20 research outputs found

    Should we screen for ovarian cancer?

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    Ovarian cancer screening using pelvic examination, CA-125 serum tumor marker, transvaginal ultrasound (TVU), or any combination of tests is not recommended in average-risk women, or in women with only 1 first-degree relative with ovarian cancer (strength of recommendation [SOR]=B). There is insufficient evidence to recommend for or against screening women with 2 or more first-degree relatives with ovarian cancer. A careful discussion of risks and benefits to screening is suggested, with referral to specialists as needed to assist in the decision-making (SOR=C)

    Helping the Working Poor: Employer- vs. Employee-Based Subsidies

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    In the United States and Europe there has been renewed interest in subsidizing firms that employ disadvantaged workers as a means of addressing poverty and other social problems. In contrast, the prevailing practice is largely to provide social welfare benefits directly to individuals. Which approach is better? We re-examine the relative merits of employee- versus employer-based labor market subsidies and conclude there are good reasons to continue to rely on the direct, employee-based approach. In practice, low-wage workers are seldom either low-skill or low-income workers. Furthermore, workers who might quality for a firm-based subsidy are reluctant to so identify themselves for fear of being stigmatized or labeled as needy. Thus, employer-based subsidy programs have lower participation rates and correspondingly higher per capita expenditures than employee-based subsidy programs

    Allogeneic Lymphocytes Persist and Traffic in Feral MHC-Matched Mauritian Cynomolgus Macaques

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    Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer.Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer.MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naïve animals may define the immune mechanisms responsible for protection and guide future vaccine development

    Point-of-care testing and treatment of sexually transmitted and genital infections to improve birth outcomes in high-burden, low-resource settings (WANTAIM): a pragmatic cluster randomised crossover trial in Papua New Guinea.

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    Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis have been associated with adverse maternal and perinatal outcomes, but there is conflicting evidence on the benefits of antenatal screening and treatment for these conditions. We aimed to determine the effect of antenatal point-of-care testing and immediate treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis on preterm birth, low birthweight, and other adverse maternal and perinatal outcomes compared with current standard of care, which included symptom-based treatment without laboratory confirmation. In this pragmatic cluster randomised crossover trial, we enrolled women (aged ≥16 years) attending an antenatal clinic at 26 weeks' gestation or earlier (confirmed by obstetric ultrasound), living within approximately 1 h drive of a study clinic, and able to provide reliable contact details at ten primary health facilities and their catchment communities (clusters) in Papua New Guinea. Clusters were randomly allocated 1:1 to receive either the intervention or control (standard care) in the first phase of the trial. Following an interval (washout period) of 2-3 months at the end of the first phase, each cluster crossed over to the other group. Randomisation was stratified by province. Individual participants were informed about trial group allocation only after completing informed consent procedures. The primary outcome was a composite of preterm birth (livebirth before 37 weeks' gestation), low birthweight (<2500 g), or both, analysed according to the intention-to-treat population. This study is registered with ISRCTN Registry, ISRCTN37134032, and is completed. Between July 26, 2017, and Aug 30, 2021, 4526 women were enrolled (2210 [63·3%] of 3492 women in the intervention group and 2316 [62·8%] of 3687 in the control group). Primary outcome data were available for 4297 (94·9%) newborn babies of 4526 women. The proportion of preterm birth, low birthweight, or both, in the intervention group, expressed as the mean of crude proportions across clusters, was 18·8% (SD 4·7%) compared with 17·8% in the control group (risk ratio [RR] 1·06, 95% CI 0·78-1·42; p=0·67). There were 1052 serious adverse events reported (566 in the intervention group and 486 in the control group) among 929 trial participants, and no differences by trial group. Point-of-care testing and treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis did not reduce preterm birth or low birthweight compared with standard care. Within the subgroup of women with N gonorrhoeae, there was a substantial reduction in the primary outcome

    Allogeneic transfer cell analysis.

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    <p>A PKH67+ PBMC from recipient MCM3 were sorted from total PBMC by flow cytometry. We performed microsatellite analysis to demonstrate that the mircosatellite profile of PKH67+ cells in the recipient animal matched the microsatellite profile of donor MCM1.</p

    Autologous adoptive transfer.

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    <p>A Diagram displaying the transfer protocol. B Selection for CD8ß+ cells. The left panel is unmanipulated PBMC. The right panel is the positive fraction collected following CD8ß enrichment gated on lymphocytes. C Transfused cell persistence after transfer. Percentages are of total CD8ß+ cells in the PBMC of the animal based on the lymphocyte gate. D PKH67+ cells in lymph node of animal MCM6. The right inguinal lymph node was processed three days post-transfer to measure persistence of PKH67+ cells. The percentage of PKH67+ cells is based on total CD8ß+ cells in the lymph node lymphocyte gate.</p

    Allogeneic adoptive transfer from MCM1 to MCM3, MCM4, and MCM5.

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    <p>Gating strategy is described in the legend to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002384#pone-0002384-g002" target="_blank">Figure 2</a>. A Diagram displaying the transfer protocol. B Donor CD8ß+ cells were transferred from MCM1 into 2-MHC-haplotype-matched MCM3, 0-MHC-haplotype-matched MCM4, and 1-MHC-haplotype-matched MCM5 and monitored for persistence in recipient PBMC. 220 million CD8ß+ were transferred to each animal. Donor cells were a composite of CD8ß+ cells enriched from PBMC, mesenteric lymph node and spleen. C Left inguinal lymph node sample 9 days post-transfer.</p

    Allogeneic transfer from MCM1 to MCM2.

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    <p>A Diagram displaying the transfer protocol. B PKH67+ donor cells from MCM1 in PBMC of recipient 2-MHC-haplotype-matched MCM2. Dot plots are gated on lymphocytes and display CD8ß+ lymphocytes only. C Right Axillary lymph node sample 10 days post-transfer.</p
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