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Guzman posted an update 7 months, 1 week ago
Background Patients afflicted with pancreatic ductal adenocarcinoma (PDAC) face a dismal prognosis, but headway could be made if physicians could identify the disease earlier. A compelling strategy to broaden the use of surveillance for PDAC is to incorporate molecular biomarkers in combination with clinical analysis and imaging tools. Methods This article summarizes the components involved in accomplishing biomarker validation and an analysis of the requirements of molecular biomarkers for disease surveillance. Results We highlight the significance of consortia for this research and highlight resources and infrastructure of the Early Detection Research Network (EDRN). The EDRN brings together the multifaceted expertise and resources needed for biomarker validation, such as study design, clinical care, biospecimen collection and handling, molecular technologies, and biostatistical analysis, and studies coming out of the EDRN have yielded biomarkers that are moving forward in validation. We close the article with an overview of the current investigational biomarkers, an analysis of their performance relative to the established benchmarks, and an outlook on the current needs in the field. Conclusions The outlook for improving the early detection of PDAC looks promising, and the infrastructure of the EDRN has yielded biomarkers that are currently progressing in validation. Impact The pace of further research should be quickened through the resources and expertise of the EDRN and other consortia.Cancer mortality rates are approximately 8% higher in rural populations and mortality rates are falling more slowly in rural communities, resulting in widening rural-urban health disparities in the United States. The NCI has a long history of supporting health disparities research, including research to understand the health needs, strengths, and opportunities in rural communities. However, the portfolio analysis described in this article underscores the need to significantly accelerate rural cancer control research in partnership with state and local communities. This commentary outlines NCI’s efforts over the last four years to address gaps in rural cancer control research and improve cancer prevention, control, and care delivery in rural populations. Future directions, challenges, and opportunities are also discussed.Background Approximately 85% of the U.S. military active duty population is male and less than 50 years of age, with elevated levels of known risk factors for oropharyngeal squamous cell carcinoma (OPSCC), including smoking, excessive use of alcohol, and greater numbers of sexual partners, and elevated prevalence of human papilloma virus (HPV). Given the recent rise in incidence of OPSCC related to the HPV, the Department of Defense Serum Repository provides an unparalleled resource for longitudinal studies of OPSCC in the military for the identification of early detection biomarkers. Kaempferide solubility dmso Methods We identified 175 patients diagnosed with OPSCC with 175 matched healthy controls and retrieved a total of 978 serum samples drawn at the time of diagnosis, 2 and 4 years prior to diagnosis, and 2 years after diagnosis. Following immunoaffinity depletion, serum samples were analyzed by targeted proteomics assays for multiplexed quantification of a panel of 146 candidate protein biomarkers from the curated literature. Results Using a Random Forest machine learning approach, we derived a 13-protein signature that distinguishes cases versus controls based on longitudinal changes in serum protein concentration. The abundances of each of the 13 proteins remain constant over time in control subjects. The AUC for the derived Random Forest classifier was 0.90. Conclusions This 13-protein classifier is highly promising for detection of OPSCC prior to overt symptoms. Impact Use of longitudinal samples has significant potential to identify biomarkers for detection and risk stratification.Research Ethics Committees (RECs) play a critical gatekeeping role in clinical trials. This role is meant to ensure that only those trials that meet certain ethical thresholds proceed through their gate. Two of these thresholds are that the potential benefits of trials are reasonable in relation to risks and that trials are capable of producing a requisite amount of social value. While one ought not expect perfect execution by RECs of their gatekeeping role, one should expect routine success in it. This article reviews a range of evidence showing that substantial numbers of ethically tainted trials are receiving REC approvals. Many of the trials are early phase trials that evidence shows have benefits that may not be reasonable compared with their risks and many others are later trials that evidence shows may lack sufficient social value. The evidence pertains to such matters as methodologically inadequate preclinical studies incapable of supporting the inferences that REC members must make about the prospects for potential benefit needed to offset the risks in early phase trials and sponsorship bias that can cause improperly designed, conducted, analysed and reported later phase trials. The analysis of the evidence makes clear that REC practices need to be strengthened if they are to adequately fulfil their gatekeeping role. The article also explores options that RECs could use in order to improve their gatekeeping function.The urgent drive for vaccine development in the midst of the current COVID-19 pandemic has prompted public and private organisations to invest heavily in research and development of a COVID-19 vaccine. Organisations globally have affirmed the commitment of fair global access, but the means by which a successful vaccine can be mass produced and equitably distributed remains notably unanswered. Barriers for low-income countries include the inability to afford vaccines as well as inadequate resources to vaccinate, barriers that are exacerbated during a pandemic. Fair distribution of a pandemic vaccine is unlikely without a solid ethical framework for allocation. This piece analyses four allocation paradigms ability to develop or purchase; reciprocity; ability to implement; and distributive justice, and synthesises their ethical considerations to develop an allocation model to fit the COVID-19 pandemic.