Comparison of Commercial and Self-Initiated Weight Loss Programs in People With Prediabetes: A Randomized Control Trial

To determine if a widely available weight-management program (Weight Watchers) could achieve sufficient weight loss in persons with prediabetes compared with a Diabetes Prevention Program-based individual counseling program supported by National Diabetes Education Program materials. METHODS: We conducted an individual, randomized intervention trial in Indianapolis, Indiana, in 2013 to 2014, in 225 persons with prediabetes. We compared the Weight Watchers weight-management program (n = 112) with Your Game Plan to Prevent Type 2 Diabetes, a program developed by the National Diabetes Education Program. Outcomes were weight and metabolic markers measured at baseline, 6 months, and 12 months. RESULTS: Intervention participants lost significantly more weight than controls at 6 months (5.5% vs 0.8%) and 12 months (5.5% vs 0.2%; both P < .001). The intervention group also had significantly greater improvements in hemoglobin A1c and high-density lipoprotein cholesterol level than did controls. CONCLUSIONS: A large weight-management program is effective for achieving lifestyle changes associated with diabetes prevention. Such programs could significantly increase the availability of diabetes prevention programs worldwide making an immediate and significant public health impact

Diversity in lac Operon Regulation among Diverse Escherichia coli Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness

This work is licensed under a Creative Commons Attribution 4.0 International License.Transcription of bacterial genes is controlled by the coordinated action of cis- and trans-acting regulators. The activity and mode of action of these regulators can reflect different requirements for gene products in different environments. A well-studied example is the regulatory function that integrates the environmental availability of glucose and lactose to control the Escherichia coli lac operon. Most studies of lac operon regulation have focused on a few closely related strains. To determine the range of natural variation in lac regulatory function, we introduced a reporter construct into 23 diverse E. coli strains and measured expression with combinations of inducer concentrations. We found a wide range of regulatory functions. Several functions were similar to the one observed in a reference lab strain, whereas others depended weakly on the presence of cAMP. Some characteristics of the regulatory function were explained by the genetic relatedness of strains, indicating that differences varied on relatively short time scales. The regulatory characteristics explained by genetic relatedness were among those that best predicted the initial growth of strains following transition to a lactose environment, suggesting a role for selection. Finally, we transferred the lac operon, with the lacI regulatory gene, from five natural isolate strains into a reference lab strain. The regulatory function of these hybrid strains revealed the effect of local and global regulatory elements in controlling expression. Together, this work demonstrates that regulatory functions can be varied within a species and that there is variation within a species to best match a function to particular environments

Elevating Voices, Addressing Depression, Toxic Stress, and Equity through Group Prenatal Care: A pilot study

INTRODUCTION: Elevating Voices, Addressing Depression, Toxic Stress and Equity (EleVATE) is a group prenatal care (GC) model designed to improve pregnancy outcomes and promote health equity for Black birthing people. This article outlines the foundational community-engaged process to develop EleVATE GC and pilot study results. METHODS: We used community-based participatory research principles and the Ferguson Commission Report to guide creation of EleVATE GC. The intervention, designed by and for Black birthing people, centers trauma-informed care, antiracism, and integrates behavioral health strategies into group prenatal care to address unmet mental health needs. Using a convenience sample of patients seeking care at one of three safety-net health care sites, we compared preterm birth, small for gestational age, depression scores, and other pregnancy outcomes between patients in individual care (IC), CenteringPregnancy™ (CP), and EleVATE GC. RESULTS: Forty-eight patients enrolled in the study ( DISCUSSION: Our findings model a systematic approach to design a feasible, patient-centered, community-based, trauma-informed, antiracist intervention. Further study is needed to determine whether EleVATE GC improves perinatal outcomes and promotes health equity

Anticancer properties of distinct antimalarial drug classes

We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC 50 s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC 50 s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings

A Comparison of Temperatures Inside Protective Headgear With Indicators of Physiological Strain and Core Temperatures During Exercise in a Hot Environment

Introduction: Non-invasive temperature monitoring with a sensor mounted inside protective headgear such as a football or military helmet or a construction hardhat may be an effective method of detecting temperatures that are indicative of increased risk of heat illness. Hothead Technologies has developed a system for providing temperature information to medical personnel responsible for the health of the individual. Purpose: The purposes of this study were to establish the relationship between in-hardhat temperature (Tih) readings, markers of physiological strain and perceptual responses, and to determine the differences between the in-helmet temperature readings and core temperature (Tc) as measured by rectal (Tre) and esophageal (Tes) probes. Methods: Thirty males (age, 24.57 ± 4.32 years; height 180.51 ±7.06 cm; body mass, 81.06 ±9.35 kg; percent body fat, 13.76 ±5.11; VO2max, 46.84 ± 7.10 mL/Kg/min) completed two experimental trials separated by a minimum of one week: a continuous submaximal exercise (CSE) condition and a series of high intensity 30-second sprints (HIE) with a one-minute rest period between each sprint. Exercise in both conditions was carried out in a 36o C environment with a relative humidity of 40% while wearing a standard construction hardhat with a sensor mounted in the forehead area of the head strap, and continued until one of the following two criteria was met: the subject voluntarily terminated the session, or the subject’s Tc reached 39.5oC. Temperatures, heart rate, cardiorespiratory, and perceptual responses were monitored throughout, and balance error scoring system (BESS) and mental function tests were conducted before and after exercise. A physiological strain index (PSI) was calculated from Tc and HR. Results: CV- Calculated from final temp. Conclusion: The general agreement between the Tih and other temperature measures along with the consistency as indicated by the low coefficient of variation in the recordings of the Tih sensors at the point of termination suggest that this device may have application as a warning system for impending heat-related problems

A randomised placebo-controlled Phase III multicentre trial: low-dose intravenous immunoglobulin treatment for long-standing complex regional pain syndrome (LIPS trial)

BACKGROUND: Complex regional pain syndrome (CRPS) is a rare, severe post-traumatic pain condition affecting distal limbs. Patients who do not spontaneously improve in 12 months are classed as having ‘long-standing CRPS’ and often cannot be effectively treated, leading to a poor prognosis. CRPS is associated with functional autoantibodies. Two small trials, including a randomised controlled trial, have suggested that low-dose intravenous immunoglobulin (IVIg) may be an effective treatment for some patients. OBJECTIVE: We hypothesised that low-dose IVIg is effective for reducing pain in long-standing CRPS. METHODS: A randomised, double blinded placebo-controlled multicentre trial in seven UK pain management centres. Patients were eligible if they had moderate or severe long-standing CRPS that they had experienced for up to 5 years. Participants were randomly allocated to receive 0.5 g/kg IVIg, the active intervention, or visually indistinguishable 0.1% albumin in saline placebo. Randomisation was initiated by study sites via an independent online randomisation system and was 1 : 1 with varying block sizes, stratified by study centre. Participants, investigators and assessors were blinded to group assignment. The study drug/placebo was infused intravenously at the study centres on day 1 and day 23 after randomisation. The primary outcome was the 24-hour average pain intensity between day 6 and day 42, on an 11-point (0–10) numeric rating scale, compared between the groups. Outcomes were analysed using a mixed-effects regression model that used 37 measurements of pain intensity (the primary outcome) per participant. All patients who received an infusion and provided any outcome were included in the intention-to-treat analysis. RESULTS: A total of 111 patients were recruited and assigned between 27 August 2013 and 28 October 2015. Three patients were excluded because they had been inappropriately randomised, five patients were withdrawn from the primary analysis because they provided no outcomes and 103 patients were analysed for the primary outcome. The average pain score in the IVIg group was 0.27 units (95% confidence interval –0.24 to 0.80 units) higher than in the placebo group. Therefore, there is no significant evidence of a treatment effect at the 5% level and there was no significant difference between groups. Six serious adverse events but no suspected unexpected serious adverse reactions were reported during the blinded and open-label phase. CONCLUSION AND FUTURE WORK: Low-dose immunoglobulin was not effective in relieving pain in patients with moderate to severe CRPS of 1–5 years’ duration. Better drug treatments for long-standing CRPS are urgently required. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42179756. FUNDING: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership. Additional funding was obtained by the Pain Relief Foundation. Biotest UK Ltd provided the active study medication at no cost

Accommodating 'others'?: housing dispersed, forced migrants in the UK

Utilising insights from a qualitative study in the city of Leeds (UK), this paper considers issues related to the housing of dispersed forced migrants. The term 'dispersed forced migrants' is used here as a general label to include four groups of international migrants (i.e. refugees, asylum seekers, those with humanitarian protection status and failed asylum seekers) who have previously been dispersed, on a no choice basis, to a variety of locations across the UK under the requirements of the Immigration and Asylum Act (1999). The tiering of housing entitlement that exists within the generic population of dispersed forced migrants (a consequence of the particular socio-legal status assigned to individuals), and its role in rendering migrants susceptible to homelessness is outlined. The adequacy/standard of accommodation made available to forced migrants is also discussed. It is concluded that current arrangements fail to meet the basic housing needs of many forced migrants. Any future improvement in this situation will require a significant shift in government policy

A Precision Photometric Comparison between SDSS-II and CSP Type Ia Supernova Data

Consistency between Carnegie Supernova Project (CSP) and SDSS-II supernova (SN) survey ugri measurements has been evaluated by comparing SDSS and CSP photometry for nine spectroscopically confirmed Type Ia supernova observed contemporaneously by both programs. The CSP data were transformed into the SDSS photometric system. Sources of systematic uncertainty have been identified, quantified, and shown to be at or below the 0.023 magnitude level in all bands. When all photometry for a given band is combined, we find average magnitude differences of equal to or less than 0.011 magnitudes in ugri, with rms scatter ranging from 0.043 to 0.077 magnitudes. The u band agreement is promising, with the caveat that only four of the nine supernovae are well-observed in u and these four exhibit an 0.038 magnitude supernova-to-supernova scatter in this filter.Comment: This paper has been accepted for publication in The Astronomical Journa

The effect of progenitor age and metallicity on luminosity and 56Ni yield in Type Ia supernovae

Timmes, Brown & Truran found that metallicity variations could theoretically account for a 25% variation in the mass of 56Ni synthesized in Type Ia supernovae (SNe Ia), and thus account for a large fraction of the scatter in observed SN Ia luminosities. Higher-metallicity progenitors are more neutron-rich, producing more stable burning products relative to radioactive 56Ni. We develop a new method for estimating bolometric luminosity and 56Ni yield in SNe Ia and use it to test the theory with data from the Supernova Legacy Survey. We find that the average 56Ni yield does drop in SNe Ia from high metallicity environments, but the theory can only account for 7%--10% of the dispersion in SN Ia 56Ni mass, and thus luminosity. This is because the effect is dominant at metallicities significantly above solar, whereas we find that SN hosts have predominantly subsolar or only moderately above-solar metallicities. We also show that allowing for changes in O/Fe with the metallicity [Fe/H] does not have a major effect on the theoretical prediction of Timmes, Brown & Truran, so long as one is using the O/H as the independent variable. Age may have a greater effect than metallicity -- we find that the luminosity weighted age of the host galaxy is correlated with 56Ni yield, and thus more massive progenitors give rise to more luminous explosions. This is hard to understand if most SNe Ia explode when the primaries reach the Chandrasekhar mass. Finally, we test the findings of Gallagher et al., that the residuals of SNe Ia from the Hubble diagram are correlated with host galaxy metallicity, and we find no such correlation.Comment: ApJ, accepted, 34 pages, 11 figures, apologies for one column format -- necessary for the equation