Assessing the impact of intervention strategies against Taenia solium cysticercosis using the EPICYST transmission model

Background The pork tapeworm, Taenia solium, and associated human infections, taeniasis, cysticercosis and neurocysticercosis, are serious public health problems, especially in developing countries. The World Health Organization (WHO) has set goals for having a validated strategy for control and elimination of T. solium taeniasis/cysticercosis by 2015 and interventions scaled-up in selected countries by 2020. Timely achievement of these internationally-endorsed targets requires that the relative benefits and effectiveness of potential interventions be explored rigorously within a quantitative framework. Methods A deterministic, compartmental transmission model (EPICYST) was developed to capture the dynamics of the taeniasis/cysticercosis disease system in the human and pig hosts. Cysticercosis prevalence in humans, an outcome of high epidemiological and clinical importance, was explicitly modelled. A next generation matrix approach was used to derive an expression for the basic reproduction number, R 0. A full sensitivity analysis was performed using a methodology based on Latin-hypercube sampling partial rank correlation coefficient index. Results EPICYST outputs indicate that chemotherapeutic intervention targeted at humans or pigs would be highly effective at reducing taeniasis and cysticercosis prevalence when applied singly, with annual chemotherapy of humans and pigs resulting, respectively, in 94 and 74% of human cysticercosis cases averted. Improved sanitation, meat inspection and animal husbandry are less effective but are still able to reduce prevalence singly or in combination. The value of R 0 for taeniasis was estimated at 1.4 (95% Credible Interval: 0.5–3.6). Conclusions Human- and pig-targeted drug-focussed interventions appear to be the most efficacious approach from the options currently available. The model presented is a forward step towards developing an informed control and elimination strategy for cysticercosis. Together with its validation against field data, EPICYST will be a valuable tool to help reach the WHO goals and to conduct economic evaluations of interventions in varying epidemiological settings

‘I am worthless and kind’: the specificity of positive and negative self-evaluation in adolescent depression

Objectives: Adolescence represents a critical phase when the concept of self is developed and consolidated. Depressed adolescents globally endorse more negative and fewer positive self-descriptive words compared with non-depressed adolescents. Yet the methods used have not allowed for more detailed exploration of the specific content of these self-endorsements. Methods: Adolescents, aged 12-18 years, were recruited from the community (n = 204) and from a child and adolescent mental health service in the UK (n = 87). Participants completed measures of depression and a self-description questionnaire which included 12 positive and 12 negative self-descriptive adjectives. Results: As expected, we replicated previous findings that depressive symptoms are associated with global positive and negative self-endorsements. The difference between mean scores was examined for each adjective. Depressed adolescents endorsed all negative adjectives more highly relative to community adolescents; ratings of ‘worthless’ and ‘useless’ had the biggest difference between community and depressed adolescents. Surprisingly, a group of positive prosocial self-descriptors were endorsed equally by depressed and community adolescents and were not associated with severity of depressive symptoms. Conclusions: Although depressed adolescents endorsed more negative descriptions of themselves than community adolescents, positive self-endorsements related to their relationships with other people were not impaired

Search for the Hypothetical pi -> mu x Decay

The KARMEN collaboration has reported the possible observation of a hitherto unknown neutral and weakly interacting particle x, which is produced in the decay pi -> mu + x with a mass m(x) = 33.9 MeV. We have searched for this hypothetical decay branch by studying muons from pion decay in flight with the LEPS spectrometer at the piE3 channel at PSI and find branching ratios BR(pi- to mu- anti-x) < 4e-7 and BR(pi+ to mu+ x) < 7e-8 (95\% C.L.). Together with the limit BR > 2e-8 derived in a recent theoretical paper our result would leave only a narrow region for the existence of x if it is a heavy neutrino.Comment: 10 pages, TeX (uses epsf), 3 Postscript figures uu-encode

The Muonium Atom as a Probe of Physics beyond the Standard Model

The observed interactions between particles are not fully explained in the successful theoretical description of the standard model to date. Due to the close confinement of the bound state muonium ($M = \mu^+ e^-$) can be used as an ideal probe of quantum electrodynamics and weak interaction and also for a search for additional interactions between leptons. Of special interest is the lepton number violating process of sponteanous conversion of muonium to antimuonium.Comment: 15 pages,6 figure

Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs

Evidence for a two component magnetic response in UPt3

The magnetic response of the heavy fermion superconductor UPt_3 has been investigated on a microscopic scale by muon Knight shift studies. Two distinct and isotropic Knight shifts have been found for the field in the basal plane. While the volume fractions associated with the two Knight shifts are approximately equal at low and high temperatures, they show a dramatic and opposite temperature dependence around T_N. Our results are independent on the precise muon localization site. We conclude that UPt_3 is characterized by a two component magnetic response.Comment: 5 pages, 4 figure

Target product profiles for the diagnosis of Taenia solium taeniasis, neurocysticercosis and porcine cysticercosis

Target Product Profiles (TPPs) are process tools providing product requirements to guide researchers, developers and manufacturers in their efforts to develop effective and useful products such as biologicals, drugs or diagnostics. During a WHO Stakeholders Meeting on Taenia solium diagnostics, several TPPs were initiated to address diagnostic needs for different stages in the parasite's transmission (taeniasis, human and porcine cysticercosis). Following the meeting, draft TPPs were completed and distributed for consultation to 100 people/organizations, including experts in parasitology, human and pig cysticercosis, diagnostic researchers and manufacturers, international organizations working with neglected or zoonotic diseases, Ministries of Health and Ministries of Livestock in some of the endemic countries, WHO regional offices and other interested parties. There were 53 respondents. All comments and feedback received were considered and discussions were held with different experts according to their area of expertise. The comments were consolidated and final TPPs are presented here. They are considered to be live documents which are likely to undergo review and updating in the future when new knowledge and technologies become available

The Mythic Experience: The Audiovisual Spectacle of the Biwa Hoshi Narrative and Performance in Ghost of Tsushima

The Mythic Tales side quests in Ghost of Tsushima (2020) explore folkloric and supernatural narratives using the themes from legends and lore surrounding Tsushima Island. However, as a historical video game that reimagines a thirteenth-century medieval Japanese society during the events of the Mongol invasion of Japan in 1274, careful examination of its represented form is necessary since it can tell us how a player is instructed to play with the reimagined past or what about the past is deemed important (Chapman; Balela and Mundy; McCall). Furthermore, the side quests provide a deeper exploration of the game-world setting, which can provide a historical and sociocultural understanding of the represented past through gameplay. In line with this, this paper examines the Mythic Tales experience by exploring the representations of the in-game version of a Japanese traditional performance art called the heikyoku, performed by a medieval storyteller known as the biwa hoshi. This includes a discussion of the tradition and how it translates into a video game format, highlighting the special audiovisual spectacle that relies on familiar Japanese imageries such as the sumi-e and ukiyo-e, which are unique to this part of the game. A case study of one of the Mythic Tales, “The Curse of Uchitsune,” will serve as critical analysis toward the kind of in-game mythic narrative and experience the game provides

Mixing of Active and Sterile Neutrinos

We investigate mixing of neutrinos in the $\nu$MSM (neutrino Minimal Standard Model), which is the MSM extended by three right-handed neutrinos. Especially, we study elements of the mixing matrix $\Theta_{\alpha I}$ between three left-handed neutrinos $\nu_\alpha$ ($\alpha = e,\mu,\tau$) and two sterile neutrinos $N_I$ ($I=2,3$) which are responsible to the seesaw mechanism generating the suppressed masses of active neutrinos as well as the generation of the baryon asymmetry of the universe (BAU). It is shown that $\Theta_{eI}$ can be suppressed by many orders of magnitude compared with $\Theta_{\mu I}$ and $\Theta_{\tau I}$, when the Chooz angle $\theta_{13}$ is large in the normal hierarchy of active neutrino masses. We then discuss the neutrinoless double beta decay in this framework by taking into account the contributions not only from active neutrinos but also from all the three sterile neutrinos. It is shown that $N_2$ and $N_3$ give substantial, destructive contributions when their masses are smaller than a few 100 MeV, and as a results $\Theta_{e I}$ receive no stringent constraint from the current bounds on such decay. Finally, we discuss the impacts of the obtained results on the direct searches of $N_{2,3}$ in meson decays for the case when $N_{2,3}$ are lighter than pion mass. We show that there exists the allowed region for $N_{2,3}$ with such small masses in the normal hierarchy case even if the current bound on the lifetimes of $N_{2,3}$ from the big bang nucleosynthesis is imposed. It is also pointed out that the direct search by using $\pi^+ \to e^+ + N_{2,3}$ and $K^+ \to e^+ + N_{2,3}$ might miss such $N_{2,3}$ since the branching ratios can be extremely small due to the cancellation in $\Theta_{eI}$, but the search by $K^+ \to \mu^+ + N_{2,3}$ can cover the whole allowed region by improving the measurement of the branching ratio by a factor of 5.Comment: 30 pages, 32 figure