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The vast pain of Marguerite Duras’ traumatic past occupies many of her texts. Meyer analyzes the Holocaust’s effect on Duras’ representation of space, place, and memory in La Douleur (1984) in dial...

Background and aims ROTAVIN-M1® (licensed, frozen vaccine) and ROTAVIN (second-generation, liquid candidate vaccine) are two rotavirus vaccine formulations developed from a live attenuated G1P8 (KH0118) strain by Center for Research and Production of Vaccines and Biologicals (POLYVAC), Vietnam. This study compared the safety and immunogenicity of these two formulations. Methods A Phase 3, randomized, partially double-blinded, active-controlled study was conducted in healthy infants aged 60–91 days in Vietnam. Infants received two doses of ROTAVIN or ROTAVIN-M1 in a ratio of 2:1 with an interval of 8 weeks. Solicited reactions were collected for 7 days after each vaccination. Blood samples were collected pre-vaccination and 4 weeks after the second vaccination in a subset of infants. Non-inferiority criteria required that the lower bound of 95% confidence intervals (CIs) of the post-vaccination anti-rotavirus IgA GMC (Geometric Mean Concentration) ratio of ROTAVIN/ROTAVIN-M1 should be >0.5. A co-primary objective was to compare the safety of the two vaccines in terms of solicited reactions. Results A total of 825 infants were enrolled. The post-vaccination GMC was 48.25 (95% CI: 40.59, 57.37) in the ROTAVIN group and 35.04 (95% CI: 27.34, 44.91) in the ROTAVIN-M1 group with an IgA GMC ratio of 1.38 (95% CI: 1.02, 1.86) thus meeting the pre-set criteria for non-inferiority. A total of 605 solicited reactions were reported in 297 (36.0%) participants with 35.4% in the ROTAVIN group and 37.2% in the ROTAVIN-M1 group. There were no cases of intussusception or death reported in the study. Conclusions Based on the data generated, it can be concluded that ROTAVIN is immunologically non-inferior and has similar safety profile to ROTAVIN-M1 when administered to infants in a two-dose schedule. Therefore, it can be considered as a more suitable option for programmatic use to prevent rotavirus diarrhoea in Vietnam and the Mekong region. Trial registration number ClinicalTrials.gov identifier: NCT03703336, October 11, 2018.

Background and Aims ROTAVAC® (frozen formulation stored at −20 °C) and ROTAVAC 5D® (liquid formulation stable at 2–8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia. Methods We conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89–12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose. Results The study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period. Conclusions Among Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.

Handtherapeuten begegnen sensiblen Störungen mit Sensibilitätstraining oder Desensibilisierungstechniken. Doch oft sind sowohl die Begrifflichkeiten als auch die entsprechenden Behandlungsmaßnahmen nicht klar voneinander abgegrenzt. Tara Packham erklärt die Unterschiede, prüft kritisch die vorhandene Evidenz und schlägt schließlich einen Algorithmus für die Behandlung dieser Störungen vor.

Engaging the French Language Student Adult learners tend to be self-directed learners who prefer active-learning approaches, according to Malcolm Knowles's concept of andragogy (see also: [...]creating a flipped classroom, where students study concepts and lessons before class sessions permits instructors to focus on our proficiency-oriented goals, rather than the simple introduction of grammar. Mine contains my Teaching Philosophy (which emphasizes student success, collaboration, student-centered active-learning approach, safe climate, etc.), Student Learning Objectives (shared by all course sections), Transferable Skills (10 skills that transfer to the work world), Teaching Methods, Study Tips for Success in Learning French, Classroom Environment, a list of student expectations and of instructor expectations. [...]as French teachers we are uniquely positioned to assure respectful discourse, and sensitivity to issues of race, equity, and diversity. [...]assessment should focus on the values we teach.

The aim of this study was to analyze whether dermal exposure to benzophenone 3 (BP-3) during pregnancy affects criticalparameters of pregnancy, and whether this exposure may affect the outcome of a second pregnancy in mice. Pregnant micewere exposed to 50-mg BP-3/kg body weight/day or olive oil (vehicle) from gestation day (gd) 0 to gd6 by dermal exposure.High-frequency ultrasound imaging was used to follow up fetal and placental growth in vivo. Blood flow parameters inuterine and umbilical arteries were analyzed by Doppler measurements. Mice were killed at gd5, gd10, and gd14 on the firstpregnancy, and at gd10 and 14 on the second pregnancy. The weight of the first and second progenies was recorded, and sexratio was analyzed. BP-3 levels were analyzed in serum and amniotic fluid. BP-3 reduced the fetal weight at gd14 and fetoplacentaindex of first pregnancy, with 16.13% of fetuses under the 5th percentile; arteria uterina parameters showed alteredpattern at gd10. BP-3 was detected in serum 4 h after the exposure at gd6, and in amniotic fluid at gd14. Offspring weightof first progeny was lower in BP-3 group. Placenta weights of BP-3 group were decreased in second pregnancy. First andsecond progenies of mothers exposed to BP-3 showed a higher percentage of females (female sex ratio). Dermal exposureto low dose of BP-3 during early pregnancy resulted in an intrauterine growth restriction (IUGR) phenotype, disturbed sexratio and alterations in the growth curve of the offspring in mouse model. Fil: Santamaría, Clarisa Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Meyer, Nicole. Otto-von-Guericke-Universität Magdeburg; Alemania Fil: Schumacher, Anne. Otto-von-Guericke-Universität Magdeburg; Alemania Fil: Zenclussen, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Teglia, Carla Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentina Fil: Culzoni, Maria Julia. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química. Cátedra de Química Analítica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Zenclussen, Ana Claudia. Otto-von-Guericke-Universität Magdeburg; Alemania Fil: Rodriguez, Horacio Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina

The enzyme heme oxygenase-1 (HO-1), encoded by the HMOX1 gene, mediates heme catabolism by cleaving free heme. We have previously revealed the importance of HO-1 in pregnancy. Here, we determined the impact of maternal or paternal HO-1 deficiency on fetal growth and placental parameters throughout gestation. We mated Hmox1-sufficient (WT), partial (HET)-, or total (KO)-deficient BALB/c female mice with Hmox1-WT or -KO BALB/c males and performed ultrasound analysis to monitor placental and fetal growth. Doppler measurements were used to determine maternal blood flow parameters. Offspring weights and feto-placental indices (FPI) were also determined. We found a significantly increased number of underdeveloped fetuses at gd10 in HET females that were mated with WT males compared with WT × WT pairings. At the same gestational age, underdeveloped placentas could be detected in HET females mated with KO males. Many fetuses from the KO × KO combination died in utero between gd12 and gd14. At gd14, abnormal placental parameters were found in surviving fetuses, which had significant reduced weights. Moreover, only 3.11% female and 5.33% male KO pups resulted from 10 HET × HET breeding pairs over 1 year. Our results show that HO-1 from both maternal and paternal origins is important for proper placental and fetal growth. Placental growth restriction and occurrence of abortions in mice that were partially or totally deficient in HO-1 were recorded in vivo from gd10 onwards. Future studies will focus on elucidating the cellular and molecular mechanisms behind these observations.

During the solar minimum, when the Sun is at its least active, the solar wind1,2 is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvenic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind3 of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain4; theories and observations suggest that they may originate at the tips of helmet streamers5,6, from interchange reconnection near coronal hole boundaries7,8, or within coronal holes with highly diverging magnetic fields9,10. The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfven-wave turbulence11,12, heating by reconnection in nanoflares13, ion cyclotron wave heating14 and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe15 at 36 to 54 solar radii that show evidence of slow Alfvenic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities10,16 that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind. Measurements from the Parker Solar Probe show that slow solar wind near the Sun’s equator originates in coronal holes.

This scoping review is to identify experiences, unmet needs, and health-related quality of life (HRQoL) of family caregivers transitioning their care recipients with dementia into long-term care (LTC). The methodological framework of Arksey and O'Malley guided the review. Themes from nineteen selected studies were organized around three categories. First, caregiver experiences during LTC placement featured challenges around placement decision-making and distress and changes in relationships and responsibilities. Second, unmet needs of caregivers were desired emotional support and information about transitions. Finally, caregivers' HRQoL varies around transition. Family caregivers experience unique challenges and can have unmet needs during the LTC placement of their care recipients with dementia. Findings suggest the need for interventions that teach skills, care planning, assistance with conflict resolution, communication training, and guidance finding services and resources.

After decades of rising prevalence of atopic and airway-related diseases, studies showed stagnating prevalence in western industrialised countries. Objective of this study is to analyse the time trend of prevalence of atopic diseases and airway-related symptoms among Bavarian children before starting primary school.Five cross-sectional studies from 2004/2005, 2006/2007, 2012/2013, 2014/2015 and 2016/2017 took place in urban and rural regions in Bavaria, Germany. Using standardized parent questionnaires children's atopic diseases and airway-related symptoms were surveyed. Logistic regression analysis (Bonferroni correction: adjusted significance level 0.005) was performed to analyse prevalence of symptoms and diseases from 2004 to 2017 for time trends.The surveys included 27384 Bavarian children aged 5-6 years (52.6% male). In all children the calculated 12-month prevalence of symptoms '≥four episodes of wheeze' (p-value = .0880) and 'rhinoconjunctivitis' (p-value = .3994) reported by parents stagnated, whereas 'wheeze' (p-value.0001; OR = 0.97; CI = [0.96-0.98]) and 'rhinitis' (p-value = .0007; OR = 0.98; CI = [0.97-0.99]) decreased. In all children the calculated lifetime prevalence of physician-diagnosed 'asthma' (p-value = .5337), and 'hay fever' (p-value = .8206) stagnated, whereas of 'bronchitis' (p-value.0001; OR = 0.98; CI = [0.98-0.99]) decreased over time. The calculated lifetime prevalence of physician-diagnosed 'atopic eczema' (p-value = .0002; OR = 0.98; CI = [0.97-0.99]) decreased in all children, whereas the calculated 12-month prevalence of the symptom 'itchy rash' increased (p-value = .0033; OR = 1.07; CI = [1.05-1.08]) over time.Several calculated prevalence of children's atopic diseases and airway-related symptoms reported by parents stagnated in a subgroup of Bavarian children before starting primary school between 2004 and 2017. The time trend of prevalence in 'wheeze', 'rhinitis' and 'bronchitis' decreased. Prevalence of 'atopic eczema' decreased over time, whereas 'itchy rash' increased.

Poster no. 1038317 Poster no. 1038317

Progestogens are frequently administered during early pregnancy to patients undergoing assisted reproductive techniques (ART) to overcome progesterone deficits following ART procedures. Orally administered dydrogesterone (DG) shows equal efficacy to other progestogens with a higher level of patient compliance. However, potential harmful effects of DG on critical pregnancy processes and on the health of the progeny are not yet completely ruled out. We treated pregnant mice with DG in the mode, duration, and doses comparable to ART patients. Subsequently, we studied DG effects on embryo implantation, placental and fetal growth, fetal-maternal circulation, fetal survival, and the uterine immune status. After birth of in utero DG-exposed progeny, we assessed their sex ratios, weight gain, and reproductive performance. Early-pregnancy DG administration did not interfere with placental and fetal development, fetal-maternal circulation, or fetal survival, and provoked only minor changes in the uterine immune compartment. DG-exposed offspring grew normally, were fertile, and showed no reproductive abnormalities with the exception of an altered spermiogram in male progeny. Notably, DG shifted the sex ratio in favor of female progeny. Even though our data may be reassuring for the use of DG in ART patients, the detrimental effects on spermatogenesis in mice warrants further investigations and may be a reason for caution for routine DG supplementation in early pregnancy.

Our goalwas to study the effect of BP3 (benzophenone 3) in the follicular assembly and thepotential involvement of Foxl2 pathway using whole ovary cultures. Ovaries werecollected from Wistar rats at birth, treated in vitro with vehicle (0.01 %DMSO), BP3 (5.8 nM, 276 nM, 576 nM and 876 nM) or ESR2 inhibitor (0.1 nM), andcultured for 7 days. Nest breakdown, follicular assembly and the expression ofseveral regulators of these processes (p27, Foxl2, Sox9, Bmp2, Cyp19 and Fst)were evaluated. In vitro exposure to BP3 (5.8 nM) decreased the population oftotal oocytes, the number of nests per ovary and early primary folliclespopulation. In addition, BP3 (5.8 nM) induced overexpression of Foxl2 mRNAlevels through ESR2 but increased Fst mRNA levels independently from ESR2 orFoxl2. We also observed that the number of p27-positive oocytes was decreasedafter BP3 (5.8 nM). On the other hand, exposure to BP3-276 increased totaloocytes, the number of nests per ovary and decreased primary follicles. Inaddition, BP3-276 induced no changes of Foxl2 mRNA levels through ESR2 but increasedFst mRNA levels independently from ESR2 or Foxl2. In conclusion, our studyclearly shows that exposure to BP3 is to perturb the early events of germ cell developmentas showed here in whole ovary cultures. Fil: Santamaría, Clarisa Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Abud, Julián Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Porporato, Melina Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Meyer, N.. Otto-von-guericke University; Alemania Fil: Zenclussen, A. C.. Otto-von-guericke University; Alemania Fil: Kass, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Rodriguez, Horacio Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina

Chronic hepatitis B (CHB) comorbidity data are limited. Using insurance claims databases, our aims were to determine the prevalence and incidence of nonliver comorbidities in CHB patients over time and the predictors of select comorbidities in CHB patients. Patients were adults with continuous coverage (commercial/Medicare or Medicaid) 6 months prior to and after the first CHB diagnosis and matched non‐CHB patients. Deyo‐Charlson Comorbidity Index (DCCI) and comorbidities were analyzed (cardiovascular disease [CVD], carcinoma, diabetes mellitus [DM], obesity, hypertension [HTN], hyperlipidemia, alcohol use, renal impairment, chronic kidney disease [CKD], and osteoporosis/fracture [OF]). The study population included 44,026 CHB cases and 121,568 matched controls. CHB patient mean age increased from 48.1 ± 11.9 years in 2006 to 51.8 ± 12.4 years in 2015 for commercial/Medicare and from 44.1 ± 11.1 years to 50.2 ± 10.2 years for Medicaid (P < 0.001 for both). The Medicaid CHB cohort was the sickest (DCCI, 2.6, P < 0.001). The commercial/Medicare 2006 CKD prevalence rate was 36.1/1,000 in CHB patients and 10.2/1,000 in controls, increasing to 97.6 and 38.8 in 2015, respectively. The 2006 CKD incidence (per 1,000 person‐years) was 10.3 and 4.8 and 15.2 and 11.3 by 2015, respectively (P < 0.05 for all). The strongest predictors for CKD were DM (hazard ratio [HR], 2.48), HTN (HR, 3.29), and CVD (HR, 2.61) (all P < 0.0001). Similar prevalence and incidence changes were observed for OF. The strongest predictors for OF were female gender (HR, 2.22), alcohol use (HR, 2.02), and viral coinfection (HR, 1.37) (all P < 0.0001). Conclusion: Insured CHB patients were older, had more comorbidities, and experienced higher incidence and prevalence of CKD and OF than controls.

Objective Real-world data on patients with cancer developing secondary malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are lacking. This study assessed the incidence and impact of select DNA-damaging therapy exposure on risk of secondary MDS and AML in patients with ovarian cancer (OC) or breast cancer (BC). Methods Adults with a first observed OC or BC diagnosis (index date) between 1/1/2000 and 6/30/2014 were identified from MarketScan® Commercial and Medicare databases. Patients had ≥12 months of pre-index and ≥1 month of post-index continuous health plan enrollment. Incidence of MDS/AML was evaluated over a variable-length period following the index date for each cancer cohort. Risk factors for secondary MDS/AML, including duration of DNA-damaging therapy exposure, were assessed using Poisson regression. Results Study selection criteria identified 23,862 patients with OC and 281,473 patients with BC (mean [SD] follow-up: 35.8 [31.4] and 46.0 [37.2] months, respectively). Incidence of MDS/AML was 2.77 and 1.44 per 1000 person-years among patients with OC and BC, respectively. Within both cohorts, incidence of MDS and AML was higher among patients exposed than those not exposed to select DNA-damaging therapy (alkylating agents, antimetabolites, platinum-based antineoplastic agents, and topoisomerase inhibitors). Duration of exposure to DNA-damaging therapy was a significant risk factor for developing MDS/AML during follow-up. Conclusions Data suggest that there is likely a background risk of secondary MDS/AML associated with use of DNA-damaging therapies in earlier lines of chemotherapy and it is elevated in subcohorts exposed to select DNA-damaging therapies.