n-type chalcogenides by ion implantation.

Carrier-type reversal to enable the formation of semiconductor p-n junctions is a prerequisite for many electronic applications. Chalcogenide glasses are p-type semiconductors and their applications have been limited by the extraordinary difficulty in obtaining n-type conductivity. The ability to form chalcogenide glass p-n junctions could improve the performance of phase-change memory and thermoelectric devices and allow the direct electronic control of nonlinear optical devices. Previously, carrier-type reversal has been restricted to the GeCh (Ch=S, Se, Te) family of glasses, with very high Bi or Pb 'doping' concentrations (~5-11 at.%), incorporated during high-temperature glass melting. Here we report the first n-type doping of chalcogenide glasses by ion implantation of Bi into GeTe and GaLaSO amorphous films, demonstrating rectification and photocurrent in a Bi-implanted GaLaSO device. The electrical doping effect of Bi is observed at a 100 times lower concentration than for Bi melt-doped GeCh glasses.This work was supported by the UK EPSRC grants EP/I018417/1, EP/I019065/1 and EP/I018050/1.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncomms634

Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Parameter identification problems in the modelling of cell motility

We present a novel parameter identification algorithm for the estimation of parameters in models of cell motility using imaging data of migrating cells. Two alternative formulations of the objective functional that measures the difference between the computed and observed data are proposed and the parameter identification problem is formulated as a minimisation problem of nonlinear least squares type. A Levenberg–Marquardt based optimisation method is applied to the solution of the minimisation problem and the details of the implementation are discussed. A number of numerical experiments are presented which illustrate the robustness of the algorithm to parameter identification in the presence of large deformations and noisy data and parameter identification in three dimensional models of cell motility. An application to experimental data is also presented in which we seek to identify parameters in a model for the monopolar growth of fission yeast cells using experimental imaging data. Our numerical tests allow us to compare the method with the two different formulations of the objective functional and we conclude that the results with both objective functionals seem to agree

ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value

Target product profiles for protecting against outdoor malaria transmission.

BACKGROUND\ud \ud Long-lasting insecticidal nets (LLINs) and indoor residual sprays (IRS) have decimated malaria transmission by killing indoor-feeding mosquitoes. However, complete elimination of malaria transmission with these proven methods is confounded by vectors that evade pesticide contact by feeding outdoors.\ud \ud METHODS\ud \ud For any assumed level of indoor coverage and personal protective efficacy with insecticidal products, process-explicit malaria transmission models suggest that insecticides that repel mosquitoes will achieve less impact upon transmission than those that kill them outright. Here such models are extended to explore how outdoor use of products containing either contact toxins or spatial repellents might augment or attenuate impact of high indoor coverage of LLINs relying primarily upon contact toxicity.\ud \ud RESULTS\ud \ud LLIN impact could be dramatically enhanced by high coverage with spatial repellents conferring near-complete personal protection, but only if combined indoor use of both measures can be avoided where vectors persist that prefer feeding indoors upon humans. While very high levels of coverage and efficacy will be required for spatial repellents to substantially augment the impact of LLINs or IRS, these ambitious targets may well be at least as practically achievable as the lower requirements for equivalent impact using contact insecticides.\ud \ud CONCLUSIONS\ud \ud Vapour-phase repellents may be more acceptable, practical and effective than contact insecticides for preventing outdoor malaria transmission because they need not be applied to skin or clothing and may protect multiple occupants of spaces outside of treatable structures such as nets or houses

Using a New Odour-Baited Device to Explore Options for Luring and Killing Outdoor-Biting Malaria Vectors: A Report on Design and Field Evaluation of the Mosquito Landing Box.

Mosquitoes that bite people outdoors can sustain malaria transmission even where effective indoor interventions such as bednets or indoor residual spraying are already widely used. Outdoor tools may therefore complement current indoor measures and improve control. We developed and evaluated a prototype mosquito control device, the 'Mosquito Landing Box' (MLB), which is baited with human odours and treated with mosquitocidal agents. The findings are used to explore technical options and challenges relevant to luring and killing outdoor-biting malaria vectors in endemic settings. Field experiments were conducted in Tanzania to assess if wild host-seeking mosquitoes 1) visited the MLBs, 2) stayed long or left shortly after arrival at the device, 3) visited the devices at times when humans were also outdoors, and 4) could be killed by contaminants applied on the devices. Odours suctioned from volunteer-occupied tents were also evaluated as a potential low-cost bait, by comparing baited and unbaited MLBs. There were significantly more Anopheles arabiensis, An. funestus, Culex and Mansonia mosquitoes visiting baited MLB than unbaited controls (P<=0.028). Increasing sampling frequency from every 120 min to 60 and 30 min led to an increase in vector catches of up to 3.6 fold (P<=0.002), indicating that many mosquitoes visited the device but left shortly afterwards. Outdoor host-seeking activity of malaria vectors peaked between 7:30 and 10:30pm, and between 4:30 and 6:00am, matching durations when locals were also outdoors. Maximum mortality of mosquitoes visiting MLBs sprayed or painted with formulations of candidate mosquitocidal agent (pirimiphos-methyl) was 51%. Odours from volunteer occupied tents attracted significantly more mosquitoes to MLBs than controls (P<0.001). While odour-baited devices such as the MLBs clearly have potential against outdoor-biting mosquitoes in communities where LLINs are used, candidate contaminants must be those that are effective at ultra-low doses even after short contact periods, since important vector species such as An. arabiensis make only brief visits to such devices. Natural human odours suctioned from occupied dwellings could constitute affordable sources of attractants to supplement odour baits for the devices. The killing agents used should be environmentally safe, long lasting, and have different modes of action (other than pyrethroids as used on LLINs), to curb the risk of physiological insecticide resistance

Results of the MAJORANA DEMONSTRATOR's Search for Double-Beta Decay of 76Ge to Excited States of 76Se

The MAJORANA DEMONSTRATOR is searching for double-beta decay of 76Ge to excited states (E.S.) in 76Se using a modular array of high purity Germanium detectors. 76Ge can decay into three E.S.s of 76Se. The E.S. decays have a clear event signature consisting of a ββ-decay with the prompt emission of one or two γ-rays, resulting in with high probability in a multi-site event. The granularity of the DEMONSTRATOR detector array enables powerful discrimination of this event signature from backgrounds. Using 21.3 kg-y of isotopic exposure, the DEMONSTRATOR has set world leading limits for each E.S. decay, with 90% CL lower half-life limits in the range of (0.56 2.1) ⋅ 1024 y. In particular, for the 2v transition to the first 0+ E.S. of 76Se, a lower half-life limit of 0.68 ⋅ 1024 at 90% CL was achieved

Antimicrobial prescription patterns and ventilator associated pneumonia: Findings from a 10-site prospective audit

© 2018 The Author(s). Objective: To examine anti-microbial prescribing practices associated with ventilator-associated pneumonia from data gathered during an audit of practice and outcomes in intensive care units (ICUs) in a previously published study. Results: The patient sample of 169 was 65% male with an average age of 59.7 years, a mean APACHE II score of 20.6, and a median ICU stay of 11 days. While ventilator-associated pneumonia was identified using a specific 4-item checklist in 29 patients, agreement between the checklist and independent physician diagnosis was only 17%. Sputum microbe culture reporting was sparse. Approximately 75% of the sample was administered an antimicrobial (main indications: lung infection [54%] and prophylaxis [11%]). No clinical justification was documented for 20% of prescriptions. Piperacillin/tazobactam was most frequently prescribed (1/3rd of all antimicrobial prescriptions) with about half of those for prophylaxis. Variations in prescribing practices were identified, including apparent gaps in antimicrobial stewardship; particularly in relation to prescribing for prophylaxis and therapy de-escalation. Sputum microbe culture reports for VAP did not appear to contribute to prescribing decisions but physician suspicion of lung infection and empiric therapy rather than ventilator-associated pneumonia criteria and guideline concordance

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns