Experiments on Multidimensional Solitons

This article presents an overview of experimental efforts in recent years related to multidimensional solitons in Bose-Einstein condensates. We discuss the techniques used to generate and observe multidimensional nonlinear waves in Bose-Einstein condensates with repulsive interactions. We further summarize observations of planar soliton fronts undergoing the snake instability, the formation of vortex rings, and the emergence of hybrid structures.Comment: review paper, to appear as Chapter 5b in "Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P. G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez (Springer-Verlag

Fast, quantitative, murine cardiac ¹⁹F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T

Purpose: To a) achieve cardiac ¹⁹F-Magnetic Resonance Imaging (MRI) of perfluoro-crown-ether (PFCE) labeled cardiac progenitor stem cells (CPCs) and bone-derived bone marrow macrophages, b) determine label concentration and cellular load limits, and c) achieve spectroscopic and image-based quantification. Methods: Theoretical simulations and experimental comparisons of spoiled-gradient echo (SPGR), rapid acquisition with relaxation enhancement (RARE), and steady state at free precession (SSFP) pulse sequences, and phantom validations, were conducted using ¹⁹F MRI/Magnetic Resonance Spectroscopy (MRS) at 9.4 T. Successful cell labeling was confirmed using flow cytometry and confocal microscopy. For CPC and macrophage concentration quantification, in vitro and post-mortem cardiac validations were pursued with the use of the transfection agent FuGENE. Feasibility of fast imaging is demonstrated in murine cardiac acquisitions in vivo, and in post-mortem murine skeletal and cardiac applications. Results: SPGR/SSFP proved favorable imaging sequences yielding good signal-to-noise ratio values. Confocal microscopy confirmed heterogeneity of cellular label uptake in CPCs. ¹⁹F MRI indicated lack of additional benefits upon label concentrations above 7.5–10 mg/ml/million cells. The minimum detectable CPC load was ~500k (~10k/voxel) in two-dimensional (2D) acquisitions (3–5 min) using the butterfly coil. Additionally, absolute ¹⁹F based concentration and intensity estimates (trifluoroacetic-acid solutions, macrophages, and labeled CPCs in vitro and post-CPC injections in the post-mortem state) scaled linearly with fluorine concentrations. Fast, quantitative cardiac ¹⁹F-MRI was demonstrated with SPGR/SSFP and MRS acquisitions spanning 3–5 min, using a butterfly coil. Conclusion: The developed methodologies achieved in vivo cardiac ¹⁹F of exogenously injected labeled CPCs for the first time, accelerating imaging to a total acquisition of a few minutes, providing evidence for their potential for possible translational work

Persistence of lipoatrophy after a four-year long interruption of antiretroviral therapy for HIV1 infection: case report

BACKGROUND: HIV-infected patients on long-term highly active antiretroviral therapy often present peculiar patterns of fat redistribution, referred to as lipodystrophy. In spite of recent investigations, it is not known whether and to what extent the main features of lipodystrophy – that is lipoatrophy of peripheral fat at face, limbs and buttocks, as well as fat accumulation at breasts, abdomen and the dorso-cervical region – can be reversible once clinically manifest. CASE PRESENTATION: A 35 year old Caucasian HIV infected female developed severe diffuse lipodystrophy while on highly active antiretroviral therapy. A remarkable increase of breast size, fat accumulation at waist, and a fat pad on her lumbar spine were paralleled by progressive and disfiguring lipoatrophy of face, limbs and buttocks. The patient decided to interrupt her therapy after 20 months, with a stably suppressed viremia and a CD4 lymphocyte count >500/μL. She could carry on a safe treatment interruption for longer than 4 years. Most sites of fat accumulation switched to nearly normal appearance, whereas lipoatrophy was substantially unchanged at all affected sites. CONCLUSION: our observation provides pictorial evidence that lipoatrophy may not be reversible even under ideal circumstances. Therefore, strategies to prevent lipoatrophy should be considered when defining therapeutic regimens for HIV infected patients, especially those at high risk

Coherent Signal Amplification in Bistable Nanomechanical Oscillators by Stochastic Resonance

Stochastic resonance is a counter-intuitive concept[1,2], ; the addition of noise to a noisy system induces coherent amplification of its response. First suggested as a mechanism for the cyclic recurrence of ice ages, stochastic resonance has been seen in a wide variety of macroscopic physical systems: bistable ring lasers[3], SQUIDs[4,5], magnetoelastic ribbons[6], and neurophysiological systems such as the receptors in crickets[7] and crayfish[8]. Although it is fundamentally important as a mechanism of coherent signal amplification, stochastic resonance is yet to be observed in nanoscale systems. Here we report the observation of stochastic resonance in bistable nanomechanical silicon oscillators, which can play an important role in the realization of controllable high-speed nanomechanical memory cells. Our nanomechanical systems were excited into a dynamic bistable state and modulated in order to induce controllable switching; the addition of white noise showed a marked amplification of the signal strength. Stochastic resonance in nanomechanical systems paves the way for exploring macroscopic quantum coherence and tunneling, and controlling nanoscale quantum systems for their eventual use as robust quantum logic devices.Comment: 18 pages, 4 figure

Robust diagnostic genetic testing using solution capture enrichment and a novel variant-filtering interface.

Targeted hybridization enrichment prior to next-generation sequencing is a widespread method for characterizing sequence variation in a research setting, and is being adopted by diagnostic laboratories. However, the number of variants identified can overwhelm clinical laboratories with strict time constraints, the final interpretation of likely pathogenicity being a particular bottleneck. To address this, we have developed an approach in which, after automatic variant calling on a standard unix pipeline, subsequent variant filtering is performed interactively, using AgileExomeFilter and AgilePindelFilter (http://dna.leeds.ac.uk/agile), tools designed for clinical scientists with standard desktop computers. To demonstrate the method's diagnostic efficacy, we tested 128 patients using (1) a targeted capture of 36 cancer-predisposing genes or (2) whole-exome capture for diagnosis of the genetically heterogeneous disorder primary ciliary dyskinesia (PCD). In the cancer cohort, complete concordance with previous diagnostic data was achieved across 793 variant genotypes. A high yield (42%) was also achieved for exome-based PCD diagnosis, underscoring the scalability of our method. Simple adjustments to the variant filtering parameters further allowed the identification of a homozygous truncating mutation in a presumptive new PCD gene, DNAH8. These tools should allow diagnostic laboratories to expand their testing portfolios flexibly, using a standard set of reagents and techniques

Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio

Unexpected Consequences: Women’s experiences of a self-hypnosis intervention to help with pain relief during labour.

Background Self-hypnosis is becoming increasingly popular as a means of labour pain management. Previous studies have produced mixed results. There are very few data on women’s views and experiences of using hypnosis in this context. As part of a randomized controlled trial of self-hypnosis for intra-partum pain relief (the SHIP Trial) we conducted qualitative interviews with women randomized to the intervention arm to explore their views and experiences of using self-hypnosis during labour and birth. Methods Participants were randomly selected from the intervention arm of the study, which consisted of two antenatal self-hypnosis training sessions and a supporting CD that women were encouraged to listen to daily from 32 weeks gestation until the birth of their baby. Those who consented were interviewed in their own homes 8-12 weeks after birth. Following transcription, the interviews were analysed iteratively and emerging concepts were discussed amongst the authors to generate organizing themes. These were then used to develop a principal organizing metaphor or global theme, in a process known as thematic networks analysis. Results Of the 343 women in the intervention group, 48 were invited to interview, and 16 were interviewed over a 12 month period from February 2012 to January 2013. Coding of the data and subsequent analysis revealed a global theme of ‘unexpected consequences’, supported by 5 organising themes, ‘calmness in a climate of fear’, ‘from sceptic to believer’, ‘finding my space’, ‘delays and disappointments’ and ‘personal preferences’. Most respondents reported positive experiences of self-hypnosis and highlighted feelings of calmness, confidence and empowerment. They found the intervention to be beneficial and used a range of novel strategies to personalize their self-hypnosis practice. Occasionally women reported feeling frustrated or disappointed when their relaxed state was misinterpreted by midwives on admission or when their labour and birth experiences did not match their expectations. Conclusion The women in this study generally appreciated antenatal self-hypnosis training and found it to be beneficial during labour and birth. The state of focused relaxation experienced by women using the technique needs to be recognized by providers if the intervention is to be implemented into the maternity service

‘Trying to pin down jelly’ - exploring intuitive processes in quality assessment for meta-ethnography

Background: Studies that systematically search for and synthesise qualitative research are becoming more evident in health care, and they can make an important contribution to patient care. However, there is still no agreement as to whether, or how we should appraise studies for inclusion. We aimed to explore the intuitive processes that determined the ‘quality’ of qualitative research for inclusion in qualitative research syntheses. We were particularly interested to explore the way that knowledge was constructed. Methods: We used qualitative methods to explore the process of quality appraisal within a team of seven qualitative researchers funded to undertake a meta-ethnography of chronic non-malignant musculoskeletal pain. Team discussions took place monthly between October 2010 and June 2012 and were recorded and transcribed. Data was coded and organised using constant comparative method. The development of our conceptual analysis was both iterative and collaborative. The strength of this team approach to quality came from open and honest discussion, where team members felt free to agree, disagree, or change their position within the safety of the group. Results: We suggest two core facets of quality for inclusion in meta-ethnography - (1) Conceptual clarity; how clearly has the author articulated a concept that facilitates theoretical insight. (2) Interpretive rigour; fundamentally, can the interpretation ‘be trusted?’ Our findings showed that three important categories help the reader to judge interpretive rigour: (ii) What is the context of the interpretation? (ii) How inductive is the interpretation? (iii) Has the researcher challenged their interpretation? Conclusions: We highlight that methods alone do not determine the quality of research for inclusion into a meta-ethnography. The strength of a concept and its capacity to facilitate theoretical insight is integral to meta-ethnography, and arguably to the quality of research. However, we suggest that to be judged ‘good enough’ there also needs to be some assurance that qualitative findings are more than simply anecdotal. Although our conceptual model was developed specifically for meta-ethnography, it may be transferable to other research methodologies

Repetitive arm functional tasks after stroke (RAFTAS): a pilot randomised controlled trial

Background Repetitive functional task practise (RFTP) is a promising treatment to improve upper limb recovery following stroke. We report the findings of a study to determine the feasibility of a multi-centre randomised controlled trial to evaluate this intervention. Methods A pilot randomised controlled trial was conducted. Patients with new reduced upper limb function were recruited within 14 days of acute stroke from three stroke units in North East England. Participants were randomised to receive a four week upper limb RFTP therapy programme consisting of goal setting, independent activity practise, and twice weekly therapy reviews in addition to usual post stroke rehabilitation, or usual post stroke rehabilitation. The recruitment rate; adherence to the RFTP therapy programme; usual post stroke rehabilitation received; attrition rate; data quality; success of outcome assessor blinding; adverse events; and the views of study participants and therapists about the intervention were recorded. Results Fifty five eligible patients were identified, 4-6% of patients screened at each site. Twenty four patients participated in the pilot study. Two of the three study sites met the recruitment target of 1-2 participants per month. The median number of face to face therapy sessions received was 6 [IQR 3-8]. The median number of daily repetitions of activities recorded was 80 [IQR 39-80]. Data about usual post stroke rehabilitation were available for 18/24 (75%). Outcome data were available for 22/24 (92%) at one month and 20/24 (83%) at three months. Outcome assessors were unblinded to participant group allocation for 11/22 (50%) at one month and 6/20 (30%) at three months. Four adverse events were considered serious as they resulted in hospitalisation. None were related to study treatment. Feedback from patients and local NHS therapists about the RFTP programme was mainly positive. Conclusions A multi-centre randomised controlled trial to evaluate an upper limb RFTP therapy programme provided early after stroke is feasible and acceptable to patients and therapists, but there are issues which needed to be addressed when designing a Phase III study. A Phase III study will need to monitor and report not only recruitment and attrition but also adherence to the intervention, usual post stroke rehabilitation received, and outcome assessor blinding