Space degradation of triple junction solar cells at low temperatures: II-electron irradiation

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Inconsistencies among European Union Pharmaceutical Regulator Safety Communications: A Cross-Country Comparison

The European Medicines Agency (EMA) and national regulators share the responsibility to communicate to healthcare providers postmarketing safety events but little is known about the consistency of this process. We aimed to compare public availability of safety-related communications and drug withdrawals from the EMA and European Union member countries for novel medicines. We performed a cross-sectional analysis using public Dear Healthcare Professional Communications (DHPCs) for all novel medicines authorized between 2001 and 2010 by the EMA and available for use in France, Netherlands, Spain, and the United Kingdom. Between 2001 and 2010, the EMA approved 185 novel medicines. DHPCs could not be ascertained for the EMA. Among the 4 national regulators, as of April 30, 2013, at least one safety DHPC or withdrawal occurred for 53 (28.6%) medicines, totaling 90 DHPCs and 5 withdrawals. Among these 53 medicines, all 4 national agencies issued at least one communication for 17 (32.1%), three of the four for 25 (47.2%), two of the four for 6 (11.3%), and one of the four for 5 (9.4%). Five drugs were reported to be withdrawn, three by all four countries, one by three and one by two. Among the 95 DHPCs and withdrawals, 20 (21.1%) were issued by all 4 national regulators, 37 (38.9%) by 3 of the 4, 22 (23.2%) by 2 of the 4, and 16 (16.8%) by one. Consistency of making publicly available all identified safety DHPC or withdrawal across regulator pairs varied from 33% to 73% agreement. Safety communications were not made publicly available by the EMA. Among the 4 European member countries with national regulators that make DHPCs publicly available since at least 2001, there were substantial inconsistencies in safety communications for novel medicines. The impact of those inconsistencies in terms of public health remains to be determined

It's Complicated: People and Their Democracy in Germany, France, Britain, Poland, and the United States

This in-depth study explores how citizens in five countries (Germany, France, Britain, Poland, and the United States) feel about democracy, their frustrations, and their demands, with a particular focus on those with an ambivalent relationship with democracy

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Génétique du cancer colorectal : polyposes adénomateuses non liées à APC et cancers de survenue précoce

Colorectal cancer (CRC) is the third most frequent cancer in the world and has become a major issue for public health. Around 5% of CRC are inherited: the Familial Adenomatous Polyposis (FAP), Lynch syndrome (LS) and the MAP syndrome (MUTYH-Associated Polyposis). Implication of MAP syndrome in adenomatous polyposis: Among 31 patients with a polyposis with no mutation found in APC, 6 (20%) had biallelic mutation in MUTYH. Transversions were observed in Kras or APC in 5 patients (83%). Prevalence of the c.1185_1186dup mutation in MAP: Among a group of 36 families with a proven biallelic mutation in MUTYH, 11 had an homozygous biallelic mutation c.1185_1186dup. This mutation was significantly observed more frequently in patients with North African origin (79% vs. 5%, p<0.0001). Search for a funder effect using 10 microsatellites around MUTYH showed a common haplotype of at least 1.3 cM in every patients with c.1185_1186dup mutation. Rare variants (RV) in Cyclin D1: comparison of the frequency of RV in Cyclin D1 was performed between cases (112 undetermined polyposis and 44 early onset CRC) and 866 controls. VR were more frequently observed in cases. When combining VR, an increased in the risk of polyposis was observed in cases (OR= 2.2); 95%CI, 1.1-4.4; P=0,03). In silico analysis showed that the majority of rare variants had a functional effect. Role of rare variants: 70 variants among 17 genes were analyzed in the same set of patients. 21 were RV (frequency < 1%) and 4 were more frequently observed in cases (EXO1-12, MLH1-1, CTNNB1-1 and BRCA2-37, p<0,05). When combining all RV with a frequency below 0.5%, a risk of 3.2 was observed (95%CI=1.1-9.5; p=0.04)Le cancer colorectal (CCR) est le troisième cancer dans le monde et devenu un véritable enjeu de santé publique. Environ 5% sont associés à une forme familiale : la polypose adénomateuse familiale, le Syndrome de Lynch et la MAP (MUTYH-Associated Polyposis). Implication du syndrome MAP dans les polyposes: Parmi 31 patients avec une polypose sans mutation sur APC, 6 (20%) présentaient une mutation biallélique sur MUTYH. Fréquence de la mutation c.1185_1186dup dans les MAP: Au sein d'un groupe de 36 familles mutées sur MUTYH, 11 avaient une mutation biallélique homozygote c.1185_1186dup. Cette mutation était significativement plus fréquemment observée chez les patients d'Afrique du Nord (79% vs. 5%, p<0,0001). La recherche d'un haplotype commun en utilisant 10 microsatellites a identifié un segment de 1,3 cM présent chez tous les patients avec la mutation c.1185_1186dup. Variants rares (VR) de la cycline D1 : La comparaison des fréquences alléliques des VR de la cycline D1 fut réalisée entre les cas (112 patients avec une polypose indéterminée et 44 avec un CCR précoce) et 866 témoins. Les VR étaient plus fréquemment observés dans le groupe de malades. En combinant les VR, une augmentation du risque était retrouvée pour le groupe de patients avec une polypose indéterminée: (OR=2,2); 95%IC, 1,1-4,4; P=0,03). Rôle des variants rares : 70 variants provenant de 17 gènes ont été examinés au sein de la même population. 21 était des VR (fréquence<1%) et 4 étaient plus fréquemment observés chez les cas (EXO1-12, MLH1-1, CTNNB1-1 et BRCA2-37, p<0,05). En combinant tous les VR avec une fréquence allélique <0,5%, un sur risque de 3,2 était observé (95%CI=1,1-9,5; p=0,04

Human papillomavirus vaccine uptake among men in France: a national time series analysis for 2015-2018.

While national authorities recommended and provided reimbursement for men who have sex with men under 27 in 2016 and 2017, respectively, we aimed to comprehensively analyze human papillomavirus (HPV) vaccine uptake in French men over a 4-year period surrounding these changes. Data regarding HPV vaccine sales to men in all French pharmacies from 2015 through 2018 were retrieved through query made to the national public insurance database. Data were classified according to the age of patients and the time of dispensation so as to display aggregate uptake according to age over time. Time-series analysis was conducted and an exponential smoothing extrapolation was selected to analyze the impact of the reimbursement. Overall, 12,814 HPV vaccines were dispensed in men over the study period. Age was available for the majority of cases (12,793; 99.8%), averaging 29. Dispensation data for each year were the following: 1,917 (2015), 1,921 (2016), 2,643 (2017), 6,312 (2018). Age analysis showed that vaccine uptake among men over 26 was substantial (n = 5974; 46.7%). The exponential increase in the number of vaccines sold started after the second quarter of 2017. In conclusion, we found that HPV vaccine uptake among French men is partly misaligned with recommendations and reimbursement in terms of age, and still moderate overall even though we found signs of marked increase in uptake over the most recent period, suggesting an effective impact of insurance coverage

Dedicated Tool for Irradiation and Electrical Measurement of Large Surface Samples on the Beamline of a 2.5 Mev Pelletron Electron Accelerator: Application to Solar Cells

We designed a tool allowing irradiation of large samples over a surface of A5 size dimension by means of a 2.5 MeV Pelletron electron accelerator. in situ electrical measurements (I-V, conductivity, etc.) can also be performed, in the dark or under illumination, to study radiation effects in materials. Irradiations and electrical measurements are achievable over a temperature range from 100 K to 300 K. The setup was initially developed to test real-size triple junction solar cells at low temperature within the framework of the ESA’s JUICE mission. It will be made available to users at the beginning of 2017. After a brief description of the SIRIUS irradiation facility hosted at Laboratoire des Solides Irradiés (LSI), this paper gives detailed information about the Large Surface Irradiated-Cell (LSIC) device. Preliminary results obtained during the ongoing qualification phase of the setup are also discussed

Regulatory anticipation of postmarket safety problems for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study

The aim of the study is to describe preapproval safety concerns expressed by the European Medicines Agency (EMA) following regulatory review and to compare those concerns with subsequent issuance of postmarket safety communications. All novel medicines approved by the EMA through the centralized authorization procedure from 2001 to 2010 were included. Preapproval safety concerns were identified through examination of information related to regulatory review publicly available on the EMA’s website. Relevant postmarket safety events were identified through Dear Healthcare Professional Communications (DHPCs), including those resulting in a withdrawal, issued by at least one of four leading national regulators of the European Union. Among the 184 novel medicines included, the EMA had expressed at least one preapproval safety concern for 110 (59.8%) of them. Then, at least one safety communication was issued for 53 (28.8%) medicines within the postmarket period of study, totaling 90 DHPCs and 5 withdrawals. Overall, these 95 DHPCs and withdrawals were pertaining to 66 different clinical safety events. The EMA had expressed a preapproval concern consistent with the postmarket safety event for 22.7% (15 of 66). The rate of issuance of a postmarket safety communication was not statistically different between medicines with or without any preapproval safety concern (31.8% vs. 24%, p = 0.25). Preapproval safety concerns are frequently expressed by the EMA following regulatory review. However, when comparing postmarket safety communications with prior concerns, anticipation was low. Our findings emphasize the need to systematically conduct postmarket studies dedicated to safety evaluation

Instabilité des microsatellites et cancer: De l’instabilité du génome à la médecine personnalisée

International audienceThe human tumor phenotype referred to as MSI (Microsatellite Instability) is associated with inactivating alterations in MMR genes (Mismatch Repair). MSI was first observed in inherited malignancies associated with Lynch syndrome and later in sporadic colon, gastric and endometrial cancers. MSI tumors develop through a distinctive molecular pathway characterized by genetic instability in numerous microsatellite DNA repeat sequences throughout the genome. In this article, french researchers and physicians who have been recently awarded by the Fondation de France (Jean and Madeleine Schaeverbeke prize) make a sum of their activity in the MSI cancer field for more than 20 years. Their findings have greatly contributed to increase our knowledge of this original cancer model, laying the foundation for a personalized medicine of MSI tumors

Bondy (Seine-Saint-Denis), Quartier De Lattre de Tassigny : Place du 11 novembre et rue Jules Guesde : rapport de fouille

Depuis 50 ans, des fouilles archéologiques ont été effectuées dans le centre ville de Bondy. Au total, ce sont près de 15 000 m2 qui ont été fouillés. Les résultats de ces recherches aboutissent à la mise en évidence d'un terroir occupé dès le Néolithique. A l'époque gallo-romaine, une occupation assez importante s'installe dans ce secteur, les structures découvertes sont pour la plupart funéraires, avec un total de 500 sépultures. A l'époque mérovingienne, la nécropole se développe plus au sud et ce sont 250 sépultures qui ont été fouillées. A l'époque carolingienne, les structures d'habitat et artisanales se densifient. Puis, au bas Moyen Âge, le cimetière se déplace un peu plus vers le sud-ouest, tout comme l'occupation humaine.La fouille de 2011 a permis de mettre en évidence les limites nord et sud-est de la nécropole gallo-romaine et une importante aire artisanale au nord comportant des fonds de cabane, des fours et quelques bâtiments