‘Who’s on My Side?’ In what ways can creativity be used to discover what young people with behavioural, social and emotional difficulties think of the multi-agency services they receive? (Sharing our experience, Practitioner-led research 2008-2009; PLR0809/056)

In what ways can creativity be used to discover what young people with behavioural, social and emotional difficulties think of the multi-agency services they receive? The research investigates the effectiveness of using creativity as a catalyst for successful consultation with young people with behavioural, social and emotional difficulties. The aims of the research were to explore what the sample group thought of the integrated workings of the multi-agency services they received. The sample group consisted of eight young people from CYCES and the research encompassed the following areas: boundaries and clarity of purpose; confidentiality and organizational limitations; and informed consent. CYCES is a service delivered and maintained by The Together Trust and is for eight to 16 year olds with emotional, social and behavioural difficulties. The Together Trust is a charitable organization (established in 1870) that schools and homes young people in the care service. Each pupil received a pack of toy soldiers. One soldier represented the pupil and the rest represented the professional adults involved in their lives, both past and present. They were asked to choose which soldiers they felt were on their side and which were not. They were then asked to discuss their choices. Film was used as my method of recording and presenting data and involved recording the sessions with the young people and analysing the information obtained. The research discovered several important findings: • Having a physical representation of services allowed pupils to make and challenge connections in a way conversation alone would not. • There is a need for appropriate youth activities and recreational services for young people. The integration of home and school services at CYCES is successful. Giving young people responsibility for other young people promotes greater understanding and betterment of children’s services. In times of change, children need services the most

Traffic barriers : the impact of traffic on pedestrian behaviour

Abstract unavailable please refer to PDF

Treating progressive disseminated histoplasmosis in people living with HIV

Background Progressive disseminated histoplasmosis (PDH) is a serious fungal infection that affects people living with HIV. The best way to treat the condition is unclear. Objectives We assessed evidence in three areas of equipoise. 1. Induction. To compare efficacy and safety of initial therapy with liposomal amphotericin B versus initial therapy with alternative antifungals. 2. Maintenance. To compare efficacy and safety of maintenance therapy with 12 months of oral antifungal treatment with shorter durations of maintenance therapy. 3. Antiretroviral therapy (ART). To compare the outcomes of early initiation versus delayed initiation of ART. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane CENTRAL; MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded, Conference Proceedings Citation Index‐Science, and BIOSIS Previews (all three in the Web of Science); the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry, all up to 20 March 2020. Selection criteria We evaluated studies assessing the use of liposomal amphotericin B and alternative antifungals for induction therapy; studies assessing the duration of antifungals for maintenance therapy; and studies assessing the timing of ART. We included randomized controlled trials (RCT), single‐arm trials, prospective cohort studies, and single‐arm cohort studies. Data collection and analysis Two review authors assessed eligibility and risk of bias, extracted data, and assessed certainty of evidence. We used the Cochrane 'Risk of bias' tool to assess risk of bias in randomized studies, and ROBINS‐I tool to assess risk of bias in non‐randomized studies. We summarized dichotomous outcomes using risk ratios (RRs), with 95% confidence intervals (CI). Main results We identified 17 individual studies. We judged eight studies to be at critical risk of bias, and removed these from the analysis. 1. Induction We found one RCT which compared liposomal amphotericin B to deoxycholate amphotericin B. Compared to deoxycholate amphotericin B, liposomal amphotericin B may have higher clinical success rates (RR 1.46, 95% CI 1.01 to 2.11; 1 study, 80 participants; low‐certainty evidence). Compared to deoxycholate amphotericin B, liposomal amphotericin B has lower rates of nephrotoxicity (RR 0.25, 95% CI 0.09 to 0.67; 1 study, 77 participants; high‐certainty evidence). We found very low‐certainty evidence to inform comparisons between amphotericin B formulations and azoles for induction therapy. 2. Maintenance We found no eligible study that compared less than 12 months of oral antifungal treatment to 12 months or greater for maintenance therapy. For both induction and maintenance, fluconazole performed poorly in comparison to other azoles. 3. ART We found one study, in which one out of seven participants in the 'early' arm and none of the three participants in the 'late' arm died. Authors' conclusions Liposomal amphotericin B appears to be a better choice compared to deoxycholate amphotericin B for treating PDH in people with HIV; and fluconazole performed poorly compared to other azoles. Other treatment choices for induction, maintenance, and when to start ART have no evidence, or very low certainty evidence. PDH needs prospective comparative trials to help inform clinical decisions

Factors influencing the distribution of charge in polar nanocrystals

We perform first-principles calculations of wurtzite GaAs nanorods to explore the factors determining charge distributions in polar nanostructures. We show that both the direction and magnitude of the dipole moment $\mathbf{d}$ of a nanorod, and its electic field, depend sensitively on how its surfaces are terminated and do not depend strongly on the spontaneous polarization of the underlying lattice. We identify two physical mechanisms by which $\mathbf{d}$ is controlled by the surface termination, and we show that the excess charge on the nanorod ends is not strongly localized. We discuss the implications of these results for tuning nanocrystal properties, and for their growth and assembly.Comment: Accepted for publication in Phys. Rev. B Rapid Communication

Atovaquone‐proguanil for treating uncomplicated Plasmodium falciparum malaria

Background The World Health Organization (WHO) in 2015 stated atovaquone‐proguanil can be used in travellers, and is an option in malaria‐endemic areas in combination with artesunate, as an alternative treatment where first‐line artemisinin‐based combination therapy (ACT) is not available or effective. This review is an update of a Cochrane Review undertaken in 2005. Objectives To assess the efficacy and safety of atovaquone‐proguanil (alone and in combination with artemisinin drugs) versus other antimalarial drugs for treating uncomplicated Plasmodium falciparum malaria in adults and children. Search methods The date of the last trial search was 30 January 2020. Search locations for published trials included the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, and LILACS. To include recently published and unpublished trials, we also searched ClinicalTrials.gov, the metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform Search Portal. Selection criteria Randomized controlled trials (RCTs) reporting efficacy and safety data for atovaquone‐proguanil or atovaquone‐proguanil with a partner drug compared with at least one other antimalarial drug for treating uncomplicated Plasmodium falciparum infection. Data collection and analysis For this update, two review authors re‐extracted data and assessed certainty of evidence. We meta‐analyzed data to calculate risk ratios (RRs) with 95% confidence intervals (CI) for treatment failures between comparisons, and for safety outcomes between and across comparisons. Outcome measures include unadjusted treatment failures and polymerase chain reaction (PCR)‐adjusted treatment failures. PCR adjustment differentiates new infection from recrudescent infection. Main results Seventeen RCTs met our inclusion criteria providing 4763 adults and children from Africa, South‐America, and South‐East Asia. Eight trials reported PCR‐adjusted data to distinguish between new and recrudescent infection during the follow‐up period. In this abstract, we report only the comparisons against the three WHO‐recommended antimalarials which were included within these trials. There were two comparisons with artemether‐lumefantrine, one trial from 2008 in Ethiopia with 60 participants had two failures with atovaquone‐proguanil compared to none with artemether‐lumefantrine (PCR‐adjusted treatment failures at day 28). A second trial from 2012 in Colombia with 208 participants had one failure in each arm (PCR‐adjusted treatment failures at day 42). There was only one comparison with artesunate‐amodiaquine from a 2014 trial conducted in Cameroon. There were six failures with atovaquone‐proguanil at day 28 and two with artesunate‐amodiaquine (PCR‐adjusted treatment failures at day 28: 9.4% with atovaquone‐proguanil compared to 2.9% with artesunate‐amodiaquine; RR 3.19, 95% CI 0.67 to 15.22; 1 RCT, 132 participants; low‐certainty evidence), although there was a similar number of PCR‐unadjusted treatment failures (9 (14.1%) with atovaquone‐proguanil and 8 (11.8%) with artesunate‐amodiaquine; RR 1.20, 95% CI 0.49 to 2.91; 1 RCT, 132 participants; low‐certainty evidence). There were two comparisons with artesunate‐mefloquine from a 2012 trial in Colombia and a 2002 trial in Thailand where there are high levels of multi‐resistant malaria. There were similar numbers of PCR‐adjusted treatment failures between groups at day 42 (2.7% with atovaquone‐proguanil compared to 2.4% with artesunate‐mefloquine; RR 1.15, 95% CI 0.57 to 2.34; 2 RCTs, 1168 participants; high‐certainty evidence). There were also similar PCR‐unadjusted treatment failures between groups (5.3% with atovaquone‐proguanil compared to 6.6% with artesunate‐mefloquine; RR 0.8, 95% CI 0.5 to 1.3; 1 RCT, 1063 participants; low‐certainty evidence). When atovaquone‐proguanil was combined with artesunate, there were fewer treatment failures with and without PCR‐adjustment at day 28 (PCR‐adjusted treatment failures at day 28: 2.16% with atovaquone‐proguanil compared to no failures with artesunate‐atovaquone‐proguanil; RR 5.14, 95% CI 0.61 to 43.52; 2 RCTs, 375 participants, low‐certainty evidence) and day 42 (PCR‐adjusted treatment failures at day 42: 3.82% with atovaquone‐proguanil compared to 2.05% with artesunate‐atovaquone‐proguanil (RR 1.84, 95% CI 0.95 to 3.56; 2 RCTs, 1258 participants, moderate‐certainty evidence). In the 2002 trial in Thailand, there were fewer treatment failures in the artesunate‐atovaquone‐proguanil group compared to the atovaquone‐proguanil group at day 42 with PCR‐adjustment. Whilst there were some small differences in which adverse events were more frequent in the atovaquone‐proguanil groups compared to comparator drugs, there were no recurrent associations to suggest that atovaquone‐proguanil is strongly associated with any specific adverse event. Authors' conclusions Atovaquone‐proguanil was effective against uncomplicated P falciparum malaria, although in some instances treatment failure rates were between 5% and 10%. The addition of artesunate to atovaquone‐proguanil may reduce treatment failure rates. Artesunate‐atovaquone‐proguanil and the development of parasite resistance may represent an area for further researc

Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV

Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum . This disease is highly endemic in some regions of North America, Central America, and South America and is also reported in certain countries of Asia and Africa. It often affects people with impaired immunity, including people living with HIV, among whom the most frequent clinical presentation is disseminated histoplasmosis. The symptoms of disseminated histoplasmosis are non-specific and may be indistinguishable from those of other infectious diseases, especially disseminated tuberculosis (TB), thus complicating diagnosis and treatment. Histoplasmosis is one of the most frequent opportunistic infections caused by fungal pathogens among people living with HIV in the Americas and may be responsible for 5–15% of AIDS-related deaths every year in this Region. These guidelines aim to provide recommendations for the diagnosis, treatment, and management of disseminated histoplasmosis in persons living with HIV. Although the burden of disease is concentrated in the Americas, the recommendations contained within these guidelines are applicable globally. These guidelines were produced in accordance with the World Health Organization (WHO) handbook for guideline development. The Guideline Development Group elaborated the final recommendations based on systematic review of scientific literature and critical evaluation of the evidence available using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. These guidelines are intended for health-care providers, HIV program managers, policy-makers, national treatment advisory boards, and other professionals involved in caring for people who either have or may be at risk of developing disseminated histoplasmosi

Visualizing electrostatic gating effects in two-dimensional heterostructures

The ability to directly observe electronic band structure in modern nanoscale field-effect devices could transform understanding of their physics and function. One could, for example, visualize local changes in the electrical and chemical potentials as a gate voltage is applied. One could also study intriguing physical phenomena such as electrically induced topological transitions and many-body spectral reconstructions. Here we show that submicron angle-resolved photoemission (micro-ARPES) applied to two-dimensional (2D) van der Waals heterostructures affords this ability. In graphene devices, we observe a shift of the chemical potential by 0.6 eV across the Dirac point as a gate voltage is applied. In several 2D semiconductors we see the conduction band edge appear as electrons accumulate, establishing its energy and momentum, and observe significant band-gap renormalization at low densities. We also show that micro-ARPES and optical spectroscopy can be applied to a single device, allowing rigorous study of the relationship between gate-controlled electronic and excitonic properties.Comment: Original manuscript with 9 pages with 4 figures in main text, 5 pages with 4 figures in supplement. Substantially edited manuscript accepted at Natur

Pyronaridine‐artesunate for treating uncomplicated Plasmodium falciparum malaria

Background The World Health Organization (WHO) recommends artemisinin‐based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria. Concerns about artemisinin resistance have led to global initiatives to develop new partner drugs to protect artemisinin derivatives in ACT. Pyronaridine‐artesunate is a novel ACT. Objectives To evaluate the efficacy of pyronaridine‐artesunate compared to alternative ACTs for treating people with uncomplicated P falciparum malaria, and to evaluate the safety of pyronaridine‐artesunate and other pyronaridine treatments compared to alternative treatments. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; Embase; and LILACS. We also searched ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and the ISRCTN registry for ongoing or recently completed trials. The date of the last search was 27 October 2021. Selection criteria For the efficacy analysis, we included randomized controlled trials (RCTs) of pyronaridine‐artesunate for treating uncomplicated P falciparum malaria. For the safety analysis, we included RCTs that used pyronaridine alone or in combination with any other antimalarials. In addition to these analyses, we conducted a separate systematic review summarizing data on safety from non‐randomized studies (NRS) of any patient receiving pyronaridine (NRS safety review). Data collection and analysis Two review authors independently extracted all data and assessed the certainty of the evidence. We meta‐analysed data to calculate risk ratios (RRs) for treatment failures between comparisons, and for safety outcomes between and across comparisons. Main results We included 10 relevant RCTs. Seven RCTs were co‐funded by Shin Poong Pharmaceuticals, and three were funded by government agencies. Efficacy analysis (RCTs) For the efficacy analysis, we identified five RCTs comprising 5711 participants. This included 4465 participants from 13 sites in Africa, and 1246 participants from five sites in Asia. The analysis included 541 children aged less than five years. Overall, pyronaridine‐artesunate had a polymerase chain reaction (PCR)‐adjusted treatment failure rate of less than 5%. We evaluated pyronaridine‐artesunate versus the following. • Artemether‐lumefantrine. Pyronaridine artesunate may perform better for PCR‐adjusted failures at day 28 (RR 0.59, 95% confidence interval (CI) 0.26 to 1.31; 4 RCTs, 3068 participants, low‐certainty evidence); for unadjusted failures at day 28 (RR 0.27, 95% CI 0.13 to 0.58; 4 RCTs, 3149 participants, low‐certainty evidence); and for unadjusted failures at day 42 (RR 0.61, 95% CI 0.46 to 0.82; 4 RCTs, 3080 participants, low‐certainty evidence). For PCR‐adjusted failures at day 42, there may be little or no difference between groups (RR 0.86, 95% CI 0.49 to 1.51; 4 RCTs, 2575 participants, low‐certainty evidence). • Artesunate‐amodiaquine. Pyronaridine artesunate may perform better for PCR‐adjusted failures at day 28 (RR 0.55, 95% CI 0.11 to 2.77; 1 RCT, 1245 participants, low‐certainty evidence); probably performs better for unadjusted failures at day 28 (RR 0.49, 95% CI 0.30 to 0.81; 1 RCT, 1257 participants, moderate‐certainty evidence); may make little or no difference for PCR‐adjusted failures at day 42 (RR 0.98, 95% CI 0.20 to 4.83; 1 RCT, 1091 participants, low‐certainty evidence); and probably makes little or no difference for unadjusted failures at day 42 (RR 0.98, 95% CI 0.78 to 1.23; 1 RCT, 1235 participants, moderate‐certainty evidence). • Mefloquine plus artesunate. Pyronaridine artesunate may perform better for PCR‐adjusted failures at day 28 (RR 0.37, 95% CI 0.13 to 1.05; 1 RCT, 1117 participants, low‐certainty evidence); probably performs better for unadjusted failures at day 28 (RR 0.36, 95% CI 0.17 to 0.78; 1 RCT, 1120 participants, moderate‐certainty evidence); may make little or no difference for unadjusted failures at day 42 (RR 0.84, 95% CI 0.54 to 1.31; 1 RCT, 1059 participants, low‐certainty evidence); but may lead to higher PCR‐adjusted failures at day 42 (RR 1.80, 95% CI 0.90 to 3.57; 1 RCT, 1037 participants, low‐certainty evidence). Safety analysis (RCTs) For the RCT safety analysis, we identified eight RCTs, one of which was delineated by study site, comparing pyronaridine‐artesunate to other antimalarials. Pyronaridine‐artesunate was associated with raised liver enzymes compared to other antimalarials: alanine aminotransferase (ALT) (RR 3.59, 95% CI 1.76 to 7.33; 8 RCTS, 6669 participants, high‐certainty evidence) and aspartate transaminase (AST) (RR 2.22, 95% CI 1.12 to 4.41; 8 RCTs, 6669 participants, moderate‐certainty evidence). No such effect was demonstrated with bilirubin (RR 1.03, 95% CI 0.49 to 2.18; 7 RCTs, 6384 participants, moderate‐certainty evidence). There was one reported case in which raised ALT occurred with raised bilirubin. No study reported severe drug‐induced liver injury. Electrocardiograph (ECG) abnormalities were less common with pyronaridine‐artesunate compared to other antimalarials. We identified no other safety concerns. NRS safety review A review on safety in NRS allowed us to increase the population within which safety was assessed. We included seven studies with 9546 participants: five single‐arm observational studies, one cohort event monitoring study, and one dose‐escalation study. All studies provided data on adverse event frequency, with a small number of participants experiencing serious adverse events and adverse effects related to pyronaridine: serious adverse events average 0.37%; drug‐related 9.0%. In two studies reporting elevations in liver enzymes, small percentages of participants (2.4% and 14.1% respectively) experienced increases in either ALT, AST, or bilirubin on day 7; however, these were small increases that returned to normal by day 42. Authors' conclusions Pyronaridine‐artesunate was efficacious against uncomplicated P falciparum malaria; achieved a PCR‐adjusted treatment failure rate of less than 5% at days 28 and 42; and may be at least as good as, or better than, other marketed ACTs. Pyronaridine‐artesunate increases the risk of episodes of abnormally raised ALT. The observational data did not signal an excess of clinically important adverse effects

Early Results from the Lunar Atmosphere and Dust Environment Explorer (LADEE)

On 6 September, 2013, a near-perfect launch of the first Minotaur V rocket successfully carried NASA's Lunar Atmosphere and Dust Environment Explorer (LADEE) into a high-eccentricity geocentric orbit. After 30 days of phasing, LADEE arrived at the Moon on 6 October, 2013. LADEE's science objectives are twofold: (1) Determine the composition of the lunar atmosphere, investigate processes controlling its distribution and variability, including sources, sinks, and surface interactions; (2) Characterize the lunar exospheric dust environment, measure its spatial and temporal variability, and effects on the lunar atmosphere, if any. After a successful commissioning phase, the three science instruments have made systematic observations of the lunar dust and exospheric environment. These include initial observations of argon, neon and helium exospheres, and their diurnal variations; the lunar micrometeoroid impact ejecta cloud and its variations; spatial and temporal variations of the sodium exosphere; and the search for sunlight extinction caused by dust. LADEE also made observations of the effects of the Chang'e 3 landing on 14 December 2013