Indexing dialysis dose for gender, body size and physical activity: Impact on survival

Current practice basing dialysis dose on urea distribution volume (V) has been questioned. We explored the impact on survival of scaling dialysis dose (Kt) to parameters reflective of metabolic activity. In a multicentre prospective cohort study of 1500 patients on thrice-weekly haemodialysis, body surface area (BSA) and resting energy expenditure (REE) were estimated using validated equations and physical activity by the Recent Physical Activity Questionnaire. Total energy expenditure (TEE) was estimated from REE and physical activity data. Kt was calculated from delivered (single-pool Kt/V)*Watson V. Kt/BSA, Kt/ REE and Kt/TEE were then calculated at baseline and 6 monthly during follow-up for 2 years. In adjusted Cox models Kt/TEE, Kt/BSA, Kt/REE, in that order, had lower hazard ratios for death than single-pool Kt/V. On the basis of adjusted survival differences, putative minimum target doses were estimated for Kt/BSA as 27119 ml/m 2 and Kt/TEE as 25.79 ml/ kcal. We identified spKt/V values equivalent to these estimated targets, ranging from 1.4 to 1.8 in patient groups based on gender, body size and physical activity. For sedentary patients, the minimum target dose was 1.4 for large males, 1.5 for small males and 1.7 for women. For active patients the target was 1.8 irrespective of gender and body-weight. Patients achieving these individualised minimum targets had greater adjusted two-year survival compared to those achieving conventional minimum targets. Metabolic activity related parameters, such as Kt/TEE and Kt/BSA, may have a clinically important role in scaling haemodialysis dose. Using such parameters or their spKt/V equivalents to adjust minimum target doses based on gender, body size and habitual physical activity may have a positive impact on survival.Peer reviewe

Self-reported depression symptoms in haemodialysis patients: Bi-factor structures of two common measures and their association with clinical factors

Copyright © 2018 Elsevier Inc. All rights reserved.Objective: To validate the factor structure of two common self-report depression tools in a large sample of haemodialysis (HD) patients and to examine their demographic and clinical correlates, including urine output, history of depression and transplantation. Methods: Factor structures of the Beck Depression Inventory (BDI-II) and Patient Health Questionnaire (PHQ-9) were evaluated using confirmatory factor analysis (CFA). Data was utilised from the screening phase (n = 709) of a placebo-controlled feasibility randomised control trial (RCT) of sertraline in HD patients with mild to moderate Major Depressive Disorder. Alternative factor models including bi-factor models for the BDI-II and PHQ-9 were evaluated. Coefficient omega and omega-hierarchical were calculated. Results: For both measures, bi-factor measurement models had the overall best fit to the data, with dominant general depression factors. Omega-hierarchical for the general BDI-II and PHQ-9 factors was 0.94 and 0.88 respectively. Both general factors had high reliability (coefficient omega = 0.97 and 0.94 respectively) and explained over 85% of the explained common variance within their respective models. BDI-II and PHQ-9 general depression factors were negatively associated with age and urine output and positively with a history of depression, antidepressant use within the last 3 months and a history of failed transplantation. In adjusted regression models, age, urine output and a history of depression remained significant. Conclusions: These data suggest that both the BDI-II and PHQ-9 are sufficiently unidimensional to warrant the use of a total score. Younger age, lower urine output and a history of depression appear consistent correlates of depression severity among HD patients.Peer reviewedFinal Accepted Versio

Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation

Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart. Here we describe three novel mouse models of rhinovirus infection: minor-group rhinovirus infection of BALB/c mice, major-group rhinovirus infection of transgenic BALB/c mice expressing a mouse-human ICAM-1 chimera and rhinovirus-induced exacerbation of allergic airway inflammation. These models have features similar to those observed in rhinovirus infection in humans, including augmentation of allergic airway inflammation, and will be useful in the development of future therapies for colds and asthma exacerbations

Self-productivity and complementarities in human development : evidence from MARS

This paper investigates the role of self-productivity and home resources in capability formation from infancy to adolescence. In addition, we study the complementarities between basic cognitive, motor and noncognitive abilities and social as well as academic achievement. Our data are taken from the Mannheim Study of Children at Risk (MARS), an epidemiological cohort study following the long-term outcome of early risk factors. Results indicate that initial risk conditions cumulate and that differences in basic abilities increase during development. Self-productivity rises in the developmental process and complementarities are evident. Noncognitive abilities promote cognitive abilities and social achievement. There is remarkable stability in the distribution of the economic and socio-emotional home resources during the early life cycle. This is presumably a major reason for the evolution of inequality in human development

Species difference in ANP32A underlies influenza A virus polymerase host restriction.

Influenza pandemics occur unpredictably when zoonotic influenza viruses with novel antigenicity acquire the ability to transmit amongst humans. Host range breaches are limited by incompatibilities between avian virus components and the human host. Barriers include receptor preference, virion stability and poor activity of the avian virus RNA-dependent RNA polymerase in human cells. Mutants of the heterotrimeric viral polymerase components, particularly PB2 protein, are selected during mammalian adaptation, but their mode of action is unknown. We show that a species-specific difference in host protein ANP32A accounts for the suboptimal function of avian virus polymerase in mammalian cells. Avian ANP32A possesses an additional 33 amino acids between the leucine-rich repeats and carboxy-terminal low-complexity acidic region domains. In mammalian cells, avian ANP32A rescued the suboptimal function of avian virus polymerase to levels similar to mammalian-adapted polymerase. Deletion of the avian-specific sequence from chicken ANP32A abrogated this activity, whereas its insertion into human ANP32A, or closely related ANP32B, supported avian virus polymerase function. Substitutions, such as PB2(E627K), were rapidly selected upon infection of humans with avian H5N1 or H7N9 influenza viruses, adapting the viral polymerase for the shorter mammalian ANP32A. Thus ANP32A represents an essential host partner co-opted to support influenza virus replication and is a candidate host target for novel antivirals

A study of sertraline in dialysis (ASSertID) : a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis

© 2015 Friedli et al. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedBACKGROUND: The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder.METHODS/DESIGN: The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial.DISCUSSION: There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression.TRIAL REGISTRATION: ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.Peer reviewedFinal Published versio

"Feed from the Service": Corruption and Coercion in the State-University Relations in Central Eurasia

Education in Central Eurasia has become one of the industries, most affected by corruption. Corruption in academia, including bribery, extortions, embezzlement, nepotism, fraud, cheating, and plagiarism, is reflected in the region’s media and addressed in few scholarly works. This paper considers corruption in higher education as a product of interrelations between the government and academia. A substantial block of literature considers excessive corruption as an indicator of a weak state. In contrast to standard interpretations, this paper argues that in non-democratic societies corruption is used on a systematic basis as a mechanism of direct and indirect administrative control over higher education institutions. Informal approval of corrupt activities in exchange for loyalty and compliance with the regime may be used in the countries of Central Eurasia for the purposes of political indoctrination. This paper presents the concept of corruption and coercion in the state-university relations in Central Eurasia and outlines the model which incorporates this concept and the “feed from the service” approach. It presents implications of this model for the state-university relations and the national educational systems in Central Eurasia in general and offers some suggestions on curbing corruption

Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits Suggests a Role of an Efficient Polymerase for Virus Adaptation

Amongst all the internal gene segments (PB2. PB1, PA, NP, M and NS), the avian PB1 segment is the only one which was reassorted into the human H2N2 and H3N2 pandemic strains. This suggests that the reassortment of polymerase subunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission. To test this hypothesis, we tested the compatibility between PB2, PB1, PA and NP derived from a H5N1 virus and a mammalian H1N1 virus. All 16 possible combinations of avian-mammalian chimeric viral ribonucleoproteins (vRNPs) were characterized. We showed that recombinant vRNPs with a mammalian PB2 and an avian PB1 had the strongest polymerase activities in human cells at all studied temperature. In addition, viruses with this specific PB2-PB1 combination could grow efficiently in cell cultures, especially at a high incubation temperature. These viruses were potent inducers of proinflammatory cytokines and chemokines in primary human macrophages and pneumocytes. Viruses with this specific PB2-PB1 combination were also found to be more capable to generate adaptive mutations under a new selection pressure. These results suggested that the viral polymerase activity might be relevant for the genesis of influenza viruses of human health concern

Immunization with Single-Cycle SIV Significantly Reduces Viral Loads After an Intravenous Challenge with SIVmac239

Strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type SIVmac239 infection of rhesus macaques by two different vaccine regimens. Six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle SIV (scSIV). Six additional animals were primed with a mixture of cytoplasmic domain-truncated envelope variants of scSIV and boosted with two doses of vesicular stomatitis virus glycoprotein (VSV G) trans-complemented scSIV. While both regimens elicited detectable virus-specific T cell responses, SIV-specific T cell frequencies were more than 10-fold higher after boosting with VSV G trans-complemented scSIV (VSV G scSIV). Broad T cell recognition of multiple viral antigens and Gag-specific CD4+ T cell responses were also observed after boosting with VSV G scSIV. With the exception of a single animal in the repeated immunization group, all of the animals became infected following an intravenous challenge with SIVmac239. However, significantly lower viral loads and higher memory CD4+ T cell counts were observed in both immunized groups relative to an unvaccinated control group. Indeed, both scSIV immunization regimens resulted in containment of SIVmac239 replication after challenge that was as good as, if not better than, what has been achieved by other non-persisting vaccine vectors that have been evaluated in this challenge model. Nevertheless, the extent of protection afforded by scSIV was not as good as typically conferred by persistent infection with live, attenuated SIV. These observations have potentially important implications to the design of an effective AIDS vaccine, since they suggest that ongoing stimulation of virus-specific immune responses may be essential to achieving the degree of protection afforded by live, attenuated SIV