Holographic three-point functions of semiclassical states

We calculate the holographic three-point functions in N = 4 super-Yang-Mills theory in the case when two of the operators are semiclassical and one is dual to a supergravity mode. We further discuss the transition to the regime when all three operators are semiclassical.Comment: 17 pages, 3 figures; v2: refs. added, discussion in sec. 2.1 expanded; v3: misprint in (2.28) corrected, published versio

Arcanobacterium phocae infection in mink (Neovison vison), seals (Phoca vitulina, Halichoerus grypus) and otters (Lutra lutra)

Abstract Background Infectious skin disorders are not uncommon in mink. Such disorders are important as they have a negative impact on animal health and welfare as well as on the quality and value of the fur. This study presents the isolation of Arcanobacterium phocae from mink with severe skin lesions and other pathological conditions, and from wild seals and otters. Results In 2015, A. phocae was isolated for the first time in Denmark from outbreaks of dermatitis in mink farms. The outbreaks affected at least 12 farms. Originating from these 12 farms, 23 animals cultured positive for A. phocae. The main clinical findings were necrotizing pododermatitis or dermatitis located to other body sites, such as the lumbar and cervical regions. A. phocae could be isolated from skin lesions and in nine animals also from liver, spleen and lung, indicating a systemic spread. The bacterium was also, for the first time in Denmark, detected in dead seals (n = 9) (lungs, throat or wounds) and otters (n = 2) (throat and foot). Conclusions An infectious skin disorder in mink associated with A. phocae has started to occur in Danish farmed mink. The origin of the infection has not been identified and it is still not clear what the pathogenesis or the port of entry for A. phocae infections are

Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses

AIMS/HYPOTHESIS: Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes. METHODS: Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593). RESULTS: Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001). CONCLUSIONS/INTERPRETATION: Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract

Assessment of the multidisciplinary education for a major change in clinical practice; a prospective cohort study

Background: New approaches are often introduced to the neonatal intensive care unit (NICU) and other areas of the health service in either a haphazard or cataclysmic fashion. The needs of staff education are often addressed incompletely or too late. Rarely is education assessed after the introduction of a major change. We changed the basis of our NICU respiratory support. We conducted a major educational and support program before this intervention. This study documented and assessed the educational components of this change in our health service provision. Methods: Senior medical and nursing staff attended training abroad and an education program was applied for one year prior to the change. Multidisciplinary educational support for doctors, nurses and allied health was continued after the change. Assessment was by anonymous questionnaire, prior to change, at one and at nine months. Our hypothesis was that dissatisfaction with education would be greatest at one month. Results: Both theory education and practical education aspects of the new approach were rated as good to very good and this did not change with time. Difficulty of applying the technique was rated as ambivalent initially but decreased significantly over 9 months until it was rated easy to very easy (p < 0.001). Over all, the change was rated by staff as beneficial, both at the end of the education period and at nine months, with no decrease at one month. Conclusion: If education and training reaches all staff, with a system of mutual and continued support, even large changes in clinical practice can be achieved without the dissatisfaction with the educational process that is often otherwise seen

Methodology in conducting a systematic review of systematic reviews of healthcare interventions

<p>Abstract</p> <p>Background</p> <p>Hundreds of studies of maternity care interventions have been published, too many for most people involved in providing maternity care to identify and consider when making decisions. It became apparent that systematic reviews of individual studies were required to appraise, summarise and bring together existing studies in a single place. However, decision makers are increasingly faced by a plethora of such reviews and these are likely to be of variable quality and scope, with more than one review of important topics. Systematic reviews (or overviews) of reviews are a logical and appropriate next step, allowing the findings of separate reviews to be compared and contrasted, providing clinical decision makers with the evidence they need.</p> <p>Methods</p> <p>The methods used to identify and appraise published and unpublished reviews systematically, drawing on our experiences and good practice in the conduct and reporting of systematic reviews are described. The process of identifying and appraising all published reviews allows researchers to describe the quality of this evidence base, summarise and compare the review's conclusions and discuss the strength of these conclusions.</p> <p>Results</p> <p>Methodological challenges and possible solutions are described within the context of (i) sources, (ii) study selection, (iii) quality assessment (i.e. the extent of searching undertaken for the reviews, description of study selection and inclusion criteria, comparability of included studies, assessment of publication bias and assessment of heterogeneity), (iv) presentation of results, and (v) implications for practice and research.</p> <p>Conclusion</p> <p>Conducting a systematic review of reviews highlights the usefulness of bringing together a summary of reviews in one place, where there is more than one review on an important topic. The methods described here should help clinicians to review and appraise published reviews systematically, and aid evidence-based clinical decision-making.</p

Methodological considerations for a randomised controlled trial of podiatry care in rheumatoid arthritis: lessons from an exploratory trial

<p>Abstract</p> <p>Background</p> <p>Whilst evidence exists to support the use of single treatments such as orthoses and footwear, the effectiveness of podiatry-led care as a complex intervention for patients with rheumatoid arthritis (RA) related foot problems is unknown. The aim of this study was to undertake an exploratory randomised controlled parallel arm clinical trial (RheumAFooT) to inform the design and implementation of a definitive trial and to understand the potential benefits of this care.</p> <p>Methods</p> <p>Patients with a definite diagnosis of RA, stable drug management 3 months prior to entry, and a current history of foot problems (pain, deformity, stiffness, skin or nail lesions, or footwear problems) were recruited from a hospital outpatient rheumatology clinic and randomised to receive 12 months of podiatry treatment or no care. The primary outcome was change in foot health status using the impairment/footwear (LFIS_IF) and activity limitation/participation restriction (LFIS_AP) subscales of the Leeds Foot Impact Scale. Disease Activity Score (DAS), Health Assessment Questionnaire (HAQ) score and walking speed (m/s) were also recorded.</p> <p>Results</p> <p>Of the 80 patients identified, 64 patients were eligible to participate in the pilot and 34 were recruited. 16 patients were randomised to receive podiatry led foot care and 18 received no care. Against a backdrop of stable disease (DAS and HAQ scores), there was a statistically significant between group difference in the change in foot health status for foot impairment (LFIS_IF) but not activity/participation (LFIS_AP) or function (walking speed) over 12 months. In the podiatry arm, 1 patient declined treatment following randomisation (did not want additional hospital visits) and 3 self-withdrew (lost to follow-up). Patients received an average of 3 consultations for assessment and treatment comprising routine care for skin and nail lesions (n = 3), foot orthoses (n = 9), footwear referral to the orthotist (n = 5), and ultrasound guided intra-articular steroid injection (n = 1).</p> <p>Conclusion</p> <p>In this exploratory trial patients were difficult to recruit (stable drug management and co-morbid disease) and retain (lack of benefit/additional treatment burden) but overall the intervention was safe (no adverse reactions). Twelve months of podiatry care maintained but did not improve foot health status. These observations are important for the design and implementation of a definitive randomised controlled trial.</p> <p>Trial Registration</p> <p>ISRCTN: 01982076</p

Regional differences in prostaglandin E₂ metabolism in human colorectal cancer liver metastases

Background: Prostaglandin (PG) E₂ plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGE₂ catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGE₂ content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGE₂ in human CRC cells in vitro. Methods: Tissue from the periphery and centre of 20 human CRCLM was analysed for PGE₂ levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) β. Results: PGE₂ levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGE₂. Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo.Conclusions: There is significant intra-tumoral heterogeneity in PGE₂ content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGE₂ metabolism should be targeted for novel treatment of advanced CRC

Selective Ion Changes during Spontaneous Mitochondrial Transients in Intact Astrocytes

The bioenergetic status of cells is tightly regulated by the activity of cytosolic enzymes and mitochondrial ATP production. To adapt their metabolism to cellular energy needs, mitochondria have been shown to exhibit changes in their ionic composition as the result of changes in cytosolic ion concentrations. Individual mitochondria also exhibit spontaneous changes in their electrical potential without altering those of neighboring mitochondria. We recently reported that individual mitochondria of intact astrocytes exhibit spontaneous transient increases in their Na+ concentration. Here, we investigated whether the concentration of other ionic species were involved during mitochondrial transients. By combining fluorescence imaging methods, we performed a multiparameter study of spontaneous mitochondrial transients in intact resting astrocytes. We show that mitochondria exhibit coincident changes in their Na+ concentration, electrical potential, matrix pH and mitochondrial reactive oxygen species production during a mitochondrial transient without involving detectable changes in their Ca2+ concentration. Using widefield and total internal reflection fluorescence imaging, we found evidence for localized transient decreases in the free Mg2+ concentration accompanying mitochondrial Na+ spikes that could indicate an associated local and transient enrichment in the ATP concentration. Therefore, we propose a sequential model for mitochondrial transients involving a localized ATP microdomain that triggers a Na+-mediated mitochondrial depolarization, transiently enhancing the activity of the mitochondrial respiratory chain. Our work provides a model describing ionic changes that could support a bidirectional cytosol-to-mitochondria ionic communication