2,823 research outputs found

    Psychiatric morbidity and suicidal behaviour in low- and middle-income countries: a systematic review and meta-analysis

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    Background: Psychiatric disorders are reported to be present in 80-90% of suicide deaths in high-income countries (HIC), but this association is less clear in low- and middle-income countries (LMIC). There has been no previous systematic review of this issue in LMIC. The current study aims to estimate the prevalence of psychiatric morbidity in individuals with suicidal behaviour in LMIC. Methods and findings: PubMed, PsycINFO, and EMBASE searches were conducted to identify quantitative research papers (any language) between 1990 and 2018 from LMIC which reported on the prevalence of psychiatric morbidity in suicidal behaviour. We used meta-analytic techniques to generate pooled estimates for any psychiatric disorder and specific diagnosis based on ICD-10 criteria. A total of 112 studies (154 papers) from 26 LMIC (India: 25%; China: 15%; and Other LMIC: 60%) were identified, including 18 non-English articles. They included 30030 individuals with non-fatal suicidal behaviour and 4996 individuals who had died by suicide. Of the 15 studies (5 LMIC) that scored highly on our quality assessment, prevalence estimates for psychiatric disorders ranged between 30% and 80% in suicide deaths, and between 3% and 86% in those who engaged in non-fatal suicidal behaviour. There was substantial heterogeneity between study estimates. Fifty-eight percent (95% CI 46-71%) of those who died by suicide and 45% (95% CI 30-61%) of those who engaged in non-fatal suicidal behaviour had a psychiatric disorder. The most prevalent disorder in both fatal and non-fatal suicidal behaviour was mood disorder (25% and 21% respectively). Schizophrenia and related disorders were identified in 8% (4-12%) of those who died by suicide and 7% (3-11%) of those who engaged in non-fatal suicidal behaviour. In non-fatal suicidal behaviour, anxiety disorders, and substance misuse were identified in 19% (1-36%) and 11% (7-16%) of individuals respectively. This systematic review was limited by the low number of high-quality studies and restricting our searches to databases which mainly indexed English language journals. Conclusions: Our findings suggest a possible lower prevalence of psychiatric disorders in suicidal behaviour in LMIC. We found very few high-quality studies and high levels of heterogeneity in pooled estimates of psychiatric disorder, which could reflect differing study methods or real differences. There is a clear need for more robust evidence in order for LMIC to strike the right balance between community-based and mental health focused interventions

    The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia

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    Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (V-mem) and quiescence. We found that V-mem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas V-mem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high V-mem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and up-regulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and V-mem in the Artemia model

    Teacherā€“researcher partnership in the translation and implementing of PALS (Peerā€Assisted Learning Strategies): An international perspective

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    Funding Information: We would like to thank the schools, teachers and students who have alongside us developed PALS for each international context outlined. Publisher Copyright: Ā© 2022 The Authors. Journal of Research in Reading published by John Wiley & Sons Ltd on behalf of United Kingdom Literacy Association.Peer-Assisted Learning Strategies (PALS) is a class-wide structured supplementary paired reading programme to support learners with their reading (Fuchs et al., 1997). What remains at the core of implementing PALS in any given location is the co-creation with teachers to ensure PALS fits with that educational context. This paper discusses the involvement of teachers as co-creators in the process of adapting PALS in England, United Arab Emirates (UAE), Taiwan and Iceland. The aim is to demonstrate the importance of careful adaptation when implementing a programme adopted from another country. Each adaption used a different methodological approach to co-creation. For example, in England, field notes, informal conversations and interviews were utilised for co-creation. In Iceland, preschool and elementary teachers were instrumental in translating and adapting the PALS materials to the Icelandic context. From each adaption, the teachers supported the development of a literacy programme that was suitable for classroom use. In England, teachers' involvement resulted in the removal of the motivational point system. For the UAE context, PALS began in English to support second language learning, but the instructional routines were a good ā€˜fitā€™ for the school culture and were developed in Arabic. For the Taiwan context, PALS provided an empirical basis for a model of differentiated instruction to enhance the reading literacy of Chinese-speaking elementary students. In Iceland, teachers trained other teachers in PALS as a research-based and efficient approach to meeting diverse learning needs of students, especially those with Icelandic as an additional language. Careful adaptation, piloting and the involvement of key stakeholders is important for the successful implementation of a reading programme.Peer reviewe

    Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma-expressed self-antigen

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    Adoptive transfer (AT) T-cell therapy provides significant clinical benefits in patients with advanced melanoma. However, approaches to non-invasively visualize the persistence of transferred T cells are lacking. We examined whether positron emission tomography (PET) can monitor the distribution of self-antigen-specific T cells engineered to express an herpes simplex virus 1 thymidine kinase (sr39tk) PET reporter gene. Micro-PET imaging using the sr39tk-specific substrate 9-[4-[18F]fluoro-3-(hydroxymethyl)-butyl]guanine ([18F]FHBG) enabled the detection of transplanted T cells in secondary lymphoid organs of recipient mice over a 3-week period. Tumor responses could be predicted as early as 3 days following AT when a >25-fold increase of micro-PET signal in the spleen and 2-fold increase in lymph nodes (LNs) were observed in mice receiving combined immunotherapy versus control mice. The lower limit of detection was āˆ¼7 Ɨ 105 T cells in the spleen and 1 Ɨ 104 T cells in LNs. Quantification of transplanted T cells in the tumor was hampered by the sr39tk-independent trapping of [18F]FHBG within the tumor architecture. These data support the feasibility of using PET to visualize the expansion, homing and persistence of transferred T cells. PET may have significant clinical utility by providing the means to quantify anti-tumor T cells throughout the body and provide early correlates for treatment efficacy

    Anemia is an independent risk for mortality after acute myocardial infarction in patients with and without diabetes

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    INTRODUCTION: Anemia and diabetes are risk factors for short-term mortality following an acute myocardial infarction(AMI). Anemia is more prevalent in patients with diabetes. We performed a retrospective study to assess the impact of the combination of diabetes and anemia on post-myocardial infarction outcomes. METHODS: Data relating to all consecutive patients hospitalized with AMI was obtained from a population-based disease-specific registry. Patients were divided into 4 groups: diabetes and anemia (group A, n = 716), diabetes and no anemia (group B, n = 1894), no diabetes and anemia (group C, n = 869), and no diabetes and no anemia (group D, n = 3987). Mortality at 30 days and 31 days to 36 months were the main outcome measures. RESULTS: 30-day mortality was 32.3% in group A, 16.1% in group B, 21.5% in group C, 6.6% in group D (all p < 0.001). 31-day to 36-month mortality was 47.6% in group A, 20.8% in group B, 34.3% in group C, and 10.4% in group D (all p < 0.001). Diabetes and anemia remained independent risk factors for mortality with odds ratios of 1.61 (1.41ā€“1.85, p < 0.001) and 1.59 (1.38ā€“1.85, p < 0.001) respectively at 36 months. Cardiovascular death from 31-days to 36-months was 43.7% of deaths in group A, 54.1% in group B, 47.0% in group C, 50.8% group D (A vs B, p < 0.05). INTERPRETATION: Patients with both diabetes and anemia have a significantly higher mortality than those with either diabetes or anemia alone. Cardiovascular death remained the most likely cause of mortality in all groups

    The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: single-probe measurements from CMASS anisotropic galaxy clustering

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    With the largest spectroscopic galaxy survey volume drawn from the SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), we can extract cosmological constraints from the measurements of redshift and geometric distortions at quasi-linear scales (e.g. above 50 hāˆ’1h^{-1}Mpc). We analyze the broad-range shape of the monopole and quadrupole correlation functions of the BOSS Data Release 12 (DR12) CMASS galaxy sample, at the effective redshift z=0.59z=0.59, to obtain constraints on the Hubble expansion rate H(z)H(z), the angular-diameter distance DA(z)D_A(z), the normalized growth rate f(z)Ļƒ8(z)f(z)\sigma_8(z), and the physical matter density Ī©mh2\Omega_mh^2. We obtain robust measurements by including a polynomial as the model for the systematic errors, and find it works very well against the systematic effects, e.g., ones induced by stars and seeing. We provide accurate measurements {DA(0.59)rs,fid/rs\{D_A(0.59)r_{s,fid}/r_s Mpc\rm Mpc, H(0.59)rs/rs,fidH(0.59)r_s/r_{s,fid} kmsāˆ’1Mpcāˆ’1km s^{-1} Mpc^{-1}, f(0.59)Ļƒ8(0.59)f(0.59)\sigma_8(0.59), Ī©mh2}\Omega_m h^2\} = {1427Ā±26\{1427\pm26, 97.3Ā±3.397.3\pm3.3, 0.488Ā±0.0600.488 \pm 0.060, 0.135Ā±0.016}0.135\pm0.016\}, where rsr_s is the comoving sound horizon at the drag epoch and rs,fid=147.66r_{s,fid}=147.66 Mpc is the sound scale of the fiducial cosmology used in this study. The parameters which are not well constrained by our galaxy clustering analysis are marginalized over with wide flat priors. Since no priors from other data sets, e.g., cosmic microwave background (CMB), are adopted and no dark energy models are assumed, our results from BOSS CMASS galaxy clustering alone may be combined with other data sets, i.e., CMB, SNe, lensing or other galaxy clustering data to constrain the parameters of a given cosmological model. The uncertainty on the dark energy equation of state parameter, ww, from CMB+CMASS is about 8 per cent. The uncertainty on the curvature fraction, Ī©k\Omega_k, is 0.3 per cent. We do not find deviation from flat Ī›\LambdaCDM.Comment: 15 pages, 11 figures. The latest version matches and the accepted version by MNRAS. A bug in the first version has been identified and fixed in the new version. We have redone the analysis with newest data (BOSS DR12

    Immunomodulation by imiquimod in patients with high-risk primary melanoma.

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    Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted
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