Fish on the run: facilitating fish passage from drying floodplains

In the Murray-Darling Basin, river managers are implementing site-scale managed floodplain inundations for vegetation outcomes but there is a risk of native fish stranding during floodplain recession due to the absence of natural cues. In 2014, at the 5,000 ha Gunbower floodplain, central Murray River, we devised a fish exit strategy which included: (i) a fish ‘exit hydrograph’, a designed recession to cue fish to leave the floodplain, (ii) evaluation of a new fishlock to facilitate fish passage from the floodplain to the permanent Gunbower Creek. During our evaluation of the exit strategy we collected 113,099 fish exiting the fishlock at up to 20,000 fish/hr, with juvenile non-native carp, native Australian smelt and native carp gudgeons dominating the catch. Fish were 15-500 mm long. Native fish exited the floodplain during the initial drop where carp exited during the later half of the recession. In addition, 30 golden perch were acoustic tagged to identify their floodplain exit pathways. The implications of our results are discussed in the context of maximizing safe exit of fish from other temporary floodplain habitats

The Sharpe ratio of estimated efficient portfolios

Investors often adopt mean-variance efficient portfolios for achieving superior risk-adjusted returns. However, such portfolios are sensitive to estimation errors, which affect portfolio performance. To understand the impact of estimation errors, I develop simple and intuitive formulas of the squared Sharpe ratio that investors should expect from estimated efficient portfolios. The new formulas show that the expected squared Sharpe ratio is a function of the length of the available data, the number of assets and the maximum attainable Sharpe ratio. My results enable the portfolio manager to assess the value of efficient portfolios as investment vehicles, given the investment environment

Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques

Factors Influencing Optical Coherence Tomography Peripapillary Choroidal Thickness: A Multicenter Study.

Purpose:To quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population. Methods:A total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 μm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions. Results:Globally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%-20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance. Conclusions:In healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors

Co-expression of C9orf72 related dipeptide-repeats over 1000 repeat units reveals age-A nd combination-specific phenotypic profiles in Drosophila

A large intronic hexanucleotide repeat expansion (GGGGCC) within the C9orf72 (C9orf72-SMCR8 Complex Subunit) locus is the most prevalent genetic cause of both Frontotemporal Dementia (FTD) and Motor Neuron Disease (MND). In patients this expansion is typically hundreds to thousands of repeat units in length. Repeat associated non-AUG translation of the expansion leads to the formation of toxic, pathological Dipeptide-Repeat Proteins (DPRs). To date there remains a lack of in vivo models expressing C9orf72 related DPRs with a repeat length of more than a few hundred repeats. As such our understanding of how physiologically relevant repeat length DPRs effect the nervous system in an ageing in vivo system remains limited. In this study we generated Drosophila models expressing DPRs over 1000 repeat units in length, a known pathological length in humans. Using these models, we demonstrate each DPR exhibits a unique, age-dependent, phenotypic and pathological profile. Furthermore, we show co-expression of specific DPR combinations leads to distinct, age-dependent, phenotypes not observed through expression of single DPRs. We propose these models represent a unique, in vivo, tool for dissecting the molecular mechanisms implicated in disease pathology, opening up new avenues in the study of both MND and FTD

PROTOCOL: What is the effect of intergenerational activities on the wellbeing and mental health of older people?

This is the protocol for a Campbell systematic review. The objectives are as follows: This systematic review will examine the impact of intergenerational interventions on the mental health and wellbeing of older people and will identify areas for future research as well as key messages for service commissioners

What is the effect of intergenerational activities on the wellbeing and mental health of older people?: A systematic review

BACKGROUND: Opportunities for social connection between generations have diminished over the last few decades around the world as a result of changes in the way that we live and work. The COVID-19 pandemic has exacerbated loneliness for many with young and old being kept apart for safety. The Public Health England prevention concordat for better mental health (Office for Health Improvement and Disparities) aims to bring a prevention-focused approach to improving public mental health. The concordat promotes evidence-based planning and commissioning to increase the impact on reducing health inequalities using sustainable and cost-effective interventions that impact on the wider determinants of mental health and wellbeing for children and young people and older people. Intergenerational activities could provide an opportunity to support both populations. In 2023, we produced an evidence and gap map to illustrate the amount and variety of research on intergenerational interventions and the gaps in research that still exist in this area. The review conducted here is based on the evidence in that map. OBJECTIVES: This systematic review examines the impact of intergenerational interventions on the wellbeing and mental health of older people and identifies areas for future research as well as key messages for service commissioners. SEARCH METHODS: We searched an evidence and gap map published in 2022 (comprehensive searches conducted July 2021 and updated June 2023) to identify randomised controlled trials of intergenerational interventions that report mental health and wellbeing outcomes for older people. SELECTION CRITERIA: Randomised controlled trials of intergenerational interventions that involved unrelated younger and older people with at least one skipped generation between them and reported mental health or wellbeing outcomes for older people were included in this review. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Campbell Collaboration. We conducted data extraction and Cochrane risk of bias assessments in EPPI reviewer. Where data allowed meta-analyses were conducted in STATA. MAIN RESULTS: This review includes 14 trials from six different countries. The trials had some important methodological weaknesses. Interventions were mainly delivered in-person and often in groups. They included visiting programmes, school volunteering programmes, music-based interventions and task-oriented interventions such as activities set in a multigenerational park, reminiscing activities, aggression management programmes, learning a language, making local environmental changes and in-school project work. Intergenerational interventions showed a small positive trend towards improving self-esteem (effect size [ES]: 0.33, 95% confidence interval [CI]: -0.35, 1.01) and depression (ES: 0.19, 95% CI: -0.23, 0.60) for older people participating. However, due to the small study sizes and low number of studies available, we cannot be confident about any effects. The results for other mental health and wellbeing outcomes are reported but due to little overlap in similar assessments across the studies, we could not combine them to assess the strength of evidence. There were no data about social isolation, spiritual health or sense of community. There are no long-term studies and no data on equity. We still know very little about what works and how or why. Whilst some interventions do use theories and logic to inform their development others do not. More exploration of this is needed. AUTHORS’ CONCLUSIONS: Commissioners and intervention developers should ensure interventions provide sufficient theoretical evidence for the logic behind the proposed intervention and should improve their consideration of equity within the interventions Research on intergenerational interventions need more consistent and agreed measures for reporting outcomes including community outcomes (core outcome sets). More understanding is needed on how best to measure 'community' outcomes. Research on intergenerational interventions should measure outcomes for BOTH the older and younger population engaged in the intervention-these may or may not be the same outcomes reflected in both populations. Further research is needed on the long-term impact of interventions on outcomes (whether participants need to keep being involved in an 'intervention' to continue to benefit) and sustainability of interventions beyond the initial funding of the research project. Supporting this our stakeholders highlighted that interventions that are initiated for research and then end (usually within a year) are not helpful

A Global χ2\chi^2 Analysis of Electroweak Data (including Fermion Masses and Mixing Angles) in SO(10) SUSY GUTs

We present a global $\chi^2$ analysis of electroweak data, including fermion masses and mixing angles, in SO(10) SUSY GUTs. Just as precision electroweak data is used to test the Standard Model, the well determined Standard Model parameters are the precision electroweak data for testing theories beyond the Standard Model. In this talk we use the latest experimentally measured values for these parameters. We study several models discussed in the literature. One of these models provides an excellent fit to the low energy data with $\chi^2 \sim 1$ for 3 degrees of freedom. We present our predictions for a few selected points in parameter space.Comment: 8 pages, LateX type, talk presented by S. Raby at the Fourth International Conference on Supersymmetry (SUSY96), College Park, MD, May 29,199

Potent immunogenicity and protective efficacy of a multi-pathogen vaccination targeting Ebola, Sudan, Marburg and Lassa viruse

Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model