Poiseuille geometry shear flow apparatus for small-angle scattering experiments

Published versio

Influence of Ebola on tuberculosis case finding and treatment outcomes in Liberia.

Setting: National Leprosy and Tuberculosis (TB) Control Programme, Liberia. Objectives: To assess TB case finding, including human immunodeficiency virus (HIV) associated interventions and treatment outcomes, before (January 2013-March 2014), during (April 2014-June 2015) and after (July-December 2015) the Ebola virus disease outbreak. Design: A cross-sectional study and retrospective cohort analysis of outcomes. Results: The mean quarterly numbers of individuals with presumptive TB and the proportion diagnosed as smear-positive were: pre-Ebola (n = 7032, 12%), Ebola (n = 6147, 10%) and post-Ebola (n = 6795, 8%). For all forms of TB, stratified by category and age group, there was a non-significant decrease in the number of cases from the pre-Ebola to the Ebola and post-Ebola periods. There were significant decreases in numbers of cases with smear-positive pulmonary TB (PTB) from the pre-Ebola period (n = 855), to the Ebola (n = 640, P < 0.001) and post-Ebola (n = 568, P < 0.001) periods. The proportions of patients tested for HIV, found to be HIV-positive and started on antiretroviral therapy decreased as follows: pre-Ebola (respectively 72%, 15% and 34%), Ebola (69%, 14% and 30%) and post-Ebola (68%, 12% and 26%). Treatment success rates among TB patients were: 80% pre-Ebola, 69% Ebola (P < 0.001) and 73% post-Ebola (P < 0.001). Loss to follow-up was the main contributing adverse outcome. Conclusion: The principal negative effects of Ebola were the significant decreases in diagnoses of smear-positive PTB, the declines in HIV testing and antiretroviral therapy uptake and poor treatment success. Ways to prevent these adverse effects from recurring in the event of another Ebola outbreak need to be found

A study to explore specific stressors and coping strategies in primary dental care practice

Background and Aims: It is widely acknowledged that dentists experience occupational stress. This qualitative study aimed to explore previously identified specific stressors in more detail in order to inform the development of a future stress management programme. Method: Two focus groups of dentists (N: 7 & 6) were conducted to explore, in more detail, nine specific stressors and concepts; being out of one’s comfort zone, zoning out from the patient, celebrating the positive aspects of work, thinking aloud, the effect of hurting patients, the impact of perfectionism, responsibility for patient’s self-care, the emotional impact of difficult situations as a foundation dentist. Participants were also asked for their views on the structure and contents of the proposed stress management package. Verbatim transcripts were subjected to thematic analysis. Results and Discussion: Dentists described the impact of these stressors and their current coping methods; thematic analysis revealed 9 themes which covered the above concepts and a further overall theme of need for control. The findings are elaborated in connection to their relevant stress, coping and emotion psychological theory. Their implications for personal well-being and clinical outcomes are discussed. Conclusion: Dentists’ stressful and coping experiences are complex and it is essential that any stress management programme reflects this and that the skills are easily accessible and sustainable within the context of a busy dental practice

Mercury Exposure and Antinuclear Antibodies among Females of Reproductive Age in the United States: NHANES

Background: Immune dysregulation associated with mercury has been suggested, though data in the general population are lacking. Chronic exposure to low levels of methylmercury (organic) and inorganic mercury is common, such as through fish consumption and dental amalgams. Objective: To examine associations between mercury biomarkers and antinuclear antibody (ANA) positivity and titer strength. Methods: Among females 16-49 years (n=1352) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, we examined cross-sectional associations between mercury and ANAs (indirect immunofluorescence; cutoff ≥1:80). Three biomarkers of mercury exposure were utilized: hair (available 1999-2000) and total blood (1999-2004) predominantly represented methylmercury, and urinary (1999-2002) inorganic. Survey statistics were used. Multivariable modeling adjusted for several covariates, including age and omega-3 fatty acids. Results: 16% of females were ANA-positive; 96% of ANA-positives had a nuclear staining pattern of speckled. Mercury geometric means (standard deviations) were: 0.22 (0.03) ppm hair, 0.92 (0.05) µg/L blood, and 0.62 (0.04) µg/L urinary. Hair and blood, but not urinary, mercury were associated with ANA positivity (sample sizes 452, 1352, and 804, respectively), adjusting for confounders: hair odds ratio (OR)=4.10 (95% CI: 1.66, 10.13); blood OR=2.32 (95% CI: 1.07, 5.03) comparing highest versus lowest quantiles. Magnitudes of association were strongest for high-titer (≥1:1280) ANA: hair OR=11.41 (95% CI: 1.60, 81.23); blood OR=5.93 (95% CI: 1.57, 22.47). Conclusions: Methylmercury, at low levels generally considered safe, was associated with subclinical autoimmunity among reproductive-age females. Autoantibodies may predate clinical disease by years, thus methylmercury exposure may be relevant to future autoimmune disease risk.This work was supported by NIH/NIEHS K01ES019909, NIH/NIEHS P30ES017885, and NIH/NCRR UL1RR024986. ECS was supported in part by an Arthritis Foundation Health Professional New Investigator Award.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110512/1/SOMERS_EHP.AdvancePubl 02102015.acco.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110512/2/Somers_EHP Suppl-1408751.s001.508.pdf114Description of SOMERS_EHP.AdvancePubl 02102015.acco.pdf : Main ArticleDescription of Somers_EHP Suppl-1408751.s001.508.pdf : Supplementary Materia

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120

Molecular Genetics of T Cell Development

T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment

Is group cognitive behaviour therapy for postnatal depression evidence-based practice? A systematic review

Background: There is evidence that psychological therapies including cognitive behaviour therapy (CBT) may be effective in reducing postnatal depression (PND) when offered to individuals. In clinical practice, this is also implemented in a group therapy format, which, although not recommended in guidelines, is seen as a cost-effective alternative. To consider the extent to which group methods can be seen as evidence-based, we systematically review and synthesise the evidence for the efficacy of group CBT compared to currently used packages of care for women with PND, and we discuss further factors which may contribute to clinician confidence in implementing an intervention. Methods: Seventeen electronic databases were searched. All full papers were read by two reviewers and a third reviewer was consulted in the event of a disagreement on inclusion. Selected studies were quality assessed, using the Cochrane Risk of Bias Tool, were data extracted by two reviewers using a standardised data extraction form and statistically synthesised where appropriate using the fixed-effect inverse-variance method. Results: Seven studies met the inclusion criteria. Meta-analyses showed group CBT to be effective in reducing depression compared to routine primary care, usual care or waiting list groups. A pooled effect size of d = 0.57 (95% CI 0.34 to 0.80, p < 0.001) was observed at 10–13 weeks post-randomisation, reducing to d = 0.28 (95% CI 0.03 to 0.53, p = 0.025) at 6 months. The non-randomised comparisons against waiting list controls at 10–13 weeks was associated with a larger effect size of d = 0.94 (95% CI 0.42 to 1.47, p < 0.001). However due to the limitations of the available data, such as ill-specified definitions of the CBT component of the group programmes, these results should be interpreted with caution. Conclusions: Although the evidence available is limited, group CBT was shown to be effective. We argue, therefore, that there is sufficient evidence to implement group CBT, conditional upon routinely collected outcomes being benchmarked against those obtained in trials of individual CBT, and with other important factors such as patient preference, clinical experience, and information from the local context taken into account when making the treatment decision

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

&lt;p&gt;Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.&lt;/p&gt; &lt;p&gt;Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.&lt;/p&gt; &lt;p&gt;Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].&lt;/p&gt; &lt;p&gt;Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.&lt;/p&gt