Objectives To assess heat related mortalities in relation to climate within Europe. Design Observational population study. Setting North Finland, south Finland, Baden-Württemberg, Netherlands, London, north Italy, and Athens. Subjects People aged 65-74. Main outcome measures Mortalities at temperatures above, below, and within each region's temperature band of minimum mortality. Results Mortality was lowest at 14.3-17.3°C in north Finland but at 22.7-25.7°C in Athens. Overall the 3°C minimum mortality temperature bands were significantly higher in regions with higher than lower mean summer temperatures (P = 0.027). This was not due to regional differences in wind speeds, humidity, or rain. As a result, regions with hot summers did not have significantly higher annual heat related mortality per million population than cold regions at temperatures above these bands. Mean annual heat related mortalities were 304 (95% confidence interval 126 to 482) in North Finland, 445 (59 to 831) in Athens, and 40 (13 to 68) in London. Cold related mortalities were 2457 (1130 to 3786), 2533 (965 to 4101), and 3129 (2319 to 3939) respectively. Conclusions Populations in Europe have adjusted successfully to mean summer temperatures ranging from 13.5°C to 24.1°C, and can be expected to adjust to global warming predicted for the next half century with little sustained increase in heat related mortality. Active measures to accelerate adjustment to hot weather could minimise temporary rises in heat related mortality, and measures to maintain protection against cold in winter could permit substantial reductions in overall mortality as temperatures rise.

The clinical success of small-molecule vascular disrupting agents (VDAs) depends on their combination with conventional therapies. Scheduling and sequencing remain key issues in the design of VDA -chemotherapy combination treatments. This study examined the antitumour activity of ZD6126, a microtubule destabilising VDA, in combination with paclitaxel (PTX), a microtubule-stabilising cytotoxic drug, and the influence of schedule and sequence on the efficacy of the combination. Nude mice bearing MDA-MB-435 xenografts received weekly cycles of ZD6126 (200 mg kg À1 i.p.) administered at different times before or after PTX (10, 20, and 40 mg kg À1 i.v.). ZD6126 given 2 or 24 h after PTX showed no significant benefit, a result that was attributed to a protective effect of PTX against ZD6126-induced vascular damage and tumour necrosis, a hallmark of VDA activity. Paclitaxel counteracting activity was reduced by distancing drug administrations, and ZD6126 given 72 h after PTX potentiated the VDA's antitumour activity. Schedules with ZD6126 given before PTX improved therapeutic activity, which was paralleled by a VDA-induced increase in cell proliferation in the viable tumour tissue. Paclitaxel given 72 h after ZD6126 yielded the best response (50% tumours regressing). A single treatment with ZD6126 followed by weekly administration of PTX was sufficient to achieve a similar response (57% remissions). These findings show that schedule, sequence and timing are crucial in determining the antitumour efficacy of PTX in combination with ZD6126. Induction of tumour necrosis and increased proliferation in the remaining viable tumour tissue could be exploited as readouts to optimise schedules and maximise therapeutic efficacy.

Starting from the radiative transport equation we derive the scaling relationships that enable a single Monte Carlo (MC) simulation to predict the spatially- and temporally-resolved reflectance from homogeneous semi-infinite media with arbitrary scattering and absorption coefficients. This derivation shows that a rigorous application of this single Monte Carlo (sMC) approach requires the rescaling to be done individually for each photon biography. We examine the accuracy of the sMC method when processing simulations on an individual photon basis and also demonstrate the use of adaptive binning and interpolation using non-uniform rational B-splines (NURBS) to achieve order of magnitude reductions in the relative error as compared to the use of uniform binning and linear interpolation. This improved implementation for sMC simulation serves as a fast and accurate solver to address both forward and inverse problems and is available for use at http://www.virtualphotonics.org/.

Several studies have investigated the effect of various anthropometric factors on the risk of cutaneous malignant melanoma (CMM). As the results are controversial, we analysed this issue in a case-control study conducted in Italy. The roles of several body size measures were investigated in a hospital-based case-control study of CMM conducted in Italy. The cases were 542 patients with CMM and the controls were 538 subjects admitted to the same hospitals as the cases for non-dermatological and non-neoplastic diseases. The odds ratios for the highest versus the lowest quartile were 2.06 [95% confidence interval (CI), 1.39-3.05] for weight, 1.16 (95% CI, 0.80-1.68) for height, 1.90 (95% CI, 1.28-2.80) for the body mass index (BMI) and 1.87 (95% CI, 1.28-2.72) for the body surface area (BSA). When allowing for BMI and BSA in the same model, the odds ratios were 1.55 (95% CI, 0.92-2.62) for BMI and 1.41 (95% CI, 0.85-2.33) for BSA. The present findings confirm that obesity increases the risk of CMM. BSA is also related to the risk of CMM. In terms of the population attributable risk, overweight and obesity would account for 31% of the cases of CMM in this Italian population, indicating the scope of prevention.

Amiodarone is a potent antiarrhythmic agent, indicated for the treatment of refractory arrhythmias, which may lead to thyrotoxicosis. In these patients, thyroidectomy is a valid therapeutic option. Antithyroid therapy in the immediate preoperative setting and the subsequently accepted minimal delay until thyroidectomy have not been clearly defined yet. The aim of the present study was to show, that total thyroidectomy under general anaesthesia in patients with amiodarone-induced thyrotoxicosis (AIT) is safe without necessarily obtaining an euthyroid state preoperatively.We conducted a retrospective cohort study of prospectively gathered data on 11 patients undergoing total thyroidectomy under general anaesthesia between January 2008 and December 2013 for AIT at our University Hospital.All patients were preoperatively treated with carbimazole, steroids and β-receptor antagonists. Additionally, 3 patients received potassium perchlorate and in one patient carbimazole was changed to propylthiouracil. Plasmapheresis was performed in 3 patients. Only one patient was euthyroid at the time of operation. There were no significant intra- and postoperative complications, especially no signs of thyroid storm. One patient could postoperatively be removed from the cardiac transplant waiting list due to improved cardiac function.Improvements in the interdisciplinary surgical management for AIT between cardiologists, endocrinologists, anaesthetists and endocrine surgeons provide the basis of safe total thyroidectomy under general anaesthesia in hyperthyroid state. Early surgery without long delay for medical antithyroid treatment (with its potential negative side effects) is recommended.