FROM LANGUAGE TO LITERACY: STRUCTURAL FEATURES OF ACQUIRED LANGUAGES FACILITATING ENGLISH MORPHOLOGICAL AWARENESS

Morphological awareness is a crucial metalinguistic skill, specifically for English Language Learners (ELLs). Since languages differ widely in degree of orthographic opacity, degree of morphological fusion, and degree of morphological synthesis, this thesis sought to evaluate the impact of the structural features of other languages upon ELLs’ levels of English morphological awareness. Additionally, the study investigated the relationship between morphological awareness and perceived levels of literacy and oracy proficiency. Multilingual individuals responded to an online survey containing a morphological awareness task and a language history questionnaire. Each language represented in the sample was coded according to its structural features. Subsequently, the relationship between the features and morphological awareness was analyzed. Morphological awareness was impacted by a confluence of all three structural features. Knowledge of languages with higher degrees of morphological synthesis or higher degrees of orthographic opacity was found to predict higher levels of morphological awareness. Additionally, perceived English literacy proficiency explained a larger degree of the variance in English morphological awareness than perceived English oracy proficiency, though both were statistically significant. The findings indicate the acquisition of English may be impacted by familiarity with other languages and by perceptions of English proficienc

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

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

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Black Heterogeneity in Cancer Mortality: US-blacks, Haitians, and Jamaicans

INTRODUCTION: The quantitative intraracial burden of cancer incidence, survival and mortality within black populations in the US is virtually unknown. METHODS: We computed cancer mortality rates of US- and Caribbean-born residents of Florida, specifically focusing on black populations (US, Haiti, Jamaica) and compared them using age-adjusted mortality ratios obtained from Poisson regression models. We compared the mortality of Haitians and Jamaicans residing in Florida to populations in their countries of origin using Globocan. RESULTS: We analyzed 185,113 cancer deaths from 2008–2012, of which 20,312 occurred in black populations. The overall risk of death from cancer was 2.1 (95% CI: 1.97–2.17) and 1.6 (95% CI: 1.55–1.71) times higher for US-born blacks than black Caribbean men and women, respectively (p<0.001). CONCLUSIONS: Race alone is not a determinant of cancer mortality. Among all analyzed races and ethnicities, including Whites and Hispanics, US-born blacks had the highest mortality rates while black Caribbeans had the lowest. The biggest intraracial difference was observed for lung cancer, for which US-blacks had nearly 4 times greater mortality risk than black Caribbeans. Migration from the islands of Haiti and Jamaica to Florida resulted in lower cancer mortality for most cancers including cervical, stomach, and prostate, but increased or stable mortality for two obesity-related cancers, colorectal and endometrial cancers. Mortality results in Florida suggest that US-born blacks have the highest incidence rate of “aggressive” prostate cancer in the world, rather than Caribbean men

Kidney cancer mortality disparities among Hispanics in the US

•Mexican Hispanics and American Indians are at high risk for fatal kidney cancer.•Strong correlation between kidney cancer mortality and smoking/obesity prevalence.•For Hispanics, birthplace impacts cancer patterns, should be included in studies. Kidney cancer incidence is increasing among Hispanics but rate differences by distinct group, such as Cuban, Puerto Rican, and Mexican have not been studied. To fill this knowledge gap, we use mortality data, reflecting fatal kidney cancers, to examine patterns by race-ethnicity, including detailed Hispanic groups, and correlate the mortality rates with each group’s prevalence of known kidney cancer risk factors: smoking, obesity, hypertension, diabetes, and chronic kidney disease. We used individual-level death data for California, Florida, and New York (2008–2018), and population prevalence data from the National Health Interview Surveys (2008–2018). Age-adjusted mortality rates (AAMRs) and regression-derived mortality rate ratios (MRRs) were computed. Pearson correlation analyses assessed the extent to which group-specific risk factor prevalence explained variability in observed AAMRs. US-born Mexican Americans and American Indians had the highest rates and MRRs compared to Whites: 1.44 (95 %CI: 1.35−1.53) and 1.51 (1.38−1.64) for Mexican American men and women, respectively, and 1.54 (95 %CI: 1.25−1.89) and 1.53 (95 %CI: 1.15−2.04) for American Indians. In contrast, non-Mexican Hispanics had lower rates than Whites. Among males, positive correlations between AAMRs and smoking, obesity, and chronic kidney disease prevalence by race-ethnicity were found. Mexican Americans and American Indians are high-risk for fatal kidney cancer. Disparities are only partially attributable to higher smoking and obesity prevalence, and more so among men than women. A shared risk factor profile, as well as possible genetic similarities, may explain their disproportionately higher kidney cancer mortality, but further research is warranted

Lung cancer in never smokers: Distinct population-based patterns by age, sex, and race/ethnicity

Epidemiological patterns for lung cancer among never smokers (LCNS) are largely unknown, even though LCNS cases comprise 15% of lung cancers. Past studies were based on epidemiologic or health system cohorts, and not fully representative of the underlying population. The objective was to analyze rates (and trends) of LCNS by sex, age group, and race and ethnicity based on all-inclusive truly population-based sources. Individual-level data from 2014 to 2018 on smoking status among microscopically-confirmed lung cancer cases from Florida’s cancer registry were combined with population denominators adjusted with NHIS data on smoking prevalence to compute population-based LCNS incidence rates and rate ratios. Incidence rates and proportional mortality were ranked against other cancers. Joinpoint regression analyses examined trends. Proportions of LCNS ranged from 9% among White men to 83% among Chinese women. Overall, LCNS was 13% (IRR 1.13, 95%CI 1.08–1.17) more common among men than women, but variation occurred by age group, with female rates exceeding male in younger ages. Age-adjusted rates per 100,000 were highest among Asian/Pacific Islander (API) men and women (15.3 and 13.5, respectively) and Black populations (14.6, 12.9), intermediate for White (13.2, 11.8) and lowest among the Hispanic population (12.1, 10.6). Among API women, LCNS was the second leading cause of cancer death, surpassed only by breast cancer. LCNS trends were stable over time. LCNS is the 11th most frequently occurring cancer in men and 8th in women. LCNS differences by race/ethnicity are small, within a 15% range of the White population’s rates. Surprisingly, API men and women have the highest LCNS rates and proportional mortality. As smoking prevalence decreases in the US, LCNS cases will inevitably increase, warranting inquiry into risk factors across the lifespan

Cancer mortality among US blacks: Variability between African Americans, Afro-Caribbeans, and Africans

•Aggregating Black populations in the US overlooks important cancer differences.•US Blacks had the highest mortality rates for common and infection-related cancers.•Caribbean Blacks had intermediate rates; African Blacks had the lowest rates.•Prostate cancer rates were higher in West Africans; East Africans had high liver rates.•Research on genetic and environmental cancer risk within Black populations is needed.Aggregation of all Black populations in US cancer mortality profiles masks remarkable heterogeneity by place of birth. Comparing U.S-born African Americans with African and Afro-Caribbean immigrants may highlight specific cancer prevention and control needs and clarify global cancer epidemiology. Such a comparison has yet to be undertaken on a population basis.Using 2012–2017 vital statistics data from California, Florida, Minnesota and New York, age-standardized cancer mortality rates were computed for distinct Black populations. Comparisons were made to the majority White population using mortality rate ratios (MRR) obtained from negative binomial regression.Of the 83,460 cancer deaths analyzed among Blacks, nearly 20 % were immigrants. African males and females had the lowest all-sites-combined cancer mortality rates (121 and 99 per 100,000, respectively), African Americans had the highest (232 and 163), while Afro-Caribbean were in between (140 and 106 respectively). The average Black:White MRR was significant for prostate (2.11), endometrial (2.05), stomach (2.02), multiple myeloma (1.87), premenopausal breast (1.66), liver (1.58) and cervical (1.56) cancers, (P < 0.05).While, in aggregate, Blacks in the US have high cancer mortality rates, race itself is not the primary determinant of these disparities. Black immigrant populations show lower cancer mortality than both African Americans and Whites, especially for cancers where environmental factors feature more predominantly: lung, colorectal and breast. Even for cancers with high mortality among all African-descent groups, this study suggests a complex interplay between genetic and environmental factors. Endometrial cancer was unique; mortality rates were similarly high for all three analyzed Black groups