Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity

Biomarker discovery applied to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disabling disease of inconclusive aetiology, has identified several cytokines to potentially fulfil a role as a quantitative blood/serum marker for laboratory diagnosis, with activin B a recent addition. We explored further the potential of serum activin B as a ME/CFS biomarker, alone and in combination with a range of routine test results obtained from pathology laboratories. Previous pilot study results showed that activin B was significantly elevated for the ME/CFS participants compared to healthy (control) participants. All the participants were recruited via CFS Discovery and assessed via the Canadian/International Consensus Criteria. A significant difference for serum activin B was also detected for ME/CFS and control cohorts recruited for this study, but median levels were significantly lower for the ME/CFS cohort. Random Forest (RF) modelling identified five routine pathology blood test markers that collectively predicted ME/CFS at ≥62% when compared via weighted standing time (WST) severity classes. A closer analysis revealed that the inclusion of activin B to the panel of pathology markers improved the prediction of mild to moderate ME/CFS cases. Applying correct WST class prediction from RFA modelling, new reference intervals were calculated for activin B and associated pathology markers, where 24-h urinary creatinine clearance, serum urea and serum activin B showed the best potential as diagnostic markers. While the serum activin B results remained statistically significant for the new participant cohorts, activin B was found to also have utility in enhancing the prediction of symptom severity, as represented by WST class.This research was funded by the Judith. J. Mason and Harold S. Williams Memorial Foundation (The Mason Foundation), grant number CT23141–23142

Time periods of altered risk for severe injection drug use-associated skin and soft-tissue infections: protocol for a self-controlled case series in New South Wales, Australia, 2001-2018

Injection drug use-associated bacterial and fungal infections (e.g., skin and soft-tissue infections, endocarditis, osteomyelitis, etc.) are common health problems among people who inject drugs, associated with pain, disability, and death. The incidence of these infections is rising, and better understanding of the social and environmental factors that shape individual injecting practices and risk for injecting-related infections is urgently needed. Using a self-controlled study design, the aim of this proposed study is to quantify the risks of injecting-related skin and soft-tissue infections associated with initiation of, exposure to, and discontinuation of incarceration and OAT among a sample of people with opioid use disorder

Targeted identification of genomic regions using TAGdb

Background: The introduction of second generation sequencing technology has enabled the cost effective sequencing of genomes and the identification of large numbers of genes and gene promoters. However, the assembly of DNA sequences to create a representation of the complete genome sequence remains costly, especially for the larger and more complex plant genomes. Results: We have developed an online database, TAGdb, that enables researchers to identify paired read sequences that share identity with a submitted query sequence. These tags can be used to design oligonucleotide primers for the PCR amplification of the region in the target genome. Conclusions: The ability to produce large numbers of paired read genome tags using second generation sequencing provides a cost effective method for the identification of genes and promoters in large, complex or orphan species without the need for whole genome assembly

Defining the determinants of vaccine uptake and undervaccination in migrant populations in Europe to improve routine and COVID-19 vaccine uptake: a systematic review

Understanding why some migrants in Europe are at risk of underimmunisation and show lower vaccination uptake for routine and COVID-19 vaccines is critical if we are to address vaccination inequities and meet the goals of WHO's new Immunisation Agenda 2030. We did a systematic review (PROSPERO: CRD42020219214) exploring barriers and facilitators of vaccine uptake (categorised using the 5As taxonomy: access, awareness, affordability, acceptance, activation) and sociodemographic determinants of undervaccination among migrants in the EU and European Economic Area, the UK, and Switzerland. We searched MEDLINE, CINAHL, and PsycINFO from 2000 to 2021 for primary research, with no restrictions on language. 5259 data sources were screened, with 67 studies included from 16 countries, representing 366 529 migrants. We identified multiple access barriers-including language, literacy, and communication barriers, practical and legal barriers to accessing and delivering vaccination services, and service barriers such as lack of specific guidelines and knowledge of health-care professionals-for key vaccines including measles-mumps-rubella, diphtheria-pertussis-tetanus, human papillomavirus, influenza, polio, and COVID-19 vaccines. Acceptance barriers were mostly reported in eastern European and Muslim migrants for human papillomavirus, measles, and influenza vaccines. We identified 23 significant determinants of undervaccination in migrants (p<0·05), including African origin, recent migration, and being a refugee or asylum seeker. We did not identify a strong overall association with gender or age. Tailored vaccination messaging, community outreach, and behavioural nudges facilitated uptake. Migrants' barriers to accessing health care are already well documented, and this Review confirms their role in limiting vaccine uptake. These findings hold immediate relevance to strengthening vaccination programmes in high-income countries, including for COVID-19, and suggest that tailored, culturally sensitive, and evidence-informed strategies, unambiguous public health messaging, and health system strengthening are needed to address access and acceptance barriers to vaccination in migrants and create opportunities and pathways for offering catch-up vaccinations to migrants

Saquinavir Inhibits the malaria parasite's chloroquine resistance transporter

The antiretroviral protease inhibitors (APIs) ritonavir, saquinavir, and lopinavir, used to treat HIV infection, inhibit the growth of Plasmodium falciparum at clinically relevant concentrations. Moreover, it has been reported that these APIs potentiate the activity of chloroquine (CQ) against this parasite in vitro. The mechanism underlying this effect is not understood, but the degree of chemosensitization varies between the different APIs and, with the exception of ritonavir, appears to be dependent on the parasite exhibiting a CQ-resistant phenotype. Here we report a study of the role of the P. falciparum chloroquine resistance transporter (PfCRT) in the interaction between CQ and APIs, using transgenic parasites expressing different PfCRT alleles and using the Xenopus laevis oocyte system for the heterologous expression of PfCRT. Our data demonstrate that saquinavir behaves as a CQ resistance reverser and that this explains, at least in part, its ability to enhance the effects of CQ in CQ-resistant P. falciparum parasites. Copyrigh

Modifying and validating the social responsiveness scale edition 2 for use with deaf children and young people

A Delphi consensus methodology was used to adapt a screening tool, the Social Responsiveness Scale- 2 (SRS-2), for use with deaf children including those whose preferred communication method is sign language. Using this approach; 27 international experts (The Delphi International Expert Panel), on the topic of autism spectrum disorder (ASD) in deaf people, contributed to the review of item content. A criterion for agreement was set at 80% of experts on each item (with 75% acceptable in the final fourth round). The agreed modifications are discussed. The modified SRS-2 research adaptation for deaf people (referred to here as the "SRS-2 Deaf adaptation") was then translated into British Sign Language using a robust translation methodology and validated in England in a sample of 198 deaf children, 76 with Autism Spectrum Disorders (ASD) and 122 without ASD. The SRS-2 Deaf adaptation was compared blind to a NICE (National Institute for Health and Care Excellence) guideline standard clinical assessment. The area under the Receiver Operating (ROC) curve was 0.811 (95% CI: 0.753, 0.869), with an optimal cut-off value of 73, which gave a sensitivity of 82% and a specificity of 67%. The Cronbach Alpha coefficient was 0.968 suggesting high internal consistency. The Intraclass Correlation Coefficient was 0.897, supporting test-retest reliability. This performance is equivalent to similar instruments used for screening ASD in the hearing population

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Burning in Banksia Woodlands: How Does the Fire-Free Period Influence Reptile Communities?

Fire is an important management tool for both hazard reduction burning and maintenance of biodiversity. The impact of time since last fire on fauna is an important factor to understand as land managers often aim for prescribed burning regimes with specific fire-free intervals. However, our current understanding of the impact of time since last fire on fauna is largely unknown and likely dependent on vegetation type. We examined the responses of reptiles to fire age in banksia woodlands, and the interspersed melaleuca damplands among them, north of Perth, Western Australia, where the current prescribed burning regime is targeting a fire-free period of 8–12 years. The response of reptiles to fire was dependent on vegetation type. Reptiles were generally more abundant (e.g. Lerista elegans and Ctenophorus adelaidensis) and specious in banksia sites. Several species (e.g. Menetia greyii, Cryptoblepharus buchananii) preferred long unburnt melaleuca sites (>16 years since last fire, YSLF) compared to recently burnt sites (<12 YSLF). Several of the small elapids (e.g. the WA priority listed species Neelaps calonotus) were only detected in older-aged banksia sites (>16 YSLF). The terrestrial dragon C. adelaidensis and the skink Morethia obscura displayed a strong response to fire in banksia woodlands only. Highest abundances of the dragon were detected in the recently burnt (<7 YSLF) and long unburnt (>35 YSLF) banksia woodlands, while the skink was more abundant in older sites. Habitats from a range of fire ages are required to support the reptiles we detected, especially the longer unburnt (>16 YSLF) melaleuca habitat. Current burning prescriptions are reducing the availability of these older habitats

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured