Input of tritium to intermediate depth water in the South Pacific

Tritium concentrations have been determined for seawater samples collected near the western boundary of the South Pacific. The deepest penetration of tritium, in terms of either depth or isopycnal surface, occurs between latitudes 14 and 30S and the penetration is greater than that observed in the mid-South Pacific during the Geochemical Ocean Sections Study (GEOSECS) cruise...

Outcomes of tuberculosis patients who start antiretroviral therapy under routine programme conditions in Malawi

SETTING: Public sector facilities in Malawi providing antiretroviral therapy (ART) to human immunodeficiency virus (HIV) positive patients, including those with tuberculosis (TB). OBJECTIVES: To compare 6-month and 12-month cohort treatment outcomes of HIV-positive TB patients and HIV-positive non-TB patients treated with ART. DESIGN: Retrospective data collection using ART patient master cards and ART patient registers. RESULTS: Between July and September 2005, 7905 patients started ART, 6967 with a non-TB diagnosis and 938 with a diagnosis of active TB. 6-month cohort outcomes of non-TB and TB patients censored on 31 March 2006 showed significantly more TB patients alive and on ART (77%) compared with non-TB patients (71%) (P < 0.001). Between January and March 2005, 4580 patients started ART, 4179 with a non-TB diagnosis and 401 with a diagnosis of active TB. 12-month cohort outcomes of non-TB and TB patients censored on 31 March 2006 showed significantly more TB patients alive and on ART (74%) compared with non-TB patients (66%) (P < 0.001). Other outcomes of default and transfer out were also significantly less frequent in TB compared with non-TB patients. CONCLUSION: HIV-positive TB patients on ART in Malawi have generally good treatment outcomes, and more patients need to access this HIV treatment

Circumstellar environment of RX Puppis

The symbiotic Mira, RX Pup, shows long-term variations in its mean light level due to variable obscuration by circumstellar dust. The last increase in extinction towards the Mira, between 1995 and 2000, has been accompanied by large changes in the degree of polarization in the optical and red spectral range. The lack of any obvious associated changes in the position angle may indicate the polarization variations are driven by changes in the properties of the dust grains (e.g. variable quantity of dust and variable particle size distribution, due to dust grain formation and growth) rather than changes in the viewing geometry of the scattering region(s), e.g. due to the binary rotation.Comment: Paper presented at Torun 2000 conference on Post-AGB objects as a phase of stellar evolution; 8 pages, 3 figure

A dynamical systems model for the measurement of cellular senescence

This is the final version. Available on open access from the Royal Society via the DOI in this recordData accessibility All experimental data and source material required to reproduce our modelling results (Matlab code) are available at the following GitHub repository: https://github.com/dgalvis/Senescence_Model.Senescent cells provide a good in vitro model to study ageing. However, cultures of 'senescent' cells consist of a mix of cell subtypes (proliferative, senescent, growth-arrested and apoptotic). Determining the proportion of senescent cells is crucial for studying ageing and developing new anti-degenerative therapies. Commonly used markers such as doubling population, senescence-associated β-galactosidase, Ki-67, γH2AX and TUNEL assays capture diverse and overlapping cellular populations and are not purely specific to senescence. A newly developed dynamical systems model follows the transition of an initial culture to senescence tracking population doubling, and the proportion of cells in proliferating, growth-arrested, apoptotic and senescent states. Our model provides a parsimonious description of transitions between these states accruing towards a predominantly senescent population. Using a genetic algorithm, these model parameters are well constrained by an in vitro human primary fibroblast dataset recording five markers at 16 time points. The computational model accurately fits to the data and translates these joint markers into the first complete description of the proportion of cells in different states over the lifetime. The high temporal resolution of the dataset demonstrates the efficacy of strategies for reconstructing the trajectory towards replicative senescence with a minimal number of experimental recordings.Wellcome TrustEngineering and Physical Sciences Research Council (EPSRC)Dunhill Medical Trus

Operational research in Malawi: making a difference with cotrimoxazole preventive therapy in patients with tuberculosis and HIV.

BACKGROUND: In Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions. DISCUSSION: District and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART. SUMMARY: Key lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not

Understanding the Role of Relationship Maintenance in Enduring Couple Partnerships in Later Adulthood

Intimate relationships in later adulthood are understudied despite their positive association with health and well-being. This cross-sectional mixed methods study sought to redress this gap by investigating relationship maintenance in later adulthood. Our international sub-sample comprised 1,565 participants aged 55 + and in an ongoing relationship. Results from hierarchical multiple regression indicated that overall happiness with the relationship had the largest effect size on relationship maintenance, with 53% of the variance explained. Content analyses of open-ended questions identified companionship and laughter as some of the “best liked” aspects of the relationship. Housework/cooking and saying “I love you” were among the behaviors that made participants feel appreciated. Results illustrated the types of maintenance behaviors adults in later adulthood who are in enduring partnerships employ

Dietary restriction in ILSXISS mice is associated with widespread changes in splicing regulatory factor expression levels.

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Dietary restriction (DR) represents one of the most reproducible interventions to extend lifespan and improve health outcomes in a wide range of species, but substantial variability in DR response has been observed, both between and within species. The mechanisms underlying this variation in effect are still not well characterised. Splicing regulatory factors have been implicated in the pathways linked with DR-induced longevity in C. elegans and are associated with lifespan itself in mice and humans. We used qRT-PCR to measure the expression levels of a panel of 20 age- and lifespan-associated splicing regulatory factors in brain, heart and kidney derived from three recombinant inbred strains of mice with variable lifespan responses to short-term (2 months) or long-term (10 months) 40% DR to determine their relationship to DR-induced longevity. We identified 3 patterns of association; i) splicing factors associated with DR alone, ii) splicing factors associated with strain alone or iii) splicing factors associated with both DR and strain. Tissue specific variation was noted in response to short term or long-term DR, with the majority of effects noted in brain following long term DR in the positive responder strain TejJ89. Association in heart and kidney were less evident, and occurred following short term DR. Splicing factors associated with both DR and strain may be mechanistically involved in strain-specific differences in response to DR. We provide here evidence concordant with a role for some splicing factors in the lifespan modulatory effects of DR across different mouse strains and in different tissues

Species-specific differences in the expression of the HNF1A, HNF1B and HNF4A genes

Background: The HNF1A, HNF1B and HNF4A genes are part of an autoregulatory network in mammalian pancreas, liver, kidney and gut. The layout of this network appears to be similar in rodents and humans, but inactivation of HNF1A, HNF1B or HNF4A genes in animal models cause divergent phenotypes to those seen in man. We hypothesised that some differences may arise from variation in the expression profile of alternatively processed isoforms between species. Methodology/Principal Findings: We measured the expression of the major isoforms of the HNF1A, HNF1B and HNF4A genes in human and rodent pancreas, islet, liver and kidney by isoform-specific quantitative real-time PCR and compared their expression by the comparative Ct (??Ct) method. We found major changes in the expression profiles of the HNF genes between humans and rodents. The principal difference lies in the expression of the HNF1A gene, which exists as three isoforms in man, but as a single isoform only in rodents. More subtle changes were to the balance of HNF1B and HNF4A isoforms between species; the repressor isoform HNF1B(C) comprised only 6% in human islets compared with 24–26% in rodents (p = 0.006) whereas HNF4A9 comprised 22% of HNF4A expression in human pancreas but only 11% in rodents (p = 0.001). Conclusions/Significance: The differences we note in the isoform-specific expression of the human and rodent HNF1A, HNF1B and HNF4A genes may impact on the absolute activity of these genes, and therefore on the activity of the pancreatic transcription factor network as a whole. We conclude that alterations to expression of HNF isoforms may underlie some of the phenotypic variation caused by mutations in these genes