Probing Relativity using Space-Based Experiments

An overview of space tests searching for small deviations from special relativity arising at the Planck scale is given. Potential high-sensitivity space-based experiments include ones with atomic clocks, masers, and electromagnetic cavities. We show that a significant portion of the coefficient space in the Standard-Model Extension, a framework that covers the full spectrum of possible effects, can be accessed using space tests. Some remarks on Lorentz violation in the gravitational sector are also given.Comment: 12 pages, invited talk at International Workshop, From Quantum to Cosmos, Warrenton, VA, USA, May 22-24, 200

Revamping AI Models in Dermatology: Overcoming Critical Challenges for Enhanced Skin Lesion Diagnosis

The surge in developing deep learning models for diagnosing skin lesions through image analysis is notable, yet their clinical black faces challenges. Current dermatology AI models have limitations: limited number of possible diagnostic outputs, lack of real-world testing on uncommon skin lesions, inability to detect out-of-distribution images, and over-reliance on dermoscopic images. To address these, we present an All-In-One \textbf{H}ierarchical-\textbf{O}ut of Distribution-\textbf{C}linical Triage (HOT) model. For a clinical image, our model generates three outputs: a hierarchical prediction, an alert for out-of-distribution images, and a recommendation for dermoscopy if clinical image alone is insufficient for diagnosis. When the recommendation is pursued, it integrates both clinical and dermoscopic images to deliver final diagnosis. Extensive experiments on a representative cutaneous lesion dataset demonstrate the effectiveness and synergy of each component within our framework. Our versatile model provides valuable decision support for lesion diagnosis and sets a promising precedent for medical AI applications

Vanadium Complexes Are in vitro Inhibitors of Leishmania Secreted Acid Phosphatases

Leishmaniasis is a parasitic disease caused by the protozoa Leishmania. These organisms secrete acid phosphatases during their growth cycle as an important part of cell targeting to host macrophage cells thus allowing for a successful infection. Secreted acid phosphatases (SAP) are reported to play a significant role in the survival of Leishmania cells, thus evaluation of these enzymes is of interest. The inhibition of SAP can be the focus of a new drug therapy. We tested for SAP activity from Leishmania tarentolae following the addition of a series of vanadium complexes including decavanadate. Cell cultures at different stages in their growth curve were harvested by centrifugation and supernatant was collected. The SAP activity in the supernatant was assayed with the artificial substrate p-nitrophenylphosphate (pNPP). Incubation with orthovanadate resulted in a decrease in activity of 18% ± 1 relative to the control, in comparison to decavanadate, which resulted in a 35% ± 4 decrease in activity. Other vanadium complexes showed smaller inhibitory effects than orthovanadate. Some vanadium complexes appeared to have an effect on reducing cell clumping when compared to control cells. The SAP was partially isolated through anion exchange chromatography and results indicate that SAP isozyme forms are present in the supernatant from cells. Future work is focused on obtaining recombinant enzyme which can be more completely characterized for inhibition by vanadium complexes

Cost Analysis of Adjuvant Whole‑Brain Radiotherapy Treatment Versus No Whole‑Brain Radiotherapy After Stereotactic Radiosurgery and/or Surgery Among Adults with One to Three Melanoma Brain Metastases: Results from a Randomized Trial

Purpose We aimed to compare Australian health system costs at 12 months for adjuvant whole-brain radiotherapy (WBRT) treatment after stereotactic radiosurgery (SRS) and/or surgery versus observation among adults with one to three melanoma brain metastases. We hypothesized that treatment with adjuvant WBRT and subsequent healthcare would be more expensive than SRS/surgery alone. Methods The analysis was conducted alongside a multicentre, randomized phase III trial. A bespoke cost questionnaire was used to measure healthcare use, including hospitalizations, specialist and primary care visits, imaging, and medicines over 12 months. Mean per-patient costs were calculated based on the quantity of resources used and unit costs, reported in Australian dollars ($AU), year 2018 values. Skewness of cost data was determined using normality tests and censor-adjusted costs reported using the Kaplan–Meier sample average method. The analysis of diference in mean costs at each 2-month time point and at 12 months was performed and checked using Kruskal–Wallis, generalized linear models with gamma distribution and log link, modifed Park test, ordinary least squares, and non-parametric bootstrapping. Results In total, 89 patients with similar characteristics at baseline were included in the cost analysis (n = 43 WBRT; n = 46 observation). Hospitalization cost was the main cost, ranging from 63 to 8912-monthly cost for WBRT was$AU71,138 ± standard deviation 41,475 and for observation $AU69,848 ± 33,233; p = 0.7426. The censor-adjusted 12-monthly cost for WBRT was$AU90,277 ± 36,274 and $AU82,080 ± 34,411 for observation. There was no signifcant diference in 2-monthly costs between groups (p > 0.30 for all models). Conclusions Most costs were related to inpatient hospitalizations associated with disease recurrence. Adding WBRT after local SRS/surgery for patients with one to three melanoma brain metastases did not signifcantly increase health system costs during the frst 12 months. Trial Registration ACTRN12607000512426, prospectively registered 14 September 200

Standard survey methods for estimating colony losses and explanatory risk factors in Apis mellifera

This chapter addresses survey methodology and questionnaire design for the collection of data pertaining to estimation of honey bee colony loss rates and identification of risk factors for colony loss. Sources of error in surveys are described. Advantages and disadvantages of different random and non-random sampling strategies and different modes of data collection are presented to enable the researcher to make an informed choice. We discuss survey and questionnaire methodology in some detail, for the purpose of raising awareness of issues to be considered during the survey design stage in order to minimise error and bias in the results. Aspects of survey design are illustrated using surveys in Scotland. Part of a standardized questionnaire is given as a further example, developed by the COLOSS working group for Monitoring and Diagnosis. Approaches to data analysis are described, focussing on estimation of loss rates. Dutch monitoring data from 2012 were used for an example of a statistical analysis with the public domain R software. We demonstrate the estimation of the overall proportion of losses and corresponding confidence interval using a quasi-binomial model to account for extra-binomial variation. We also illustrate generalized linear model fitting when incorporating a single risk factor, and derivation of relevant confidence intervals

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

Minimum information and guidelines for reporting a Multiplexed Assay of Variant Effect

Multiplexed Assays of Variant Effect (MAVEs) have emerged as a powerful approach for interrogating thousands of genetic variants in a single experiment. The flexibility and widespread adoption of these techniques across diverse disciplines has led to a heterogeneous mix of data formats and descriptions, which complicates the downstream use of the resulting datasets. To address these issues and promote reproducibility and reuse of MAVE data, we define a set of minimum information standards for MAVE data and metadata and outline a controlled vocabulary aligned with established biomedical ontologies for describing these experimental designs

An investigation of factors associated with the health and well-being of HIV-infected or HIV-affected older people in rural South Africa

BackgroundDespite the severe impact of HIV in sub-Saharan Africa, the health of older people aged 50+ is often overlooked owing to the dearth of data on the direct and indirect effects of HIV on older people's health status and well-being. The aim of this study was to examine correlates of health and well-being of HIV-infected older people relative to HIV-affected people in rural South Africa, defined as participants with an HIV-infected or death of an adult child due to HIV-related cause. MethodsData were collected within the Africa Centre surveillance area using instruments adapted from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE). A stratified random sample of 422 people aged 50+ participated. We compared the health correlates of HIV-infected to HIV-affected participants using ordered logistic regressions. Health status was measured using three instruments: disability index, quality of life and composite health score. ResultsMedian age of the sample was 60 years (range 50-94). Women HIV-infected (aOR 0.15, 95% confidence interval (CI) 0.08-0.29) and HIV-affected (aOR 0.20, 95% CI 0.08-0.50), were significantly less likely than men to be in good functional ability. Women's adjusted odds of being in good overall health state were similarly lower than men's; while income and household wealth status were stronger correlates of quality of life. HIV-infected participants reported better functional ability, quality of life and overall health state than HIV-affected participants. Discussion and Conclusions The enhanced healthcare received as part of anti-retroviral treatment as well as the considerable resources devoted to HIV care appear to benefit the overall well-being of HIV-infected older people; whereas similar resources have not been devoted to the general health needs of HIV uninfected older people. Given increasing numbers of older people, policy and programme interventions are urgently needed to holistically meet the health and well-being needs of older people beyond the HIV-related care system. <br/

A Late Role for bmp2b in the Morphogenesis of Semicircular Canal Ducts in the Zebrafish Inner Ear

BACKGROUND:The Bone Morphogenetic Protein (BMP) genes bmp2 and bmp4 are expressed in highly conserved patterns in the developing vertebrate inner ear. It has, however, proved difficult to elucidate the function of BMPs during ear development as mutations in these genes cause early embryonic lethality. Previous studies using conditional approaches in mouse and chicken have shown that Bmp4 has a role in semicircular canal and crista development, but there is currently no direct evidence for the role of Bmp2 in the developing inner ear. METHODOLOGY/PRINCIPAL FINDINGS:We have used an RNA rescue strategy to test the role of bmp2b in the zebrafish inner ear directly. Injection of bmp2b or smad5 mRNA into homozygous mutant swirl (bmp2b(-/-)) embryos rescues the early patterning defects in these mutants and the fish survive to adulthood. As injected RNA will only last, at most, for the first few days of embryogenesis, all later development occurs in the absence of bmp2b function. Although rescued swirl adult fish are viable, they have balance defects suggestive of vestibular dysfunction. Analysis of the inner ears of these fish reveals a total absence of semicircular canal ducts, structures involved in the detection of angular motion. All other regions of the ear, including the ampullae and cristae, are present and appear normal. Early stages of otic development in rescued swirl embryos are also normal. CONCLUSIONS/SIGNIFICANCE:Our findings demonstrate a critical late role for bmp2b in the morphogenesis of semicircular canals in the zebrafish inner ear. This is the first demonstration of a developmental role for any gene during post-embryonic stages of otic morphogenesis in the zebrafish. Despite differences in the early stages of semicircular canal formation between zebrafish and amniotes, the role of Bmp2 in semicircular canal duct outgrowth is likely to be conserved between different vertebrate species