TBCRC 002: A phase II, randomized, open-label trial of preoperative letrozole with or without bevacizumab in postmenopausal women with newly diagnosed stage 2/3 hormone receptor-positive and HER2-negative breast cancer

Background: In preclinical studies, the expression of vascular endothelial growth factor (VEGF) in hormone receptor-positive breast cancer is associated with estrogen-independent tumor growth and resistance to endocrine therapies. This study investigated whether the addition of bevacizumab, a monoclonal antibody against VEGF, to letrozole enhanced the antitumor activity of the letrozole in the preoperative setting. Methods: Postmenopausal women with newly diagnosed stage 2 or 3 estrogen and/or progesterone receptor-positive, HER2-negative breast cancer were randomly assigned (2:1) between letrozole 2.5 mg PO daily plus bevacizumab 15 mg/kg IV every 3 weeks (Let/Bev) and letrozole 2.5 mg PO daily (Let) for 24 weeks prior to definitive surgery. Primary objective was within-arm pathologic complete remission (pCR) rate. Secondary objectives were safety, objective response, and downstaging rate. Results: Seventy-five patients were randomized (Let/Bev n = 50, Let n = 25). Of the 45 patients evaluable for pathological response in the Let/Bev arm, 5 (11%; 95% CI, 3.7-24.1%) achieved pCR and 4 (9%; 95% CI, 2.5-21.2%) had microscopic residual disease; no pCRs or microscopic residual disease was seen in the Let arm (0%; 95% CI, 0-14.2%). The rates of downstaging were 44.4% (95% CI, 29.6-60.0%) and 37.5% (95% CI, 18.8-59.4%) in the Let/Bev and Let arms, respectively. Adverse events typically associated with letrozole (hot flashes, arthralgias, fatigue, myalgias) occurred in similar frequencies in the two arms. Hypertension, headache, and proteinuria were seen exclusively in the Let/Bev arm. The rates of grade 3 and 4 adverse events and discontinuation due to adverse events were 18% vs 8% and 16% vs none in the Let/Bev and Let arms, respectively. A small RNA-based classifier predictive of response to preoperative Let/Bev was developed and confirmed on an independent cohort. Conclusion: In the preoperative setting, the addition of bevacizumab to letrozole was associated with a pCR rate of 11%; no pCR was seen with letrozole alone. There was additive toxicity with the incorporation of bevacizumab. Responses to Let/Bev can be predicted from the levels of 5 small RNAs in a pretreatment biopsy. Trial registration: This trial is registered with ClinicalTrials.gov (Identifier: NCT00161291), first posted on September 12, 2005, and is completed

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Oxidation of ethambutol by sodium N-chlorobenzene sulfonamide. Kinetic and mechanistic studies

The kinetics of oxidation of ethambutol (EMB) by chloramine-B (sodium N-chlorobenzene sulfonamide, CAB) has been investigated in alkaline buffer solution of pH 9.2 at 303 K. The reaction follows kinetics with first order in both CAB and EMB and fractional order in OH-. The dependence of the reaction rate on ionic stength, reaction product dielectric constant and D2O has been studied. Activation parameters are evaluated from the kinetic data at different temperatures. The reaction mechanism involving an electrophilic attack by RNHCI (derived from CAB) at the alcoholic group in EMB, forming a reaction intermediate (hypochlorite ester) which on the subsequent stepwise oxidation, hydrolysis and decomposition giving products is proposed. The rate equation is derived to account for the proposed mechanism and the observed kinetic data

Mechanism of oxidation of diazepam by 1-chlorobenzotriazole in acidic medium. A kinetic approach

The kinetics of oxidation of diazepam (DZ) by 1-chlorobenzotriazole (CBT) has been studied in HClO4 medium in the temperature range of 293 - 323 K. The reactions followed a first order dependence on CBT, fractional order each in H+ and DZ. Activation parameters were evaluated. A negative entropy of activation indicated the involvement of a rigid complex in the activated state. Variation of reaction rate with dielectric constant and the ionic strength are consistent with a mechanism involving the decomposition of a dipole in the rate-determining step. Rate equation is derived to account for the observed kinetic data and the proposed reaction mechanism. © Akadémiai Kiadó, All rights reserved

Characterisation of rice fallow period for increasing cropping intensity in Khordha district of Odisha

The possibility of increasing the cropping intensity in Khordha district was assessed by block-wise characterisation of rainfall, soil texture, available water holding capacity of soil and district level temperature during the rice fallow period as well as deciding the appropriate sowing window for both kharif and rabi crops. More than 50% chances of occurrence of wet weeks at the beginning of the kharif season (20-22 SMW) indicated that the summer ploughing and initial seed bed preparation could be taken up during the period followed by sowing of rice from 23 SMW. The 42-43 SMW with greater than 30% initial probability of wet week at 20 mm threshold limit. Considering the length of growing period (LGP) available, the adjustment of rice variety duration by 10-15 days in medium land and advancement of pulse sowing almost by 15 days before harvest of the rice crop (Pira crop) in low land was registered as the best su  suitable option for rabi pulses to ensure better utilisation of rice fallow. In addition to these, harvesting surplus water during kharif and storing in farm ponds for judicious utilisation during rabi season further enhanced the possibility of utilisation of rice fallow and increasing the cropping intensity. In the event of delayed monsoon the rice duration has to be adjusted accordingly not to sacrifice the designated suitable period for rabi pulses

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Not AvailableThis document is a comprehensive record of the Academy’s activities and accomplishments during 2005-2006. The Academy has completed 29 years of dedicated service to the nation. During these years the Academy has made significant contribution in manpower development in National Agricultural Research System (NARS) of India, and also other developing countries in South Asia and Africa. The Academy has also taken up research and consultancy projects and services, depending upon the specific needs of the clientele organizations. A significant achievement of the year was that the Academy has been identified as the major center for Learning and Capacity Building (L & CB) activities. At the behest of the Council, the Academy through a series of policy dialogues, developed guidelines for material transfer in inter institutional collaborative projects under the overall framework of BD Act 2002. During this period, 44 programmes were held, and a total of 969 scientists, teachers, administrators and finance officers were trained. Six off-campus programmes, one international programme for administrative and finance officers of Nepal Agricultural Research Council and five ICAR sponsored Summer Schools were the other highlights of the year. This year, many of our faculty and staff members participated and presented papers in various workshops and seminars at various institutes in the country. Research projects were prioritized with reference to the current needs. Broad outline for the protection of various forms of intellectual property (IP) in the ICAR system at the level of individual scientists, institutes and headquarters was prepared, which may serve as a background material for the Special Task Force constituted by ICAR for developing guidelines for IP protection. The efforts brought recognition to the Academy in different forms. Dr T. Balaguru, Head, ARSMP Division received “The World Medal of Freedom” for significant accomplishments in the field of Agricultural Research Management. Dr Jagannadham Challa was awarded Fellow of the National Academy of Veterinary Sciences for his contribution as a Veterinarian. The ICAR Inter-institutional Tournament (Southern Zone) was hosted by the Academy, and NAARM won several prizes in various events. The Academy also bagged several trophies at the Annual Rose Show organized by Hyderabad and Secunderabad Rose Societies.Not Availabl

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Not AvailableApplication of ICT in Development of Agriculture Water Management PortalNot Availabl

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Not AvailableIt gives me immense pleasure in presenting this document as a comprehensive record of the Academy’s activities and accomplishments during 2006-2007. This report details the progress and achievements of the Academy in its mandated areas of training, research, collaboration, consultancy and policy support. A significant achievement of the year was that the Academy was recognized as the focal point for initiating activities under National Agricultural Innovation Project (NAIP) and working as an extended arm of its PIU. A Help Desk was created at the Academy for facilitating the concept note and proposal writing under the key components of NAIP. National Workshop on Training Needs Assessment for Learning and Capacity Building (L&CB) (under NAIP), NAIP Awareness Building Workshop, Induction Workshop-cum-Training on Development of Research Proposals in Public–Private Consortia mode (under NAIP), Sensitization Workshop on Information and Communication Technology (ICT) Projects under (NAIP) were organized. During this period, 62 programmes were held, and a total of 1547 scientists, teachers, administrators and finance officers were trained. Thirteen off-campus programmes, one international programme on Research Extension Linkages for Effective Delivery of Agricultural Technologies in South Asian Association for Regional Cooperation (SAARC) Countries (in collaboration with SAARC Agricultural Information Centre, Dhaka, Bangladesh), five ICAR sponsored Summer Schools and two Winter Schools, were the other highlights of the year. This year, one of our colleagues was deputed abroad for training and many of our faculty and staff members participated and presented papers in various workshops and seminars at various institutes in the country and abroad. The research papers, technical bulletins and other materials published by the scientists of the Academy are appreciable. Research projects were prioritized with reference to the current needs. Application of GRAM GIS in micro-level planning and development for sustainable agriculture was streamlined, a new methodology is being developed and standardized for qualitative rating of colleges under the Agricultural Universities, recommendations were drawn on various aspects of higher education in agriculture to face the challenges of GATS. The ICAR Inter-institutional Tournament (Southern Zone) was hosted by the Academy, and NAARM won several prizes in various events. The Overall Team Championship was awarded to NAARM. The Academy also bagged several trophies at the Annual Rose Show organized by Hyderabad and Secunderabad Rose SocietiesNot Availabl