Democracy and its advocates must adapt to the Covid-19 pandemic

The COVID-19 pandemic has put much of American life on hold, and efforts to ensure the robustness of US democracy have not been exempt. Fernando Tormos-Aponte and Michael Latner write that, to ensure November’s general election is as free and fair as possible, electoral democracy advocates must now find new ways of exerting policy influence online and to open up virtual spaces to constituents and advocacy groups. Read this article in Spanish/Lee este [...

Dynamics of double-semidilute liquid coacervates formed by oppositely charged polyelectrolytes

Mixtures of oppositely charged polyelectrolytes can undergo a phase separation to form a polymer rich phase, typically called a coacervate, and a polymer depleted phase1. The polymer rich phase can be a soft, viscous liquid, or a solid like complex. Both types have drawn much attention in the literature due to their applications in the food2, pharmaceutical3,4, and other industries as well as their role in many biological systems1. Studies have focused on the formation of the coacervate phase5, and models have been developed to predict phase separation and static properties6. However, much less attention has been given to the dynamic properties of coacervates, and how these can be predicted and controlled through the experimentally controllable parameters of the system. In this work, we develop a scaling theory for the dynamic behavior of asymmetric liquid-like coacervates formed from oppositely charged polyelectrolyte solutions. We consider asymmetric coacervates, characterized by having a different number density of charges in the polyanion and polycation. Depending on the degree of polymerization, the asymmetric liquid coacervate can form either an interpenetrating double-semidilute structure, wherein both polyanion and polycation are found above their overlap concentration, or a dilute-semidilute structure, where only one of the polyelectrolytes is found above their overlap concentration6. We will discuss a scaling theory for the unentangled dynamics of double-semidilute and dilute-semidilute coacervates, providing scaling predictions for the relaxation modulus and steady state shear viscosity of the coacervate, and the diffusivity of the polyelectrolyte chains. The scaling theory will highlight the different dynamical regimes of the system, and how the dynamic properties depend on experimentally controllable parameters such as the degree of polymerization, the number density of charges of the polyanion and polycation, and the strength of electrostatic interactions throughout different regimes. This scaling theory should provide useful guidelines for the tuning of dynamic and rheological properties for future application in the cosmetics, food, and other industries. Srivastava S, Tirrell M V. 2016. Polyelectrolyte complexation. In Advances in Chemical Physics, ed SA Rice, AR Dinner. 161:499–544. John Wiley & Sons. First Edit ed. De Kruif CG, Weinbreck F, De Vries R. 2004. Complex coacervation of proteins and anionic polysaccharides. Curr. Opin. Colloid Interface Sci. 9(5):340–49 Black KA, Priftis D, Perry SL, Yip J, Byun WY, Tirrell M. 2014. Protein encapsulation via polypeptide complex coacervation. ACS Macro Lett. 3(10):1088–91 Davis ME. 2009. The first targeted delivery of sirna in humans via a nanoparticle : from concept to clinic. Mol. Pharm. 6(3):659–68 Sing CE. 2017. Development of the modern theory of polymeric complex coacervation. Adv. Colloid Interface Sci. 239:2–16 Rubinstein, Liao, Panyukov 2018. In preparation

La democracia y sus defensores deben de adaptarse al coronavirus

La pandemia del COVID-19 ha detenido muchos aspectos de la vida norteramericana, y los esfuerzos por mejorar la democracia estadounidense no han estado exentos. Fernando Tormos-Aponte y Michael Latner escriben que activistas por la reforma electoral deben encontrar nuevos modos de ejercer influencia política en línea y abrir espacios virtuales para asegurar que las elecciones sean justas

Predicting Walking Ability and Prosthetic Candidacy Following Lower Extremity Amputation; An Updated Systematic Review and Treatment Pathway

Background: There is not a clear compilation of existing literature that determines walking ability and prosthetic candidacy following lower extremity amputation (LEA). There is no multi-disciplinary instrument or patient centric decision-making protocol accepted that can predict walking ability and prosthetic candidacy nor support a treatment pathway. It is important to determine these factors to better assist clinicians in determining a patient’s MFCL K-level to assist with the delivery of proper prosthetic componentry. Medicare Functional Classification Level (MFCL) K-level is a 0 to 4-point scale of functional level for those with limb loss. The purpose of this systematic literature review is to further develop evidence-based LEA patient centric treatment pathways that determine prosthetic candidacy decisions for LEAs. This evidence will assist the healthcare team in the decision-making process. In a similar systematic review (SR), Kahle., et al. reported into 2016 on the prediction of walking ability following lower limb amputation (LLA). Methods: This search strategy was designed and similarly implemented from the previous Kahle SR based on predicting walking ability. An electronic literature search was executed from 8/1/2007 to 12/31/2015 using MEDLINE, EMBASE, CINAHL, and Cochrane. Results: After electronic search and a thorough review and elimination of articles, a total of 104 quality studies were identified. Of these, 78 were systematically reviewed in two previous reviews and eliminated. Twenty-six remained for full evaluation. These updated study conclusions are drawn from a total sample (n) of 46,651 subjects. The size of this updated study has increased the original Kahle., et al. report by including 300% more subjects for a combined total of 61,858 subjects in the two SRs. Conclusion: In the two combined SRs, cause of amputation (etiology), physical fitness, pre-amputation living status, amputation level, age, cognitive/mood disturbances, social support and comorbidities are included as moderate to strongly supported predictive factors of walking ability and prosthetic candidacy. These factors should be strongly considered in a detailed history and physical examination by the rehabilitation team and documented in the patient healthcare record

Acute or delayed treatment with anatabine improves spatial memory and reduces pathological sequelae at late time-points after repetitive mild traumatic brain injury

Traumatic brain injury (TBI) has chronic and long-term consequences for which there are currently no approved pharmacological treatments. We have previously characterized the chronic neurobehavioral and pathological sequelae of a mouse model of repetitive mild TBI (r-mTBI) through to 2 years post-TBI. Despite the mild nature of the initial insult, secondary injury processes are initiated that involve neuroinflammatory and neurodegenerative pathways persisting and progressing for weeks and months post-injury and providing a potential window of opportunity for therapeutic intervention. In this study we examined the efficacy of a novel anti-inflammatory compound, anatabine, in modifying outcome after TBI. Our model of r-mTBI involves a series of five mild impacts (midline impact at 5 m/sec, 1 mm strike depth, 200 msec dwell time) with an interval of 48 h. Anatabine treatment was administered starting 30 min after injury and was delivered continuously through drinking water. At 6 months after TBI, anatabine treatment improved spatial memory in injured mice. Nine months after TBI, a cohort of mice was euthanized for pathological analysis that revealed reductions in astroglial (glial fibrillary acid protein, GFAP) and microglial (ionized calcium-binding adapter molecule 1, IBA1) responses in treated, injured animals. Treatments for the remaining mice were then crossed-over to assess the effects of late treatment administration and the effects of treatment termination. Nine months following crossover the remaining mice showed no effect of injury on their spatial memory, and whereas pathological analysis showed improvements in mice that had received delayed treatment, corpus callosum IBA1 increased in post-crossover placebo r-mTBI mice. These data demonstrate efficacy of both early and late initiation of treatment with anatabine in improving long term behavioral and pathology outcomes after mild TBI. Future studies will characterize the treatment window, the time course of treatment needed, and the dose needed to achieve therapeutic levels of anatabine in humans after injury

Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data.

BACKGROUND: The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial. Early results show significant, albeit partial, protection against clinical malaria and severe malaria. To ascertain variations in vaccine efficacy according to covariates such as transmission intensity, choice of adjuvant, age at vaccination, and bednet use, we did an individual-participant pooled analysis of phase 2 clinical data. METHODS: We analysed data from 11 different sites in Africa, including 4453 participants. We measured heterogeneity in vaccine efficacy by estimating the interactions between covariates and vaccination in pooled multivariable Cox regression and Poisson regression analyses. Endpoints for measurement of vaccine efficacy were infection, clinical malaria, severe malaria, and death. We defined transmission intensity levels according to the estimated local parasite prevalence in children aged 2-10 years (PrP₂₋₁₀), ranging from 5% to 80%. Choice of adjuvant was either AS01 or AS02. FINDINGS: Vaccine efficacy against all episodes of clinical malaria varied by transmission intensity (p=0·001). At low transmission (PrP₂₋₁₀ 10%) vaccine efficacy was 60% (95% CI 54 to 67), at moderate transmission (PrP₂₋₁₀ 20%) it was 41% (21 to 57), and at high transmission (PrP₂₋₁₀ 70%) the efficacy was 4% (-10 to 22). Vaccine efficacy also varied by adjuvant choice (p<0·0001)--eg, at low transmission (PrP₂₋₁₀ 10%), efficacy varied from 60% (95% CI 54 to 67) for AS01 to 47% (14 to 75) for AS02. Variations in efficacy by age at vaccination were of borderline significance (p=0·038), and bednet use and sex were not significant covariates. Vaccine efficacy (pooled across adjuvant choice and transmission intensity) varied significantly (p<0·0001) according to time since vaccination, from 36% efficacy (95% CI 24 to 45) at time of vaccination to 0% (-38 to 38) after 3 years. INTERPRETATION: Vaccine efficacy against clinical disease was of limited duration and was not detectable 3 years after vaccination. Furthermore, efficacy fell with increasing transmission intensity. Outcomes after vaccination cannot be gauged accurately on the basis of one pooled efficacy figure. However, predictions of public-health outcomes of vaccination will need to take account of variations in efficacy by transmission intensity and by time since vaccination. FUNDING: Medical Research Council (UK); Bill & Melinda Gates Foundation Vaccine Modelling Initiative; Wellcome Trust

SIRT3‐dependent deacetylation exacerbates acetaminophen hepatotoxicity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102226/1/embr2011121.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102226/2/embr2011121-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102226/3/embr2011121.reviewer_comments.pd