ANALYZING TRENDS AND PATTERNS IN ADVERSE BIRTH OUTCOMES IN MASSACHUSETTS FROM 2000-2014

This study explores spatio-temporal trends and patterns in adverse birth outcomes (ABO) in the state of Massachusetts from 2000-2014. ABO include low birth weight (\u3c 2500 g) and preterm deliveries (gestational age \u3c 37 weeks). This research evaluates if there are areas in Massachusetts that have experienced statistically significant increases or decreases in ABO throughout the study period. Birth data was obtained from the Massachusetts Department of Public Health and only singleton, live births were included for the analysis. The data were aggregated to census tracts, and the total number of births and the number of ABOs were calculated for each census tract for each year. In total, 1478 census tracts were included in this analysis. Births to non-Hispanic black mothers and births to non-Hispanic white mothers were separated to evaluate if trends in ABO are similar regardless of race as previous literature has identified a much higher rate of ABO in births to non-Hispanic black women. Trends and patterns of ABO were evaluated using the Space Time Cube and the Mann-Kendall statistic and a multivariate regression was conducted to identify potential correlations between socioeconomic factors and prevalence of ABO. Results of this study can be used to identify areas that are experiencing an increase in ABO to potentially allow for more effective, targeted intervention methods

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk : a case-control study

Abstract Introduction We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P trend = 0.005) but not cases (P trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P trend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; P trend = 0.29). Conclusions To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Using Space–Time Cube to Analyze Trends in Adverse Birth Outcomes and Maternal Characteristics in Massachusetts, USA

Rates of preterm births (\u3c 37 gestational weeks) and low birthweight (≤ 2500 g) are rising throughout the United States. This study uses singleton live birth data, Empirical Bayes approach, space–time cube and Mann–Kendall statistic to evaluate temporal trends in these adverse birth outcomes (ABO) and maternal characteristics over 15 years (2000–2014) at the census tract level for non-Hispanic white and black women in Massachusetts. In addition to analyzing trends for each variable individually, the study analyzes spatial coincidence of trends to determine which maternal characteristics exhibited trends that most strongly correlated with the ABO trends. The 15-year average rate of ABO was 7.34% for white women, and 12.05% for black women. Results show that more census tracts exhibited an increasing trend than decreasing trend in birth outcomes and in several maternal characteristics for both races (gestational and chronic hypertension, gestational diabetes, and previous preterm birth). Study identified 52 census tracts concurrently experiencing an increasing trend in ABO and in four maternal characteristics for black women, indicating that multiple negative trends in health outcomes are concentrated at the same location creating a potential for even more adverse outcomes in the future. This study provides a novel, spatially explicit analytical framework based on Empirical Bayes rates and space–time cube, which could be extended to analyze trends in other health outcomes at various spatial scales

Analyzing Temporal Trends and Spatial Patterns in adverse Birth Outcomes in Massachusetts from 2000–2014

This study explores temporal trends and spatial patterns in adverse birth outcomes (ABO) in the state of Massachusetts from 2000 to 2014. ABO include low birthweight (\u3c2500 \u3eg) and preterm births (gestational age \u3c37 \u3eweeks). This research evaluates if there are areas in Massachusetts that have experienced statistically significant increases or decreases in ABO throughout the study period. Birth data was obtained from the Massachusetts Department of Public Health and only singleton, live births were included for the analysis. The data were aggregated to census tracts, and the total number of births and the number of ABOs were calculated for each census tract for each year. In total, 1478 census tracts were included in this analysis. Trends and patterns of ABO were evaluated using the Space Time Cube and the Mann-Kendall statistic and a multiple linear regression was conducted to identify potential associations between socioeconomic factors and prevalence of ABO. Results showed that there were associations between the socioeconomic indicators and the ABO rate (particularly educational attainment, income, and diversity) though there were no conclusive racial disparities present throughout the state or 15-year study period. Results of this study can be used to identify areas that are experiencing an increase in ABO to potentially allow for more effective, targeted intervention methods

Dai Castra Noua alla Basilica Lateranensis, trasformazioni della Roma costantiniana

Short history of the Lateran area in Rome, recently researched with new digital methods as well as classic research approaches

Dai Castra Noua alla Basilica Lateranensis, trasformazioni della Roma costantiniana

Short history of the Lateran area in Rome, recently researched with new digital methods as well as classic research approaches

Genomewide Scan for Linkage Reveals Evidence of Several Susceptibility Loci for Alopecia Areata

Alopecia areata (AA) is a genetically determined, immune-mediated disorder of the hair follicle that affects 1%–2% of the U.S. population. It is defined by a spectrum of severity that ranges from patchy localized hair loss on the scalp to the complete absence of hair everywhere on the body. In an effort to define the genetic basis of AA, we performed a genomewide search for linkage in 20 families with AA consisting of 102 affected and 118 unaffected individuals from the United States and Israel. Our analysis revealed evidence of at least four susceptibility loci on chromosomes 6, 10, 16 and 18, by use of several different statistical approaches. Fine-mapping analysis with additional families yielded a maximum multipoint LOD score of 3.93 on chromosome 18, a two-point affected sib pair (ASP) LOD score of 3.11 on chromosome 16, several ASP LOD scores >2.00 on chromosome 6q, and a haplotype-based relative risk LOD of 2.00 on chromosome 6p (in the major histocompatibility complex locus). Our findings confirm previous studies of association of the human leukocyte antigen locus with human AA, as well as the C3H-HeJ mouse model for AA. Interestingly, the major loci on chromosomes 16 and 18 coincide with loci for psoriasis reported elsewhere. These results suggest that these regions may harbor gene(s) involved in a number of different skin and hair disorders