Single-Step Charge Transport through DNA over Long Distances

Quantum yields for charge transport across adenine tracts of increasing length have been measured by monitoring hole transport in synthetic oligonucleotides between photoexcited 2-aminopurine, a fluorescent analogue of adenine, and N_2-cyclopropyl guanine. Using fluorescence quenching, a measure of hole injection, and hole trapping by the cyclopropyl guanine derivative, we separate the individual contributions of single- and multistep channels to DNA charge transport and find that with 7 or 8 intervening adenines the charge transport is a coherent, single-step process. Moreover, a transition occurs from multistep to single-step charge transport with increasing donor/acceptor separation, opposite to that generally observed in molecular wires. These results establish that coherent transport through DNA occurs preferentially across 10 base pairs, favored by delocalization over a full turn of the helix

Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus—a prospective single-blinded randomised crossover trial

Aims/hypothesis: We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels. Methods: This was a single-blinded randomised crossover study at a university diabetes unit in Switzerland. We studied seven physically active men with type 1 diabetes (mean ± SEM age 33.5 ± 2.4years, diabetes duration 20.1 ± 3.6years, HbA1c 6.7 ± 0.2% and peak oxygen uptake [ $$\mathop {\text{V}}\limits^{\text{.}} {\text{O}}_{2{\text{peak}}}$$ ] 50.3 ± 4.5ml min−1 kg−1). Men were studied twice while cycling for 120min at 55 to 60% of $$\mathop {\text{V}}\limits^{\text{.}} {\text{O}}_{{\text{2peak}}}$$ , with a blood glucose level randomly set either at 5 or 11mmol/l and identical insulinaemia. The participants were blinded to the glycaemic level; allocation concealment was by opaque, sealed envelopes. Magnetic resonance spectroscopy was used to quantify intramyocellular glycogen and lipids before and after exercise. Indirect calorimetry and measurement of stable isotopes and counter-regulatory hormones complemented the assessment of local and systemic fuel metabolism. Results: The contribution of lipid oxidation to overall energy metabolism was higher in euglycaemia than in hyperglycaemia (49.4 ± 4.8 vs 30.6 ± 4.2%; p < 0.05). Carbohydrate oxidation accounted for 48.2 ± 4.7 and 66.6 ± 4.2% of total energy expenditure in euglycaemia and hyperglycaemia, respectively (p < 0.05). The level of intramyocellular glycogen before exercise was higher in hyperglycaemia than in euglycaemia (3.4 ± 0.3 vs 2.7 ± 0.2 arbitrary units [AU]; p < 0.05). Absolute glycogen consumption tended to be higher in hyperglycaemia than in euglycaemia (1.3 ± 0.3 vs 0.9 ± 0.1 AU). Cortisol and growth hormone increased more strongly in euglycaemia than in hyperglycaemia (levels at the end of exercise 634 ± 52 vs 501 ± 32nmol/l and 15.5 ± 4.5 vs 7.4 ± 2.0ng/ml, respectively; p < 0.05). Conclusions/interpretation: Substrate oxidation in type 1 diabetic patients performing aerobic exercise in euglycaemia is similar to that in healthy individuals revealing a shift towards lipid oxidation during exercise. In hyperglycaemia fuel metabolism in these patients is dominated by carbohydrate oxidation. Intramyocellular glycogen was not spared in hyperglycaemia. Trial registration: ClinicalTrials.Gov NCT00325559 Funding: This study was supported by unrestricted grants from the Oetliker-Stiftung für Physiologie, from the Swiss Diabetes Foundation, from NovoNordisk, Switzerland, and from the Swiss National Science Foundatio

Mutuality as a method: advancing a social paradigm for global mental health through mutual learning.

PURPOSE: Calls for "mutuality" in global mental health (GMH) aim to produce knowledge more equitably across epistemic and power differences. With funding, convening, and publishing power still concentrated in institutions in the global North, efforts to decolonize GMH emphasize the need for mutual learning instead of unidirectional knowledge transfers. This article reflects on mutuality as a concept and practice that engenders sustainable relations, conceptual innovation, and queries how epistemic power can be shared. METHODS: We draw on insights from an online mutual learning process over 8 months between 39 community-based and academic collaborators working in 24 countries. They came together to advance the shift towards a social paradigm in GMH. RESULTS: Our theorization of mutuality emphasizes that the processes and outcomes of knowledge production are inextricable. Mutual learning required an open-ended, iterative, and slower paced process that prioritized trust and remained responsive to all collaborators' needs and critiques. This resulted in a social paradigm that calls for GMH to (1) move from a deficit to a strength-based view of community mental health, (2) include local and experiential knowledge in scaling processes, (3) direct funding to community organizations, and (4) challenge concepts, such as trauma and resilience, through the lens of lived experience of communities in the global South. CONCLUSION: Under the current institutional arrangements in GMH, mutuality can only be imperfectly achieved. We present key ingredients of our partial success at mutual learning and conclude that challenging existing structural constraints is crucial to prevent a tokenistic use of the concept

Choosing to live with home dialysis-patients' experiences and potential for telemedicine support: a qualitative study

<p>Abstract</p> <p>Background</p> <p>This study examines the patients' need for information and guidance in the selection of dialysis modality, and in establishing and practicing home dialysis. The study focuses on patients' experiences living with home dialysis, how they master the treatment, and their views on how to optimize communication with health services and the potential of telemedicine.</p> <p>Methods</p> <p>We used an inductive research strategy and conducted semi-structured interviews with eleven patients established in home dialysis. Our focus was the patients' experiences with home dialysis, and our theoretical reference was patients' empowerment through telemedicine solutions. Three informants had home haemodialysis (HHD); eight had peritoneal dialysis (PD), of which three had automated peritoneal dialysis (APD); and five had continuous ambulatory peritoneal dialysis (CAPD). The material comprises all PD-patients in the catchment area capable of being interviewed, and all known HHD-users in Norway at that time.</p> <p>Results</p> <p>All of the interviewees were satisfied with their choice of home dialysis, and many experienced a normalization of daily life, less dominated by disease. They exhibited considerable self-management skills and did not perceive themselves as ill, but still required very close contact with the hospital staff for communication and follow-up. When choosing a dialysis modality, other patients' experiences were often more influential than advice from specialists. Information concerning the possibility of having HHD, including knowledge of how to access it, was not easily available. Especially those with dialysis machines, both APD and HHD, saw a potential for telemedicine solutions.</p> <p>Conclusions</p> <p>As home dialysis may contribute to a normalization of life less dominated by disease, the treatment should be organized so that the potential for home dialysis can be fully exploited. Pre-dialysis information should be unbiased and include access to other patients' experiences. Telemedicine may potentially facilitate a communication-based follow-up and improve safety within the home setting, making it easier to choose and live with home dialysis.</p

A study of sertraline in dialysis (ASSertID) : a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis

© 2015 Friedli et al. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedBACKGROUND: The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder.METHODS/DESIGN: The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial.DISCUSSION: There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression.TRIAL REGISTRATION: ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.Peer reviewedFinal Published versio

Panel IV: The President and International Law in the War on Terrorism

Curtis A. Bradley (University of Virginia School of Law), chair, Derek Jinks (Arizona State University College of Law), Michael D. Ramsey (University of San Diego School of Law), Ingrid Wuerth (University of Cincinnati College of Law), John C. Harrison (University of Virginia School of Law), panelists