Exploring the risk of hypospadias in children born from mothers living close to a vineyard.

Hypospadias (H) is a common birth defect affecting the male urinary tract. It has been suggested that exposure to endocrine disrupting chemicals might increase the risk of H by altering urethral development. However, whether H risk is increased in places heavily exposed to agricultural pesticides, such as vineyards, remains debated and difficult to ascertain. The objective of the work is to test the possible association of H with residential proximity to vineyards. Residential address at birth of 8,766 H cases born 1980-2011 was taken from 17 specialized surgery centers. The geographical distribution of vineyards was obtained from the European Land Parcel Identification System (LPIS) and the distance of address to the nearest vineyard was computed. A first estimate of the variation of H relative risk with distance to vineyards was obtained using as controls 13,105 cryptorchidism (C) cases operated during the same period in the same centers. A separate estimate was obtained from a case-control study using "virtual controls" (VC) defined as points of the map sampled to match the demographic distribution of births within the recruitment territories of the study centers. Non-exposed patients were defined as those with a residence between 5,000 and 10,000 m from the closest vineyard. The residential distance to vineyard was smaller for H than for C cases (p<10-4). We found 42/8766 H cases (0.48%) and 50/13,105 C cases (0.38%) born to mothers living within 20 m of a vineyard. The odds ratios for H were 2.48 (CI: 1.0 to 5.1) and 2.4 (CI: 1.3 to 4.4), vs C or vs VC, respectively, when pregnant mothers lived 10-20 m from a vineyard. In conclusion, our study supports that children born to mothers living close to a vineyard have a two-fold increased risk of H. For environmental research, the use of VC provides an alternative to classical case control technique.

Serum antimüllerian hormone is associated with the number of oocytes matured in vitro and with primordial follicle density in candidates for fertility preservation.

OBJECTIVE: To assess whether serum antimüllerian hormone (AMH) levels and antral follicle count (AFC) can predict primordial follicle density within ovarian cortex and the number of oocytes cryopreserved after in vitro maturation (IVM). DESIGN: Retrospective analysis of a case series of patients. SETTING: University hospital. PATIENT(S): Fifty-four women, 18 to 35 years of age, with breast cancer who were candidates for fertility preservation (FP) using ovarian tissue cryopreservation (OTC) associated with oocyte vitrification after unstimulated IVM between July 2013 and December 2016. INTERVENTION(S): Serum AMH levels and transvaginal AFC evaluated before FP, cumulus-oocyte complexes (COC) recovered under ultrasound guidance and incubated for IVM, and ovarian tissue laparoscopically harvested and cryopreserved. MAIN OUTCOME MEASURE(S): Univariate and multivariate analysis between ovarian reserve tests, number of recovered and in vitro matured oocytes, and primordial follicle density histologically obtained within ovarian cortex. RESULT(S): Univariate analysis showed a statistically significant correlation between AMH or AFC and primordial follicle density. Multivariate analysis showed a predominant statistically significant correlation of serum AMH with density. Antimüllerian hormone also correlated with the number of COC and in vitro matured oocytes. CONCLUSION(S): Serum AMH levels may reflect the primordial follicle stockpile and may predict outcomes of IVM and OTC when performed for FP. Further analyses are required to evaluate the relevance of performing such procedures in young women who have low values on ovarian reserve tests.

Using spatio-temporal surveillance data to test the infectious environment of children before type 1 diabetes diagnosis.

The "hygiene hypothesis" postulates that reduced exposure to infections favours the development of autoimmunity and childhood type 1 diabetes (T1D). But on the other side, viruses, notably enteroviruses, are suspected to trigger T1D. The assessment of the possible relationships between infections and T1D still defies the classical tools of epidemiology. We report the methods and results of a geographical approach that maps the addresses of patients to a communicable diseases surveillance database. We mapped the addresses of patients at birth, infancy and T1D diagnosis to the weekly estimates of the regional incidences of 5 frequent communicable diseases routinely collected since 1984 by the French Sentinel network. The pre-diagnostic infectious environment of 3548 patients with T1D diagnosed between 0.5 and 15 years was compared to those of 100 series of age-matched "virtual controls" drawn randomly on the map. Associations were classified as "suggestive" (summer diarrhea, SD, and varicella, V) when p< 0.05, or "significant" (influenza-like infections, ILI) when they passed the Bonferroni correction for FDR. Exposure to ILI and SD were associated with T1D risk, while V seemed protective. In the subset of 2521 patients for which we had genome wide data, we used a case-only approach to search for interactions between SNPs and the infectious environment as defined by the Sentinel database. Two SNPs, rs116624278 and rs77232854, showed significant interaction with exposure to V between 1 and 3 years of life. The infectious associations found should be taken as possible markers of patients' environment, not as direct causative factors of T1D. They require replication in other populations. The increasing public availability of geographical environmental databases will expand the present approach to map thousands of environmental factors to the lifeline of patients affected by various diseases.

Age distribution of cases and deaths during the 1889 influenza pandemic.

Using historical data taken from archival records from five European countries and the United States, we evaluate the age distributions of influenza cases and deaths during the 1889 influenza pandemic. We found that the clinical attack rate in 1889 was relatively high and constant between the ages of 1 and 60 years, but was lower outside of the extremes of this age range. By contrast, age-specific influenza-related mortality rates were J-shaped and increased with age beyond 20 years. We conclude that the age-specific attack rates of the 1889 pandemic were most similar to those of the 1968 pandemic and that influenza-related mortality rates did not follow a W-shaped curve as was observed during the 1918 pandemic. Adding 1889 to the short catalogue of influenza pandemics previously studied makes the 1918 pandemic even more exceptional in terms of mortality burden and age distribution of deaths.

Transmissibility and geographic spread of the 1889 influenza pandemic.

Until now, mortality and spreading mechanisms of influenza pandemics have been studied only for the 1918, 1957, and 1968 pandemics; none have concerned the 19th century. Herein, we examined the 1889 "Russian" pandemic. Clinical attack rates were retrieved for 408 geographic entities in 14 European countries and in the United States. Case fatality ratios were estimated from datasets in the French, British and German armies, and morbidity and mortality records of Swiss cities. Weekly all-cause mortality was analyzed in 96 European and American cities. The pandemic spread rapidly, taking only 4 months to circumnavigate the planet, peaking in the United States 70 days after the original peak in St. Petersburg. The median and interquartile range of clinical attack rates was 60% (45-70%). The case fatality ratios ranged from 0.1% to 0.28%, which is comparable to those of 1957 and 1968, and 10-fold lower than in 1918. The median basic reproduction number (R(0)) was 2.1, which is comparable to the values found for the other pandemics, despite the different viruses and contact networks. R(0) values varied widely from one city to another, and only a small minority of those values was within the range in which modelers' mitigation scenarios predicted effectiveness. The 1889 and 1918 R(0) correlated for the subset of cities for which both values were available. Social and geographic factors probably shape the local R(0) , and they could be identified to design optimal mitigation scenarios tailored to each city.