Altered sense of humor in dementia.

Sense of humor is potentially relevant to social functioning in dementias, but has been little studied in these diseases. We designed a semi-structured informant questionnaire to assess humor behavior and preferences in patients with behavioral variant frontotemporal dementia (bvFTD; n = 15), semantic dementia (SD; n = 7), progressive nonfluent aphasia (PNFA; n = 10), and Alzheimer's disease (AD; n = 16) versus healthy age-matched individuals (n = 21). Altered (including frankly inappropriate) humor responses were significantly more frequent in bvFTD and SD (all patients) than PNFA or AD (around 40% of patients). All patient groups liked satirical and absurdist comedy significantly less than did healthy controls. This pattern was reported premorbidly for satirical comedy in bvFTD, PNFA, and AD. Liking for slapstick comedy did not differ between groups. Altered sense of humor is particularly salient in bvFTD and SD, but also frequent in AD and PNFA. Humor may be a sensitive probe of social cognitive impairment in dementia, with diagnostic, biomarker and social implications

What is the optimum time to start antiretroviral therapy in people with HIV and tuberculosis coinfection? A systematic review and meta-analysis.

BACKGROUND: HIV and tuberculosis are frequently diagnosed concurrently. In March 2021, World Health Organization recommended that antiretroviral therapy (ART) should be started within two weeks of tuberculosis treatment start, at any CD4 count. We assessed whether earlier ART improved outcomes in people with newly diagnosed HIV and tuberculosis. METHODS: We did a systematic review by searching nine databases for trials that compared earlier ART to later ART initiation in people with HIV and tuberculosis. We included studies published from database inception to 12 March 2021. We compared ART within four weeks versus ART more than four weeks after TB treatment, and ART within two weeks versus ART between two and eight weeks, and stratified analysis by CD4 count. The main outcome was death; secondary outcomes included IRIS and AIDS-defining events. We pooled effect estimates using random effects meta-analysis. RESULTS AND DISCUSSION: We screened 2468 abstracts, and identified nine trials. Among people with all CD4 counts, there was no difference in mortality by earlier ART (≤4 week) versus later ART (>4 week) (risk difference [RD] 0%, 95% confidence interval [CI] -2% to +1%). Among people with CD4 count ≤50 cells/mm3 , earlier ART (≤4 weeks) reduced risk of death (RD -6%, -10% to -1%). Among people with all CD4 counts earlier ART (≤4 weeks) increased the risk of IRIS (RD +6%, 95% CI +2% to +10%) and reduced the incidence of AIDS-defining events (RD -2%, 95% CI -4% to 0%). Results were similar when trials were restricted to the four trials which permitted comparison of ART within two weeks to ART between two and eight weeks. Trials were conducted between 2004 and 2014, before recommendations to treat HIV at any CD4 count or to rapidly start ART in people without TB. No trials included children or pregnant women. No trials included integrase inhibitors in ART regimens. DISCUSSION: Earlier ART did not alter risk of death overall among people living with HIV who had TB disease. For logistical and patient preference reasons, earlier ART initiation for everyone with TB and HIV may be preferred to later ART

Know your tuberculosis epidemic–Is it time to add Mycobacterium tuberculosis immunoreactivity back into global surveillance?

Tuberculosis (TB) still causes 1.5 million deaths globally each year. Over recent decades, slow and uneven declines in TB incidence have resulted in a falling prevalence of TB disease, which increasingly concentrates in vulnerable populations. Falling prevalence, while welcome, poses new challenges for TB surveillance. Cross-sectional disease surveys require very large sample sizes to accurately estimate disease burden, and even more participants to detect trends over time or identify high-risk areas or populations, making them prohibitively resource-intensive. In the past, tuberculin skin surveys measuring Mycobacterium tuberculosis (Mtb) immunoreactivity were widely used to monitor TB epidemiology in high-incidence settings, but were limited by challenges with both delivering and interpreting the test. Here we argue that the shifting epidemiology of tuberculosis, and the development of new tests for Mtb infection, make it timely and important to revisit the strategy of TB surveillance based on infection or immunoreactivity. Mtb infection surveys carry their own operational challenges and fundamental questions, for example: around survey design and frequency; which groups should be included; how the prevalence of immunoreactivity in a population should be used to estimate force of infection; how individual results should be interpreted and managed; and how surveillance can be delivered efficiently and ethically. However, if these knowledge gaps are addressed, the relative feasibility and lower costs of Mtb infection surveillance offer a powerful and affordable opportunity to better “know your TB epidemic”, understand trends, identify high-risk and underserved communities, and tailor public health responses to dynamic epidemiology

Community-based active-case finding for tuberculosis: navigating a complex minefield

Community-based active case finding (ACF) for tuberculosis (TB) involves an offer of screening to populations at risk of TB, oftentimes with additional health promotion, community engagement and health service strengthening. Recently updated World Health Organization TB screening guidelines conditionally recommend expanded offer of ACF for communities where the prevalence of undiagnosed pulmonary TB is greater than 0.5% among adults, or with other structural risk factors for TB. Subclinical TB is thought to be a major contributor to TB transmission, and ACF, particularly with chest X-ray screening, could lead to earlier diagnosis. However, the evidence base for the population-level impact of ACF is mixed, with effectiveness likely highly dependent on the screening approach used, the intensity with which ACF is delivered, and the success of community- and health-system participation. With recent changes in TB epidemiology due to the effective scale-up of treatment for HIV in Africa, the impacts of the COVID-19 pandemic, and the importance of subclinical TB, researchers and public health practitioners planning to implement ACF programmes must carefully and repeatedly consider the potential population and individual benefits and harms from these programmes. Here we synthesise evidence and experience from implementing ACF programmes to provide practical guidance, focusing on the selection of populations, screening algorithms, selecting outcomes, and monitoring and evaluation. With careful planning and substantial investment, community-based ACF for TB can be an impactful approach to accelerating progress towards elimination of TB in high-burden countries. However, ACF cannot and should not be a substitute for equitable access to responsive, affordable, accessible primary care services for all

Tuberculosis Immunoreactivity Surveillance in Malawi (Timasamala)—A protocol for a cross-sectional Mycobacterium tuberculosis immunoreactivity survey in Blantyre, Malawi

Tuberculosis (TB) transmission and prevalence are dynamic over time, and heterogeneous within populations. Public health programmes therefore require up-to-date, accurate epidemiological data to appropriately allocate resources, target interventions, and track progress towards End TB goals. Current methods of TB surveillance often rely on case notifications, which are biased by access to healthcare, and TB disease prevalence surveys, which are highly resource-intensive, requiring many tens of thousands of people to be tested to identify high-risk groups or capture trends. Surveys of “latent TB infection”, or immunoreactivity to Mycobacterium tuberculosis (Mtb), using tests such as interferon-gamma release assays (IGRAs) could provide a way to identify TB transmission hotspots, supplementing information from disease notifications, and with greater spatial and temporal resolution than is possible to achieve in disease prevalence surveys. This cross-sectional survey will investigate the prevalence of Mtb immunoreactivity amongst young children, adolescents and adults in Blantyre, Malawi, a high HIV-prevalence city in southern Africa. Through this study we will estimate the annual risk of TB infection (ARTI) in Blantyre and explore individual- and area-level risk factors for infection, as well as investigating geospatial heterogeneity of Mtb infection (and its determinants), and comparing these to the distribution of TB disease case-notifications. We will also evaluate novel diagnostics for Mtb infection (QIAreach QFT) and sampling methodologies (convenience sampling in healthcare settings and community sampling based on satellite imagery), which may increase the feasibility of measuring Mtb infection at large scale. The overall aim is to provide high-resolution epidemiological data and provide new insights into methodologies which may be used by TB programmes globally

Tuberculosis immunoreactivity surveillance in Malawi (Timasamala) – a protocol for a cross-sectional Mycobacterium tuberculosis immunoreactivity survey in Blantyre, Malawi

Tuberculosis (TB) transmission and prevalence are dynamic over time, and heterogeneous within populations. Public health programmes therefore require up-to-date, accurate epidemiological data to appropriately allocate resources, target interventions, and track progress towards End TB goals. Current methods of TB surveillance often rely on case notifications, which are biased by access to healthcare, and TB disease prevalence surveys, which are highly resource-intensive, requiring many tens of thousands of people to be tested to identify high-risk groups or capture trends. Surveys of “latent TB infection”, or immunoreactivity to Mycobacterium tuberculosis (Mtb), using tests such as interferon-gamma release assays (IGRAs) could provide a way to identify TB transmission hotspots, supplementing information from disease notifications, and with greater spatial and temporal resolution than is possible to achieve in disease prevalence surveys. This cross-sectional survey will investigate the prevalence of Mtb immunoreactivity amongst young children, adolescents and adults in Blantyre, Malawi, a high HIV-prevalence city in southern Africa. Through this study we will estimate the annual risk of TB infection (ARTI) in Blantyre and explore individual- and area-level risk factors for infection, as well as investigating geospatial heterogeneity of Mtb infection (and its determinants), and comparing these to the distribution of TB disease case-notifications. We will also evaluate novel diagnostics for Mtb infection (QIAreach QFT) and sampling methodologies (convenience sampling in healthcare settings and community sampling based on satellite imagery), which may increase the feasibility of measuring Mtb infection at large scale. The overall aim is to provide high-resolution epidemiological data and provide new insights into methodologies which may be used by TB programmes globally

The 2023 terahertz science and technology roadmap

Terahertz (THz) radiation encompasses a wide spectral range within the electromagnetic spectrum that extends from microwaves to the far infrared (100 GHz-∼30 THz). Within its frequency boundaries exist a broad variety of scientific disciplines that have presented, and continue to present, technical challenges to researchers. During the past 50 years, for instance, the demands of the scientific community have substantially evolved and with a need for advanced instrumentation to support radio astronomy, Earth observation, weather forecasting, security imaging, telecommunications, non-destructive device testing and much more. Furthermore, applications have required an emergence of technology from the laboratory environment to production-scale supply and in-the-field deployments ranging from harsh ground-based locations to deep space. In addressing these requirements, the research and development community has advanced related technology and bridged the transition between electronics and photonics that high frequency operation demands. The multidisciplinary nature of THz work was our stimulus for creating the 2017 THz Science and Technology Roadmap (Dhillon et al 2017 J. Phys. D: Appl. Phys. 50 043001). As one might envisage, though, there remains much to explore both scientifically and technically and the field has continued to develop and expand rapidly. It is timely, therefore, to revise our previous roadmap and in this 2023 version we both provide an update on key developments in established technical areas that have important scientific and public benefit, and highlight new and emerging areas that show particular promise. The developments that we describe thus span from fundamental scientific research, such as THz astronomy and the emergent area of THz quantum optics, to highly applied and commercially and societally impactful subjects that include 6G THz communications, medical imaging, and climate monitoring and prediction. Our Roadmap vision draws upon the expertise and perspective of multiple international specialists that together provide an overview of past developments and the likely challenges facing the field of THz science and technology in future decades. The document is written in a form that is accessible to policy makers who wish to gain an overview of the current state of the THz art, and for the non-specialist and curious who wish to understand available technology and challenges. A such, our experts deliver a ‘snapshot’ introduction to the current status of the field and provide suggestions for exciting future technical development directions. Ultimately, we intend the Roadmap to portray the advantages and benefits of the THz domain and to stimulate further exploration of the field in support of scientific research and commercial realisation

Oxygen-regulated gene expression in murine cumulus cells

Oxygen is an important component of the environment of the cumulus–oocyte complex (COC), both in vivo within the ovarian follicle and during in vitro oocyte maturation (IVM). Cumulus cells have a key role in supporting oocyte development, and cumulus cell function and gene expression are known to be altered when the environment of the COC is perturbed. Oxygen-regulated gene expression is mediated through the actions of the transcription factors, the hypoxia-inducible factors (HIFs). In the present study, the effect of oxygen on cumulus cell gene expression was examined following in vitro maturation of the murine COC at 2%, 5% or 20% oxygen. Increased expression of HIF-responsive genes, including glucose transporter-1, lactate dehydrogenase A and BCL2/adenovirus E1B interacting protein 3, was observed in cumulus cells matured at 2% or 5%, compared with 20% oxygen. Stabilisation of HIF1α protein in cumulus cells exposed to low oxygen was confirmed by western blot and HIF-mediated transcriptional activity was demonstrated using a transgenic mouse expressing green fluorescent protein under the control of a promoter containing hypoxia response elements. These results indicate that oxygen concentration influences cumulus cell gene expression and support a role for HIF1α in mediating the cumulus cell response to varying oxygen.Karen L. Kind, Kimberley K. Y. Tam, Kelly M. Banwell, Ashley D. Gauld, Darryl L. Russell, Anne M. Macpherson, Hannah M. Brown, Laura A. Frank, Daniel J. Peet and Jeremy G. Thompso