242 research outputs found

    Translocation as a Population Restoration Technique for Northern Bobwhites: A Review and Synthesis

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    Northern bobwhite (Colinus virginianus) abundance has declined precipitously for decades across much of the species range, to the point of widespread local, regional, and statewide extirpation. Because of successful translocations of other gallinaceous birds, bobwhite enthusiasts increasingly call for use of the approach. Consequently, the National Bobwhite Technical Committee (NBTC), on behalf of state agencies, requested a review and recommendation by the NBTC Science Subcommittee. Thus, our paper is co-authored by invited experts and includes reviews of peer-reviewed publications, manuscripts in these proceedings, state agency reports, experience by co-authors, and a survey of perspectives on translocations by state wildlife agency members of the NBTC. We discuss the state of science on key aspects of bobwhite conservation, offer best management practices (BMPs) for using translocation as a potential bobwhite restoration technique, and suggest ways to reduce uncertainty about implementation. We note that although conservationists operate on a relatively solid foundation of improving bobwhite abundance via increased quantity, connectivity, and quality of habitat, population restoration success to- date is relatively rare and unpredictable. Similarly, some past translocations have been unreliable with an abundance of failures and inadequate experimental designs. We conclude that because of major uncertainties regarding habitat, population phenomena (e.g., Allee effect) and restoration techniques, outcomes of translocations remain unpredictable; thus, future efforts must be a part of sound and rigorous peer-reviewed research. To improve scientific efforts, we recommend the following BMPs for future translocations: (1) target bobwhite abundance should be \u3e800 post-translocation which will likely necessitate ≥600 ha of suitable and accessible habitat while a larger (e.g., \u3e800 ha) area will be needed in areas with lower carrying capacity and when sites are highly fragmented or isolated, (2) personnel should identify and avoid stressors to bobwhites in all phases of the translocation process (i.e., capture, holding, transportation, and release), (3) source populations should be disease free and from similar environments and latitude; preferably from the nearest suitable source, (4) conspecifics should be present on recipient sites (5) birds should be released just before the breeding season (i.e., March or April), and (6) the translocation should incorporate robust short- and long-term bird (i.e., abundance and/or density) and habitat monitoring efforts (i.e., the Coordinated Implementation Program (CIP) of the National Bobwhite Conservation Initiative (NBCI)). In conclusion, we note that translocation of bobwhites is not a panacea for broad scale restoration of bobwhites; however, the technique should remain at the forefront of bobwhite science, taking into account knowledge of the species’ life history and ecology, so that a practical and reliable solution can be developed. We recognize this paper is just the beginning of vigorous debate, testing of concepts, and on-the ground implementation of successful bobwhite conservation

    Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

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    BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

    Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21

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    Background: The oncolytic virus, coxsackievirus A21 (CVA21), has shown promise as a single agent in several clinical trials and is now being tested in combination with immune checkpoint blockade. Combination therapies offer the best chance of disease control; however, the design of successful combination strategies requires a deeper understanding of the mechanisms underpinning CVA21 efficacy, in particular, the role of CVA21 anti-tumor immunity. Therefore, this study aimed to examine the ability of CVA21 to induce human anti-tumor immunity, and identify the cellular mechanism responsible. Methods: This study utilized peripheral blood mononuclear cells from i) healthy donors, ii) Acute Myeloid Leukemia (AML) patients, and iii) patients taking part in the STORM clinical trial, who received intravenous CVA21; patients receiving intravenous CVA21 were consented separately in accordance with local institutional ethics review and approval. Collectively, these blood samples were used to characterize the development of innate and adaptive anti-tumor immune responses following CVA21 treatment. Results: An Initial characterization of peripheral blood mononuclear cells, collected from cancer patients following intravenous infusion of CVA21, confirmed that CVA21 activated immune effector cells in patients. Next, using hematological disease models which were sensitive (Multiple Myeloma; MM) or resistant (AML) to CVA21-direct oncolysis, we demonstrated that CVA21 stimulated potent anti-tumor immune responses, including: 1) cytokine-mediated bystander killing; 2) enhanced natural killer cell-mediated cellular cytotoxicity; and 3) priming of tumor-specific cytotoxic T lymphocytes, with specificity towards known tumor-associated antigens. Importantly, immune-mediated killing of both MM and AML, despite AML cells being resistant to CVA21-direct oncolysis, was observed. Upon further examination of the cellular mechanisms responsible for CVA21-induced anti-tumor immunity we have identified the importance of type I IFN for NK cell activation, and demonstrated that both ICAM-1 and plasmacytoid dendritic cells were key mediators of this response. Conclusion: This work supports the development of CVA21 as an immunotherapeutic agent for the treatment of both AML and MM. Additionally, the data presented provides an important insight into the mechanisms of CVA21-mediated immunotherapy to aid the development of clinical biomarkers to predict response and rationalize future drug combinations

    Mental health consumer and caregiver perceptions of stigma in Australian community pharmacies

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    Background: The stigma of mental illness can be a barrier to effective medication management in the community pharmacy setting. This article explored mental health consumers’ or caregivers’ experiences of stigma in Australian community pharmacies. Materials: Semi-structured interviews and focus groups were conducted with a purposive sample of consumers or caregivers (n = 74). Interview transcripts were analysed using a general inductive approach. Discussion: Stigma presented a barrier to effective mental health management. Self-stigma impeded consumers’ community pharmacy engagement. Positive relationships with knowledgeable staff are fundamental to reducing stigma. Conclusions: Findings provide insight into the stigma of mental illness in community pharmacies

    On the co-evolution of supermassive black holes and their host galaxies since z = 3

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    [Abridged] To investigate the evolution in the relation between galaxy stellar and central black hole mass we construct a volume limited complete sample of 85 AGN with host galaxy stellar masses M_{*} > 10^{10.5} M_{sol}, and specific X-ray luminosities L_{X} > 2.35 x 10^{43} erg s^{-1} at 0.4 < z < 3. We calculate the Eddington limiting masses of the supermassive black holes residing at the centre of these galaxies, and observe an increase in the average Eddington limiting black hole mass with redshift. By assuming that there is no evolution in the Eddington ratio (\mu) and then that there is maximum possible evolution to the Eddington limit, we quantify the maximum possible evolution in the M_{*} / M_{BH} ratio as lying in the range 700 < M_{*}/M_{BH} < 10000, compared with the local value of M_{*}/M_{BH} ~ 1000. We furthermore find that the fraction of galaxies which are AGN (with L_{X} > 2.35 x 10^{43} erg s^{-1}) rises with redshift from 1.2 +/- 0.2 % at z = 0.7 to 7.4 +/- 2.0 % at z = 2.5. We use our results to calculate the maximum timescales for which our sample of AGN can continue to accrete at their observed rates before surpassing the local galaxy-black hole mass relation. We use these timescales to calculate the total fraction of massive galaxies which will be active (with L_{X} > 2.35 x 10^{43} erg s^{-1}) since z = 3, finding that at least ~ 40% of all massive galaxies will be Seyfert luminosity AGN or brighter during this epoch. Further, we calculate the energy density due to AGN activity in the Universe as 1.0 (+/- 0.3) x 10^{57} erg Mpc^{-3} Gyr^{-1}, potentially providing a significant source of energy for AGN feedback on star formation. We also use this method to compute the evolution in the X-ray luminosity density of AGN with redshift, finding that massive galaxy Seyfert luminosity AGN are the dominant source of X-ray emission in the Universe at z < 3.Comment: 25 pages, 10 figures, accepted for publication in MNRA

    Glucose Depletion in the Airway Surface Liquid Is Essential for Sterility of the Airways

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    Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL) and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources –including glucose– in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung

    Decline in Health-Related Quality of Life reported by more than half of those waiting for joint replacement surgery: a prospective cohort study

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    <p>Abstract</p> <p>Background</p> <p>In many healthcare systems, people with severe joint disease wait months to years for joint replacement surgery. There are little empirical data on the health consequences of this delay and it is unclear whether people with substantial morbidity at entry to the waiting list continue to deteriorate further while awaiting surgery. This study investigated changes in Health-Related Quality of Life (HRQoL), health status and psychological distress among people waiting for total hip (THR) and knee replacement (TKR) surgery at a major metropolitan Australian public hospital.</p> <p>Methods</p> <p>134 patients completed questionnaires including the Assessment of Quality of Life (AQoL) instrument, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Kessler Psychological Distress Scale after entering an orthopaedic waiting list (baseline) and before surgery (preadmission). To quantify potential decline in wellbeing, we calculated the proportion of people experiencing clinically important deterioration using published guidelines and compared HRQoL and psychological distress outcomes with population norms.</p> <p>Results</p> <p>Most participants (69%) waited ≥6 months for surgery (median 286 days, IQR 169-375 days). Despite poor physical and psychological wellbeing at baseline, there was an overall deterioration in HRQoL during the waiting period (mean AQoL change -0.04, 95%CI -0.08 to -0.01), with 53% of participants experiencing decline in HRQoL (≥0.04 AQoL units). HRQoL prior to surgery remained substantially lower than Australian population norms (mean sample AQoL 0.37, 95%CI 0.33 to 0.42 vs mean population AQoL 0.83, 95%CI 0.82 to 0.84). Twenty-five per cent of participants showed decline in health status (≥9.6 WOMAC units) over the waiting period and prevalence of high psychological distress remained high at preadmission (RR 3.5, 95%CI 2.8 to 4.5). Most participants considered their pain (84%), fatigue (76%), quality of life (73%) and confidence in managing their health (55%) had worsened while waiting for surgery.</p> <p>Conclusions</p> <p>Despite substantial initial morbidity, over half of the participants awaiting joint replacement experienced deterioration in HRQoL during the waiting period. These data provide much-needed evidence to guide health professionals and policymakers in the design of care pathways and resource allocation for people who require joint replacement surgery.</p

    The Glycosylphosphatidylinositol-PLC in Trypanosoma brucei Forms a Linear Array on the Exterior of the Flagellar Membrane Before and After Activation

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    Bloodstream forms of Trypanosoma brucei contain a glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC) that cleaves the GPI-anchor of the variable surface glycoprotein (VSG). Its location in trypanosomes has been controversial. Here, using confocal microscopy and surface labelling techniques, we show that the GPI-PLC is located exclusively in a linear array on the outside of the flagellar membrane, close to the flagellar attachment zone, but does not co-localize with the flagellar attachment zone protein, FAZ1. Consequently, the GPI-PLC and the VSG occupy the same plasma membrane leaflet, which resolves the topological problem associated with the cleavage reaction if the VSG and the GPI-PLC were on opposite sides of the membrane. The exterior location requires the enzyme to be tightly regulated to prevent VSG release under basal conditions. During stimulated VSG release in intact cells, the GPI-PLC did not change location, suggesting that the release mechanism involves lateral diffusion of the VSG in the plane of the membrane to the fixed position of the GPI-PLC

    Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA.</p> <p>Methods/Design</p> <p>Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics.</p> <p>Discussion</p> <p>Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA.</p> <p>Trial registration</p> <p>ACTR12605000503628; NCT00415259.</p
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