Pancreas and islet cell transplantation

Currently, for the patient with type 1 diabetes, a definitive treatment without resorting to the use of exogenous insulin can be achieved only with pancreas or islet cell transplantation. These means of restoring β-cell mass can completely maintain essentially normal long-term glucose homeostasis, although the need for powerful immunosuppressive regimens limits their application to only a subgroup of adult patients. Apart from the shortage of donors that has limited all kinds of transplantation, however, the widespread use of β-cell replacement has been precluded until recently by the drawbacks associated with both organ and islet cell transplantation. Although the study of recurrence of diabetes has generated attention, the fundamental obstacle to pancreas and islet transplantation has been, and remains, the alloimmune response. With a better elucidation of the mechanisms of alloengraftment achieved during the last 3 years, the stage has been set for further advances

Integration and continuity of primary care: polyclinics and alternatives - a patient-centred analysis of how organisation constrains care co-ordination

Background An ageing population, the increasing specialisation of clinical services and diverse health-care provider ownership make the co-ordination and continuity of complex care increasingly problematic. The way in which the provision of complex health care is co-ordinated produces – or fails to produce – six forms of continuity of care (cross-sectional, longitudinal, flexible, access, informational and relational). Care co-ordination is accomplished by a combination of activities by patients themselves; provider organisations; care networks co-ordinating the separate provider organisations; and overall health-system governance. This research examines how far organisational integration might promote care co-ordination at the clinical level. Objectives To examine (1) what differences the organisational integration of primary care makes, compared with network governance, to horizontal and vertical co-ordination of care; (2) what difference provider ownership (corporate, partnership, public) makes; (3) how much scope either structure allows for managerial discretion and ‘performance’; (4) differences between networked and hierarchical governance regarding the continuity and integration of primary care; and (5) the implications of the above for managerial practice in primary care. Methods Multiple-methods design combining (1) the assembly of an analytic framework by non-systematic review; (2) a framework analysis of patients’ experiences of the continuities of care; (3) a systematic comparison of organisational case studies made in the same study sites; (4) a cross-country comparison of care co-ordination mechanisms found in our NHS study sites with those in publicly owned and managed Swedish polyclinics; and (5) the analysis and synthesis of data using an ‘inside-out’ analytic strategy. Study sites included professional partnership, corporate and publicly owned and managed primary care providers, and different configurations of organisational integration or separation of community health services, mental health services, social services and acute inpatient care. Results Starting from data about patients’ experiences of the co-ordination or under-co-ordination of care, we identified five care co-ordination mechanisms present in both the integrated organisations and the care networks; four main obstacles to care co-ordination within the integrated organisations, of which two were also present in the care networks; seven main obstacles to care co-ordination that were specific to the care networks; and nine care co-ordination mechanisms present in the integrated organisations. Taking everything into consideration, integrated organisations appeared more favourable to producing continuities of care than did care networks. Network structures demonstrated more flexibility in adding services for small care groups temporarily, but the expansion of integrated organisations had advantages when adding new services on a longer term and a larger scale. Ownership differences affected the range of services to which patients had direct access; primary care doctors’ managerial responsibilities (relevant to care co-ordination because of their impact on general practitioner workload); and the scope for doctors to develop special interests. We found little difference between integrated organisations and care networks in terms of managerial discretion and performance. Conclusions On balance, an integrated organisation seems more likely to favour the development of care co-ordination and, therefore, continuities of care than a system of care networks. At least four different variants of ownership and management of organisationally integrated primary care providers are practicable in NHS-like settings. Future research is therefore required, above all to evaluate comparatively the different techniques for coordinating patient discharge across the triple interface between hospitals, general practices and community health services; and to discover what effects increasing the scale and scope of general practice activities will have on continuity of care

Health care providers' attitudes towards termination of pregnancy: A qualitative study in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite changes to the abortion legislation in South Africa in 1996, barriers to women accessing abortion services still exist including provider opposition to abortions and a shortage of trained and willing abortion care providers. The dearth of abortion providers undermines the availability of safe, legal abortion, and has serious implications for women's access to abortion services and health service planning.</p> <p>In South Africa, little is known about the personal and professional attitudes of individuals who are currently working in abortion service provision. Exploring the factors which determine health care providers' involvement or disengagement in abortion services may facilitate improvement in the planning and provision of future services.</p> <p>Methods</p> <p>Qualitative research methods were used to collect data. Thirty four in-depth interviews and one focus group discussion were conducted during 2006 and 2007 with health care providers who were involved in a range of abortion provision in the Western Cape Province, South Africa. Data were analysed using a thematic analysis approach.</p> <p>Results</p> <p>Complex patterns of service delivery were prevalent throughout many of the health care facilities, and fragmented levels of service provision operated in order to accommodate health care providers' willingness to be involved in different aspects of abortion provision. Related to this was the need expressed by many providers for dedicated, stand-alone abortion clinics thereby creating a more supportive environment for both clients and providers. Almost all providers were concerned about the numerous difficulties women faced in seeking an abortion and their general quality of care. An overriding concern was poor pre and post abortion counselling including contraceptive counselling and provision.</p> <p>Conclusion</p> <p>This is the first known qualitative study undertaken in South Africa exploring providers' attitudes towards abortion and adds to the body of information addressing the barriers to safe abortion services. In order to sustain a pool of abortion providers, programmes which both attract prospective abortion providers, and retain existing providers, needs to be developed and financial compensation for abortion care providers needs to be considered.</p

Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of <it>c-KIT </it>in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of <it>c-KIT </it>and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (<it>PDGFRA</it>), all of which have been implicated in human GISTs.</p> <p>Methods</p> <p>Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of <it>c-KIT </it>and exons 12, 14, and 18 of <it>PDGFRA</it>, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples.</p> <p>Results</p> <p>Of these seventeen cases, six amplicons of exon 11 of <it>c-KIT </it>showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of <it>c-KIT </it>and exons 12, 14, and 18 of <it>PDGFRA </it>had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of <it>c-KIT </it>and exons 12 and 14 of <it>PDGFRA</it>.</p> <p>Conclusions</p> <p>The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of <it>c-KIT </it>in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other <it>c-KIT </it>or <it>PDGFRA </it>exons showed any abnormalities in our cases. This finding underlines the critical importance of <it>c-KIT </it>in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in <it>c-KIT </it>implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in <it>c-KIT </it>may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these malignant tumors. This study further demonstrates that spontaneously occurring canine GISTs share molecular features with human GISTs and are an appropriate model for human GISTs.</p

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Psychological approaches to understanding and promoting recovery in psychosis and bipolar disorder:a mixed-methods approach

BackgroundRecovery in mental health is a relatively new concept, but it is becoming more accepted that people can recover from psychosis. Recovery-orientated services are recommended for adult mental health, but with little evidence base to support this. ObjectivesTo facilitate understanding and promotion of recovery in psychosis and bipolar disorder (BD), in a manner that is empowering and acceptable to service users. MethodThere were six linked projects using qualitative and quantitative methodologies: (1) developing and piloting a service user-defined measure of recovery; (2) a Delphi study to determine levels of consensus around the concept of recovery; (3) examination of the psychological factors associated with recovery and how these fluctuate over time; (4) development and evaluation of cognitive–behavioural approaches to guided self-help including a patient preference trial (PPT); (5) development and evaluation of cognitive–behavioural therapy (CBT) for understanding and preventing suicide in psychosis including a randomised controlled trial (RCT); and (6) development and evaluation of a cognitive–behavioural approach to recovery in recent onset BD, including a RCT of recovery-focused cognitive–behavioural therapy (RfCBT). Service user involvement was central to the programme. ResultsMeasurement of service user-defined recovery from psychosis (using the Subjective Experience of Psychosis Scale) and BD (using the Bipolar Recovery Questionnaire) was shown to be feasible and valid. The consensus study revealed a high level of agreement among service users for defining recovery, factors that help or hinder recovery and items which demonstrate recovery. Negative emotions, self-esteem and hope predicted recovery judgements, both cross-sectionally and longitudinally, whereas positive symptoms had an indirect effect. In the PPT, 89 participants entered the study, three were randomised, 57 were retained in the trial until 15-month follow-up (64%). At follow-up there was no overall treatment effect on the primary outcome (Questionnaire about the Process of Recovery total; p = 0.82). In the suicide prevention RCT, 49 were randomised and 35 were retained at 6-month follow-up (71%). There were significant improvements in suicidal ideation [Adult Suicidal Ideation Questionnaire; treatment effect = –12.3, 95% confidence interval (CI) –24.3 to –0.14], Suicide Probability Scale (SPS; treatment effect = –7.0, 95% CI –15.5 to 0) and hopelessness (subscale of the SPS; treatment effect = –3.8, 95% CI –7.3 to –0.5) at follow-up. In the RCT for BD, 67 participants were randomised and 45 were retained at the 12-month follow-up (67%). Recovery score significantly improved in comparison with treatment as usual (TAU) at follow-up (310.87, 95% CI 75.00 to 546.74). At 15-month follow-up, 32 participants had experienced a relapse of either depression or mania (20 TAU vs. 12 RfCBT). The difference in time to recurrence was significant (estimated hazard ratio 0.38, 95% CI 0.18 to 0.78; p < 0.006). ConclusionsThis research programme has improved our understanding of recovery in psychosis and BD. Key findings indicate that measurement of recovery is feasible and valid. It would be feasible to scale up the RCTs to assess effectiveness of our therapeutic approaches in larger full trials, and two of the studies (CBT for suicide prevention in psychosis and recovery in BD) found significant benefits on their primary outcomes despite limited statistical power, suggesting definitive trials are warranted. FundingThe National Institute for Health Research Programme Grants for Applied Research programme

Journeys from quantum optics to quantum technology

Sir Peter Knight is a pioneer in quantum optics which has now grown to an important branch of modern physics to study the foundations and applications of quantum physics. He is leading an effort to develop new technologies from quantum mechanics. In this collection of essays, we recall the time we were working with him as a postdoc or a PhD student and look at how the time with him has influenced our research

Patient involvement in improving the evidence base on mental health inpatient care: the PERCEIVE programme

BackgroundDespite the movement towards care in the community, 40% of the NHS budget on mental health care is still attributed to inpatient services. However, long before the Francis Report highlighted grave shortcomings in inpatient care, there were reports by service user groups on the poor quality of these services in mental health. The programme provides a particular focus on the inclusion of the patient’s perspective in the development and evaluation of evidence.ObjectivesTo understand how changes to inpatient care affect the perceptions of the ward by service users and staff by using stakeholder participatory methods.DesignThe programme consisted of four work packages (WPs). (1) Lasting Improvements for Acute Inpatient SEttings (LIAISE): using participatory methods we developed two new scales [Views On Therapeutic Environment (VOTE) for staff and Views On Inpatient CarE (VOICE) for service users]. (2) Client Services Receipt Inventory – Inpatient (CITRINE): working with nurses and service users we developed a health economic measure of the amount of contact service users have with staff. The self-report measure records interactions with staff as well as the number of therapeutic activities attended. (3) Delivering Opportunities for Recovery (DOORWAYS): a stepped-wedge randomised controlled trial to test if training ward nurses to deliver therapeutic group activities would improve the perception of the ward by service users and staff. A total of 16 wards were progressively randomised and we compared the VOICE, VOTE and CITRINE measures before and after the intervention. A total of 1108 service users and 539 staff participated in this trial. (4) Bringing Emergency TreatmenT to Early Resolution (BETTER PATHWAYS) was an observational study comparing two service systems. The first was a ‘triage’ system in which service users were admitted to the triage ward and then either transferred to their locality wards or discharged back into the community within 7 days. The second system was routine care. We collected data from 454 service users and 284 nurses on their perceptions of the wards.Main outcome measuresThe main outcomes for the DOORWAYS and BETTER project were service user and staff perceptions of the ward (VOICE and VOTE, respectively) and the health economic measure was CITRINE. All were developed in WPs 1 and 2.ResultsWe developed reliable and valid measures of (1) the perceptions of inpatient care from the perspectives of service users and nurses (VOICE and VOTE) and (2) costs of interactions that were valued by service users (CITRINE). In the DOORWAYS project, after adjusting for legal status, we found weak evidence for benefit (standardised effect of –0.18, 95% CI 0.38 improvement to 0.01 deterioration; p = 0.062). There was only a significant benefit for involuntary patients following the staff training (N582, standardised effect of –0.35, 95% CI –0.57 to –0.12; p = 0.002; interaction p-value 0.006). VOTE scores did not change over time (standardised effect size of 0.04, 95% CI –0.09 to 0.18; p = 0.54). We found no evidence of an improvement in cost-effectiveness (estimated effect of £33, 95% CI –£91 to £146; p = 0.602), but resource allocation did change towards patient-perceived meaningful contacts by an average of £12 (95% CI –£76 to £98; p = 0·774). There were no significant differences between the triage and routine models of admission in terms of better perceptions by service users (estimated effect 0.77-point improvement in VOICE score on the triage ward; p = 0.68) or nurses (estimated effect of 1.68-point deterioration in VOTE on the triage ward; p = 0.38) or in terms of the cost of the length of care provided (£391 higher on triage; p = 0.77).Strengths and limitationsWe have developed measures using methods involving both service users and staff from mental health services. The measures were developed specifically for acute inpatient services and, therefore, cannot be assumed to be useful for other services. For instance, extensions of the measures are under construction for use in mother and baby units. The strength of the BETTER PATHWAYS and DOORWAYS projects is the large-scale data collection. However, we were testing specific services based in inner city areas and stretching to inner urban areas. It may be that different effects would be found in more rural communities or in different types of inpatient care.Future workOur database will be used to develop an understanding of the mediating and moderating factors for improving care quality.Trial registrationCurrent Controlled Trials ISRCTN06545047.FundingThis project was funded by the NIHR Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 6, No. 7. See the NIHR Journals Library website for further project information

Sensitivity of the Advanced LIGO detectors at the beginning of gravitational wave astronomy

The Laser Interferometer Gravitational Wave Observatory (LIGO) consists of two widely separated 4 km laser interferometers designed to detect gravitational waves from distant astrophysical sources in the frequency range from 10 Hz to 10 kHz. The first observation run of the Advanced LIGO detectors started in September 2015 and ended in January 2016. A strain sensitivity of better than 10−23/Hz−−−√ was achieved around 100 Hz. Understanding both the fundamental and the technical noise sources was critical for increasing the astrophysical strain sensitivity. The average distance at which coalescing binary black hole systems with individual masses of 30  M⊙ could be detected above a signal-to-noise ratio (SNR) of 8 was 1.3 Gpc, and the range for binary neutron star inspirals was about 75 Mpc. With respect to the initial detectors, the observable volume of the Universe increased by a factor 69 and 43, respectively. These improvements helped Advanced LIGO to detect the gravitational wave signal from the binary black hole coalescence, known as GW150914