159 research outputs found

    Adolescents accept digital mental health support in schools: A co-design and feasibility study of a school-based app for UK adolescents

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    Schools in the UK are required to provide frontline mental health promotion and prevention to adolescents, but with few resources. School-hosted mHealth is one option which could meet needs. This study co-designed and feasibility tested a self-help, school hosted, digital intervention for adolescents showing early symptoms of deteriorating mental health. Via extensive co-design, we produced a youth-targeted web-app (MindMate2) and a low-intensity parent component (Partner2U). Feasibility was tested in four UK high schools with n = 31 young people (15-17y). We specified rules for progression to an effectiveness trial, tested candidate primary outcome measures and conducted an exploratory cost-effectiveness analysis. Co-design produced MindMate2U to be a six-week, self-help, smartphone-delivered program targeting risk and protective factors for adolescent mental health. Young people's MindMate2U account was set up by school after which they progressed independently through six topics of their choosing. User ratings (n = 19) and post- intervention interviews (n = 6) showed resource acceptability. We met our recruitment, retention and pre-post measure completion targets and identified the Strengths and Difficulties Questionnaire as the most sensitive outcome measure. This study established the feasibility of a co-designed, mental health app as a low-burden, school-hosted resource for symptomatic young people and opens up new possibilities for the integration of mHealth in schools. Support via schools to parents of symptomatic young people may need to be universal rather than targeted. Following some refinements of MindMate2U, a phase 2 randomised controlled trial is warranted to test its effectiveness

    Fluoromycobacteriophages for rapid, specific, and sensitive antibiotic susceptibility testing of Mycobacterium tuberculosis

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    Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis is of paramount importance as multiple- and extensively- drug resistant strains of M. tuberculosis emerge and spread. We describe here a virus-based assay in which fluoromycobacteriophages are used to deliver a GFP or ZsYellow fluorescent marker gene to M. tuberculosis, which can then be monitored by fluorescent detection approaches including fluorescent microscopy and flow cytometry. Pre-clinical evaluations show that addition of either Rifampicin or Streptomycin at the time of phage addition obliterates fluorescence in susceptible cells but not in isogenic resistant bacteria enabling drug sensitivity determination in less than 24 hours. Detection requires no substrate addition, fewer than 100 cells can be identified, and resistant bacteria can be detected within mixed populations. Fluorescence withstands fixation by paraformaldehyde providing enhanced biosafety for testing MDR-TB and XDR-TB infections. © 2009 Piuri et al

    A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts

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    Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 mu L) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 mu L) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 x 10(-5)). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.Peer reviewe

    Aspects of the breeding biology of Janaira gracilis Moreira & Pires (Crustacea, Isopoda, Asellota)

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    The biological aspects of incubating females of Janaira gracilis Mbreira & Pires, are described. The marsupium is formed by 4 pairs of oostegites arising from pereopods I-IV. The oostegites appear for the first time at the post-marsupial stage 7 (preparatory stage 1), growing successively at each moult until stage 9 (brooding stage 1), when they reach fully development. The sizes of the eggs increase with the body size of the females. The number of eggs, per female, is a linear function of the body volume, i.e., the fecundity increases with the female's body size. The number of eggs, embryos and juveniles decrease during the marsupial development. This decrease in brood number is higher between the last two marsupial stages, i.e., from stage C to D, than between the preceding marsupial stages. The average and overall brood mortality rate is of 38.95%.SĂŁo descritos, no presente trabalho, vĂĄrios aspectos relacionados Ă  biologia de fĂȘmeas grĂĄvidas de Janaira gracilis Moreira & Pires. O marsĂșpio Ă© formado por 4 pares de oostĂ©gitos, que partem dos pereĂłpodos I-IV. Os oostĂ©gitos, que surgem pela primeira vez no estĂĄdio 7 do desenvolvimento pĂłs-marsupial (estĂĄgio preparatĂłrio 1), crescem nas sucessivas mudas, atingindo no estĂĄgio 9 (estĂĄgio reprodutor 1) seu pleno desenvolvimento. O tamanho dos ovos Ă© proporcional ao tamanho das fĂȘmeas. O nĂșmero de ovos, por fĂȘmeas, e proporcional ao volume das fĂȘmeas, isto Ă©, a fecundidade Ă© mais elevada nos exemplares de maior comprimento. O nĂșmero de ovos, embriĂ”es e jovens decresce com o desenvolvimento marsupial, sendo este decrĂ©scimo maior entre os dois Ășltimos estĂĄgios marsupials (i.Ă©., entre os estĂĄgios C e D) do que entre os estĂĄgios precedentes. A taxa mĂ©dia de mortalidade marsupial Ă© de 38.95%

    Incorporation of albumin fusion proteins into fibrin clots in vitro and in vivo: comparison of different fusion motifs recognized by factor XIIIa

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    <p>Abstract</p> <p>Background</p> <p>The transglutaminase activated factor XIII (FXIIIa) acts to strengthen pathological fibrin clots and to slow their dissolution, in part by crosslinking active α<sub>2</sub>-antiplasmin (α<sub>2</sub>AP) to fibrin. We previously reported that a yeast-derived recombinant fusion protein comprising α<sub>2</sub>AP residues 13-42 linked to human serum albumin (HSA) weakened <it>in vitro </it>clots but failed to become specifically incorporated into <it>in vivo </it>clots. In this study, our aims were to improve both the stability and clot localization of the HSA fusion protein by replacing α<sub>2</sub>AP residues 13-42 with shorter sequences recognized more effectively by FXIIIa.</p> <p>Results</p> <p>Expression plasmids were prepared encoding recombinant HSA with the following N-terminal 23 residue extensions: H<sub>6</sub>NQEQVSPLTLLAG<sub>4</sub>Y (designated XL1); H<sub>6</sub>DQMMLPWAVTLG<sub>4</sub>Y (XL2); H<sub>6</sub>WQHKIDLPYNGAG<sub>4</sub>Y (XL3); and their 17 residue non-His-tagged equivalents (XL4, XL5, and XL6). The HSA moiety of XL4- to XL6-HSA proteins was C-terminally His-tagged. All chimerae were efficiently secreted from transformed <it>Pichia pastoris </it>yeast except XL3-HSA, and following nickel chelate affinity purification were found to be intact by amino acid sequencing, as was an N-terminally His-tagged version of α<sub>2</sub>AP(13-42)-HSA. Of the proteins tested, XL5-HSA was cross-linked to biotin pentylamine (BPA) most rapidly by FXIIIa, and was the most effective competitor of α<sub>2</sub>AP crosslinking not only to BPA but also to plasma fibrin clots. In the mouse ferric chloride <it>vena cava </it>thrombosis model, radiolabeled XL5-HSA was retained in the clot to a greater extent than recombinant HSA. In the rabbit jugular vein stasis thrombosis model, XL5-HSA was also retained in the clot, in a urea-insensitive manner indicative of crosslinking to fibrin, to a greater extent than recombinant HSA.</p> <p>Conclusions</p> <p>Fusion protein XL5-HSA (DQMMLPWAVTLG<sub>4</sub>Y-HSAH<sub>6</sub>) was found to be more active as a substrate for FXIIIa-mediated transamidation than seven other candidate fusion proteins <it>in vitro</it>. The improved stability and reactivity of this chimeric protein was further evidenced by its incorporation into <it>in vivo </it>clots formed in thrombosis models in both mice and rabbits.</p

    A new method to determine the diet of pygmy hippopotamus in Taï National Park, Cîte d’Ivoire

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    This research was funded by “Fond des donations” of the University of NeuchĂątel and the “Willy MĂŒller Award” of the Centre Suisse de Recherches Scientifiques en CĂŽte d’Ivoire.Diet determination of endangered species is an essential element in defining successful conservation strategies and optimising captive breeding programmes. In this study, we developed a new diet identification system, derived from standard faecal analysis, to determine the diet of an elusive and endangered herbivore, the pygmy hippopotamus (Choeropsis liberiensis). We collected faecal samples from 10 free-ranging individuals covering a combined home range area of about 50 km2 in TaĂŻ National Park, CĂŽte d’Ivoire. In subsequent laboratory analyses, we extracted a large number of leaf epidermis fragments from spatially separated faecal samples and compared them with a reference plant database. Using Multiple Correspondence Analysis (MCA) of epidermis fragments combined with direct visual inspection, we identified the most frequently consumed plant species, which revealed that pygmy hippopotami qualified as intermediate feeders. Their diet was based on at least seven species of monocotyledonae, dicotyledonae and fern groups, with a preference for a small number of other plant species. We evaluate the merit of our method and discuss our findings for developing effective conservation and captive breeding strategies in an endangered species with a wild population of less than 2500 adult individuals.PostprintPeer reviewe

    New Protocetid Whale from the Middle Eocene of Pakistan: Birth on Land, Precocial Development, and Sexual Dimorphism

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    BACKGROUND: Protocetidae are middle Eocene (49-37 Ma) archaeocete predators ancestral to later whales. They are found in marine sedimentary rocks, but retain four legs and were not yet fully aquatic. Protocetids have been interpreted as amphibious, feeding in the sea but returning to land to rest. METHODOLOGY/PRINCIPAL FINDINGS: Two adult skeletons of a new 2.6 meter long protocetid, Maiacetus inuus, are described from the early middle Eocene Habib Rahi Formation of Pakistan. M. inuus differs from contemporary archaic whales in having a fused mandibular symphysis, distinctive astragalus bones in the ankle, and a less hind-limb dominated postcranial skeleton. One adult skeleton is female and bears the skull and partial skeleton of a single large near-term fetus. The fetal skeleton is positioned for head-first delivery, which typifies land mammals but not extant whales, evidence that birth took place on land. The fetal skeleton has permanent first molars well mineralized, which indicates precocial development at birth. Precocial development, with attendant size and mobility, were as critical for survival of a neonate at the land-sea interface in the Eocene as they are today. The second adult skeleton is the most complete known for a protocetid. The vertebral column, preserved in articulation, has 7 cervicals, 13 thoracics, 6 lumbars, 4 sacrals, and 21 caudals. All four limbs are preserved with hands and feet. This adult is 12% larger in linear dimensions than the female skeleton, on average, has canine teeth that are 20% larger, and is interpreted as male. Moderate sexual dimorphism indicates limited male-male competition during breeding, which in turn suggests little aggregation of food or shelter in the environment inhabited by protocetids. CONCLUSIONS/SIGNIFICANCE: Discovery of a near-term fetus positioned for head-first delivery provides important evidence that early protocetid whales gave birth on land. This is consistent with skeletal morphology enabling Maiacetus to support its weight on land and corroborates previous ideas that protocetids were amphibious. Specimens this complete are virtual 'Rosetta stones' providing insight into functional capabilities and life history of extinct animals that cannot be gained any other way
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