First report of human Thelazia callipaeda infection in Portugal

The zoonotic parasitic nematode Thelazia callipaeda, also known as the oriental eye worm, is endemic in several European countries, including Portugal. Infections may result in ocular disease in domestic and wild animals as well as humans, with more or less severe manifestations. We report the first human case of ocular thelaziosis by T. callipaeda in Portugal, a country where the parasite had already been found to infect dogs, cats, red foxes, wild rabbits and a beech marten. An 80-year-old patient from east-central Portugal, who had been suffering from tearing for a few years, had whitish filiform fragments removed from the left eye. Polymerase chain reaction of partial cytochrome c oxidase subunit 1 and 18S small subunit rRNA genes followed by bidirectional sequencing and BLAST analysis confirmed T. callipaeda haplotype 1, the only haplotype previously reported in Europe. The endemicity of T. callipaeda in domestic and wild animals in east-central Portugal makes it very likely that infection of the human patient had occurred locally. In east-central and other geographical areas of Portugal, veterinarians and physicians, especially ophthalmologists, should regard T. callipaeda as a cause of ocular pathology in animals and humans. © 2022This work was supported by national funds, through Fundação para a Ciência e Tecnologia (FCT, Portuguese Foundation for Science and Technology), under projects UIDB/CVT/00772/2020 and LA/P/0059/2020, and also projects UIDB/04750/2020 and LA/P/0064/2020

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems

Clinical criteria/Family history-based BRCA testing misses a large proportion of BRCA carriers who can benefit from screening/prevention. We estimate the cost-effectiveness of population-based BRCA testing in general population women across different countries/health systems. A Markov model comparing the lifetime costs and effects of BRCA1/BRCA2 testing all general population women ≥30 years compared with clinical criteria/FH-based testing. Separate analyses are undertaken for the UK/USA/Netherlands (high-income countries/HIC), China/Brazil (upper–middle income countries/UMIC) and India (low–middle income countries/LMIC) using both health system/payer and societal perspectives. BRCA carriers undergo appropriate screening/prevention interventions to reduce breast cancer (BC) and ovarian cancer (OC) risk. Outcomes include OC, BC, and additional heart disease deaths and incremental cost-effectiveness ratio (ICER)/quality-adjusted life year (QALY). Probabilistic/one-way sensitivity analyses evaluate model uncertainty. For the base case, from a societal perspective, we found that population-based BRCA testing is cost-saving in HIC (UK-ICER = $−5639/QALY; USA-ICER =$−4018/QALY; Netherlands-ICER = $−11,433/QALY), and it appears cost-effective in UMIC (China-ICER =$18,066/QALY; Brazil-ICER = $13,579/QALY), but it is not cost-effective in LMIC (India-ICER =$23,031/QALY). From a payer perspective, population-based BRCA testing is highly cost-effective in HIC (UK-ICER = $21,191/QALY, USA-ICER =$16,552/QALY, Netherlands-ICER = $25,215/QALY), and it is cost-effective in UMIC (China-ICER =$23,485/QALY, Brazil−ICER = $20,995/QALY), but it is not cost-effective in LMIC (India-ICER =$32,217/QALY). BRCA testing costs below $172/test (ICER =$19,685/QALY), which makes it cost-effective (from a societal perspective) for LMIC/India. Population-based BRCA testing can prevent an additional 2319 to 2666 BC and 327 to 449 OC cases per million women than the current clinical strategy. Findings suggest that population-based BRCA testing for countries evaluated is extremely cost-effective across HIC/UMIC health systems, is cost-saving for HIC health systems from a societal perspective, and can prevent tens of thousands more BC/OC cases

Imaging Electronic Correlations in Twisted Bilayer Graphene near the Magic Angle

Twisted bilayer graphene with a twist angle of around 1.1{\deg} features a pair of isolated flat electronic bands and forms a strongly correlated electronic platform. Here, we use scanning tunneling microscopy to probe local properties of highly tunable twisted bilayer graphene devices and show that the flat bands strongly deform when aligned with the Fermi level. At half filling of the bands, we observe the development of gaps originating from correlated insulating states. Near charge neutrality, we find a previously unidentified correlated regime featuring a substantially enhanced flat band splitting that we describe within a microscopic model predicting a strong tendency towards nematic ordering. Our results provide insights into symmetry breaking correlation effects and highlight the importance of electronic interactions for all filling factors in twisted bilayer graphene.Comment: Main text 9 pages, 4 figures; Supplementary Information 25 page

Projected sensitivity of the LUX-ZEPLIN experiment to the 0νββ decay of Xe 136

The LUX-ZEPLIN (LZ) experiment will enable a neutrinoless double β decay search in parallel to the main science goal of discovering dark matter particle interactions. We report the expected LZ sensitivity to Xe136 neutrinoless double β decay, taking advantage of the significant (>600 kg) Xe136 mass contained within the active volume of LZ without isotopic enrichment. After 1000 live-days, the median exclusion sensitivity to the half-life of Xe136 is projected to be 1.06×1026 years (90% confidence level), similar to existing constraints. We also report the expected sensitivity of a possible subsequent dedicated exposure using 90% enrichment with Xe136 at 1.06×1027 years

Conflict in the Indian Kashmir Valley II: psychosocial impact

ABSTRACT: BACKGROUND: India and Pakistan have disputed ownership of the Kashmir Valley region for many years, resulting in high level of exposure to violence among the civilian population of Kashmir (India). A survey was done as part of routine programme evaluation to assess confrontation with violence and its consequences on mental health, health service usage, and socio-economic functioning. METHODS: We undertook a two-stage cluster household survey in two districts of Kashmir (India) using questionnaires adapted from other conflict areas. Analysis was stratified for gender. RESULTS: Over one-third of respondents (n=510) were found to have symptoms of psychological distress (33.3%, CI: 28.3-38.4); women scored significantly higher (OR 2.5; CI: 1.7-3.6). A third of respondents had contemplated suicide (33.3%, CI: 28.3-38.4). Feelings of insecurity were associated with higher levels of psychological distress for both genders (males: OR 2.4, CI: 1.3-4.4; females: OR 1.9, CI: 1.1-3.3). Among males, violation of modesty, (OR 3.3, CI: 1.6-6.8), forced displacement, (OR 3.5, CI: 1.7-7.1), and physical disability resulting from violence (OR 2.7, CI: 1.2-5.9) were associated with greater levels of psychological distress; for women, risk factors for psychological distress included dependency on others for daily living (OR 2.4, CI: 1.3-4.8), the witnessing of killing (OR 1.9, CI: 1.1-3.4), and torture (OR 2.1, CI: 1.2-3.7). Self-rated poor health (male: OR 4.4, CI: 2.4-8.1; female: OR 3.4, CI: 2.0-5.8) and being unable to work (male: OR 6.7, CI: 3.5-13.0; female: OR 2.6, CI: 1.5-4.4) were associated with mental distress. CONCLUSIONS: The ongoing conflict exacts a huge toll on the communities' mental well-being. We found high levels of psychological distress that impacts on daily life and places a burden on the health system. Ongoing feelings of personal vulnerability (not feeling safe) were associated with high levels of psychological distress. Community mental health programmes should be considered as a way reduce the pressure on the health system and improve socio-economic functioning of those suffering from mental health problems

Projected WIMP sensitivity of the LUX-ZEPLIN dark matter experiment

LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4×10-48 cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3×10-43 cm2 (7.1×10-42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020

Distinct Methylation Changes at the IGF2-H19 Locus in Congenital Growth Disorders and Cancer

Background: Differentially methylated regions (DMRs) are associated with many imprinted genes. In mice methylation at a DMR upstream of the H19 gene known as the Imprint Control region (IC1) is acquired in the male germline and influences the methylation status of DMRs 100 kb away in the adjacent Insulin-like growth factor 2 (Igf2) gene through long-range interactions. In humans, germline-derived or post-zygotically acquired imprinting defects at IC1 are associated with aberrant activation or repression of IGF2, resulting in the congenital growth disorders Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, respectively. In Wilms tumour and colorectal cancer, biallelic expression of IGF2 has been observed in association with loss of methylation at a DMR in IGF2. This DMR, known as DMR0, has been shown to be methylated on the silent maternal IGF2 allele presumably with a role in repression. The effect of IGF2 DMR0 methylation changes in the aetiology of BWS or SRS is unknown. Methodology/Principal Findings: We analysed the methylation status of the DMR0 in BWS, SRS and Wilms tumour patients by conventional bisulphite sequencing and pyrosequencing. We show here that, contrary to previous reports, the IGF2 DMR0 is actually methylated on the active paternal allele in peripheral blood and kidney. This is similar to the IC