Oceanographic observations at the Amundsen sea shelf break

Introduction: The continental shelf environment of the Amundsen and Bellingshausen seas differs markedly from that of the other circumpolar seas, where water temperatures are close to the surface freezing point throughout. In the Amundsen/Bellingshausen sector near-freezing temperatures are encountered only in the upper few hundred metres of the water column. Below this surface layer a broad thermocline trends towards upper Circumpolar Deep Water (uCDW), which is found in a form that is almost unmodified from its off-shelf manifestation (Giulivi and Jacobs, 1996). This means that the ice shelves of the Amundsen and Bellingshausen seas experience ocean temperatures some three degrees warmer than those experienced by the other Antarctic ice shelves, and the rates of basal melting are correspondingly high (Jacobs et al., 1996)

pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4

Nitrophorins are NO carrier proteins that transport and release NO through a pH-dependent conformational change. They bind NO tightly in a low pH environment and release it in a higher pH environment. Experimental evidence shows that the increase in the NO dissociation equilibrium constant, K d, is due mainly to an increase in the NO release rate. Structural and kinetic data strongly suggest that NPs control NO escape by modulating its migration from the active site to the solvent through a pH-dependent conformational change. NP2 and NP4 are two representative proteins of the family displaying a 39% overall sequence identity, and interestingly, NP2 releases NO slower than NP4. The proposal that NPs' NO release relies mainly on the NO escape rate makes NPs a very peculiar case among typical heme proteins. The connection between the pH-dependent conformational change and ligand release mechanism is not fully understood and the structural basis for the pH induced structural transition and the different NO release patterns in NPs are unresolved, yet interesting issues. In this work, we have used state of the art molecular dynamics simulations to study the NO escape process in NP2 and NP4 in both the low and high pH states. Our results show that both NPs modulate NO release by switching between a "closed" conformation in a low pH environment and an "open" conformation at higher pH. In both proteins, the change is caused by the differential protonation of a common residue Asp30 in NP4 and Asp29 in NP2, and the NO escape route is conserved. Finally, our results show that, in NP2, the conformational change to the "open" conformation is smaller than that for NP4 which results in a higher barrier for NO release.Fil: Swails, Jason M.. University of Florida; Estados UnidosFil: Meng, Yilin. University of Florida; Estados UnidosFil: Walker, F. Ann. University of Arizona; Estados UnidosFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Roitberg, Adrián. University of Florida; Estados Unido

Gapless spin-liquid state in the structurally disorder-free triangular antiferromagnet NaYbO2_2

We present the structural characterization and low-temperature magnetism of the triangular-lattice delafossite NaYbO$_2$. Synchrotron x-ray diffraction and neutron scattering exclude both structural disorder and crystal-electric-field randomness, whereas heat-capacity measurements and muon spectroscopy reveal the absence of magnetic order and persistent spin dynamics down to at least 70\,mK. Continuous magnetic excitations with the low-energy spectral weight accumulating at the $K$-point of the Brillouin zone indicate the formation of a novel spin-liquid phase in a triangular antiferromagnet. This phase is gapless and shows a non-trivial evolution of the low-temperature specific heat. Our work demonstrates that NaYbO$_2$ practically gives the most direct experimental access to the spin-liquid physics of triangular antiferromagnets.Comment: 6 pages, 4figure

The Knee Arthroplasty Trial (KAT) : design features, baseline characteristics and two-year functional outcomes after alternative approaches to knee replacement

Background: The aim of continued development of total knee replacement systems has been the further improvement of the quality of life and increasing the duration of prosthetic survival. Our goal was to evaluate the effects of several design features, including metal backing of the tibial component, patellar resurfacing, and a mobile bearing between the tibial and femoral components, on the function and survival of the implant. Methods: A pragmatic, multicenter, randomized, controlled trial involving 116 surgeons in thirty-four centers in the United Kingdom was performed; 2352 participants were randomly allocated to be treated with or without a metal backing of the tibial component (409), with or without patellar resurfacing (1715), and/or with or without a mobile bearing (539). Randomization to more than one comparison was allowed. The primary outcome measures were the Oxford Knee Score (OKS), Short Form-12, EuroQol-5D, and the need for additional surgery. The results up to two years postoperatively are reported. Results: Functional status and quality-of-life scores were low at baseline but improved markedly across all trial groups following knee replacement (mean overall OKS, 17.98 points at baseline and 34.82 points at two years). Most of the change was observed at three months after the surgery. Six percent of the patients had additional knee surgery within two years. There was no evidence of differences in clinical, functional, or quality-of-life measures between the randomized groups at two years. Conclusions: Patients have substantial improvement following total knee replacement. This is the first adequately powered randomized controlled trial, of which we are aware, in which the effects of metal backing, patellar resurfacing, and a mobile bearing were investigated. We found no evidence of an effect of these variants on the rate of early complications or on functional recovery up to two years after total knee replacement. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.NIHR Health Technology Assessment Programme (Project Number 95/10/01); Howmedica Osteonics; Zimmer; DePuy, a Johnson and Johnson company; Corin Medical; Smith and Nephew Healthcare. Biomet Merck; and Wright CremascoliPeer reviewe

Survey and online discussion groups to develop a patient-rated outcome measure on acceptability of treatment response in vitiligo

BackgroundVitiligo is a chronic depigmenting skin disorder which affects around 0.5-1% of the world’s population. The outcome measures used most commonly in trials to judge treatment success focus on repigmentation. Patient-reported outcome measures of treatment success are rarely used, although recommendations have been made for their inclusion in vitiligo trials. This study aimed to evaluate the face validity of a new patient-reported outcome measure of treatment response, for use in future trials and clinical practice. MethodAn online survey to gather initial views on what constitutes treatment success for people with vitiligo or their parents/carers, followed by online discussion groups with patients to reach consensus on what constitutes treatment success for individuals with vitiligo, and how this can be assessed in the context of trials. Participants were recruited from an existing database of vitiligo patients and through posts on the social network sites Facebook and Twitter. ResultsA total of 202 survey responses were received, of which 37 were excluded and 165 analysed. Three main themes emerged as important in assessing treatment response: a) the match between vitiligo and normal skin (how well it blends in); b) how noticeable the vitiligo is and c) a reduction in the size of the white patches. The majority of respondents said they would consider 80% or more repigmentation to be a worthwhile treatment response after 9 months of treatment. Three online discussion groups involving 12 participants led to consensus that treatment success is best measured by asking patients how noticeable their vitiligo is after treatment. This was judged to be best answered using a 5-point Likert scale, on which a score of 4 or 5 represents treatment success. ConclusionsThis study represents the first step in developing a patient reported measure of treatment success in vitiligo trials. Further work is now needed to assess its construct validity and responsiveness to change.<br/

'A good method of quitting smoking' or 'just an alternative to smoking'? Comparative evaluations of e-cigarette and traditional cigarette usage by dual users

The development of e-cigarettes was initially hailed as a resource in facilitating a reduction in or cessation of cigarette smoking. Many users of e-cigarettes are ‘dual users’, smoking traditional cigarettes and e-cigarettes. The present qualitative study examines the factors that a group of 20 dual users considered to have been influential in their decisions to use e-cigarettes and their comparative evaluations of e-cigarettes and traditional cigarettes. Health concerns were not found to be sole motivators. Participants pointed to financial and contextual considerations, particularly peer influence on uptake and continued usage of e-cigarettes. E-cigarettes were evaluated as comparable to cigarettes in some ways but not in other important respects such as sensation and satisfaction. Different social evaluations of cigarette and e-cigarette usage were discerned which influenced how participants identified as smokers, ‘vapers’ or neither. Findings are discussed in relation to social representations, identity and implications for continued e-cigarette usage among dual users

The CRISP colorectal cancer risk prediction tool: an exploratory study using simulated consultations in Australian primary care

Abstract Background In Australia, screening for colorectal cancer (CRC) with colonoscopy is meant to be reserved for people at increased risk, however, currently there is a mismatch between individuals’ risk of CRC and the type of CRC screening they receive. This paper describes the development and optimisation of a Colorectal cancer RISk Prediction tool (‘CRISP’) for use in primary care. The aim of the CRISP tool is to increase risk-appropriate CRC screening. Methods CRISP development was informed by previous experience with developing risk tools for use in primary care and a systematic review of the evidence. A CRISP prototype was used in simulated consultations by general practitioners (GPs) with actors as patients. GPs were interviewed to explore their experience of using CRISP, and practice nurses (PNs) and practice managers (PMs) were interviewed after a demonstration of CRISP. Transcribed interviews and video footage of the ‘consultations’ were qualitatively analyzed. Themes arising from the data were mapped onto Normalization Process Theory (NPT). Results Fourteen GPs, nine PNs and six PMs were recruited from 12 clinics. Results were described using the four constructs of NPT: 1) Coherence: Clinicians understood the rationale behind CRISP, particularly since they were familiar with using risk tools for other conditions; 2) Cognitive participation: GPs welcomed the opportunity CRISP provided to discuss healthy and unhealthy behaviors with their patients, but many GPs challenged the screening recommendation generated by CRISP; 3) Collective Action: CRISP disrupted clinician-patient flow if the GP was less comfortable with computers. GP consultation time was a major implementation barrier and overall consensus was that PNs have more capacity and time to use CRISP effectively; 4) Reflexive monitoring: Limited systematic monitoring of new interventions is a potential barrier to the sustainable embedding of CRISP. Conclusions CRISP has the potential to improve risk-appropriate CRC screening in primary care but was considered more likely to be successfully implemented as a nurse-led intervention