14 research outputs found

    Whose Land Is It Anyway? Navigating Ghana\u27s Complex Land System

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    This Article dives into Ghana’s complex land-registration system, which is influenced by both statutory and customary law. Section II discusses Ghana’s statutory land laws. Section III provides a brief overview of Ghana’s customary land laws. Section IV discusses several obstacles within Ghana’s land-administration system

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

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    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

    Incidence of subsequent pancreatic adenocarcinoma in patients with a history of nonpancreatic primary cancers

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    BACKGROUND: Several environmental risk factors are known to predispose individuals to pancreatic cancer, and up to 15% of pancreatic cancers have an inherited component. Understanding metachronous cancer associations can modify pancreas cancer risk. The objective of this study was to investigate the association of nonpancreatic cancers with subsequent pancreatic adenocarcinoma. METHODS: The authors used data from the US Surveillance, Epidemiology, and End Results (SEER) registries to identify 1,618,834 individuals who had a primary malignancy and subsequent pancreatic adenocarcinoma (n=4013). Standardized incidence ratios were calculated as an approximation of relative risk (RR) for the occurrence of pancreatic adenocarcinoma after another primary malignancy. RESULTS: Among patients who were diagnosed with a first primary malignancy at ages 20 to 49 years, the risk of subsequent pancreatic adenocarcinoma was increased among patients who had cancers of the ascending colon (relative risk [RR], 4.62; 95% confidence interval [CI], 1.86-9.52), hepatic flexure (RR, 5.42; 95% CI, 1.12-15.84), biliary system (RR, 13.14; 95% CI, 4.27-30.66), breast (RR, 1.32; 95% CI, 1.09-1.59), uterine cervix (RR, 1.61; 95% CI, 1.02-2.41), testes (RR, 2.78; 95% CI, 1.83-4.05), and hematopoietic system (RR, 1.83; 95% CI, 1.28-2.53). Among patients who had a first malignancy at ages 50 to 64 years, the risk was increased after cancers of the stomach (RR, 1.88; 95% CI, 1.13-2.93), hepatic flexure (RR, 2.25; 95% CI, 1.08-4.13), lung and bronchus (RR, 1.46; 95% CI, 1.16-1.82), pharynx (RR, 2.26; 95% CI, 1.13-4.04), and bladder (RR, 1.24; 95% CI, 1.03-1.48). Among patients who had a primary cancer after age 65 years, the risk was increased after cancers of the stomach (RR, 1.79; 95% CI, 1.23-2.53), hepatic flexure (RR, 1.76; 95% CI, 1.06-2.75), biliary system (RR, 2.35; 95% CI, 1.17-4.20), and uterus (RR, 1.23; 95% CI, 1.03-1.47). CONCLUSIONS: The results from the current population-based data set suggested that pancreatic adenocarcinoma is associated with certain primary cancers. Genetic predisposition and common environmental and behavioral risk factors all may contribute to this observation. Specific tumor associations will guide future risk-stratification efforts. Cancer 2012; 118: 1244-51. (C) 2011 American Cancer Society

    The Relationship between Physical Activity, Physical Fitness, Cognition, and Academic Outcomes in School-Aged Latino Children: A Scoping Review.

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    This scoping review provides an overview of the relationship between physical activity, physical fitness, cognition, and academic outcomes in Latino school-aged children and identifies areas for future research. A primary search was conducted in PubMed, PsycINFO, Web of Science, and ERIC for original-research articles meeting the inclusion criteria; the search results were uploaded into PICO Portal and assessed by two independent reviewers. Of the 488 initial search results, 50 articles were eligible for full-text review, and 38 were included in this review. Most studies were cross-sectional, conducted in the United States or Chile, and included children 5-18 years old. Overall, the majority of articles reported positive associations between physical activity or physical fitness and cognitive outcomes (n = 11/12; 91.7%), and physical activity or physical fitness and academic outcomes (n = 22/28; 78.6%). In sum, this review provided consistent evidence for higher amounts of physical activity and greater physical fitness to be associated with various positive cognitive and academic outcomes in a school-aged Latino population. This scoping review also elucidated a substantial gap in the research regarding study design, with a discernible lack of interventional efforts. Future studies should test physical activity interventional strategies to optimize cognitive and academic outcomes in school-aged Latino populations

    Cigarette Management System: An operating procedures guide to obtaining and managing investigational tobacco products for regulatory science research

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    Investigational tobacco products, specifically variable nicotine content research cigarettes (SPECTRUM), are available through the National Institute of Drug Abuse Drug Supply Program. Randomized controlled trials using research cigarettes are intended to support tobacco regulatory science research. The current paper provides an in-depth look into managing research cigarettes for two multi-site clinical trials and the design of a computer-based Cigarette Management System (CMS). The paper provides guidance intended for any investigator using similar products on the operating procedures under Good Clinical Practice standards and describes features of the CMS. The CMS and procedures described have been field tested for the past three years and have dispensed over 160,000 cigarette packs to participants. The CMS can accommodate a range of practical issues with real-world study implementation making it a robust application that is scalable to any study

    Implementation of substance use screening in rural federally-qualified health center clinics identified high rates of unhealthy alcohol and cannabis use among adult primary care patients

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    Abstract Background Screening for substance use in rural primary care clinics faces unique challenges due to limited resources, high patient volumes, and multiple demands on providers. To explore the potential for electronic health record (EHR)-integrated screening in this context, we conducted an implementation feasibility study with a rural federally-qualified health center (FQHC) in Maine. This was an ancillary study to a NIDA Clinical Trials Network study of screening in urban primary care clinics (CTN-0062). Methods Researchers worked with stakeholders from three FQHC clinics to define and implement their optimal screening approach. Clinics used the Tobacco, Alcohol, Prescription Medication, and Other Substance (TAPS) Tool, completed on tablet computers in the waiting room, and results were immediately recorded in the EHR. Adult patients presenting for annual preventive care visits, but not those with other visit types, were eligible for screening. Data were analyzed for the first 12 months following implementation at each clinic to assess screening rates and prevalence of reported unhealthy substance use, and documentation of counseling using an EHR-integrated clinical decision support tool, for patients screening positive for moderate-high risk alcohol or drug use. Results Screening was completed by 3749 patients, representing 93.4% of those with screening-eligible annual preventive care visits, and 18.5% of adult patients presenting for any type of primary care visit. Screening was self-administered in 92.9% of cases. The prevalence of moderate-high risk substance use detected on screening was 14.6% for tobacco, 30.4% for alcohol, 10.8% for cannabis, 0.3% for illicit drugs, and 0.6% for non-medical use of prescription drugs. Brief substance use counseling was documented for 17.4% of patients with any moderate-high risk alcohol or drug use. Conclusions Self-administered EHR-integrated screening was feasible to implement, and detected substantial alcohol, cannabis, and tobacco use in rural FQHC clinics. Counseling was documented for a minority of patients with moderate-high risk use, possibly indicating a need for better support of primary care providers in addressing substance use. There is potential to broaden the reach of screening by offering it at routine medical visits rather than restricting to annual preventive care visits, within these and other rural primary care clinics
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