) was greater in litters from HF sows than from LF sows (216±24 vs. 137±22 g; P=0.02). Preweaning mortality was lower in HF than LF litters (6.2 vs. 14.7%; P=0.01). Circulating concentrations of progesterone, prolactin, estradiol-17β, and cortisol were not influenced by the treatment. Sows fed the HF diet had greater postprandial insulin concentrations than LF sows (P=0.02) whereas the postprandial glucose peak was similar. At T24, colostrum produced by HF sows contained 29% more lipid than colostrum produced by LF sows (P=0.04). Immunoglobulin A concentrations in colostrum were lower at T0 and T24 (P=0.02) in HF than LF sows (at T0: 8.6±1.1 vs. 11.9±1.1 mg/mL; at T24: 2.5±0.7 vs. 4.8±0.7 mg/mL). In conclusion, dietary fiber in late pregnancy affected sow colostrum composition but not colostrum yield, increased colostrum intake of low birth weight piglets, and decreased preweaning mortality, but these effects were not related to changes in peripartum concentrations of the main hormones involved in lactogenesis.

  • Publication . Article . 2020
    Open Access English
    Authors: 
    João Pedro Ferreira; Ulrik M. Mogensen; Pardeep S. Jhund; Akshay S. Desai; Jean-Lucien Rouleau; Michael R. Zile; Patrick Rossignol; Faiez Zannad; Milton Packer; Scott D. Solomon; +1 more
    Publisher: HAL CCSD
    Country: France

    Aims: The associations between potassium level and outcomes, the effect of sacubitril–valsartan on potassium level, and whether potassium level modified the effect of sacubitril–valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM‐HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non‐cardiovascular death and heart failure hospitalization, were examined. Methods and results: A total of 8399 patients were randomized to either enalapril or sacubitril–valsartan. Potassium level at randomization and follow‐up was examined as a continuous and categorical variable (≤3.5, 3.6–4.0, 4.1–4.9, 5.0–5.4 and ≥5.5 mmol/L) in various statistical models. Hyperkalaemia was defined as K+ ≥5.5 mmol/L and hypokalaemia as K+ ≤3.5 mmol/L. Compared with potassium 4.1–4.9 mmol/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84–3.14] and hyperkalaemia (HR 1.42, 95% CI 1.10–1.83) were associated with a higher risk for cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non‐cardiovascular death and heart failure hospitalization. Sacubitril–valsartan had no effect on potassium overall. The benefit of sacubitril–valsartan over enalapril was consistent across the range of baseline potassium levels. Conclusions: Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.

  • Authors: 
    Leonard Joseph Appleman; Michael Paul Kolinsky; William R. Berry; Margitta Retz; Loic Mourey; Josep M. Piulats; Emanuela Romano; Gwenaelle Gravis; Howard Gurney; Johann S. de Bono; +10 more
    Publisher: American Society of Clinical Oncology (ASCO)

    10 Background: For men with mCRPC, systemic therapies such as docetaxel and cabazitaxel improve survival, but more effective treatments are needed. KEYNOTE-365 (NCT02861573) is a phase 1b/2 study to examine the safety and efficacy of pembro in combination with 4 different study medications (cohorts A, B, C, D) in mCRPC. Previous data from cohort B with a median of 20 months of follow-up showed that pembro + docetaxel and prednisone was well tolerated and had antitumor activity in patients (pts) with mCRPC previously treated with abi or enza. New efficacy and safety data after an additional year of follow-up are presented. Methods: Cohort B enrolled pts who did not respond to or were intolerant to ≥4 weeks of abi or enza in the prechemotherapy mCRPC state and whose disease progressed within 6 months of screening (determined by PSA progression or radiologic bone/soft tissue progression). Pts received pembro 200 mg IV every 3 weeks (Q3W), docetaxel 75 mg/m2 IV Q3W, and oral prednisone 5 mg twice daily. Primary end points were safety, PSA response rate (PSA decrease >50% from baseline), and ORR per RECIST v1.1 by blinded independent central review. Efficacy and safety were assessed in all pts as treated. Results: Of the 104 treated pts, median age was 68.0 years (range, 50-86), 23.1% had PD-L1–positive tumors (combined positive score ≥1), 25.0% had visceral disease, and 50.0% had measurable disease. Median time from enrollment to data cutoff was 32.4 months (range 13.9-40.3); 101 pts discontinued, primarily because of disease progression (77.9%). Efficacy outcomes are reported in the table below. Treatment-related adverse events (TRAEs) occurred in 100 pts (96.2%); the most frequent (≥30%) were diarrhea (41.3%), fatigue (41.3%), and alopecia (40.4%). Grade 3-5 TRAEs occurred in 46 pts (44.2%). Five pts (4.8%) died of AEs; 2 were treatment-related pneumonitis. Conclusions: After another year of follow-up, pembro + docetaxel and prednisone showed improved ORR and PSA response rates compared to the prior dataset in pts with mCRPC previously treated with abi or enza. Safety was consistent with known profiles of each agent and will be further evaluated in a phase 3 study (KEYNOTE-921). Clinical trial information: NCT02861573. [Table: see text]

  • Open Access
    Authors: 
    Alexander K. C. Leung; Joseph M. Lam; Kin Fon Leong;

    Background: The diagnosis of solitary cutaneous mastocytoma is mainly clinical, based on lesion morphology, the presence of a positive Darier sign, and the absence of systemic involvement. Knowledge of this condition is important so that an accurate diagnosis can be made. Objective: To familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of a solitary cutaneous mastocytoma. Methods: A PubMed search was completed in Clinical Queries using the key term "solitary cutaneous mastocytoma". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in English language were included. The information retrieved from the above search was used in the compilation of the present article. Results: Typically, a solitary cutaneous mastocytoma presents as an indurated, erythematous, yellow- brown or reddish-brown macule, papule, plaque or nodule, usually measuring up to 5 cm in diameter. The lesion often has a peau d'orange appearance and a leathery or rubbery consistency. A solitary cutaneous mastocytoma may urticate spontaneously or when stroked or rubbed (Darier sign). Organomegaly and lymphadenopathy are characteristically absent. The majority of patients with skin lesions that erupt within the first two years of life have spontaneous resolution of the lesions before puberty. Treatment is mainly symptomatic. Reassurance and avoidance of triggering factors suffice in most cases. Conclusion: The diagnosis is mainly clinical, based on the morphology of the lesion, the presence of a positive Darier sign, and the absence of systemic involvement. A skin biopsy is usually not necessary unless the diagnosis is in doubt.

  • Open Access English
    Authors: 
    S. Hong Lee; Enda M. Byrne; Christina M. Hultman; Anna K. Kähler; Anna A. E. Vinkhuyzen; Stephan Ripke; Ole A. Andreassen; Thomas Frisell; Alexander Gusev; Xinli Hu; +134 more
    Countries: Belgium, Switzerland, Australia, Netherlands
    Project: NIH | Genetic predictors of res... (5U01GM092691-04), NHMRC | Statistical analyses of w... (1047956), NWO | Cluster computing in gene... (2300131050), NHMRC | Using New Genomic Technol... (1053639), NIH | 1/2 A Large-Scale Schizop... (5R01MH077139-05), NHMRC | Using genomics to underst... (1078901), NHMRC | Uncoupled Research Fellow... (613602)

    Background: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. Methods: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born. Results: We estimate a small but significant negative SNP-genetic correlation between SZ and RA (−0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (−0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P = 0.00090). Conclusions: Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context. Refereed/Peer-reviewed

  • Closed Access
    Authors: 
    André Mocaer; Elisabeth Guillou; Omer Chouinard;
    Publisher: Elsevier BV

    Abstract With an increasing number of coastal issues associated with human pressure and exacerbated by climate change, this study examines how residents of coastal communities perceive their living environment and how they perceive risks in this environment and more particularly coastal risks (marine erosion and flooding). An international (Canada-France) questionnaire study was conducted among 190 people, approximately half of whom lived on New Brunswick's Acadian Coast and half on France's west coast. The results highlight, on the one hand, the residents' strong relationship with their coastal living environment and, on the other, a representation of coastal risks as an important area of concern for them. That said, the worry concerning these risks varied among the participants. The local and cultural context (media coverage of this issue and the country-specific risk management strategies) may explain the differences in attitude between the two countries.

search
Include:
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
80,696 Research products, page 1 of 8,070
  • Open Access
    Authors: 
    Muriel Tabariés; Viviane Tchernonog;
    Publisher: CAIRN
    Countries: France, Canada

    Cet article analyse l’évolution de la participation des femmes aux structures dirigeantes des associations. Les femmes apparaissent largement en retrait des fonctions de président d’association et leur accession aux postes de dirigeants s’effectue principalement à partir des associations créées récemment et dans des types d’associations orientées vers des populations fragiles ou vulnérables. L’article montre que l’on peut imputer leur plus forte présence essentiellement aux évolutions sociétales en cours depuis les années 70 : activité croissante des femmes, hausse de leur qualification, démocratisation de la société et de la vie associative, ouverture plus grande des associations récentes aux plus jeunes et à des catégories sociales plus variées. This article examines the evolution of the participation of women in the governing bodies of nonprofit organizations. There appear to be very few women CEOs in nonprofit organizations, and women who have reached executive positions have mainly done so in recently created nonprofit organizations and those concerned with people at risk and vulnerable social groups. The article shows that the increase is essentially due to societal changes since the 1970s: growing female participation in the workforce, their higher level of education, democratization of society and nonprofit organizations, and recent nonprofit organizations more open to younger people and a broader cross-section of the population.

  • Publication . Conference object . Preprint . Article . Part of book or chapter of book . 2010
    Open Access English
    Authors: 
    Britt Reichborn-Kjennerud; Asad M. Aboobaker; Peter A. R. Ade; François Aubin; Carlo Baccigalupi; Chaoyun Bao; Julian Borrill; Christopher Cantalupo; Daniel Chapman; Joy Didier; +36 more
    Countries: United States, France, France, France, France

    EBEX is a NASA-funded balloon-borne experiment designed to measure the polarization of the cosmic microwave background (CMB). Observations will be made using 1432 transition edge sensor (TES) bolometric detectors read out with frequency multiplexed SQuIDs. EBEX will observe in three frequency bands centered at 150, 250, and 410 GHz, with 768, 384, and 280 detectors in each band, respectively. This broad frequency coverage is designed to provide valuable information about polarized foreground signals from dust. The polarized sky signals will be modulated with an achromatic half wave plate (AHWP) rotating on a superconducting magnetic bearing (SMB) and analyzed with a fixed wire grid polarizer. EBEX will observe a patch covering ~1% of the sky with 8' resolution, allowing for observation of the angular power spectrum from \ell = 20 to 1000. This will allow EBEX to search for both the primordial B-mode signal predicted by inflation and the anticipated lensing B-mode signal. Calculations to predict EBEX constraints on r using expected noise levels show that, for a likelihood centered around zero and with negligible foregrounds, 99% of the area falls below r = 0.035. This value increases by a factor of 1.6 after a process of foreground subtraction. This estimate does not include systematic uncertainties. An engineering flight was launched in June, 2009, from Ft. Sumner, NM, and the long duration science flight in Antarctica is planned for 2011. These proceedings describe the EBEX instrument and the North American engineering flight. 12 pages, 9 figures, Conference proceedings for SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010)

  • Open Access
    Authors: 
    Malgorzata Milkiewicz; Emilie Roudier; Jennifer L. Doyle; Anastassia Trifonova; Olivier Birot; Tara L. Haas;
    Publisher: Elsevier BV

    Chronic limb ischemia, a complication commonly observed in conjunction with cardiovascular disease, is characterized by insufficient neovascularization despite the up-regulation of pro-angiogenic mediators. One hypothesis is that ischemia induces inhibitory signals that circumvent the normal capillary growth response. FoxO transcription factors exert anti-proliferative and pro-apoptotic effects on many cell types. We studied the regulation of FoxO1 protein in ischemic rat skeletal muscle following iliac artery ligation and in cultured endothelial cells. We found that FoxO1 expression was increased in capillaries within ischemic muscles compared with those from rats that underwent a sham operation. This finding correlated with increased expression of p27(Kip1) and reduced expression of Cyclin D1. Phosphorylated Akt was reduced concurrently with the increase in FoxO1 protein. In skeletal muscle endothelial cells, nutrient stress as well as lack of shear stress stabilized FoxO1 protein, whereas shear stress induced FoxO1 degradation. Endogenous FoxO1 co-precipitated with the E3 ubiquitin ligase murine double minute-2 (Mdm2) in endothelial cells, and this interaction varied in direct relation to the extent of Akt and Mdm2 phosphorylation. Moreover, ischemic muscles had a decreased level of Mdm2 phosphorylation and a reduced interaction between Mdm2 and FoxO1. Our results provide novel evidence that the Akt-Mdm2 pathway acts to regulate endothelial cell FoxO1 expression and illustrate a potential mechanism underlying the pathophysiological up-regulation of FoxO1 under ischemic conditions.

  • Closed Access
    Authors: 
    R. Knystautas; John H.S. Lee; Joseph E. Shepherd; Andrzej Teodorczyk;
    Publisher: Elsevier BV

    Abstract We report results on flame acceleration and transition to detonation of benzene–air mixtures at room temperature. Flame acceleration experiments were carried out in a 150-mm-diameter, 3.6-m-long steel tube. The entire length of the tube is filled with circular orifice plates (blockage or obstructed area ratio of 0.43) spaced one diameter apart. The fuel concentration was varied between 1.7% and 5% by volume of benzene in the fuel–air mixture. Three regimes of propagation were observed: (1) a turbulent deflagration with typical flame speeds less than 100 m/s, (2) a “choking” regime with the flame speed corresponding to the speed of sound of the combustion products, 700 to 900 m/s, and (3) a quasi-detonation regime with a wave speed ranging from 50% to 100% of the Chapman-Jouguet value. Transition from turbulent deflagration to the choking regime occurs at an equivalence ratio of Φ = 0.65 (1.8% C6H6) and Φ = 1.8 (4.8% C6H6) on the lean and rich sides, respectively. Transition from the choking to the quasi-detonation regime is observed at Φ = 0.88 (2.4% C6H6) on the lean side and Φ = 1.6 (4.3% C6H6) on the rich side. Detonation cell widths were measured using a small charge (8 to 50 g) of solid explosive for direct initiation of the detonation in both the 150-mm-diameter tube and a larger 300-mm-diameter, 18-m-long, steel tube. Sooted foils are used for determining the cell size, which was 66 mm for a stoichiometric composition. A detailed chemical reaction scheme was used to carry out numerical solutions of the idealized Zel’dovich–von Neumann–Doring (ZND) model. The cell widths were approximately 20 times larger than the computed reaction zone lengths. The ZND model was used to examine the effects of initial temperature and dilution by steam and nitrogen, and the effects of adding hydrogen.

  • Authors: 
    Florence Loisel; Chantal Farmer; P. Ramaekers; Hélène Quesnel;
    Publisher: Oxford University Press (OUP)

    Dietary fiber given during pregnancy may influence sow endocrinology and increase piglet BW gain during early lactation. The aim of the current study was to determine whether dietary fiber given to sows during late pregnancy induces endocrine changes that could modulate sow colostrum production and, thus, piglet performance. From d 106 of pregnancy until parturition, 29 Landrace×Large White nulliparous sows were fed gestation diets containing 23.4 [high fiber (HF); n=15] or 13.3% total dietary fiber [low fiber (LF); n=14]. In the HF diet, wheat and barley were partly replaced by soybean hulls, wheat bran, sunflower meal (undecorticated), and sugar beet pulp. After parturition, sows were fed a standard lactation diet. Colostrum production was estimated during 24 h, starting at the onset of parturition (T0) and ending at 24 h after parturition (T24) based on piglet weight gains. Jugular blood samples were collected from sows on d 101 of pregnancy, daily from d 111 of gestation to d 3 of lactation, and then on d 7 and 21 of lactation (d 0 being the day of parturition). Postprandial kinetics of plasma glucose and insulin concentrations were determined on d 112 of pregnancy. The feeding treatment did not influence sow colostrum yield (3.9±0.2 kg) or piglet weight gain during the first day postpartum to d 21 of lactation. Colostrum intake of low birth weight piglets (<900 g) was greater in litters from HF sows than from LF sows (216±24 vs. 137±22 g; P=0.02). Preweaning mortality was lower in HF than LF litters (6.2 vs. 14.7%; P=0.01). Circulating concentrations of progesterone, prolactin, estradiol-17β, and cortisol were not influenced by the treatment. Sows fed the HF diet had greater postprandial insulin concentrations than LF sows (P=0.02) whereas the postprandial glucose peak was similar. At T24, colostrum produced by HF sows contained 29% more lipid than colostrum produced by LF sows (P=0.04). Immunoglobulin A concentrations in colostrum were lower at T0 and T24 (P=0.02) in HF than LF sows (at T0: 8.6±1.1 vs. 11.9±1.1 mg/mL; at T24: 2.5±0.7 vs. 4.8±0.7 mg/mL). In conclusion, dietary fiber in late pregnancy affected sow colostrum composition but not colostrum yield, increased colostrum intake of low birth weight piglets, and decreased preweaning mortality, but these effects were not related to changes in peripartum concentrations of the main hormones involved in lactogenesis.

  • Publication . Article . 2020
    Open Access English
    Authors: 
    João Pedro Ferreira; Ulrik M. Mogensen; Pardeep S. Jhund; Akshay S. Desai; Jean-Lucien Rouleau; Michael R. Zile; Patrick Rossignol; Faiez Zannad; Milton Packer; Scott D. Solomon; +1 more
    Publisher: HAL CCSD
    Country: France

    Aims: The associations between potassium level and outcomes, the effect of sacubitril–valsartan on potassium level, and whether potassium level modified the effect of sacubitril–valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM‐HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non‐cardiovascular death and heart failure hospitalization, were examined. Methods and results: A total of 8399 patients were randomized to either enalapril or sacubitril–valsartan. Potassium level at randomization and follow‐up was examined as a continuous and categorical variable (≤3.5, 3.6–4.0, 4.1–4.9, 5.0–5.4 and ≥5.5 mmol/L) in various statistical models. Hyperkalaemia was defined as K+ ≥5.5 mmol/L and hypokalaemia as K+ ≤3.5 mmol/L. Compared with potassium 4.1–4.9 mmol/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84–3.14] and hyperkalaemia (HR 1.42, 95% CI 1.10–1.83) were associated with a higher risk for cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non‐cardiovascular death and heart failure hospitalization. Sacubitril–valsartan had no effect on potassium overall. The benefit of sacubitril–valsartan over enalapril was consistent across the range of baseline potassium levels. Conclusions: Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.

  • Authors: 
    Leonard Joseph Appleman; Michael Paul Kolinsky; William R. Berry; Margitta Retz; Loic Mourey; Josep M. Piulats; Emanuela Romano; Gwenaelle Gravis; Howard Gurney; Johann S. de Bono; +10 more
    Publisher: American Society of Clinical Oncology (ASCO)

    10 Background: For men with mCRPC, systemic therapies such as docetaxel and cabazitaxel improve survival, but more effective treatments are needed. KEYNOTE-365 (NCT02861573) is a phase 1b/2 study to examine the safety and efficacy of pembro in combination with 4 different study medications (cohorts A, B, C, D) in mCRPC. Previous data from cohort B with a median of 20 months of follow-up showed that pembro + docetaxel and prednisone was well tolerated and had antitumor activity in patients (pts) with mCRPC previously treated with abi or enza. New efficacy and safety data after an additional year of follow-up are presented. Methods: Cohort B enrolled pts who did not respond to or were intolerant to ≥4 weeks of abi or enza in the prechemotherapy mCRPC state and whose disease progressed within 6 months of screening (determined by PSA progression or radiologic bone/soft tissue progression). Pts received pembro 200 mg IV every 3 weeks (Q3W), docetaxel 75 mg/m2 IV Q3W, and oral prednisone 5 mg twice daily. Primary end points were safety, PSA response rate (PSA decrease >50% from baseline), and ORR per RECIST v1.1 by blinded independent central review. Efficacy and safety were assessed in all pts as treated. Results: Of the 104 treated pts, median age was 68.0 years (range, 50-86), 23.1% had PD-L1–positive tumors (combined positive score ≥1), 25.0% had visceral disease, and 50.0% had measurable disease. Median time from enrollment to data cutoff was 32.4 months (range 13.9-40.3); 101 pts discontinued, primarily because of disease progression (77.9%). Efficacy outcomes are reported in the table below. Treatment-related adverse events (TRAEs) occurred in 100 pts (96.2%); the most frequent (≥30%) were diarrhea (41.3%), fatigue (41.3%), and alopecia (40.4%). Grade 3-5 TRAEs occurred in 46 pts (44.2%). Five pts (4.8%) died of AEs; 2 were treatment-related pneumonitis. Conclusions: After another year of follow-up, pembro + docetaxel and prednisone showed improved ORR and PSA response rates compared to the prior dataset in pts with mCRPC previously treated with abi or enza. Safety was consistent with known profiles of each agent and will be further evaluated in a phase 3 study (KEYNOTE-921). Clinical trial information: NCT02861573. [Table: see text]

  • Open Access
    Authors: 
    Alexander K. C. Leung; Joseph M. Lam; Kin Fon Leong;

    Background: The diagnosis of solitary cutaneous mastocytoma is mainly clinical, based on lesion morphology, the presence of a positive Darier sign, and the absence of systemic involvement. Knowledge of this condition is important so that an accurate diagnosis can be made. Objective: To familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of a solitary cutaneous mastocytoma. Methods: A PubMed search was completed in Clinical Queries using the key term "solitary cutaneous mastocytoma". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in English language were included. The information retrieved from the above search was used in the compilation of the present article. Results: Typically, a solitary cutaneous mastocytoma presents as an indurated, erythematous, yellow- brown or reddish-brown macule, papule, plaque or nodule, usually measuring up to 5 cm in diameter. The lesion often has a peau d'orange appearance and a leathery or rubbery consistency. A solitary cutaneous mastocytoma may urticate spontaneously or when stroked or rubbed (Darier sign). Organomegaly and lymphadenopathy are characteristically absent. The majority of patients with skin lesions that erupt within the first two years of life have spontaneous resolution of the lesions before puberty. Treatment is mainly symptomatic. Reassurance and avoidance of triggering factors suffice in most cases. Conclusion: The diagnosis is mainly clinical, based on the morphology of the lesion, the presence of a positive Darier sign, and the absence of systemic involvement. A skin biopsy is usually not necessary unless the diagnosis is in doubt.

  • Open Access English
    Authors: 
    S. Hong Lee; Enda M. Byrne; Christina M. Hultman; Anna K. Kähler; Anna A. E. Vinkhuyzen; Stephan Ripke; Ole A. Andreassen; Thomas Frisell; Alexander Gusev; Xinli Hu; +134 more
    Countries: Belgium, Switzerland, Australia, Netherlands
    Project: NIH | Genetic predictors of res... (5U01GM092691-04), NHMRC | Statistical analyses of w... (1047956), NWO | Cluster computing in gene... (2300131050), NHMRC | Using New Genomic Technol... (1053639), NIH | 1/2 A Large-Scale Schizop... (5R01MH077139-05), NHMRC | Using genomics to underst... (1078901), NHMRC | Uncoupled Research Fellow... (613602)

    Background: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. Methods: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born. Results: We estimate a small but significant negative SNP-genetic correlation between SZ and RA (−0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (−0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P = 0.00090). Conclusions: Our results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context. Refereed/Peer-reviewed

  • Closed Access
    Authors: 
    André Mocaer; Elisabeth Guillou; Omer Chouinard;
    Publisher: Elsevier BV

    Abstract With an increasing number of coastal issues associated with human pressure and exacerbated by climate change, this study examines how residents of coastal communities perceive their living environment and how they perceive risks in this environment and more particularly coastal risks (marine erosion and flooding). An international (Canada-France) questionnaire study was conducted among 190 people, approximately half of whom lived on New Brunswick's Acadian Coast and half on France's west coast. The results highlight, on the one hand, the residents' strong relationship with their coastal living environment and, on the other, a representation of coastal risks as an important area of concern for them. That said, the worry concerning these risks varied among the participants. The local and cultural context (media coverage of this issue and the country-specific risk management strategies) may explain the differences in attitude between the two countries.