B-18 and B-27 demonstrate that preoperative therapy is equivalent to adjuvant therapy. B-27 also showed that the addition of preoperative taxanes to AC improves response.

Declines in physical activity that accompany an admission to an intensive care unit (ICU) represent a significant stress to the body. Decreases in physical activity have been demonstrated to result in losses in functional capacity of the musculoskeletal and cardiovascular systems. These two systems are central to achieving and maintaining functional independence, which is a prerequisite for discharge from a healthcare facility, as is independent functioning of the individual in the community setting. Whereas a decrease in physical activity will result in an attenuation in the functioning of the cardiovascular and musculoskeletal systems, increases in physical activity can stimulate gains in their functional capacity. The concept of improving the functional capacity of the body to withstand anticipated musculoskeletal stressors has had limited application to the effects of inactivity associated with an ICU admission. By increasing an individual's functional capacity through increased physical activity prior to an ICU admission, it seems reasonable that the patient would retain a higher level of functional capacity over their entire ICU admission. The process of enhancing functional capacity of the individual to enable them to withstand the stressor of inactivity associated with an admission to ICU is termed prehabilitation. A generic program of prehabilitation includes warm-up, aerobic, strength, flexibility, and functional task components. The initial level of prehabilitation training and the progression of the training will be different for each individual based upon their initial functional capacity and the degree to which they individually respond to increases in physical activity. Declines in physical activity among ICU patients represents a significant health risk that may be reduced through introducing prehabilitation interventions.

Nucleoside analogs are important components of treatment regimens for various malignancies. Nucleosidespecific membrane transporters mediate plasma membrane permeation of physiologic nucleosides and most nucleoside analogs, for which the initial event is cellular conversion of nucleosides to active agents. Understanding of the roles of nucleoside transporters in nucleoside drug toxicity and resistance will provide opportunities for potentiating anticancer efficacy and avoiding resistance. Because transportability is a possible determinant of toxicity and resistance of many nucleoside analogs, nucleoside transporter abundance might be a prognostic marker to assess drug resistance. Elucidation of the structural determinants of nucleoside analogs for interaction with transporter proteins as well as the structural features of transporter proteins required for permeant interaction and translocation will lead to "transportability guidelines" for the rational design and therapeutic application of nucleoside analogs as anticancer drugs. It should eventually be possible to develop clinical assays that predict sensitivity and/or resistance to nucleoside anticancer drugs and thus to identify those patient populations that will most likely benefit from optimal nucleoside analog treatments. This review discusses recent results from structure/function studies of human nucleoside transporters, the role of nucleoside transport processes in the cytotoxicity and resistance of several anticancer nucleoside analogs and strategies to improve the nucleoside transporter-related anticancer effects of nucleoside analogs.

Summary Background Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer. Methods NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1–3 breast cancer. After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661). The primary endpoint was disease-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00009945. Findings Median follow-up was 90·7 months (IQR 82·7–100·0) and 3311 patients had data for this period. Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78–1·07; p=0·27). Moreover, no differences were recorded for overall survival (0·84, 0·67–1·05; p=0·13), recurrence-free interval (0·83, 0·67–1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55–1·07; p=0·12). Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55–1·00; p=0·047). Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57–0·99; p=0·045), bone metastasis-free interval (0·62, 0·40–0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43–0·91; p=0·014), but not for overall survival (0·80, 0·61–1·04, p=0·094). Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group. Grade 3 or higher liver dysfunction was noted in 23 of 1612 patients in the clodronate group and 12 of 1623 patients in the placebo group; grade 3–4 diarrhoea was noted in 28 patients in the clodronate group and in ten in the placebo group. There was one possible case of osteonecrosis of the jaw in the clodronate group. Interpretation Findings of NSABP B-34 suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. A meta-analysis of adjuvant bisphosphonate trials is suggested before recommendations for use in non-osteoporotic postmenopausal women with primary breast cancer are made.

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Pancreatic malignancies can be subdivided into endocrine and non-endocrine processes. Of the non-endocrine tumours, ductal carcinoma is the most common, and the ductal carcinomas can be further subdivided into adenocarcinomas and squamous cell carcinomas. The adenocarcinomas constitute most of the non-endocrine pancreatic malignancies, and the treatment options for these, although limited in efficacy, are relatively well established. The squamous cell carcinoma pathology is a rare entity, and few reports of it are found in the literature. As a result, treatment options for squamous cell carcinoma of the pancreas are poorly understood. Here, we report the presentation of a 48-year-old woman with metastatic squamous cell carcinoma of the pancreas. The subsequent investigations, treatment, and outcome are described.

A moderate resolution spectroscopic survey of Fleming's sample of 54 X-ray selected M dwarfs with photometric distances less than 25 pc is presented. Radial and rotation velocities have been measured by fits to the H-alpha profiles. Radial velocities have been measured by cross correlation. Artificial broadening of an observed spectrum has produced a relationship between H-alpha FWHM and rotation speed, which we use to infer rotation speeds for the entire sample by measurement of the H-alpha emission line. We find 3 ultra-fast rotators (UFRs, vsini > 100km/s), and 8 stars with 30 < vsini < 100 km/s. The UFRs have variable emission. Cross-correlation velocities measured for ultra-fast rotators (UFRs) are shown to depend on rotation speed and the filtering used. The radial velocity dispersion of the sample is 17 km/s. A new double emission line spectroscopic binary with a period of 3.55 days has been discovered, and another known one is in the sample. Three other objects are suspected spectroscopic binaries, and at least six are visual doubles. The only star in the sample observed to have significant lithium is a known TW Hya Association member, TWA 8A. These results show that there are a number of young (< 10^8 yr) and very young (< 10^7 yr) low mass stars in the immediate solar neighbourhood. The H-alpha activity strength does not depend on rotation speed. Our fast rotators are less luminous than similarly fast rotators in the Pleiades. They are either younger than the Pleiades, or gained angular momentum in a different way.Comment: 38 pages incl. 14 figures and 4 tables, plus 12 pages of table for electronic journal only; LaTeX, aastex.cls. Accepted 07/18/02 for publication in The Astronomical Journa