Reappraising the Role of Eplerenone in the Management of Heart Failure

Background: In India, the prevalence of heart failure (HF) is increasing at 1.2/1,000 people according to a study in northern India, and the mortality rate at 1 year (INTERnational Congestive Heart Failure [INTER-CHF]) is 37%. Due to the diverse phenotypes of HF, nonadherence to guideline-directed medical therapy (GDMT), resistance to uptitration of medication and underuse of mineralocorticoid receptor antagonists (MRAs), such as eplerenone, a uniform management approach may not be feasible. This review is aimed at assessing the burden of HF, reasons for underutilization of MRAs in treatment, evaluating the evidence and reappraising the disease-modifying role of eplerenone in HF management. Methods: An electronic database search was performed to identify relevant literature. Results: The review details various studies that demonstrate the role of MRA eplerenone as a disease-modifying agent in patients with mild-to-moderate hypertension and those with acute myocardial infarction (MI) complicated by left ventricular dysfunction and HF. It also outlines different patient profiles for eplerenone use and ways to handle minor side-effects. Conclusions: Eplerenone shows a promising effect in selectively blocking aldosterone receptors to suppress fibrosis and reverse cardiac remodeling

RanDumb: a simple approach that questions the efficacy of continual representation learning

We propose RanDumb to examine the efficacy of continual representation learning. RanDumb embeds raw pixels using a fixed random transform which approximates an RBF-Kernel, initialized before seeing any data, and learns a simple linear classifier on top. We present a surprising and consistent finding: RanDumb significantly outperforms the continually learned representations using deep networks across numerous continual learning benchmarks, demonstrating the poor performance of representation learning in these scenarios. RanDumb stores no exemplars and performs a single pass over the data, processing one sample at a time. It complements GDumb [39], operating in a lowexemplar regime where GDumb has especially poor performance. We reach the same consistent conclusions when RanDumb is extended to scenarios with pretrained models replacing the random transform with pretrained feature extractor. Our investigation is both surprising and alarming as it questions our understanding of how to effectively design and train models that require efficient continual representation learning, and necessitates a principled reinvestigation of the widely explored problem formulation itself. Our code is available here

Antihydrogen-hydrogen elastic scattering at thermal energies using an atomic-orbital technique

In view of the recent interest in the trapping of antihydrogen atom (H) over bar, at very low temperatures, (H) over bar -H scattering has been investigated at low incident energies using a close-coupling model with the basis set (H) over bar (1s,2s,2 (p) over bar)+H(1s,2s,2 (p) over bar). The predicted s-wave elastic phase shifts, scattering length, and effective range are in a good agreement with the other recent predictions of Jonsell and of Armour and Chamberlain. The results indicate that the atomic orbital expansion model is suitable to study the (H) over bar -H scattering at ultracold temperatures.67

Economic evaluation of participatory learning and action with women's groups facilitated by Accredited Social Health Activists to improve birth outcomes in rural eastern India

BACKGROUND: Neonatal mortality remains unacceptably high in many low and middle-income countries, including India. A community mobilisation intervention using participatory learning and action with women’s groups facilitated by Accredited Social Health Activists (ASHAs) was conducted to improve maternal and newborn health. The intervention was evaluated through a cluster-randomised controlled trial conducted in Jharkhand and Odisha, eastern India. This aims to assess the cost-effectiveness this intervention. METHODS: Costs were estimated from the provider’s perspective and calculated separately for the women’s group intervention and for activities to strengthen Village Health Sanitation and Nutrition Committees (VHNSC) conducted in all trial areas. Costs were estimated at 2017 prices and converted to US dollar (USD). The incremental cost-effectiveness ratio (ICER) was calculated with respect to a do-nothing alternative and compared with the WHO thresholds for cost-effective interventions. ICERs were calculated for cases of neonatal mortality and disability-adjusted life years (DALYs) averted. RESULTS: The incremental cost of the intervention was USD 83 per averted DALY (USD 99 inclusive of VHSNC strengthening costs), and the incremental cost per newborn death averted was USD 2545 (USD 3046 inclusive of VHSNC strengthening costs). The intervention was highly cost-effective according to WHO threshold, as the cost per life year saved or DALY averted was less than India’s Gross Domestic Product (GDP) per capita. The robustness of the findings to assumptions was tested using a series of one-way sensitivity analyses. The sensitivity analysis does not change the conclusion that the intervention is highly cost-effective. CONCLUSION: Participatory learning and action with women’s groups facilitated by ASHAs was highly cost-effective to reduce neonatal mortality in rural settings with low literacy levels and high neonatal mortality rates. This approach could effectively complement facility-based care in India and can be scaled up in comparable high mortality settings

Discussion on a possible neutrino detector located in India

We have identified some important and worthwhile physics opportunitites with a possible neutrino detector located in India. Particular emphasis is placed on the geographical advantage with a stress on the complimentary aspects with respect to other neutrino detectors already in operation.Comment: 9 pages; arXiv copy of published proceedings contributio

Holographic GB gravity in arbitrary dimensions

We study the properties of the holographic CFT dual to Gauss-Bonnet gravity in general $D \ge 5$ dimensions. We establish the AdS/CFT dictionary and in particular relate the couplings of the gravitational theory to the universal couplings arising in correlators of the stress tensor of the dual CFT. This allows us to examine constraints on the gravitational couplings by demanding consistency of the CFT. In particular, one can demand positive energy fluxes in scattering processes or the causal propagation of fluctuations. We also examine the holographic hydrodynamics, commenting on the shear viscosity as well as the relaxation time. The latter allows us to consider causality constraints arising from the second-order truncated theory of hydrodynamics.Comment: 48 pages, 9 figures. v2: New discussion on free fields in subsection 3.3 and new appendix B on conformal tensor fields. Added comments on the relation between the central charge appearing in the two-point function and the "central charge" characterizing the entropy density in the discussion. References adde

Human-computer interaction to human-computer-context interaction : towards a conceptual framework for conducting user studies for shifting interfaces

Computer interfaces have been diversifying: from mobile and wearable technologies to the human body as an interface. Moreover, new sensing possibilities have allowed input to interfaces to go beyond the traditional mouse- and keyboard. This has resulted in a shift from manifest to latent interactions, where interactions between the human and the computer are becoming less visible. Currently, there is no framework available that fully captures the complexity of the multidimensional, multimodal, often latent interactions with these constantly shifting interfaces. In this manuscript, the Hu-man-Computer-Context Interaction (HCCI) framework is proposed. This framework defines 5 relevant interaction levels to be considered during user research in all stages of the new product development process in order to optimize user experience. More specifically, the interaction context is defined in terms of user-object, user-user, user-content, user-platform and user-context interactions. The HCCI framework serves as a concrete tool to use in a new product development process by HCI researchers, design-ers, and developers and aims to be technology independent and future-proof. This framework is a preliminary suggestion to be matched against other innovation devel-opment projects and needs to be further validated

MYC Cooperates with AKT in Prostate Tumorigenesis and Alters Sensitivity to mTOR Inhibitors

MYC and phosphoinositide 3-kinase (PI3K)-pathway deregulation are common in human prostate cancer. Through examination of 194 human prostate tumors, we observed statistically significant co-occurrence of MYC amplification and PI3K-pathway alteration, raising the possibility that these two lesions cooperate in prostate cancer progression. To investigate this, we generated bigenic mice in which both activated human AKT1 and human MYC are expressed in the prostate (MPAKT/Hi-MYC model). In contrast to mice expressing AKT1 alone (MPAKT model) or MYC alone (Hi-MYC model), the bigenic phenotype demonstrates accelerated progression of mouse prostate intraepithelial neoplasia (mPIN) to microinvasive disease with disruption of basement membrane, significant stromal remodeling and infiltration of macrophages, B- and T-lymphocytes, similar to inflammation observed in human prostate tumors. In contrast to the reversibility of mPIN lesions in young MPAKT mice after treatment with mTOR inhibitors, Hi-MYC and bigenic MPAKT/Hi-MYC mice were resistant. Additionally, older MPAKT mice showed reduced sensitivity to mTOR inhibition, suggesting that additional genetic events may dampen mTOR dependence. Since increased MYC expression is an early feature of many human prostate cancers, these data have implications for treatment of human prostate cancers with PI3K-pathway alterations using mTOR inhibitors

Predictors of Visceral Leishmaniasis Relapse in HIV-Infected Patients: A Systematic Review

Visceral leishmaniasis (VL) is the most serious form of an insect-transmitted parasitic disease prevalent in 70 countries. The disease is caused by species of the L. donovani complex found in different geographical regions. These parasites have substantially different clinical, drug susceptibility and epidemiological characteristics. According to data from the World Health Organization, the areas where HIV-Leishmania co-infection is distributed are extensive. HIV infection increases the risk of developing VL, reduces the likelihood of a therapeutic response, and greatly increases the probability of relapse. A better understanding of the factors promoting relapses is essential; therefore we performed a systematic review of articles involving all articles assessing the predictors of VL relapse in HIV-infected individuals older than 14 years of age. Out of 178 relevant articles, 18 met the inclusion criteria and in total, data from 1017 patients were analyzed. We identified previous episodes of VL relapse, CD4+ lymphocyte count fewer than 100 cells/mL at VL diagnosis, and the absence of an increase in CD4+ counts at follow-up as major factors associated with VL relapse. Knowledge of relapse predictors can help to identify patients with different degrees of risk, facilitate and direct prophylaxis choices, and aid in patient counseling

Drug Susceptibility in Leishmania Isolates Following Miltefosine Treatment in Cases of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis

Resistance to antimonials has emerged as a major hurdle to the treatment and control of VL and led to the introduction of Miltefosine as first line treatment in the Indian subcontinent. MIL is an oral drug with a long half-life, and it is feared that resistance may emerge rapidly, threatening control efforts under the VL elimination program. There is an urgent need for monitoring treatment efficacy and emergence of drug resistance in the field. In a set of VL/PKDL cases recruited for MIL treatment, we observed comparable drug susceptibility in pre- and post-treatment isolates from cured VL patients while MIL susceptibility was significantly reduced in isolates from VL relapse and PKDL cases. The PKDL isolates showed higher tolerance to MIL as compared to VL isolates. Both VL and PKDL isolates were uniformly susceptible to PMM. MIL transporter genes LdMT/LdRos3 were previously reported as potential resistance markers in strains in which MIL resistance was experimentally induced. The point mutations and the down-regulated expression of these transporters observed in vitro could, however, not be verified in natural populations of parasites. LdMT/LdRos3 genes therefore, do not appear to be suitable markers so far for monitoring drug susceptibility in clinical leishmanial isolates