Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

Determinants of fertility in rural Ethiopia: the case of Butajira Demographic Surveillance System (DSS)

<p>Abstract</p> <p>Background</p> <p>Fertility is high in rural Ethiopia. Women in the reproductive age group differed in various characteristics including access to food and encounter to drought which requisite the assessment of determinants of fertility.</p> <p>Methods</p> <p>Reproductive age women were recruited from a DSS, the Butajira DSS database. A DHS maternity history questionnaire was administered on 9996 participants. Data quality was assured besides ethical clearance. Poisson regression crude and adjusted Incidence Rate Ratio with 95 Confidence Interval were used to identify determinants of fertility.</p> <p>Results</p> <p>Delayed marriage, higher education, smaller family, absence of child death experience and living in food-secured households were associated with small number of children. Fertility was significantly higher among women with no child sex preference. However, migration status of women was not statistically significant.</p> <p>Conclusions</p> <p>Policy makers should focus on hoisting women secondary school enrollment and age at first marriage. The community should also be made aware on the negative impact of fertility on household economy, environmental degradation and the country's socio-economic development at large.</p

Determinants of survival in adult HIV patients on antiretroviral therapy in Oromiyaa, Ethiopia

Background: The antiretroviral treatment (ART) scale-up service has been a recent development in Ethiopia, but its impact on mortality has not been well investigated. The aim of this study was to assess the early survival outcome of the scale-up service by utilizing routine hospital data. Methods: All adult HIV/AIDS patients who started on antiretroviral treatment in Shashemene and Assela hospitals from January 1, 2006 to May 31, 2006 were included and followed up for 2 years. Data were extracted from standard patient medical registrations. Kaplan-Meier curves were used to estimate survival probability and the Cox proportional hazard model was applied to determine predictors of mortality. Two alterative assumptions (real case and worst case) were made in determining predictors of mortality. Results: The median age of patients was 33 years and 57% were female. Eighty-five percent had CD4 &lt;200 cells/mu L with a median CD4 count of 103 cells/mu L. The median survival time was 104.4 weeks. A total of 28 (10.3%) deaths were observed during the 2-year period and 48 patients (18%) were lost to follow up. The majority of deaths occurred in the first 4 months of treatment. In multivariate analysis, 2-year survival was significantly associated with the clinical stage of the disease, baseline hemoglobin, and cotrimoxazole prophylaxis therapy (CPT) at or before ART initiation in both assumptions. The median CD4 count and body weight showed a marked improvement during the first 6 months of treatment, followed by stagnation thereafter. Conclusion: The study has shown an overall low mortality but a high loss to follow-up rate of the cohort. Advanced clinical stage, anemia, low body weight, and lack of CPT initiation were independent predictors of mortality - but not gender. CPT initiation should be encouraged in routine HIV care services, and patient retention mechanisms have to be strengthened. Stagnation in immunological and weight recovery after the first 6 months should be further investigated. The utilization of routine data should be encouraged in order to facilitate appropriate decision making

An overview of burst, buckling, durability and corrosion analysis of lightweight FRP composite pipes and their applicability

© 2019 Elsevier Ltd. All rights reserved.The main aim of this review article was to address the performance of filament wound fibre reinforced polymer (FRP) composite pipes and their critical properties, such as burst, buckling, durability and corrosion. The importance of process parameters concerning merits and demerits of the manufacturing methods was discussed for the better-quality performance. Burst analysis revealed that the winding angle of ±55° was observed to be optimum with minimum failure mechanisms, such as matrix cracking, whitening, leakage and fracture. The reduction of buckling effect was reported in case of lower hoop stress value in the hoop to axial stress ratio against axial, compression and torsion. A significant improvement in energy absorption was observed in the hybrid composite pipes with the effect of thermal treatment. However, the varying winding angle in FRP pipe fabrication was reported as an influencing factor affecting all the aforementioned properties. Almost 90% of the reviewed studies was done using E-glass/epoxy materials for the composite pipe production. By overcoming associated limitations, such as replacing synthetic materials, designing new material combinations and cost-benefit analysis, the production cost of the lightweight FRP composite pipes can be decreased for the real-time applications.Peer reviewe

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Interorganisational conflict between national and provincial sport organisations within China's elite sport system: Perspectives from national organisations

© 2018 Sport Management Association of Australia and New Zealand. In this article, the authors examine interorganisational conflict between provincial and national sport organisations in China. The authors theoretically ground the research in work related to interorganisational relationships and interorganisational conflict. The three case studies are artistic gymnastics, swimming, and cycling, and the authors conducted interviews with 11 staff from the relevant national-level sport organisations. Secondary data was sourced from official publications, websites, and influential domestic media. The key finding is that, whilst famed for its top-down bureaucratic system, there is considerable interorganisational conflict within the Chinese sport system. The extent and characteristics of the national-provincial conflict vary between sports. But there is also some consistency regarding the causes of the conflict and the measures adopted to mitigate the tension. Interorganisational conflict provides a useful heuristic for articulating and understanding the interorganisational relationships within the Chinese elite sport system and hence advances elite sport management research