A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling

This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m−2 plus doxorubicin 60 mg m−2 (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m−2 plus cisplatin 70 mg m−2 (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with ⩾73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy

Burden of malaria in pregnancy in Jharkhand State, India

<p>Abstract</p> <p>Background</p> <p>Past studies in India included only symptomatic pregnant women and thus may have overestimated the proportion of women with malaria. Given the large population at risk, a cross sectional study was conducted in order to better define the burden of malaria in pregnancy in Jharkhand, a malaria-endemic state in central-east India.</p> <p>Methods</p> <p>Cross-sectional surveys at antenatal clinics and delivery units were performed over a 12-month period at two district hospitals in urban and semi-urban areas, and a rural mission hospital. Malaria was diagnosed by Giemsa-stained blood smear and/or rapid diagnostic test using peripheral or placental blood.</p> <p>Results</p> <p>2,386 pregnant women were enrolled at the antenatal clinics and 718 at the delivery units. 1.8% (43/2382) of the antenatal clinic cohort had a positive diagnostic test for malaria (53.5% <it>Plasmodium falciparum</it>, 37.2% <it>Plasmodium vivax</it>, and 9.3% mixed infections). Peripheral parasitaemia was more common in pregnant women attending antenatal clinics in rural sites (adjusted relative risk [aRR] 4.31, 95%CI 1.84-10.11) and in those who were younger than 20 years (aRR 2.68, 95%CI 1.03-6.98). Among delivery unit participants, 1.7% (12/717) had peripheral parasitaemia and 2.4% (17/712) had placental parasitaemia. Women attending delivery units were more likely to be parasitaemic if they were in their first or second pregnancy (aRR 3.17, 95%CI 1.32-7.61), had fever in the last week (aRR 5.34, 95%CI 2.89-9.90), or had rural residence (aRR 3.10, 95%CI 1.66-5.79). Malaria control measures including indoor residual spraying (IRS) and untreated bed nets were common, whereas insecticide-treated bed nets (ITN) and malaria chemoprophylaxis were rarely used.</p> <p>Conclusion</p> <p>The prevalence of malaria among pregnant women was relatively low. However, given the large at-risk population in this malaria-endemic region of India, there is a need to enhance ITN availability and use for prevention of malaria in pregnancy, and to improve case management of symptomatic pregnant women.</p

The crucial role of complementarity, transparency and adaptability for designing energy policies for sustainable development

The UN Sustainable Development Goals (SDGs) and the Paris Agreement have ushered in a new era of policymaking to deliver on the formulated goals. Energy policies are key to ensuring universal access to affordable, reliable, sustainable, and modern energy (SDG7). Yet they can also have considerable impact on other goals. To successfully achieve multiple goals concurrently, policies need to balance different objectives and manage their interactions. Refining previously contemplated design principles, we identify three key principles - complementary, transparency and adaptability - as highly pertinent for multiple-objective energy policies based on a synthesis of seventeen coordinated policy case studies. First, policies should entail complementary measures and design provisions that specifically target non-energy objectives (complementarity). Second, policy impacts should be tracked comprehensively in both energy and non-energy domains to uncover diminishing returns and facilitate policy learning (transparency). Third, policies should be capable of adapting to changing objectives over time (adaptability). These principles are rarely considered in current policies, implying the need to mainstream them into the next generation of policymaking by pointing to best practices and new tools

The crucial role of complementarity, transparency and adaptability for designing energy policies for sustainable development

The UN Sustainable Development Goals (SDGs) and the Paris Agreement have ushered in a new era of policymaking to deliver on the formulated goals. Energy policies are key to ensuring universal access to affordable, reliable, sustainable, and modern energy (SDG7). Yet they can also have considerable impact on other goals. To successfully achieve multiple goals concurrently, policies need to balance different objectives and manage their interactions. Refining previously contemplated design principles, we identify three key principles - complementary, transparency and adaptability - as highly pertinent for multiple-objective energy policies based on a synthesis of seventeen coordinated policy case studies. First, policies should entail complementary measures and design provisions that specifically target non-energy objectives (complementarity). Second, policy impacts should be tracked comprehensively in both energy and non-energy domains to uncover diminishing returns and facilitate policy learning (transparency). Third, policies should be capable of adapting to changing objectives over time (adaptability). These principles are rarely considered in current policies, implying the need to mainstream them into the next generation of policymaking by pointing to best practices and new tools