Application of Brownian motion theory to the analysis of membrane channel ionic trajectories calculated by molecular dynamics

This paper shows how Brownian motion theory can be used to analyze features of individual ion trajectories in channels as calculated by molecular dynamics, and that its use permits more precise determinations of diffusion coefficients than would otherwise be possible. We also show how a consideration of trajectories of single particles can distinguish between effects due to the magnitude of the diffusion coefficient and effects due to barriers and wells in the potential profile, effects which can not be distinguished by consideration of average fluxes

Advanced breast cancer and its prevention by screening.

In discussions on breast cancer screening, much attention has been focussed on the possible morbidity generated by screening. Favourable effects like the prevention of advanced disease seem underestimated, probably because quantification is that difficult. To analyse the amount of care and treatment given to women with advanced breast cancer, we report on patients followed from first recurrence until death using patient files and national sources. A random sample of 60 female cases from computerised registries of two cancer centres and a sample of 20 cases from a non-computerised hospital registry was taken. A total of 68 patient files were sufficiently documented. A woman with advanced breast cancer is estimated to have a 39% loss in utility compared to a healthy woman (range 27-45%). Hormonal treatment is the main modality during 14 and chemotherapy during 4 months. Total medical cost from diagnosis of advanced disease until death amounts to 17,100 US dollars, or 21,000 when including extramural cost. The effect of breast cancer screening by preventing the occurrence of advanced disease is quantified. The resulting gain in quality of life contributes 70% of the total gain in quality of life. In the long run, almost half of the annual cost of screening will be offset by savings in the cost for advanced disease. Only the changes in palliative surgery and/or radiotherapy will be small in contrast to primary treatment changes. Besides the mortality reduction, screening is justified by the improvements in quality of life and cost savings for women prevented from reaching advanced disease

Threat of a lion population extinction in Waza National Park, North Cameroon.

Conservation Biology - ol

An Isolated, Antegrade, Perfused, Peroneal Nerve Anterior Tibialis Muscle Model in the Rat A Novel Model Developed to Study the Factors Governing the Time Course of Action of Neuromuscular Blocking Agents

Background: A model of an antegrade, perfused, isolated rat peroneal nerve anterior tibial muscle was developed to study potentially important factors governing the time course of action of (nondepolarizing) neuromuscular blocking agents such as concentration, blood flow, and temperature. The model allows observation of the effects of selective changes in these factors. Methods: The authors isolated the anterior tibial muscle and cannulated the anterior tibial artery and vein, providing a way for single-pass perfusion with blood from a donor rat. A force transducer was connected to the tibialis anterior muscle and a stimulator was connected to the tibial nerve. The influence of intrinsic potency (EC 90 ) and muscle blood flow rate on the time course of pancuronium and rocuronium was investigated. Results: The model remained stable for at least 4 h with respect to twitch height, muscle structure and function, and blood chemistry. Doubling the muscle-blood flow resulted in a significantly faster onset and offset for both pancuronium and rocuronium. Trebling the intrinsic potency (EC 90 ) was not associated with significant changes in the time course of action of the relaxants. Conclusion: The authors developed and validated a model that allows us to study biophase kinetics of neuromuscular blocking agents in the anterior tibial muscle of the rat. In this model, muscle-blood flow rather than EC 90 appears to predominantly determine the onset and offset time of nondepolarizing muscle relaxants

Patient's needs and preferences in routine follow-up after treatment for breast cancer

The purpose of the study was to analyse the needs of women who participated in a routine follow-up programme after treatment for primary breast cancer. A cross-sectional survey was conducted using a postal questionnaire among women without any sign of relapse during the routine follow-up period. The questionnaire was sent 2-4 years after primary surgical treatment. Most important to patients was information on long-term effects of treatment and prognosis, discussion of prevention of breast cancer and hereditary factors and changes in the untreated breast. Patients preferred additional investigations (such as X-ray and blood tests) to be part of routine follow-up visits. Less satisfaction with interpersonal aspects and higher scores on the Hospital Anxiety and Depression Scale (HADS) scale were related to stronger preferences for additional investigation. Receiving adjuvant hormonal or radiotherapy was related to a preference for a more intensive follow-up schedule. There were no significant differences between patients treated with mastectomy compared to treated with breast-conserving therapy. During routine follow-up after a diagnosis of breast cancer, not all patients needed all types of information. When introducing alternative follow-up schedules, individual patients' information needs and preferences should be identified early and incorporated into the follow-up routine care, to target resources and maximise the likelihood that positive patient outcomes will result

Torsades de pointes during laparoscopic adrenalectomy of a pheochromocytoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Torsades de pointes is a rare but potentially lethal arrhythmia. The amount of literature available on Torsades de pointes occurring in patients with pheochromocytoma is limited, and we found no literature describing this dysrhythmia in a patient with pheochromocytoma under anesthesia.</p> <p>Case presentation</p> <p>We describe the case of a 42-year-old Caucasian woman without QT prolongation preoperatively with recurrent Torsades de pointes during laparoscopic removal of a pheochromocytoma. Torsades de pointes mainly occurs in the setting of a prolonged QT interval. This patient neither had a prolonged QT preoperatively nor was her family history suspect for a congenital long QT syndrome. Most likely, our patient had an acquired long QT syndrome, elicited by the combination of flecainide, hypomagnesemia and adrenergic stimulation during manipulation of the tumor.</p> <p>Conclusion</p> <p>We show that in the case of a surgical pheochromocytoma removal, perioperative conditions can elicit an acquired or previously unknown congenital long QT syndrome. Therefore, preoperative α- and β-blockade is advised, QT-prolonging drugs should be avoided and potassium and magnesium plasma levels should be kept at normal to high levels.</p

Near-field Electrical Detection of Optical Plasmons and Single Plasmon Sources

Photonic circuits can be much faster than their electronic counterparts, but they are difficult to miniaturize below the optical wavelength scale. Nanoscale photonic circuits based on surface plasmon polaritons (SPs) are a promising solution to this problem because they can localize light below the diffraction limit. However, there is a general tradeoff between the localization of an SP and the efficiency with which it can be detected with conventional far-field optics. Here we describe a new all-electrical SP detection technique based on the near-field coupling between guided plasmons and a nanowire field-effect transistor. We use the technique to electrically detect the plasmon emission from an individual colloidal quantum dot coupled to an SP waveguide. Our detectors are both nanoscale and highly efficient (0.1 electrons/plasmon), and a plasmonic gating effect can be used to amplify the signal even higher (up to 50 electrons/plasmon). These results enable new on-chip optical sensing applications and are a key step towards "dark" optoplasmonic nanocircuits in which SPs can be generated, manipulated, and detected without involving far-field radiation.Comment: manuscript followed by supplementary informatio

Design and Feasibility of an Intervention to Support Cancer Genetic Counselees in Informing their At-Risk Relatives

Cancer genetic counselees receive individualized information regarding heightened risks and medical recommendations which is also relevant for their at-risk relatives. Unfortunately, counselees often insufficiently inform these relatives. We designed an intervention aimed at improving counselees' knowledge regarding which at-risk relatives to inform and what information to disclose, their motivation to disclose, and their self-efficacy. The intervention, offered by telephone by trained psychosocial workers, is based on the principles of Motivational Interviewing. Phase 1 of the intervention covers agenda setting, exploration, and evaluation, and phase 2 includes information provision, enhancing motivation and self-efficacy, and brainstorming for solutions to disseminate information within the family. Fidelity and acceptability of the intervention were assessed using recordings of intervention sessions and by counselee self-report. A total of 144 counselees participated. Psychosocial workers (n = 5) delivered the intervention largely as intended. Counselees highly appreciated the content of the intervention and the psychosocial workers who delivered the intervention. In the sessions, psychosocial workers provided additional and/or corrective information, and brainstorming for solutions was performed in 70 %. These results indicate that this intervention is feasible and warrants testing in clinical practice. For this, a randomized controlled trial is currently in progress to test the intervention's efficacy

Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference

EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur) involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training

Cost-effectiveness of stereotactic large-core needle biopsy for nonpalpable breast lesions compared to open-breast biopsy

This paper demonstrates that the introduction of large-core needle biopsy (LCNB) replacing needle-localised breast biopsy (NLBB) for nonpalpable (screen-detected) breast lesions could result in substantial cost savings at the expense of a possible slight increase in breast cancer mortality. The cost-effectiveness of LCNB and NLBB was estimated using a microsimulation model. The sensitivity of LCNB (0.97) and resource use and costs of LCNB and NLBB were derived from a multicentre consecutive cohort study among 973 women who consented in getting LCNB and NLBB, if LCNB was negative. Sensitivity analyses were performed. Replacing NLBB with LCNB would result in approximately six more breast cancer deaths per year (in a target population of 2.1 million women), or in 1000 extra life-years lost from breast cancer (effect over 100 years). The total costs of management of breast cancer (3% discounted) are estimated at £4676 million with NLBB; introducing LCNB would save £13 million. The incremental cost-effectiveness ratio of continued NLBB vs LCNB would be £12 482 per additional life-year gained (3% discounted); incremental costs range from £-21 687 (low threshold for breast biopsy) to £74 378 (high sensitivity of LCNB)