Optimal monetary policy rules for the euro area: an analysis using the area wide model

In this paper, we analyze optimal monetary policy rules in a model of the euro area, namely the ECB’s Area Wide Model, which embodies a high degree of intrinsic persistence and a limited role for forward-looking expectations. These features allow us, in large measure, to differentiate our results from many of those prevailing in New Keynesian paradigm models. Speci?cally, our exercises involve analyzing the performance of various generalized Taylor rules both from the literature and optimized to the reference model. Given the features of our modelling framework, we ?nd that optimal policy smoothing need only be relatively mild. Furthermore, there is substantial gain from implementing forecast-based as opposed to outcome-based policies with the optimal forecast horizon for in?ation ranging between two and three years. Benchmarking against fully optimal policies, we further highlight that the gain of additional states in the rule may compensate for a reduction of communicability. Thus, the paper contributes to the debate on optimal monetary policy in the euro area, as well as to the conduct of monetary policy in face of substantial persistence in the transmission mechanism. JEL Classification: E4, E5euro area, monetary policy rule, optimization

Movement-based interfaces for problem solving in dynamics

Humans have a natural ability to cope with the problems of moving in a changing environment. The motivation for our work is to engage our natural ability to move in the understanding of more abstract problems associated with dynamical systems. The question we address is: “Can human movement be coupled to simulations of arbitrary dynamical systems to help understand these more abstract mathematical problems?” In this paper we present a case study where users perform multiple trials to try to find a solution to a well known predator-prey problem by using a simple movement-based interface. Indeed users are able to find a number of different solutions without prior expertise in this domain. While these solutions fall short of being strictly optimal the results provide a convincing proof of concept as well as raising new questions to direct our further enquiries in this area

Free Antiretrovirals Must Not Be Restricted Only to Treatment-Naive Patients: Experience in Uganda suggests that restricting access is not the way forward

In some antiretroviral drug distribution programmes, free drugs are provided only, or preferentially, to patients who are treatment-naive. Colebunders and colleagues argue that such a restricted policy is highly problematic

Evaluating spillover of HIV knowledge from study participants to their network members in a stepped-wedge behavioural intervention in Tanzania.

OBJECTIVES: We aim to describe the social network members of participants of a behavioural intervention, and examine how the effects of the intervention may spillover among network members. DESIGN: Secondary analysis of a step-wedge randomised controlled trial. SETTING: Change agents (CAs) were recruited from waiting rooms of HIV treatment facilities in Dar es Salaam, Tanzania, and their network members (NMs) were recruited directly by CAs. PARTICIPANTS: We enrolled 662 CAs in an HIV behavioural intervention. They, along with 710 of their NMs, completed baseline and follow-up interviews from 2011 to 2013. PRIMARY AND SECONDARY OUTCOMES: The primary outcome of this study was change in NMs' HIV knowledge, and the secondary outcome was whether the NM was lost to follow-up. RESULTS: At baseline, many characteristics were different between NMs and CAs. We found a number of NM characteristics significantly associated with follow-up of NMs, particularly female gender (OR=1.64, 95% CI: 1.02 to 2.63) and HIV knowledge (OR=20.0, 95% CI: 3.70 to 125); only one CA variable was significantly associated with NM follow-up: having a private source of water (OR=2.17, 95% CI: 1.33 to 3.57). The 14.2% increase in NMs' HIV knowledge was largely due to CAs feeling empowered to pass on prior knowledge, rather than transmitting new knowledge to their NMs. CONCLUSIONS: Characteristics of social network members of persons living with HIV persons living with HIV may play a role in study retention. Additionally, the HIV knowledge of these NMs increased largely as a function of CA participation in the intervention, suggesting that intervening among highly-connected individuals may maximise benefits to the potential population for whom spillover can occur. TRIAL REGISTRATION NUMBER: Clinical Trial: NCT01693458; Post-results

TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and vaccination

Adenovirus has enormous potential as a gene-therapy vector, but preexisting immunity limits its widespread application. What is responsible for this immune block is unclear because antibodies potently inhibit transgene expression without impeding gene transfer into target cells. Here we show that antibody prevention of adenoviral gene delivery in vivo is mediated by the cytosolic antibody receptor TRIM21. Genetic KO of TRIM21 or a single-antibody point mutation is sufficient to restore transgene expression to near-naïve immune levels. TRIM21 is also responsible for blocking cytotoxic T cell induction by vaccine vectors, preventing a protective response against subsequent influenza infection and an engrafted tumor. Furthermore, adenoviral preexisting immunity can lead to an augmented immune response upon i.v. administration of the vector. Transcriptomic analysis of vector-transduced tissue reveals that TRIM21 is responsible for the specific up-regulation of hundreds of immune genes, the majority of which are components of the intrinsic or innate response. Together, these data define a major mechanism underlying the preimmune block to adenovirus gene therapy and demonstrate that TRIM21 efficiently blocks gene delivery in vivo while simultaneously inducing a rapid program of immune transcription

Agents of change: Comparing HIV-related risk behavior of people attending ART clinics in Dar es Salaam with members of their social networks.

The aim of the study is to compare sociodemographic characteristics, psychosocial factors, HIV knowledge and risk behaviors of people living with HIV (PLH) and their social network members (NMs) to inform HIV prevention programs that engage PLH as prevention educators in their communities. We compared baseline characteristics of PLH enrolled in an intervention to become HIV prevention Change Agents (CAs) (n = 458) and 602 NMs they recruited. CAs and NMs responded to questionnaires through a computer-driven interface with Audio Computer-Assisted Self Interview (ACASI) software. Although NMs scored higher on socio-economic status, self-esteem and general self-efficacy, they had lower HIV knowledge (AOR 1.5; 95% CI: 1.1-2.1), greater inconsistent condom use (AOR 3.2; 95% CI: 2.4-4.9), and recent experience as perpetrators of physical (AOR 2.5; 95% CI: 1.2-5.1) or sexual (AOR 4.1; 95% CI: 1.4-12.7) intimate partner violence; and as victims of physical (AOR 1.5; 95% CI: 1.0-2.3) or sexual (AOR 2.2; 95% CI: 1.3-3.8) forms of violence than CAs. Higher HIV knowledge and lower sexual risk behaviors among CAs suggest PLH's potential as communicators of HIV prevention information to NMs. CAs' training should also focus on improving self-esteem, general self-efficacy and social support to increase their potential effectiveness as HIV prevention educators and enhance their own overall health and well-being

Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda

BACKGROUND Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda. INTERVENTION Existing laboratory infrastructure was repurposed, and new equipment was acquired. Laboratory personnel were hired and trained to optimise, validate, and develop in-house methods for testing antiretroviral, anti-tuberculosis and other drugs, including 10 high-performance liquid chromatography methods and four mass spectrometry methods. We reviewed all research collaborations and projects for which samples were assayed in the laboratory from January 2006 to November 2020. We assessed laboratory staff mentorship from collaborative relationships and the contribution of research projects towards human resource development, assay development, and equipment and maintenance costs. We further assessed the quality of testing and use of the laboratory for research and clinical care. LESSONS LEARNT Fourteen years post inception, the clinical pharmacology laboratory had contributed significantly to the overall research output at the institute by supporting 26 pharmacokinetic studies. The laboratory has actively participated in an international external quality assurance programme for the last four years. For clinical care, a therapeutic drug monitoring service is accessible to patients living with HIV at the Adult Infectious Diseases clinic in Kampala, Uganda. RECOMMENDATIONS Driven primarily by research projects, clinical pharmacology laboratory capacity was successfully established in Uganda, resulting in sustained research output and clinical support. Strategies implemented in building capacity for this laboratory may guide similar processes in other low- and middle-income countries

Agents of change among people living with HIV and their social networks: stepped-wedge randomised controlled trial of the NAMWEZA intervention in Dar es Salaam, Tanzania.

INTRODUCTION: NAMWEZA is a novel intervention that focuses on preventing HIV and promoting sexual and reproductive health and rights by addressing underlying factors related to vulnerability of acquiring HIV, such as depression, intimate partner violence (IPV) and stigma. The goal of the study was to evaluate the effect of the NAMWEZA intervention on risk behaviour as well as factors potentially contributing to this vulnerability for people living with HIV and their network members. METHODS: A stepped-wedge randomised controlled trial was conducted from November 2010 to January 2014 among people living with HIV and their network members in Dar es Salaam, Tanzania. 458 people living with HIV were randomised within age/sex-specific strata to participate in the NAMWEZA intervention at three points in time. In addition, 602 members of their social networks completed the baseline interview. Intention-to-treat analysis was performed, including primary outcomes of uptake of HIV services, self-efficacy, self-esteem, HIV risk behaviour and IPV. RESULTS: For people living with HIV, a number of outcomes improved with the NAMWEZA intervention, including higher self-efficacy and related factors, as well as lower levels of depression and stigma. IPV reduced by 40% among women. Although reductions in HIV risk behaviour were not observed, an increase in access to HIV treatment was reported for network members (72% vs 94%, p=0.002). CONCLUSION: These results demonstrate the complexity of behavioural interventions in reducing the vulnerability of acquiring HIV, since it is possible to observe a broad range of different outcomes. This study indicates the importance of formally evaluating interventions so that policymakers can build on evidence-based approaches to advance the effectiveness of HIV prevention interventions. TRIAL REGISTRATION NUMBER: NCT01693458

Rigorous Clinical Trial Design in Public Health Emergencies Is Essential.

Randomized clinical trials are the most reliable approaches to evaluating the effects of new treatments and vaccines. During the 2014-2015 West African Ebola epidemic, many argued that such trials were neither ethical nor feasible in an environment of limited health infrastructure and severe disease with a high fatality rate. Consensus among the numerous organizations providing help to the affected areas was never achieved, resulting in fragmented collaboration, delayed study initiation, and ultimately failure to provide definitive evidence on the efficacy of treatments and vaccines. Randomized trials were in fact approved by local ethics boards and initiated, demonstrating that randomized trials, even in such difficult circumstances, are feasible. Improved planning and collaboration among research and humanitarian organizations, and affected communities, in the interepidemic periods are needed to ensure that questions regarding the efficacy of vaccines and treatments can be definitively answered during future public health emergencies

Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases

BACKGROUND: New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced ability to compare new treatment strategies. The ELISPOT assay uses Mycobacterium tuberculosis-specific antigens to produce a precise quantitative readout of the immune response to pathogen. We hypothesized that TB patients in The Gambia would have reduced ELISPOT counts after successful treatment. METHODS: We recruited Gambian adults with sputum smear and culture positive tuberculosis for ELISPOT assay and HIV test, and followed them up one year later to repeat testing and document treatment outcome. We used ESAT-6, CFP-10 and Purified Protein Derivative (PPD) as stimulatory antigens. We confirmed the reliability of our assay in 23 volunteers through 2 tests one week apart, comparing within and between subject variation. RESULTS: We performed an ELISPOT test at diagnosis and 12 months later in 89 patients. At recruitment, 70/85 HIV-negative patients (82%) were ESAT-6 or CFP-10 (EC) ELISPOT positive, 77 (90%) were PPD ELISPOT positive. Eighty-two cases (96%) successfully completed treatment: 44 (55%; p < 0.001) were EC ELISPOT negative at 12 months, 17 (21%; p = 0.051) were PPD ELISPOT negative. Sixty (73%) cured cases had a CFP-10 ELISPOT count decrease, 64 (78%) had an ESAT-6 ELISPOT count decrease, 58 (70%) had a PPD ELISPOT count decrease. There was a mean decline of 25, 44 and 47 SFU/2 × 10(5 )cells for CFP-10, ESAT-6 and PPD respectively (p < 0.001 for all). Three of 4 HIV positive patients were cured, all 3 underwent ELISPOT reversion; all 4 not cured subjects (3 HIV-negative, 1 HIV positive) were ESAT-6, CFP-10 and PPD ELISPOT positive at 12 months. CONCLUSION: Successful tuberculosis treatment is accompanied by a significant reduction in the M. tuberculosis-specific antigen ELISPOT count. The ELISPOT has potential as a proxy measure of TB treatment outcome. Further investigation into the decay kinetics of T-cells with treatment is warranted