Identifying a sufficient core group for trachoma transmission.

BackgroundIn many infectious diseases, a core group of individuals plays a disproportionate role in transmission. If these individuals were effectively prevented from transmitting infection, for example with a perfect vaccine, then the disease would disappear in the remainder of the community. No vaccine has yet proven effective against the ocular strains of chlamydia that cause trachoma. However, repeated treatment with oral azithromycin may be able to prevent individuals from effectively transmitting trachoma.Methodology/principal findingsHere we assess several methods for identifying a core group for trachoma, assuming varying degrees of knowledge about the transmission process. We determine the minimal core group from a completely specified model, fitted to results from a large Ethiopian trial. We compare this benchmark to a core group that could actually be identified from information available to trachoma programs. For example, determined from the rate of return of infection in a community after mass treatments, or from the equilibrium prevalence of infection.Conclusions/significanceSufficient groups are relatively easy for programs to identify, but will likely be larger than the theoretical minimum

Sequence-Independent Cloning and Post-Translational Modification of Repetitive Protein Polymers through Sortase and Sfp-Mediated Enzymatic Ligation

Repetitive protein-based polymers are important for many applications in biotechnology and biomaterials development. Here we describe the sequential additive ligation of highly repetitive DNA sequences, their assembly into genes encoding protein-polymers with precisely tunable lengths and compositions, and their end-specific post-translational modification with organic dyes and fluorescent protein domains. Our new Golden Gate-based cloning approach relies on incorporation of only type IIS BsaI restriction enzyme recognition sites using PCR, which allowed us to install ybbR-peptide tags, Sortase c-tags, and cysteine residues onto either end of the repetitive gene polymers without leaving residual cloning scars. The assembled genes were expressed in Escherichia coli and purified using inverse transition cycling (ITC). Characterization by cloud point spectrophotometry, and denaturing polyacrylamide gel electrophoresis with fluorescence detection confirmed successful phosphopantetheinyl transferase (Sfp)-mediated post-translational N-terminal labeling of the protein-polymers with a coenzyme A-647 dye (CoA-647) and simultaneous sortase-mediated C-terminal labeling with a GFP domain containing an N-terminal GG-motif in a one-pot reaction. In a further demonstration, we installed an N-terminal cysteine residue into an elastin-like polypeptide (ELP) that was subsequently conjugated to a single chain poly(ethylene glycol)-maleimide (PEG-maleimide) synthetic polymer, noticeably shifting the ELP cloud point. The ability to straightforwardly assemble repetitive DNA sequences encoding ELPs of precisely tunable length and to post-translationally modify them specifically at the N- and C- termini provides a versatile platform for the design and production of multifunctional smart protein-polymeric materials

Multiplayer Cost Games with Simple Nash Equilibria

Multiplayer games with selfish agents naturally occur in the design of distributed and embedded systems. As the goals of selfish agents are usually neither equivalent nor antagonistic to each other, such games are non zero-sum games. We study such games and show that a large class of these games, including games where the individual objectives are mean- or discounted-payoff, or quantitative reachability, and show that they do not only have a solution, but a simple solution. We establish the existence of Nash equilibria that are composed of k memoryless strategies for each agent in a setting with k agents, one main and k-1 minor strategies. The main strategy describes what happens when all agents comply, whereas the minor strategies ensure that all other agents immediately start to co-operate against the agent who first deviates from the plan. This simplicity is important, as rational agents are an idealisation. Realistically, agents have to decide on their moves with very limited resources, and complicated strategies that require exponential--or even non-elementary--implementations cannot realistically be implemented. The existence of simple strategies that we prove in this paper therefore holds a promise of implementability.Comment: 23 page

Improving patient experiences of mental health inpatient care : a randomised controlled trial

Poorer patient views of mental health inpatient treatment predict both further admissions and, for those admitted involuntarily, longer admissions. As advocated in the UK Francis report, we investigated the hypothesis that improving staff training improves patients’ views of ward care.Cluster randomised trial with stepped wedge design in 16 acute mental health wards randomised (using the ralloc procedure in Stata) by an independent statistician in three waves to staff training. A psychologist trained ward staff on evidence-based group interventions and then supported their introduction to each ward. The main outcome was blind self-report of perceptions of care (VOICE) before or up to 2 years after staff training between November 2008 and January 2013.In total, 1108 inpatients took part (616 admitted involuntarily under the English Mental Health Act). On average 51.6 staff training sessions were provided per ward. Involuntary patient's perceptions of, and satisfaction with, mental health wards improved after staff training (N582, standardised effect −0·35, 95% CI −0·57 to −0·12, p = 0·002; interaction p value 0·006) but no benefit to those admitted voluntarily (N469, −0.01, 95% CI −0.23 to 0.22, p = 0.955) and no strong evidence of an overall effect (N1058, standardised effect −0.18 s.d., 95% CI −0.38 to 0.01, p = 0.062). The training costs around £10 per patient per week. Resource allocation changed towards patient perceived meaningful contacts by an average of £12 (95% CI −£76 to £98, p = 0.774).Staff training improved the perceptions of the therapeutic environment in those least likely to want an inpatient admission, those formally detained. This change might enhance future engagement with all mental health services and prevent the more costly admissions

Decision Problems for Nash Equilibria in Stochastic Games

We analyse the computational complexity of finding Nash equilibria in stochastic multiplayer games with $\omega$-regular objectives. While the existence of an equilibrium whose payoff falls into a certain interval may be undecidable, we single out several decidable restrictions of the problem. First, restricting the search space to stationary, or pure stationary, equilibria results in problems that are typically contained in PSPACE and NP, respectively. Second, we show that the existence of an equilibrium with a binary payoff (i.e. an equilibrium where each player either wins or loses with probability 1) is decidable. We also establish that the existence of a Nash equilibrium with a certain binary payoff entails the existence of an equilibrium with the same payoff in pure, finite-state strategies.Comment: 22 pages, revised versio

Trying Cases in the Media: Legal Ethics, Fair Trials and Free Press

The 2000 symposium consisted of a panel discussion which used role-playing and a mock trial to highlight the issues of lawyer/litigant comments to the press before and during trial and the dilemma of journalists confronted by court demands for documents, testimony, or sources of information obtained in the course of gathering news on pending trials. Participants included: As United States Attorney for the Eastern District of Freedonia: John Douglas, Associate Professor of Law at the University of Richmond. As Freedonia criminal defense lawyer: Gerald Zerkin, Private Defense Attorney. As investigative journalist: Steve Nash, Associate Professor of Journalism at the University of Richmond. As federal judge: Judge Margaret P. Spencer, Virginia Circuit Court Judge. As media attorney: Craig Thomas Merritt, Attorney. As first amendment attorney: J. Joshua Wheeler, Attorney and Director of Programs for the Thomas Jefferson Center for the Protection of Free Expression, and adjunct professor at University of Virginia. As Chief Justice: Paul D. Carrington, The Chadwick Professor of Law at Duke University. As Associate Justices of the United States Supreme Court: C. Thomas Dienes, Patricia Roberts Harris Professor of Law at George Washington University\u27s Law School; John E. Nowak, David C. Baum Professor of Law at the University of Illinois; Molly Delea, third-year law student, University of Richmond School of Law; Kate Murray, third-year law student, University of Richmond School of Law; Thomas Queen, third-year law student, University of Richmond School of Law; and Courtney Sydnor, third-year law student, University of Richmond School of Law

2+1 Dimensional QED and a Novel Phase Transition

We investigate the chiral phase transition in 2+1 dimensional QED. Previous gap equation and lattice Monte-Carlo studies of symmetry breaking have found that symmetry breaking ceases to occur when the number of fermion flavors exceeds a critical value. Here we focus on the order of the transition. We find that there are no light scalar degrees of freedom present as the critical number of flavors is approached from above (in the symmetric phase). Thus the phase transition is not second order, rendering irrelevant the renormalization group arguments for a fluctuation induced transition. However, the order parameter vanishes continuously in the broken phase, so this transition is also unlike a conventional first order phase transition.Comment: 11 pages, Late

Voice, autonomy and utopian desire in participatory film-making with young refugees

This article is a reflection on what reflexive documentary scholars call the ‘moral dimension’ (Nash 2012: 318) of a participatory filmmaking project with refugee young people, who wanted to make a film to support other new young arrivals in the process of making home in Scotland. In the first part, we highlight some of the challenges of collaborating with refugee young people, in light of the often de-humanising representations of refugees in mainstream media and the danger of the triple conflation of authenticity-voice-pain in academic narratives about refugees. In the second part, we show how honouring young people’s desire to convey the hopeful aspects of making home, emerged as a key pedagogical strategy to affirm their expert position and encourage their participation in the project. Revisiting key moments of learning and interaction, we demonstrate how young people’s process of ‘finding a voice’ in moment-by-moment filmmaking practice was not a linear, developmental process towards ‘pure’ individual empowerment and singular artistic expression. Their participation in shaping their visual (self-)representation in the final film, was embedded in the dialogical process and pragmatic requirements of a collaborative film production, in which voice, autonomy and teacher authority were negotiated on a moment-by-moment basis. We conclude that it is vital for a reflexive practice and research to not gloss over the moral dilemmas in the name of progressive ideals, for example, when representations are co-created by project filmmakers/educators, but embrace these deliberations as part of the ‘fascinating collaborative matrix’ (Chambers 2019: 29) of participatory filmmaking

Antischistosomal Properties of Sclareol and Its Heck-Coupled Derivatives:Design, Synthesis, Biological Evaluation and Untargeted Metabolomics

Sclareol, a plant-derived diterpenoid widely used as a fragrance and flavoring substance, is well-known for its promising antimicrobial and anticancer properties. However, its activity on helminth parasites has not been previously reported. Here, we show that sclareol is active against larval (IC50 ≈ 13 μM), juvenile (IC50 = 5.0 μM), and adult (IC50 = 19.3 μM) stages of Schistosoma mansoni, a parasitic trematode responsible for the neglected tropical disease schistosomiasis. Microwave-assisted synthesis of Heck-coupled derivatives improved activity, with the substituents choice guided by the Matsy decision tree. The most active derivative 12 showed improved potency and selectivity on larval (IC50 ≈ 2.2 μM, selectivity index (SI) ≈ 22 in comparison to HepG2 cells), juvenile (IC50 = 1.7 μM, SI = 28.8), and adult schistosomes (IC50 = 9.4 μM, SI = 5.2). Scanning electron microscopy studies revealed that compound 12 induced blebbing of the adult worm surface at sublethal concentration (12.5 μM); moreover, the compound inhibited egg production at the lowest concentration tested (3.13 μM). The observed phenotype and data obtained by untargeted metabolomics suggested that compound 12 affects membrane lipid homeostasis by interfering with arachidonic acid metabolism. The same methodology applied to praziquantel (PZQ)-treated worms revealed sugar metabolism alterations that could be ascribed to the previously reported action of PZQ on serotonin signaling and/or effects on glycolysis. Importantly, our data suggest that compound 12 and PZQ exert different antischistosomal activities. More studies will be necessary to confirm the generated hypothesis and to progress the development of more potent antischistosomal sclareol derivatives

Influence of rare regions on magnetic quantum phase transitions

The effects of quenched disorder on the critical properties of itinerant quantum magnets are considered. Particular attention is paid to locally ordered rare regions that are formed in the presence of quenched disorder even when the bulk system is still in the nonmagnetic phase. It is shown that these local moments or instantons destroy the previously found critical fixed point in the case of antiferromagnets. In the case of itinerant ferromagnets, the critical behavior is unaffected by the rare regions due to an effective long-range interaction between the order parameter fluctuations.Comment: 4 pp., REVTe