Guidelines for the peri-operative care of people with dementia: Guidelines from the Association of Anaesthetists.

Ageing populations have greater incidences of dementia. People with dementia present for emergency and, increasingly, elective surgery, but are poorly served by the lack of available guidance on their peri-operative management, particularly relating to pharmacological, medico-legal, environmental and attitudinal considerations. These guidelines seek to deliver such guidance, by providing information for peri-operative care providers about dementia pathophysiology, specific difficulties anaesthetising patients with dementia, medication interactions, organisational and medico-legal factors, pre-, intra- and postoperative care considerations, training, sources of further information and care quality improvement tools.

Polygenic risk for severe psychopathology among Europeans is associated with major depressive disorder in Han Chinese women.

BACKGROUND: Previous studies have demonstrated that several major psychiatric disorders are influenced by shared genetic factors. This shared liability may influence clinical features of a given disorder (e.g. severity, age at onset). However, findings have largely been limited to European samples; little is known about the consistency of shared genetic liability across ethnicities. METHOD: The relationship between polygenic risk for several major psychiatric diagnoses and major depressive disorder (MDD) was examined in a sample of unrelated Han Chinese women. Polygenic risk scores (PRSs) were generated using European discovery samples and tested in the China, Oxford, and VCU Experimental Research on Genetic Epidemiology [CONVERGE (maximum N = 10 502)], a sample ascertained for recurrent MDD. Genetic correlations between discovery phenotypes and MDD were also assessed. In addition, within-case characteristics were examined. RESULTS: European-based polygenic risk for several major psychiatric disorder phenotypes was significantly associated with the MDD case status in CONVERGE. Risk for clinically significant indicators (neuroticism and subjective well-being) was also associated with case-control status. The variance accounted for by PRS for both psychopathology and for well-being was similar to estimates reported for within-ethnicity comparisons in European samples. However, European-based PRS were largely unassociated with CONVERGE family history, clinical characteristics, or comorbidity. CONCLUSIONS: The shared genetic liability across severe forms of psychopathology is largely consistent across European and Han Chinese ethnicities, with little attenuation of genetic signal relative to within-ethnicity analyses. The overall absence of associations between PRS for other disorders and within-MDD variation suggests that clinical characteristics of MDD may arise due to contributions from ethnicity-specific factors and/or pathoplasticity.

Best practice in critical care: anaemia in acute and critical illness.

Anaemia is common in critical illness, and standard treatment is red blood cell (RBC) transfusion, typically using a restrictive transfusion threshold of 70 g L-1 . However, there are subgroups of patients in whom it is biologically plausible that a higher transfusion threshold may be beneficial, namely, acute sepsis, traumatic brain injury and coexisting cardiovascular disease. In this review article, we will discuss the pathophysiology of anaemia, as well as its prevalence and time course. We will explore the limitations of using haemoglobin concentration as a surrogate for oxygen delivery and the concept of the critical haemoglobin concentration. We will then discuss transfusion thresholds for the general intensive care unit (ICU) population and specific subgroups.

Analysis of the distribution and scholarly output from National Institute of Academic Anaesthesia (NIAA) research grants.

The National Institute of Academic Anaesthesia (NIAA) was founded in 2008 to lead a UK strategy for developing academic anaesthesia. We aimed to assess the distribution of applications and quantify the academic returns of NIAA-supported research grants, as this has hitherto not been analysed. We sought data on the baseline characteristics of all grant applicants and recipients. Every grant recipient from 2008 to 2015 was contacted to ascertain the status of their supported research projects. We also examined Google Scholar, Scopus® database and InCites Journal Citation Reports for citation, author and journal metrics, respectively. In total, 495 research project applications were made, with 150 grants being awarded. Data on 121 out of 150 (80.7%) grant awards, accounting for £3.5 million, were collected, of which 91 completed studies resulted in 140 publications and 2759 citations. The median (IQR [range]) time to first or only publication was 3 (2-4 [0-9]) years. The overall cost per publication was £14,970 (£7457-£24,998 [£2212-£73,755]) and the cost per citation was £1515 (£323-£3785 [£70-£36,182]), with 1 (0-2 [0-8]) publication and 4 (0-25 [0-265]) citations resulting per grant. The impact factor of journals in which publications arose was 4.7 (2.5-6.2 [0-47.8]), with the highest impact arising from clinical and basic science studies, particularly in the fields of pain and peri-operative medicine. Grants were most frequently awarded to clinical and basic science categories of study, but in terms of specialty, critical care medicine and peri-operative medicine received the greatest number of grants. Superficially, there seemed a geographical disparity, with 123 (82%) grants being awarded to researchers in England, London receiving 48 (32%) of these. However, this was in proportion to the number of grant applications received by country or city of application, such that there was no significant difference in overall success rates. There was no significant difference in productivity in terms of publications and citations from grants awarded to each city. The 150 grants were awarded to 107 recipients (identified as the most senior applicant for each grant), 27 of whom received ≥ two grants. Recipients had a median career total of 21 (8-76 [0-254]) publications and 302 (44-1320 [0-8167]) citations, with an h-index of 8 (3-22 [0-54]). We conclude that a key determinant of grant success is simply applying. This is the first study to report the distribution and scholarly output of individual anaesthesia research grants, particularly from a collaborative body such as the NIAA, and can be used as a benchmark to further develop academic anaesthesia in the UK and beyond.

Calculation of the expected output spectrum for a mid-infrared supercontinuum source based on As 2 S3 chalcogenide photonic crystal fibers.

We computationally investigate supercontinuum generation in an As 2 S3 solid core photonic crystal fiber (PCF) with a hexagonal cladding of air holes. With a goal of obtaining a supercontinuum output spectrum that can predict what might be seen in an experiment, we investigate the spectral and statistical behavior of a mid-infrared supercontinuum source using a large ensemble average of 106 realizations, in which the input pulse duration and energy vary. The output spectrum is sensitive to small changes (0.1%) in these pulse parameters. We show that the spectrum can be divided into three regions with distinct characteristics: a short-wavelength region with high correlation, a middle-wavelength region with minimal correlation, and a long-wavelength region where the behavior is dominated by a few rare large-bandwidth events. We show that statistically significant fluctuations exist in the experimentally expected output spectrum and that we can reproduce an excellent match to that spectrum with a converged shape and bandwidth using 5000 realizations.

Guided entropy mode Rayleigh scattering in optical fibers.

Rayleigh scattering in optical fibers has the potential to degrade the performance of low-noise opto-electronic systems. In this Letter, we measure the Rayleigh gain spectrum of optical fibers. Our data show the gain bandwidth and the offset frequency of the Rayleigh gain peak. Both the gain bandwidth and the peak frequency are 3 orders of magnitude lower than the corresponding values for bulk silica. Our data suggest that the narrower gain bandwidth and frequency shift that we observe are due to guided entropy modes in the fiber. This effect is fundamental and will be present in any medium in which light is guided so that transverse intensity gradients exist.

Pure chiral optical fibres.

We investigate the properties of optical fibres made from chiral materials, in which a contrast in optical activity forms the waveguide, rather than a contrast in the refractive index; we refer to such structures as pure chiral fibres. We present a mathematical formulation for solving the modes of circularly symmetric examples of such fibres and examine the guidance and polarisation properties of pure chiral step-index, Bragg and photonic crystal fibre designs. Their behaviour is shown to differ for left- and right-hand circular polarisation, allowing circular polarisations to be isolated and/or guided by different mechanisms, as well as differing from equivalent non-chiral fibres. The strength of optical activity required in each case is quantified.

Calculation of the expected bandwidth for a mid-infrared supercontinuum source based on As(2)S(3) chalcogenide photonic crystal fibers.

We computationally investigate supercontinuum generation in an As(2)S(3) solid core photonic crystal fiber (PCF) with a hexagonal cladding of air holes. We study the effect of varying the system (fiber and input pulse) parameters on the output bandwidth. We find that there is significant variation of the measured bandwidth with small changes in the system parameters due to the complex structure of the supercontinuum spectral output. This variation implies that one cannot accurately calculate the experimentally-expected bandwidth from a single numerical simulation. We propose the use of a smoothed and ensemble-averaged bandwidth that is expected to be a better predictor of the bandwidth of the supercontinuum spectra that would be produced in experimental systems. We show that the fluctuations are considerably reduced, allowing us to calculate the bandwidth more accurately. Using this smoothed and ensemble averaged bandwidth, we maximize the output bandwidth with a pump wavelength of 2.8 µm and obtain a supercontinuum spectrum that extends from 2.5 µm to 6.2 µm with an uncertainty of ± 0.5 µm. The optimized bandwidth is consistent with prior work, but with a significantly increased accuracy..

Finding a pathway: information and uncertainty along the prostate cancer patient journey.

OBJECTIVES: To investigate the role of information in mediating the potential negative effects of uncertainty in prostate cancer in relation to the individual patient journey, conceptualized as the individual's response to his disease over time. DESIGN: A qualitative methodology was adopted to investigate men's constructions of their experience of information and its changing role in the management of uncertainty along the pathway of care. A cross-sectional design allowed comparison of the responses of men at similar stages and along different time points in the cancer pathway. Data collection was undertaken via focus group discussions and individual interviews. METHOD: Men from 4 weeks post-diagnosis to palliative care were recruited from hospital out-patient clinic registers and a local support group. Seven focus groups and 22 semi-structured interviews were held involving a total of 22 participants. Transcripts were analysed through a process of theme comparison. RESULTS: Findings suggest that uncertainty is both multifaceted and changing. Its impact is affected by a range of personal, disease related, and social factors. For some men it may bring about positive readjustment rather than a negative response. Effective communication of information by health professionals provides reassurance, knowledge, and understanding the balance of which varies over time and between individuals. CONCLUSION: Health professionals may contribute to the reduction of the negative effects of uncertainty through communication of information regarding process of care as well as medical issues. Strategies tailored to individual differences in information requirements and to changing needs may facilitate positive adjustment.

Non-invasive treatment of ST elevation myocardial infarction.

There is good evidence that timely restoration of coronary blood flow in obstructed infarct related arteries is a significant determinant of both short and long term mortality and morbidity. This is irrespective of whether it is achieved using fibrinolytic therapy or percutaneous coronary intervention (PCI). Despite the clear advantages of primary PCI, it is thrombolysis that remains the main reperfusion strategy in the UK. Recent data have highlighted mortality benefits when antiplatelet treatment and anticoagulation are used as adjuncts to thrombolysis. Moreover, of those who receive thrombolysis, 60% proceed to coronary arteriography within 6 months of their index event. Recent studies have been published clarifying the timing of coronary arteriography in patients who receive thrombolysis as reperfusion therapy.

Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma.

The efficacy of combination therapy including an oral gelatinase inhibitor (CT1746) and cytotoxic agent was analyzed using the murine Lewis lung carcinoma model. Primary tumors, pulmonary metastases, and sera from tumor-bearing animals had increased gelatinase B activity that was inhibited by CT1746 levels achievable in vivo. The combination of CT1746 and cyclophosphamide (CTX) was significantly more effective than either single agent in delaying local tumor growth (CT1746/CTX, 30.9 +/- 1.7 days; CT1746, 2.6 +/- 0.3 days; CTX, 19.5 +/- 1.1 days; P < .001) and reducing the number and size of pulmonary metastases [CT1746/CTX, 5 +/- 2 (15% metastases > 3 mm); CT1746, 15 +/- 4 (55% > 3 mm); CTX, 11 +/- 3 (63% > 3 mm); no treatment, 24 +/- 5 (62% > 3 mm); P < .001]. These data support the notion of combining matrix metalloproteinase inhibitors and cytotoxic agents to treat certain epithelial malignancies.

SNP-based heritability estimates of the personality dimensions and polygenic prediction of both neuroticism and major depression: findings from CONVERGE.

Biometrical genetic studies suggest that the personality dimensions, including neuroticism, are moderately heritable (~0.4 to 0.6). Quantitative analyses that aggregate the effects of many common variants have recently further informed genetic research on European samples. However, there has been limited research to date on non-European populations. This study examined the personality dimensions in a large sample of Han Chinese descent (N=10 064) from the China, Oxford, and VCU Experimental Research on Genetic Epidemiology study, aimed at identifying genetic risk factors for recurrent major depression among a rigorously ascertained cohort. Heritability of neuroticism as measured by the Eysenck Personality Questionnaire (EPQ) was estimated to be low but statistically significant at 10% (s.e.=0.03, P=0.0001). In addition to EPQ, neuroticism based on a three-factor model, data for the Big Five (BF) personality dimensions (neuroticism, openness, conscientiousness, extraversion and agreeableness) measured by the Big Five Inventory were available for controls (n=5596). Heritability estimates of the BF were not statistically significant despite high power (>0.85) to detect heritabilities of 0.10. Polygenic risk scores constructed by best linear unbiased prediction weights applied to split-half samples failed to significantly predict any of the personality traits, but polygenic risk for neuroticism, calculated with LDpred and based on predictive variants previously identified from European populations (N=171 911), significantly predicted major depressive disorder case-control status (P=0.0004) after false discovery rate correction. The scores also significantly predicted EPQ neuroticism (P=6.3 × 10-6). Factor analytic results of the measures indicated that any differences in heritabilities across samples may be due to genetic variation or variation in haplotype structure between samples, rather than measurement non-invariance. Findings demonstrate that neuroticism can be significantly predicted across ancestry, and highlight the importance of studying polygenic contributions to personality in non-European populations.

Tissue inhibitor of metalloproteinases-2 inhibits the activation of 72 kDa progelatinase by fibroblast membranes.

We report that monolayers of human fibroblasts stimulated with concanavalin A were able to activate 72 kDa progelatinase but not 95 kDa progelatinase. The activating capacity of fibroblasts appeared approx. 6 h after concanavalin A stimulation and was blocked by cycloheximide. The activation of 72 kDa progelatinase was readily inhibited by TIMP-2 but only poorly by TIMP-1. Plasma membranes isolated from the fibroblasts were capable of activating 72 kDa progelatinase. The cleavage products of the plasma membrane-mediated activation of 72 kDa progelatinase corresponded to those of organomercurial-induced self-cleavage. Only inhibitors of metalloproteinase self-cleavage inhibited the activating capacity of plasma membrane preparations, although the activating capacity was destroyed by trypsin and heat. As with the fibroblast monolayers, TIMP-2 was a potent inhibitor of the membrane-mediated activation whereas TIMP-1 was less so.