864 research outputs found

    A grounded theory analysis of the experience of therapy in the context of negative change

    Get PDF
    Negative change occurring during psychotherapy is relatively underresearched and current theories take little account of social context. Eight clients and four therapists were interviewed about their therapy experience when reliable score deterioration on an outcome measure was observed, with the aim of generating a Grounded Theory model of negative change. The emerging model identified three major themes: a context of adversity, the therapeutic experience, and help withdrawn (within the context of positive outcomes). Difficulties included wanting therapy to provide more advice, talking about distressing issues, relationship difficulties, ambivalence, and a wish for support instead of change. Client context merits increased attention. Changes in outcome measures used, more diverse supervision models, training to use outcome measures constructively, and sensitive, routine analysis of negative change are indicated. Increased availability of therapies able to address clients’ interpersonal and social context and a wider choice of therapy type would allow interventions to better fit the individual in context

    A four gene signature of chromosome instability (CIN4) predicts for benefit from taxanes in the NCIC-CTG MA21 clinical trial.

    Get PDF
    Recent evidence demonstrated CIN4 as a predictive marker of anthracycline benefit in early breast cancer. An analysis of the NCIC CTG MA.21 clinical trial was performed to test the role of existing CIN gene expression signatures as prognostic and predictive markers in the context of taxane based chemotherapy.RNA was extracted from patients in cyclophosphamide, epirubicin and flurouracil (CEF) and epirubicin, cyclophosphamide and paclitaxel (EC/T) arms of the NCIC CTG MA.21 trial and analysed using NanoString technology.After multivariate analysis both high CIN25 and CIN70 score was significantly associated with an increased in RFS (HR 1.76, 95%CI 1.07-2.86, p=0.0018 and HR 1.59, 95%CI 1.12-2.25, p=0.0096 respectively). Patients whose tumours had low CIN4 gene expression scores were associated with an increase in RFS (HR: 0.64, 95% CI 0.39-1.03, p=0.06) when treated with EC/T compared to patients treated with CEF.In conclusion we have demonstrated CIN25 and CIN70 as prognostic markers in breast cancer and that CIN4 is a potential predictive maker of benefit from taxane treatment

    Experimental Determination of Activation Energies for Covalent Bond Formation via Ion/Ion Reactions and Competing Processes

    Get PDF
    The combination of ion/ion chemistry with commercially available ion mobility/mass spectrometry systems has allowed rich structural information to be obtained for gaseous protein ions. Recently, the simple modification of such an instrument with an electrospray reagent source has allowed three-dimensional gas-phase interrogation of protein structures through covalent and noncovalent interactions coupled with collision cross section measurements. However, the energetics of these processes have not yet been studied quantitatively. In this work, previously developed Monte Carlo simulations of ion temperatures inside traveling wave ion guides are used to characterize the energetics of the transition state of activated ubiquitin cation/sulfo-benzoyl-HOAt reagent anion long-lived complexes formed via ion/ion reactions. The ΔH‡ and ΔS‡ of major processes observed from collisional activation of long-lived gas-phase ion/ion complexes, namely collision induced unfolding (CIU), covalent bond formation, or neutral loss of the anionic reagent via intramolecular proton transfer, were determined. Covalent bond formation via ion/ion complexes was found to be significantly lower energy compared to unfolding and bond cleavage. The ΔG‡ values of activation of all three processes lie between 55 and 75 kJ/mol, easily accessible with moderate collisional activation. Bond formation is favored over reagent loss at lower activation energies, whereas reagent loss becomes competitive at higher collision energies. Though the ΔG‡ values between CIU of a precursor ion and covalent bond formation of its ion/ion product complex are comparable, our data suggest covalent bond formation does not require extensive isomerization

    Structural basis for phosphorylation and lysine acetylation cross-talk in a kinase motif associated with myocardial ischemia and cardioprotection

    Get PDF
    Myocardial ischemia and cardioprotection by ischemic pre-conditioning induce signal networks aimed at survival or cell death if the ischemic period is prolonged. These pathways are mediated by protein post-translational modifications that are hypothesized to cross-talk with and regulate each other. Phosphopeptides and lysine-acetylated peptides were quantified in isolated rat hearts subjected to ischemia or ischemic pre-conditioning, with and without splitomicin inhibition of lysine deacetylation. We show lysine acetylation (acetyl-Lys)-dependent activation of AMP-activated protein kinase, AKT, and PKA kinases during ischemia. Phosphorylation and acetyl-Lys sites mapped onto tertiary structures were proximal in >50% of proteins investigated, yet they were mutually exclusive in 50 ischemic pre-conditioning- and/or ischemia-associated peptides containing the KXXS basophilic protein kinase consensus motif. Modifications in this motif were modeled in the C terminus of muscle-type creatine kinase. Acetyl-Lys increased proximal dephosphorylation by 10-fold. Structural analysis of modified muscle-type creatine kinase peptide variants by two-dimensional NMR revealed stabilization via a lysine-phosphate salt bridge, which was disrupted by acetyl-Lys resulting in backbone flexibility and increased phosphatase accessibility

    Solidarity and Strife After the Atlanta Spa Shootings: A Mixed Methods Study Characterizing Twitter Discussions by Qualitative Analysis and Machine Learning

    Get PDF
    Background: On March 16, 2021, a white man shot and killed eight victims, six of whom were Asian women at Atlanta-area spa and massage parlors. The aims of the study were to: (1) qualitatively summarize themes of tweets related to race, ethnicity, and racism immediately following the Atlanta spa shootings, and (2) examine temporal trends in expressions hate speech and solidarity before and after the Atlanta spa shootings using a new methodology for hate speech analysis. Methods: A random 1% sample of publicly available tweets was collected from January to April 2021. The analytic sample included 708,933 tweets using race-related keywords. This sample was analyzed for hate speech using a newly developed method for combining faceted item response theory with deep learning to measure a continuum of hate speech, from solidarity race-related speech to use of violent, racist language. A qualitative content analysis was conducted on random samples of 1,000 tweets referencing Asians before the Atlanta spa shootings from January to March 15, 2021 and 2,000 tweets referencing Asians after the shooting from March 17 to 28 to capture the immediate reactions and discussions following the shootings. Results: Qualitative themes that emerged included solidarity (4% before the shootings vs. 17% after), condemnation of the shootings (9% after), racism (10% before vs. 18% after), role of racist language during the pandemic (2 vs. 6%), intersectional vulnerabilities (4 vs. 6%), relationship between Asian and Black struggles against racism (5 vs. 7%), and discussions not related (74 vs. 37%). The quantitative hate speech model showed a decrease in the proportion of tweets referencing Asians that expressed racism (from 1.4% 7 days prior to the event from to 1.0% in the 3 days after). The percent of tweets referencing Asians that expressed solidarity speech increased by 20% (from 22.7 to 27.2% during the same time period) (p \u3c 0.001) and returned to its earlier rate within about 2 weeks. Discussion: Our analysis highlights some complexities of discrimination and the importance of nuanced evaluation of online speech. Findings suggest the importance of tracking hate and solidarity speech. By understanding the conversations emerging from social media, we may learn about possible ways to produce solidarity promoting messages and dampen hate messages

    Educational Attainment at Age 10–11 Years Predicts Health Risk Behaviors and Injury Risk During Adolescence

    Get PDF
    Purpose: To examine the effect of educational attainment in primary school on later adolescent health. Methods: Education data attainments at age 7 and 11 were linked with (1) primary and secondary care injury consultation/admissions and (2) the Health Behaviour in School-aged Children survey. Cox regression was carried out to examine if attainment in primary school predicts time to injury in adolescence. Results: Pupils that achieve attainment at age 7 but not at age 11 (i.e., declining attainment over time in primary school) are more likely to have an injury during adolescence. These children are also more likely to self-report drinking in adolescence. Conclusions: Interventions aimed at children with declining attainment in primary school could help to improve adolescent health

    The glaciers climate change initiative: Methods for creating glacier area, elevation change and velocity products

    Get PDF
    Glaciers and their changes through time are increasingly obtained from a wide range of satellite sensors. Due to the often remote location of glaciers in inaccessible and high-mountain terrain, satellite observations frequently provide the only available measurements. Furthermore, satellite data provide observations of glacier character- istics that are difficult to monitor using ground-based measurements, thus complementing the latter. In the Glaciers_cci project of the European Space Agency (ESA), three of these characteristics are investigated in detail: glacier area, elevation change and surface velocity. We use (a) data from optical sensors to derive glacier outlines, (b) digital elevation models from at least two points in time, (c) repeat altimetry for determining elevation changes, and (d) data from repeat optical and microwave sensors for calculating surface velocity. For the latter, the two sensor types provide complementary information in terms of spatio-temporal coverage. While (c) and (d) can be generated mostly automatically, (a) and (b) require the intervention of an analyst. Largely based on the results of various round robin experiments (multi-analyst benchmark studies) for each of the products, we suggest and describe the most suitable algorithms for product creation and provide recommendations concerning their practical implementation and the required post-processing. For some of the products (area, velocity) post-processing can influence product quality more than the main-processing algorithm

    Using a population-based approach to prevent hepatocellular cancer in New South Wales, Australia: effects on health services utilisation

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Australians born in countries where hepatitis B infection is endemic are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. However, a program of screening, surveillance and treatment of chronic hepatitis B (CHB) in high risk populations could significantly reduce disease progression and death related to end-stage liver disease and HCC. Consequently we are implementing the <it>B Positive </it>pilot project, aiming to optimise the management of CHB in at-risk populations in south-west Sydney. Program participants receive routine care, enhanced disease surveillance or specialist referral, according to their stage of CHB infection, level of viral load and extent of liver injury. In this paper we examine the program's potential impact on health services utilisation in the study area.</p> <p>Methods</p> <p>Estimated numbers of CHB infections were derived from Australian Bureau of Statistics data and applying estimates of HBV prevalence rates from migrants' countries of birth. These figures were entered into a Markov model of disease progression, constructing a hypothetical cohort of Asian-born adults with CHB infection. We calculated the number of participants in different CHB disease states and estimated the numbers of GP and specialist consultations and liver ultrasound examinations the cohort would require annually over the life of the program.</p> <p>Results</p> <p>Assuming a 25% participation rate among the 5,800 local residents estimated to have chronic hepatitis B infection, approximately 750 people would require routine follow up, 260 enhanced disease surveillance and 210 specialist care during the first year after recruitment is completed. This translates into 5 additional appointments per year for each local GP, 25 for each specialist and 420 additional liver ultrasound examinations.</p> <p>Conclusions</p> <p>While the program will not greatly affect the volume of local GP consultations, it will lead to a significant increase in demand for specialist services. New models of CHB care may be required to aid program implementation and up scaling the program will need to factor in additional demands on health care utilisation in areas of high hepatitis B sero-prevalence.</p

    Independent evolution of intermediate bill widths in a seabird clade

    Get PDF
    16 pages, 5 figures, 5 tables, supplementary information https://doi.org/10.1007/s00438-021-01845-3.-- Availability of data and material: DNA sequences: GenBank accession numbers are provided in Table 1. All data are available in the manuscript or in the Supplementary information fileInterspecific introgression can occur between species that evolve rapidly within an adaptive radiation. Pachyptila petrels differ in bill size and are characterised by incomplete reproductive isolation, leading to interspecific gene flow. Salvin’s prion (Pachyptila salvini), whose bill width is intermediate between broad-billed (P. vittata) and Antarctic (P. desolata) prions, evolved through homoploid hybrid speciation. MacGillivray’s prion (P. macgillivrayi), known from a single population on St Paul (Indian Ocean), has a bill width intermediate between salvini and vittata and could also be the product of interspecies introgression or hybrid speciation. Recently, another prion population phenotypically similar to macgillivrayi was discovered on Gough (Atlantic Ocean), where it breeds 3 months later than vittata. The similarity in bill width between the medium-billed birds on Gough and macgillivrayi suggest that they could be closely related. In this study, we used genetic and morphological data to infer the phylogenetic position and evolutionary history of P. macgillivrayi and the Gough medium-billed prion relative other Pachyptila taxa, to determine whether species with medium bill widths evolved through common ancestry or convergence. We found that Gough medium-billed prions belong to the same evolutionary lineage as macgillivrayi, representing a new population of MacGillivray’s prion that originated through a colonisation event from St Paul. We show that macgillivrayi’s medium bill width evolved through divergence (genetic drift) and independently from that of salvini, which evolved through hybridisation (gene flow). This represents the independent convergence towards a similarly medium-billed phenotype. The newly discovered MacGillivray’s prion population on Gough is of utmost conservation relevance, as the relict macgillivrayi population in the Indian Ocean is very smallOpen Access funding enabled and organized by Projekt DEAL. PQ, JFM, TLC and LC were supported by the Deutsche Forschungsgemeinschaft (Germany), Heisenberg program (grant number DFG, Qu 148-5 to P.Q.). Logistical and financial support was obtained from the South African Department of Environmental Affairs, through the South African National Antarctic Programme. LDS was supported by a Rutherford Discovery Fellowship from the Royal Society of New ZealandWith the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe
    • …
    corecore