Modelling the impact and cost-effectiveness of the HIV intervention programme amongst commercial sex workers in Ahmedabad, Gujarat, India.

BACKGROUND: Ahmedabad is an industrial city in Gujarat, India. In 2003, the HIV prevalence among commercial sex workers (CSWs) in Ahmedabad reached 13.0%. In response, the Jyoti Sangh HIV prevention programme for CSWs was initiated, which involves outreach, peer education, condom distribution, and free STD clinics. Two surveys were performed among CSWs in 1999 and 2003. This study estimates the cost-effectiveness of the Jyoti Sangh HIV prevention programme. METHODS: A dynamic mathematical model was used with survey and intervention-specific data from Ahmedabad to estimate the HIV impact of the Jyoti Sangh project for the 51 months between the two CSW surveys. Uncertainty analysis was used to obtain different model fits to the HIV/STI epidemiological data, producing a range for the HIV impact of the project. Financial and economic costs of the intervention were estimated from the providers perspective for the same time period. The cost per HIV-infection averted was estimated. RESULTS: Over 51 months, projections suggest that the intervention averted 624 and 5,131 HIV cases among the CSWs and their clients, respectively. This equates to a 54% and 51% decrease in the HIV infections that would have occurred among the CSWs and clients without the intervention. In the absence of intervention, the model predicts that the HIV prevalence amongst the CSWs in 2003 would have been 26%, almost twice that with the intervention. Cost per HIV infection averted, excluding and including peer educator economic costs, was USD 59 and USD 98 respectively. CONCLUSION: This study demonstrated that targeted CSW interventions in India can be cost-effective, and highlights the importance of replicating this effort in other similar settings.Published versio

Isolation of a euryhaline microalgal strain, Tetraselmis sp CTP4, as a robust feedstock for biodiesel production

Bioprospecting for novel microalgal strains is key to improving the feasibility of microalgae-derived biodiesel production. Tetraselmis sp. CTP4 (Chlorophyta, Chlorodendrophyceae) was isolated using fluorescence activated cell sorting (FACS) in order to screen novel lipid-rich microalgae. CTP4 is a robust, euryhaline strain able to grow in seawater growth medium as well as in non-sterile urban wastewater. Because of its large cell size (9-22 mu m), CTP4 settles down after a six-hour sedimentation step. This leads to a medium removal efficiency of 80%, allowing a significant decrease of biomass dewatering costs. Using a two-stage system, a 3-fold increase in lipid content (up to 33% of DW) and a 2-fold enhancement in lipid productivity (up to 52.1 mg L-1 d(-1)) were observed upon exposure to nutrient depletion for 7 days. The biodiesel synthesized from the lipids of CTP4 contained high levels of oleic acid (25.67% of total fatty acids content) and minor amounts of polyunsaturated fatty acids with >= 4 double bonds (< 1%). As a result, this biofuel complies with most of the European (EN14214) and American (ASTM D6751) specifications, which commonly used microalgal feedstocks are usually unable to meet. In conclusion, Tetraselmis sp. CTP4 displays promising features as feedstock with lower downstream processing costs for biomass dewatering and biodiesel refining

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted approach has shifted from single-agent BRAF inhibition to combination therapy with a BRAF and a MEK inhibitor. Concurrently, immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and, now, the programmed cell-death protein 1 (PD-1) immune checkpoints. These changes in the treatment landscape have dramatically improved patient outcomes, with the median overall survival of patients with advanced-stage melanoma increasing from approximately 9 months before 2011 to at least 2 years - and probably longer for those with BRAF-V600-mutant disease. Herein, we review the clinical trial data that established the standard-of-care treatment approaches for advanced-stage melanoma. Mechanisms of resistance and biomarkers of response to BRAF-targeted treatments and immunotherapies are discussed, and the contrasting clinical benefits and limitations of these therapies are explored. We summarize the state of the field and outline a rational approach to frontline-treatment selection for each individual patient with BRAF-mutant melanoma

Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475) in the management of melanoma and other tumor types

Tara C Gangadhar,1 April KS Salama2 1Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA; 2Division of Medical Oncology, Department of Medicine, Duke&nbsp;University Medical Center, Durham, NC, USA Abstract: Preclinical work has led to an increased understanding of the immunomodulatory mechanisms involved in the regulation of the antitumor response in a variety of tumor types. PD-1 (programmed death 1) appears to be a key checkpoint involved in immune suppression in the tumor microenvironment, even in diseases not previously thought to be sensitive to immune manipulation. More recently, the subsequent clinical development of PD-1-based therapy has resulted in a major breakthrough in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data. Encouraging results have also been seen in other malignancies, and PD-1-targeted therapies are likely to markedly change the treatment landscape. Future work will center on rationally designed combination strategies in order to potentiate the antitumor immune response and overcome mechanisms of resistance. Keywords: PD-1, cancer, pembrolizumab, nivolumab, immunotherapy, antitumor activity&nbsp