What is required in terms of mass drug administration to interrupt the transmission of schistosome parasites in regions of endemic infection?

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Low-frequency noise as a source of dephasing of a qubit

With the growing efforts in isolating solid-state qubits from external decoherence sources, the material-inherent sources of noise start to play crucial role. One representative example is electron traps in the device material or substrate. Electrons can tunnel or hop between a charged and an empty trap, or between a trap and a gate electrode. A single trap typically produces telegraph noise and can hence be modeled as a bistable fluctuator. Since the distribution of hopping rates is exponentially broad, many traps produce flicker-noise with spectrum close to 1/f. Here we develop a theory of decoherence of a qubit in the environment consisting of two-state fluctuators, which experience transitions between their states induced by interaction with thermal bath. Due to interaction with the qubit the fluctuators produce 1/f-noise in the qubit's eigenfrequency. We calculate the results of qubit manipulations - free induction and echo signals - in such environment. The main problem is that in many important cases the relevant random process is both non-Markovian and non-Gaussian. Consequently the results in general cannot be represented by pair correlation function of the qubit eigenfrequency fluctuations. Our calculations are based on analysis of the density matrix of the qubit using methods developed for stochastic differential equations. The proper generating functional is then averaged over different fluctuators using the so-called Holtsmark procedure. The analytical results are compared with simulations allowing checking accuracy of the averaging procedure and evaluating mesoscopic fluctuations. The results allow understanding some observed features of the echo decay in Josephson qubits.Comment: 18 pages, 8 figures, Proc. of NATO/Euresco Conf. "Fundamental Problems of Mesoscopic Physics: Interactions and Decoherence", Granada, Spain, Sept.200

The spirit of sport: the case for criminalisation of doping in the UK

This article examines public perceptions of doping in sport, critically evaluates the effectiveness of current anti-doping sanctions and proposes the criminalisation of doping in sport in the UK as part of a growing global movement towards such criminalisation at national level. Criminalising doping is advanced on two main grounds: as a stigmatic deterrent and as a form of retributive punishment enforced through the criminal justice system. The ‘spirit of sport’ defined by the World Anti-Doping Agency (WADA) as being based on the values of ethics, health and fair-play is identified as being undermined by the ineffectiveness of existing anti-doping policy in the current climate of doping revelations, and is assessed as relevant to public perceptions and the future of sport as a whole. The harm-reductionist approach permitting the use of certain performance enhancing drugs (PEDs) is considered as an alternative to anti-doping, taking into account athlete psychology, the problems encountered in containing doping in sport through anti-doping measures and the effect of these difficulties on the ‘spirit of sport’. This approach is dismissed in favour of criminalising doping in sport based on the offence of fraud. It will be argued that the criminalisation of doping could act as a greater deterrent than existing sanctions imposed by International Federations, and, when used in conjunction with those sanctions, will raise the overall ‘price’ of doping. The revelations of corruption within the existing system of self-governance within sport have contributed to a disbelieving public and it will be argued that the criminalisation of doping in sport could assist in satisfying the public that justice is being done and in turn achieve greater belief in the truth of athletic performances

Quitting patient care and career break intentions among general practitioners in South West England: findings of a census survey of general practitioners

Objective: Given recent concerns regarding general practitioner (GP) workforce capacity, we aimed to describe GPs’ career intentions, especially those which might impact on GP workforce availability over the next 5 years. Design: Census survey, conducted between April and June 2016 using postal and online responses , of all GPs on the National Health Service performers list and eligible to practise in primary care. Two reminders were used as necessary. Setting: South West England (population 3.5  million), a region with low overall socioeconomic deprivation. Participants: Eligible GPs were 2248 out of 3370 (67 % response rate). Main outcome measures: Reported likelihood of permanently leaving or reducing hours spent in direct patient care or of taking a career break within the next 5 years and present morale weighted for non-response. Results: Responders included 217 7 GPs engaged in patient care. Of these, 863 (37% weighted, 95%  CI 35 % to 39 %) reported a high likelihood of quitting direct patient care within the next 5 years. Overall, 1535 (70% weighted, 95%  CI 68 % to 72 %) respondents reported a career intention that would negatively impact GP workforce capacity over the next 5 years, through permanently leaving or reducing hours spent in direct patient care, or through taking a career break. GP age was an important predictor of career intentions; sharp increases in the proportion of GPs intending to quit patient care were evident from 52 years. Only 305 (14% weighted, 95%  CI 13 % to 16 %) reported high morale, while 1195 ( 54 % weighted, 95%  CI 52 % to 56 %) reported low morale. Low morale was particularly common among GP partners. Current morale strongly predicted GPs’ career intentions; those with very low morale were particularly likely to report intentions to quit patient care or to take a career break. Conclusions: A substantial majority of GPs in South West England report low morale. Many are considering career intentions which, if implemented, would adversely impact GP workforce capacity within a short time period. Study registration: NIHR HS&DR - 14/196/02, UKCRN ID 20700

Social sciences research in neglected tropical diseases 3: Investment in social science research in neglected diseases of poverty: a case study of Bill and Melinda Gates Foundation

This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: The level of funding provides a good proxy for the level of commitment or prioritisation given to a particular issue. While the need for research relevant to social, economic, cultural and behavioural aspects of neglected tropical diseases (NTD) control has been acknowledged, there is limited data on the level of funding that supports NTD social science research. METHOD: A case study was carried out in which the spending of a major independent funder, the Bill and Melinda Gates Foundation (BMGF) - was analysed. A total of 67 projects funded between October 1998 and November 2008 were identified from the BMGF database. With the help of keywords within the titles of 67 grantees, they were categorised as social science or non-social science research based on available definition of social science. A descriptive analysis was conducted. RESULTS: Of 67 projects analysed, 26 projects (39%) were social science related while 41 projects (61%) were basic science or other translational research including drug development. A total of US$697 million was spent to fund the projects, of which 35$ 241 million) went to social science research. Although the level of funding for social science research has generally been lower than that for non-social science research over 10 year period, social science research attracted more funding in 2004 and 2008. CONCLUSION: The evidence presented in this case study indicates that funding on NTD social science research compared to basic and translational research is not as low as it is perceived to be. However, as there is the acute need for improved delivery and utilisation of current NTD drugs/technologies, informed by research from social science approaches, funding priorities need to reflect the need to invest significantly more in NTD social science research

DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3′-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5′-terminated strand of the DNA break and to inhibit 3′ to 5′ degradation by Dna2, actions that generate and protect the 3′-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes

Symmetries of Differential Equations via Cartan's Method of Equivalence

We formulate a method of computing invariant 1-forms and structure equations of symmetry pseudo-groups of differential equations based on Cartan's method of equivalence and the moving coframe method introduced by Fels and Olver. Our apparoach does not require a preliminary computation of infinitesimal defining systems, their analysis and integration, and uses differentiation and linear algebra operations only. Examples of its applications are given.Comment: 15 pages, LaTeX 2.0

Deep Impact Mission to Tempel 1 Favours New Explosive Cosmogony of Comets

The assumption that short-period (SP) comets are fragments of massive icy envelopes of Ganymede-like bodies saturated by products of ice electrolysis that underwent global explosions provides a plausible explanation of all known manifestations of comets, including the jet character of outflows, the presence of ions in the vicinity of the nucleus, the bursts and splitting of cometary nuclei, etc., with solar radiation initiating burning of the products of electrolysis in the nucleus. As shown persuasively by numerical simulation carried out in hydrodynamic approximation, the shock wave initiated by the Deep Impact (DI) impactor in the cometary ice saturated originally by the electrolysis products 2H2 + O2 is capable of activating under certain conditions exothermal reactions (of the type O2 + H2 + organics = H2O + CO + HCN + other products of incomplete burning of organics including its light and heavy pyrolyzed compounds, soot, etc.), which will slow down shock wave damping (forced detonation) and increase many times the energy release. As a result, the measured energetics of ejections and outflows from the crater have to exceed the DI energetics. Analysis of different clusters of the DI experiment data confirms these conclusions and expectations and thus it favours the planetary origin of comets.Comment: 21 pages incluging 3 figure

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC