Liver enzyme elevations in a cohort of HIV/AIDS patients on first-line antiretroviral therapy in Namibia: Findings and implications

Introduction: All antiretroviral therapies (ARTs) are potentially toxic to the liver. In sub-Saharan Africa, the rising incidence of ART induced adverse events has complicated treatment leading to recent revisions of Namibian ART guidelines. Unfortunately there have been limited studies to date evaluating ART induced liver injury in Namibia to guide further revisions if needed. Objective: Determine the current patterns and grades of ALT elevation in Namibia’s HIV/AIDS. Methods: Retrospective cohort analysis. Patterns of alanine amino transferase (ALT) liver enzyme elevation were determined in a cohort of ART naïve HIV patients on firstline ART regimen in a referral hospital in Namibia over a 1 year treatment period. Patterns of ALT changes at baseline, 3 months and 6 months were analyzed using ANOVA and Bonferroni test for pairwise comparisons. Results: Of 79 eligible patients, 72 developed significant ALT elevation within 3 months of ART initiation (F (3, 76) = 6.4, p = 0.002, η2 = 0.193). Four 4 (5.6%) and 1 (1.38%) patient respectively developed grade 2 and grade 3 ALT elevation by month 3. There was no significant difference between mean ALT levels at baseline and month 6. A CD4 count of <350 cells/mm3; female gender and age over 40 years were the main factors associated with moderate or severe ALT elevation. Conclusions: First line ART commonly induces mild self-limiting liver enzyme elevation in Namibian HIV patients especially in the first 3 months. Consequently, there is a need to monitor ALT levels for at least 3 months after initiation mainly in high risk patients to reduce side-effect concerns. This is already happening

Rings of real functions in pointfree topology

AbstractThis paper deals with the algebra F(L) of real functions on a frame L and its subclasses LSC(L) and USC(L) of, respectively, lower and upper semicontinuous real functions. It is well known that F(L) is a lattice-ordered ring; this paper presents explicit formulas for its algebraic operations which allow to conclude about their behaviour in LSC(L) and USC(L).As applications, idempotent functions are characterized and previous pointfree results about strict insertion of functions are significantly improved: general pointfree formulations that correspond exactly to the classical strict insertion results of Dowker and Michael regarding, respectively, normal countably paracompact spaces and perfectly normal spaces are derived.The paper ends with a brief discussion concerning the frames in which every arbitrary real function on the α-dissolution of the frame is continuous

Supersymmetry of Noncompact MQCD-like Membrane Instantons and Heat Kernel Asymptotics

We perform a heat kernel asymptotics analysis of the nonperturbative superpotential obtained from wrapping of an M2-brane around a supersymmetric noncompact three-fold embedded in a (noncompact) G_2-manifold as obtained in [1], the three-fold being the one relevant to domain walls in Witten's MQCD [2], in the limit of small "zeta", a complex constant that appears in the Riemann surfaces relevant to defining the boundary conditions for the domain wall in MQCD. The MQCD-like configuration is interpretable, for small but non-zero zeta as a noncompact/"large" open membrane instanton, and for vanishing zeta, as the type IIA D0-brane (for vanishing M-theory cicle radius). We find that the eta-function Seeley de-Witt coefficients vanish, and we get a perfect match between the zeta-function Seeley de-Witt coefficients (up to terms quadratic in zeta) between the Dirac-type operator and one of the two Laplace-type operators figuring in the superpotential. This is an extremely strong signature of residual supersymmetry for the nonperturbative configurations in M-theory considered in this work.Comment: 21 pages, LaTeX; v3: several clarifying remarks added, to appear in JHE

Temperature dependent characterization of optical fibres for distributed temperature sensing in hot geothermal wells

This study was performed in order to select a proper fibre for the application of a distributed temperature sensing system within a hot geothermal well in Iceland. Commercially available high temperature graded index fibres have been tested under in-situ temperature conditions. Experiments have been performed with four different polyimide coated fibres, a fibre with an aluminum coating and a fibre with a gold coating. To select a fibre, the relationship between attenuation, temperature, and time has been analyzed together with SEM micrographs. On the basis of these experiments, polyimide fibres have been chosen for utilisation. Further tests in ambient and inert atmosphere have been conducted with two polyimide coated fibres to set an operating temperature limit for these fibres. SEM micrographs, together with coating colour changes have been used to characterize the high temperature performance of the fibres. A novel cable design has been developed, a deployment strategy has been worked out and a suitable well for deployment has been selected.Comment: PACS: 42.81.Pa, 93.85.Fg, 47.80.Fg, 91.35.Dc, 07.20.Dt, 07.60.V

Black Hole Microstates and Attractor Without Supersymmetry

Due to the attractor mechanism, the entropy of an extremal black hole does not vary continuously as we vary the asymptotic values of various moduli fields. Using this fact we argue that the entropy of an extremal black hole in string theory, calculated for a range of values of the asymptotic moduli for which the microscopic theory is strongly coupled, should match the statistical entropy of the same system calculated for a range of values of the asymptotic moduli for which the microscopic theory is weakly coupled. This argument does not rely on supersymmetry and applies equally well to nonsupersymmetric extremal black holes. We discuss several examples which support this argument and also several caveats which could invalidate this argument.Comment: 50 pages; references adde

Chiral Supergravity

We study the linearized approximation of N=1 topologically massive supergravity around AdS3. Linearized gravitino fields are explicitly constructed. For appropriate boundary conditions, the conserved charges demonstrate chiral behavior, so that chiral gravity can be consistently extended to chiral supergravity.Comment: 30 page

Moduli and (un)attractor black hole thermodynamics

We investigate four-dimensional spherically symmetric black hole solutions in gravity theories with massless, neutral scalars non-minimally coupled to gauge fields. In the non-extremal case, we explicitly show that, under the variation of the moduli, the scalar charges appear in the first law of black hole thermodynamics. In the extremal limit, the near horizon geometry is $AdS_2\times S^2$ and the entropy does not depend on the values of moduli at infinity. We discuss the attractor behaviour by using Sen's entropy function formalism as well as the effective potential approach and their relation with the results previously obtained through special geometry method. We also argue that the attractor mechanism is at the basis of the matching between the microscopic and macroscopic entropies for the extremal non-BPS Kaluza-Klein black hole.Comment: 36 pages, no figures, V2: minor changes, misprints corrected, expanded references; V3: sections 4.3 and 4.5 added; V4: minor changes, matches the published versio

Family-led rehabilitation after stroke in India (ATTEND): a randomised controlled trial

Background: Most people with stroke in India have no access to organised rehabilitation services. The effectiveness of training family members to provide stroke rehabilitation is uncertain. Our primary objective was to determine whether family-led stroke rehabilitation, initiated in hospital and continued at home, would be superior to usual care in a low-resource setting. Methods: The Family-led Rehabilitation after Stroke in India (ATTEND) trial was a prospectively randomised open trial with blinded endpoint done across 14 hospitals in India. Patients aged 18 years or older who had had a stroke within the past month, had residual disability and reasonable expectation of survival, and who had an informal family-nominated caregiver were randomly assigned to intervention or usual care by site coordinators using a secure web-based system with minimisation by site and stroke severity. The family members of participants in the intervention group received additional structured rehabilitation training—including information provision, joint goal setting, carer training, and task-specific training—that was started in hospital and continued at home for up to 2 months. The primary outcome was death or dependency at 6 months, defined by scores 3–6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) as assessed by masked observers. Analyses were by intention to treat. This trial is registered with Clinical Trials Registry-India (CTRI/2013/04/003557), Australian New Zealand Clinical Trials Registry (ACTRN12613000078752), and Universal Trial Number (U1111-1138-6707). Findings: Between Jan 13, 2014, and Feb 12, 2016, 1250 patients were randomly assigned to intervention (n=623) or control (n=627) groups. 33 patients were lost to follow-up (14 intervention, 19 control) and five patients withdrew (two intervention, three control). At 6 months, 285 (47%) of 607 patients in the intervention group and 287 (47%) of 605 controls were dead or dependent (odds ratio 0·98, 95% CI 0·78–1·23, p=0·87). 72 (12%) patients in the intervention group and 86 (14%) in the control group died (p=0·27), and we observed no difference in rehospitalisation (89 [14%]patients in the intervention group vs 82 [13%] in the control group; p=0·56). We also found no difference in total non-fatal events (112 events in 82 [13%] intervention patients vs 110 events in 79 [13%] control patients; p=0·80). Interpretation: Although task shifting is an attractive solution for health-care sustainability, our results do not support investment in new stroke rehabilitation services that shift tasks to family caregivers, unless new evidence emerges. A future avenue of research should be to investigate the effects of task shifting to health-care assistants or team-based community care. Funding: The National Health and Medical Research Council of Australia

Developing expert international consensus statements for opioid-sparing analgesia using the Delphi method

Introduction: The management of postoperative pain in anaesthesia is evolving with a deeper understanding of associating multiple modalities and analgesic medications. However, the motivations and barriers regarding the adoption of opioid-sparing analgesia are not well known. Methods: We designed a modified Delphi survey to explore the perspectives and opinions of expert panellists with regard to opioid-sparing multimodal analgesia. 29 anaesthetists underwent an evolving three-round questionnaire to determine the level of agreement on certain aspects of multimodal analgesia, with the last round deciding if each statement was a priority. Results: The results were aggregated and a consensus, defined as achievement of over 75% on the Likert scale, was reached for five out of eight statements. The panellists agreed there was a strong body of evidence supporting opioid-sparing multimodal analgesia. However, there existed multiple barriers to widespread adoption, foremost the lack of training and education, as well as the reluctance to change existing practices. Practical issues such as cost effectiveness, increased workload, or the lack of supply of anaesthetic agents were not perceived to be as critical in preventing adoption. Conclusion: Thus, a focus on developing specific guidelines for multimodal analgesia and addressing gaps in education may improve the adoption of opioid-sparing analgesia

Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres

Objective: To determine the relation between age and troponin level and its prognostic implication. / Design: Retrospective cohort study. / Setting: Five cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC). / Participants: 257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017. / Main outcome measure: All cause mortality. / Results: 257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient’s hospital stay. Troponin levels were standardised as a multiple of each laboratory’s 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively. / Conclusions: A positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks. / Study registration: ClinicalTrials.gov NCT03507309