Pharmacokinetics of gemcitabine in non-small-cell lung cancer patients: impact of the 79A>C cytidine deaminase polymorphism

To study the impact of the 79A > C polymorphism in the cytidine deaminase (CDA) gene on the pharmacokinetics of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in non-small-cell lung cancer (NSCLC) patients. Patients (n = 20) received gemcitabine 1,125 mg/m(2) as a 30 min i.v. infusion as part of treatment for NSCLC. Plasma samples were collected during 0-6 h after gemcitabine administration. Gemcitabine and dFdU were quantified by high performance liquid chromatography with ultraviolet detection. The CDA 79A > C genotype was determined with PCR and DNA sequencing. Gemcitabine was rapidly cleared from plasma and undetectable after 3 h. The allele frequency of the 79A > C polymorphism was 0.40. Diplotypes were distributed as A/A n = 8, A/C n = 8 ,and C/C n = 4. No significant differences were found between the different CDA genotypes and gemcitabine or dFdU AUC, clearance, or half-life. The 79A > C polymorphism in the CDA gene does not have a major consistent and signficant impact on gemcitabine pharmacokinetics

Agriculture-Industry Interlinkages: Some Theoretical and Methodological Issues in the Indian Context

The inter-relationship between agriculture and industry has been a long debated issue in most of the developing countries. In the Indian context, the issue has acquired interest since the industrial stagnation of the mid 1960s. Over the years the Indian economy has undergone a structural change in its sectoral composition: from a primary agro-based economy during 1970s, the economy has emerged as predominant in the service sector since the 1990s. This structural change and uneven pattern of growth of agriculture, industry and services sector in the post reforms period is likely to appear substantial changes in the production and demand linkages among various sectors, and in turn, could have significant implication for the growth and development process of the economy. This has triggered a renewed interest in studying the inter-relationship between agriculture and industry. The present paper tries to address some of the theoretical and methodological issues in analyzing the agriculture-industry interlinkages in the Indian context

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Extending dialogues on the urban

Across the different vernaculars of the world's urban majorities, there is renewed bewilderment as to what is going on in the cities in which they reside and frequently self-build. Prices are unaffordable and they are either pushed out or strongly lured away from central locations. Work is increasingly temporary, if available at all, and there is often just too much labour involved to keep lives viably in place. Not only do they look for affordability and new opportunities in increasingly distant suburbs and hinterlands, but for orientations, for ways of reading where things are heading, increasingly hedging their bets across multiple locations and affiliations. Coming together to write this piece from our own multiple orientations, we are eight researchers who, over the past year, joined to consider how variegated trajectories of expansion unsettle the current logic of city-making. We have used the notion of extensions as a way of thinking about operating in the middle of things, as both a reflection of and a way of dealing with this unsettling. An unsettling that disrupts clear designations of points of departure and arrival, movement and settlement, centre and periphery, and time and space