Sex, drugs and superbugs: The rise of drug resistant STIs

Antimicrobial resistance (AMR) presents a swiftly advancing challenge to a wide range of healthcare and health promotion practices. While rising rates of AMR share some dimensions across contexts, the specificities of field, practice, place and population shape – and at times hinder attempts to stem – the rising tide of this health threat. Sexually transmitted infections (STIs) are one area of healthcare where the threat of AMR has traditionally been met with lethargy. In this paper, we draw on a range of stakeholder perspectives across practice, innovation and regulatory systems in Australia, the US and the UK to understand and examine the evolving nexus of STIs and AMR, including the roles of cultural reception, professional practice and political traction. We argue for a critical sociology of the nexus of sexual health and evolving resistance, which will be instructive for comprehending inaction and informing future developments. We also note that part of this critical sociology must involve challenging stigma concerning sexual practices and people/groups, and recognising the role of communities in driving positive change

"It's a revolving door": Ego-depletion among prisoners with injecting drug use histories as a barrier to post-release success

Background: People who inject drugs (PWID) are overrepresented among prisoner populations worldwide. This qualitative study used the psychological concept of “ego-depletion” as an exploratory framework to better understand the disproportionate rates of reincarceration among people with injecting drug use histories. The aim was to illuminate mechanisms by which prospects for positive post-release outcomes for PWID are enhanced or constricted. Methods: Participants were recruited from a longitudinal cohort study, SuperMIX, in Victoria, Australia. Eligible participants were invited to participate in an in-depth interview. Inclusion criteria were: aged 18+; lifetime history of injecting drug use; incarcerated for >three months and released from custody <12 months previously. Analysis of 48 interviews examined how concepts relevant to the ego-depletion framework (self-regulation; standards; consequences and mitigators of ego-depletion) manifested in participants’ narratives. Results: Predominantly, participants aimed to avoid a return to problematic drug use and recidivism, and engaged in effortful self-regulation to pursue their post-release goals. Post-release environments were found to diminish self-regulation resources, leading to states of ego-depletion and compromising the capacity to self-regulate according to their ideals. Fatalism, stress, and fatigue associated with the transition period exacerbated ego-depletion. Strategies that mitigated ego-depletion included avoidance of triggering environments; reducing stress through opioid agonist therapy; and fostering positive affect through supportive relationships. Conclusions: Post-release environments are ego-depleting and inconducive to sustaining behavioural changes for PWID leaving prison. Corrections’ behaviourist paradigms take insufficient account of the socio-structural factors impacting on an individual's self-regulation capacities in the context of drug dependence and desistance processes. Breaking the cycles of reincarceration among PWID requires new approaches that moderate ego-depletion and facilitate long-term goal-pursuit

Understanding uncertainty in temperature effects on vector-borne disease: A Bayesian approach

Extrinsic environmental factors influence the distribution and population dynamics of many organisms, including insects that are of concern for human health and agriculture. This is particularly true for vector-borne infectious diseases, like malaria, which is a major source of morbidity and mortality in humans. Understanding the mechanistic links between environment and population processes for these diseases is key to predicting the consequences of climate change on transmission and for developing effective interventions. An important measure of the intensity of disease transmission is the reproductive number $R_0$. However, understanding the mechanisms linking $R_0$ and temperature, an environmental factor driving disease risk, can be challenging because the data available for parameterization are often poor. To address this we show how a Bayesian approach can help identify critical uncertainties in components of $R_0$ and how this uncertainty is propagated into the estimate of $R_0$. Most notably, we find that different parameters dominate the uncertainty at different temperature regimes: bite rate from 15-25$^\circ$ C; fecundity across all temperatures, but especially $\sim$25-32$^\circ$ C; mortality from 20-30$^\circ$ C; parasite development rate at $\sim$15-16$^\circ$C and again at $\sim$33-35$^\circ$C. Focusing empirical studies on these parameters and corresponding temperature ranges would be the most efficient way to improve estimates of $R_0$. While we focus on malaria, our methods apply to improving process-based models more generally, including epidemiological, physiological niche, and species distribution models.Comment: 27 pages, including 1 table and 3 figure

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

Lambda Polarization in Polarized Proton-Proton Collisions at RHIC

We discuss Lambda polarization in semi-inclusive proton-proton collisions, with one of the protons longitudinally polarized. The hyperfine interaction responsible for the $\Delta$-$N$ and $\Sigma$-$\Lambda$ mass splittings gives rise to flavor asymmetric fragmentation functions and to sizable polarized non-strange fragmentation functions. We predict large positive Lambda polarization in polarized proton-proton collisions at large rapidities of the produced Lambda, while other models, based on SU(3) flavor symmetric fragmentation functions, predict zero or negative Lambda polarization. The effect of $\Sigma^0$ and $\Sigma^*$ decays is also discussed. Forthcoming experiments at RHIC will be able to differentiate between these predictions.Comment: 18 pages, 5 figure

Inference algorithms for gene networks: a statistical mechanics analysis

The inference of gene regulatory networks from high throughput gene expression data is one of the major challenges in systems biology. This paper aims at analysing and comparing two different algorithmic approaches. The first approach uses pairwise correlations between regulated and regulating genes; the second one uses message-passing techniques for inferring activating and inhibiting regulatory interactions. The performance of these two algorithms can be analysed theoretically on well-defined test sets, using tools from the statistical physics of disordered systems like the replica method. We find that the second algorithm outperforms the first one since it takes into account collective effects of multiple regulators

Effects of short-term treatment with atorvastatin in smokers with asthma - a randomized controlled trial

&lt;b&gt;Background&lt;/b&gt; The immune modulating properties of statins may benefit smokers with asthma. We tested the hypothesis that short-term treatment with atorvastatin improves lung function or indices of asthma control in smokers with asthma.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Seventy one smokers with mild to moderate asthma were recruited to a randomized double-blind parallel group trial comparing treatment with atorvastatin (40 mg per day) versus placebo for 4 weeks. After 4 weeks treatment inhaled beclometasone (400 ug per day) was added to both treatment arms for a further 4 weeks. The primary outcome was morning peak expiratory flow after 4 weeks treatment. Secondary outcome measures included indices of asthma control and airway inflammation.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; At 4 weeks, there was no improvement in the atorvastatin group compared to the placebo group in morning peak expiratory flow [-10.67 L/min, 95% CI -38.70 to 17.37, p=0.449], but there was an improvement with atorvastatin in asthma quality of life score [0.52, 95% CI 0.17 to 0.87 p=0.005]. There was no significant improvement with atorvastatin and inhaled beclometasone compared to inhaled beclometasone alone in outcome measures at 8 weeks.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Short-term treatment with atorvastatin does not alter lung function but may improve asthma quality of life in smokers with mild to moderate asthma. Clinicaltrials.gov identifier: NCT0046382

Production of pizero and eta mesons at large transverse momenta in pi-p and pi-Be interactions at 515 GeV/c

We present results on the production of high transverse momentum pizero and eta mesons in pi-p and pi-Be interactions at 515 GeV/c. The data span the kinematic ranges 1 < p_T < 11 GeV/c in transverse momentum and -0.75 < y < 0.75 in rapidity. The inclusive pizero cross sections are compared with next-to-leading order QCD calculations and to expectations based on a phenomenological parton-k_T model.Comment: RevTeX4, 15 pages, 15 figures, to be submitted to Phys. Rev.

Evaluation of MPA designs that protect highly mobile megafauna now and under climate change scenarios

Marine protected area (MPA) designs, including large-scale MPAs (LSMPAs; \u3e150,000 km2), mobile MPAs (fluid spatiotemporal boundaries), and MPA networks, may offer different benefits to species and could enhance protection by encompassing spatiotemporal scales of animal movement. We sought to understand how well LSMPAs could benefit nine highly-mobile marine species in the tropics now and into the future by: 1) evaluating current range overlap within a LSMPA; 2) evaluating range overlap under climate change projections; and 3) evaluating how well theoretical MPA designs benefit these nine species. We focused on Palmyra Atoll and Kingman Reef, a 2000 km2 area within the 1.2 million km2 U.S. Pacific Remote Islands Marine National Monument (PRIMNM) that contains marine megafauna (reef and pelagic fishes; sea turtles; seabirds; cetaceans) reflecting different behaviors and habitat use. Our approach is useful for evaluating the effectiveness of the Palmyra-Kingman MPA and PRIMNM in protecting these species, and tropical LSMPAs in general, and for informing future MPA design. Stationary MPAs provided protection at varying scales. Reef manta rays (Mobula alfredi), grey reef sharks (Carcharhinus amblyrhynchos), green sea turtles (Chelonia mydas), and bottlenose dolphins (Tursiops truncatus) had overall small ranges (\u3c100 km from Palmyra-Kingman) and could benefit from stationary MPAs that contained heterogenous reef habitats. Yellowfin tuna (Thunnus albacares), sooty terns (Onychoprion fuscatus), red-footed boobies (Sula sula), great frigatebirds (Fregata minor), and melon-headed whales (Peponocephala electra) navigated complex oceanographic processes and may benefit most from mobile MPAs that shift with features including thermal fronts, cyclic regions of elevated productivity, and eddies, if relationships with these features are established and predictable. All species had capacity to travel to nearby reef systems, illustrating potential benefits of MPA networks and protected corridors. Suitable habitats will likely contract for all species as warm water expands under climate change scenarios (species habitats were predicted to decrease by 4–49% at Palmyra-Kingman) and MPAs may not protect suitable habitats into the future. Species habitat requirements and movement ecologies are critical aspects of marine spatial planning, especially with respect to dynamic ocean processes and a changing climate

Radiation damage in the LHCb vertex locator

The LHCb Vertex Locator (VELO) is a silicon strip detector designed to reconstruct charged particle trajectories and vertices produced at the LHCb interaction region. During the first two years of data collection, the 84 VELO sensors have been exposed to a range of fluences up to a maximum value of approximately 45 × 1012 1 MeV neutron equivalent (1 MeV neq). At the operational sensor temperature of approximately −7 °C, the average rate of sensor current increase is 18 μA per fb−1, in excellent agreement with predictions. The silicon effective bandgap has been determined using current versus temperature scan data after irradiation, with an average value of Eg = 1.16±0.03±0.04 eV obtained. The first observation of n+-on-n sensor type inversion at the LHC has been made, occurring at a fluence of around 15 × 1012 of 1 MeV neq. The only n+-on-p sensors in use at the LHC have also been studied. With an initial fluence of approximately 3 × 1012 1 MeV neq, a decrease in the Effective Depletion Voltage (EDV) of around 25 V is observed. Following this initial decrease, the EDV increases at a comparable rate to the type inverted n+-on-n type sensors, with rates of (1.43±0.16) × 10−12 V/ 1 MeV neq and (1.35±0.25) × 10−12 V/ 1 MeV neq measured for n+-on-p and n+-on-n type sensors, respectively. A reduction in the charge collection efficiency due to an unexpected effect involving the second metal layer readout lines is observed