Hidden deep in the halo: Selection of a reduced proper motion halo catalogue and mining retrograde streams in the velocity space

The Milky Way halo is one of the few galactic haloes that provides a unique insight into galaxy formation by resolved stellar populations. Here, we present a catalogue of $\sim$47 million halo stars selected independent of parallax and line-of-sight velocities, using a combination of Gaia DR3 proper motion and photometry by means of their reduced proper motion. We select high tangential velocity (halo) main sequence stars and fit distances to them using their simple colour-absolute-magnitude relation. This sample reaches out to $\sim$21 kpc with a median distance of $6.6$ kpc thereby probing much further out than would be possible using reliable Gaia parallaxes. The typical uncertainty in their distances is $0.57_{-0.26}^{+0.56}$ kpc. Using the colour range $0.45<(G_0-G_\mathrm{RP,0})<0.715$ where the main sequence is narrower, gives an even better accuracy down to $0.39_{-0.12}^{+0.18}$ kpc in distance. The median velocity uncertainty for stars within this colour range is 15.5 km/s. The distribution of these sources in the sky, together with their tangential component velocities, are very well-suited to study retrograde substructures. We explore the selection of two complex retrograde streams: GD-1 and Jhelum. For these streams, we resolve the gaps, wiggles and density breaks reported in the literature more clearly. We also illustrate the effect of the kinematic selection bias towards high proper motion stars and incompleteness at larger distances due to Gaia's scanning law. These examples showcase how the full RPM catalogue made available here can help us paint a more detailed picture of the build-up of the Milky Way halo.Comment: 17 pages. Accepted for publication in MNRAS. The catalogue has been submitted as supplementary material to CDS and MNRAS for use to do more wonderful science. Comments are welcomed and appreciated

Poor Clinical Sensitivity of Rapid Antigen Test for Influenza A Pandemic (H1N1) 2009 Virus

Influenza A pandemic (H1N1) 2009 virus RNA was detected by reverse transcription–PCR in 144 clinical samples from Bonn, Germany. A common rapid antigen–based test detected the virus in only 11.1% of these samples. The paramount feature of rapid test–positive samples was high virus concentration. Antigen-based rapid tests appear unsuitable for virologic diagnostics in the current pandemic

A cross-cultural study of the Montreal Cognitive Assessment for people with hearing impairment

Background: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long-term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA-H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA-H. Methods: The current study investigated the performance of the MoCA-H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA-H. Results: In a multiple regression model accounting for age, sex, and education, cultural–linguistic group accounted for 6.89% of variance in the total MoCA-H score. Differences between languages in mean score of up to 2.6 points were observed. Conclusions: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA-H such that optimal performance cut points for identification of cognitive impairment derived in English-speaking populations are likely inappropriate for use in non-English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA-H

Feasibility of an Intervention to Support Hearing and Vision in Dementia:The SENSE-Cog Field Trial

OBJECTIVES: People with dementia (PwD) frequently experience hearing and vision impairment that is underrecognized and undertreated, resulting in reduced quality of life. Managing these impairments may be an important strategy to improve outcomes in PwD. Our objective was to field-trial a multifaceted sensory intervention (SI) to enhance hearing and vision in PwD. DESIGN: An international single-arm open-label feasibility, acceptability, and tolerability study. SETTING: Home-based setting in the United Kingdom, France, and Cyprus. PARTICIPANTS: Adults aged 60 years and older with mild-to-moderate dementia and uncorrected or suboptimally corrected hearing and/or vision impairment, and their study partners (n = 19 dyads). INTERVENTION: A sensory intervention (SI), comprising assessment of hearing and vision, fitting of corrective devices (glasses, hearing aids), and home-based support from a sensory support therapist for device adherence and maintenance, communication training, referral to support services, environmental sensory modification, and optimization of social inclusion. MEASUREMENTS: Ratings of study procedure feasibility, and intervention acceptability/tolerability, ascertained through questionnaires, participant diaries, therapist logbooks, and semistructured interviews. RESULTS: We successfully delivered all intervention components, and these were received and enacted as intended in all those who completed the intervention. No serious adverse events were reported. Acceptability (ie, understanding, motivation, sense of achievement) and tolerability (ie, effort, fatigue) ratings of the intervention were within a priori target ranges. We met recruitment and retention (93.8%) targets in two of the three sites. Participants completed more than 95% of diary entries, representing minimal missing data. Delays in the logistics circuit for the assessment and delivery of hearing aids and glasses were identified, requiring modification. The need for minor modifications to some outcome measures and the inclusion criteria were identified. CONCLUSION: This is the first study combining home-based hearing and vision remediation in PwD. The positive feasibility, acceptability, and tolerability findings suggest that a full-scale efficacy trial, with certain modifications, is achievable

Inhibition of exosome biogenesis affects cell motility in heterogeneous sub-populations of paediatric-type diffuse high-grade gliomas

Background: Paediatric-type diffuse High-Grade Gliomas (PDHGG) are highly heterogeneous tumours which include distinct cell sub-populations co-existing within the same tumour mass. We have previously shown that primary patient-derived and optical barcoded single-cell-derived clones function as interconnected networks. Here, we investigated the role of exosomes as a route for inter-clonal communication mediating PDHGG migration and invasion. Results: A comprehensive characterisation of seven optical barcoded single-cell-derived clones obtained from two patient-derived cell lines was performed. These analyses highlighted extensive intra-tumour heterogeneity in terms of genetic and transcriptional profiles between clones as well as marked phenotypic differences including distinctive motility patterns. Live single-cell tracking analysis of 3D migration and invasion assays showed that the single-cell-derived clones display a higher speed and longer travelled distance when in co-culture compared to mono-culture conditions. To determine the role of exosomes in PDHGG inter-clonal cross-talks, we isolated exosomes released by different clones and characterised them in terms of marker expression, size and concentration. We demonstrated that exosomes are actively internalized by the cells and that the inhibition of their biogenesis, using the phospholipase inhibitor GW4689, significantly reduced the cell motility in mono-culture and more prominently when the cells from the clones were in co-culture. Analysis of the exosomal miRNAs, performed with a miRNome PCR panel, identified clone-specific miRNAs and a set of miRNA target genes involved in the regulation of cell motility/invasion/migration. These genes were found differentially expressed in co-culture versus mono-culture conditions and their expression levels were significantly modulated upon inhibition of exosome biogenesis. Conclusions: In conclusion, our study highlights for the first time a key role for exosomes in the inter-clonal communication in PDHGG and suggests that interfering with the exosome biogenesis pathway may be a valuable strategy to inhibit cell motility and dissemination for these specific diseases

FunClust: a web server for the identification of structural motifs in a set of non-homologous protein structures

The occurrence of very similar structural motifs brought about by different parts of non homologous proteins is often indicative of a common function. Indeed, relatively small local structures can mediate binding to a common partner, be it a protein, a nucleic acid, a cofactor or a substrate. While it is relatively easy to identify short amino acid or nucleotide sequence motifs in a given set of proteins or genes, and many methods do exist for this purpose, much more challenging is the identification of common local substructures, especially if they are formed by non consecutive residues in the sequence

Mitogenomes from Egyptian Cattle Breeds: New Clues on the Origin of Haplogroup Q and the Early Spread of Bos taurus from the Near East

Background Genetic studies support the scenario that Bos taurus domestication occurred in the Near East during the Neolithic transition about 10 thousand years (ky) ago, with the likely exception of a minor secondary event in Italy. However, despite the proven effectiveness of whole mitochondrial genome data in providing valuable information concerning the origin of taurine cattle, until now no population surveys have been carried out at the level of mitogenomes in local breeds from the Near East or surrounding areas. Egypt is in close geographic and cultural proximity to the Near East, in particular the Nile Delta region, and was one of the first neighboring areas to adopt the Neolithic package. Thus, a survey of mitogenome variation of autochthonous taurine breeds from the Nile Delta region might provide new insights on the early spread of cattle rearing outside the Near East. Methodology Using Illumina high-throughput sequencing we characterized the mitogenomes from two cattle breeds, Menofi (N = 17) and Domiaty (N = 14), from the Nile Delta region. Phylogenetic and Bayesian analyses were subsequently performed. Conclusions Phylogenetic analyses of the 31 mitogenomes confirmed the prevalence of haplogroup T1, similar to most African cattle breeds, but showed also high frequencies for haplogroups T2, T3 and Q1, and an extremely high haplotype diversity, while Bayesian skyline plots pointed to a main episode of population growth ~12.5 ky ago. Comparisons of Nile Delta mitogenomes with those from other geographic areas revealed that (i) most Egyptian mtDNAs are probably direct local derivatives from the founder domestic herds which first arrived from the Near East and the extent of gene flow from and towards the Nile Delta region was limited after the initial founding event(s); (ii) haplogroup Q1 was among these founders, thus proving that it underwent domestication in the Near East together with the founders of the T clades

BCLA CLEAR Presbyopia: Management with contact lenses and spectacles

This paper seeks to outline the history, market situation, clinical management and product performance related to the correction of presbyopia with both contact lenses and spectacles. The history of the development of various optical forms of presbyopic correction are reviewed, and an overview is presented of the current market status of contact lenses and spectacles. Clinical considerations in the fitting and aftercare of presbyopic contact lens and spectacle lens wearers are presented, with general recommendations for best practice. Current options for contact lens correction of presbyopia include soft simultaneous, rigid translating and rigid simultaneous designs, in addition to monovision. Spectacle options include single vision lenses, bifocal lenses and a range of progressive addition lenses. The comparative performance of both contact lens and spectacle lens options is presented. With a significant proportion of the global population now being presbyopic, this overview is particularly timely and is designed to act as a guide for researchers, industry and eyecare practitioners alike

The Enigmatic Origin of Bovine mtDNA Haplogroup R: Sporadic Interbreeding or an Independent Event of Bos primigenius Domestication in Italy?

BACKGROUND: When domestic taurine cattle diffused from the Fertile Crescent, local wild aurochsen (Bos primigenius) were still numerous. Moreover, aurochsen and introduced cattle often coexisted for millennia, thus providing potential conditions not only for spontaneous interbreeding, but also for pastoralists to create secondary domestication centers involving local aurochs populations. Recent mitochondrial genomes analyses revealed that not all modern taurine mtDNAs belong to the shallow macro-haplogroup T of Near Eastern origin, as demonstrated by the detection of three branches (P, Q and R) radiating prior to the T node in the bovine phylogeny. These uncommon haplogroups represent excellent tools to evaluate if sporadic interbreeding or even additional events of cattle domestication occurred. METHODOLOGY: The survey of the mitochondrial DNA (mtDNA) control-region variation of 1,747 bovine samples (1,128 new and 619 from previous studies) belonging to 37 European breeds allowed the identification of 16 novel non-T mtDNAs, which after complete genome sequencing were confirmed as members of haplogroups Q and R. These mtDNAs were then integrated in a phylogenetic tree encompassing all available P, Q and R complete mtDNA sequences. CONCLUSIONS: Phylogenetic analyses of 28 mitochondrial genomes belonging to haplogroups P (N = 2), Q (N = 16) and R (N = 10) together with an extensive survey of all previously published mtDNA datasets revealed major similarities between haplogroups Q and T. Therefore, Q most likely represents an additional minor lineage domesticated in the Near East together with the founders of the T subhaplogroups. Whereas, haplogroup R is found, at least for the moment, only in Italy and nowhere else, either in modern or ancient samples, thus supporting an origin from European aurochsen. Haplogroup R could have been acquired through sporadic interbreeding of wild and domestic animals, but our data do not rule out the possibility of a local and secondary event of B. primigenius domestication in Italy

J Am Geriatr Soc

BACKGROUND: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment. METHODS: We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors. RESULTS: One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2-4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952-0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test-retest reliability was 0.92 (95%CI 0.78-0.97). CONCLUSION: The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.Ears, Eyes and Mind: The ‘SENSE-Cog Project’ to improve mental well-being for elderly Europeans with sensory impairmen