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Abstract With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.

BackgroundTsetse flies (Glossina sp.) are vectors of Trypanosoma brucei subspecies that cause human African trypanosomiasis (HAT). Capturing and screening tsetse is critical for HAT surveillance. Classically, tsetse have been microscopically analysed to identify trypanosomes, but this is increasingly replaced with molecular xenomonitoring. Nonetheless, sensitive T. brucei-detection assays, such as TBR-PCR, are vulnerable to DNA cross-contamination. This may occur at capture, when often multiple live tsetse are retained temporarily in the cage of a trap. This study set out to determine whether infected tsetse can contaminate naïve tsetse with T. brucei DNA via faeces when co-housed.Methodology/principle findingsInsectary-reared teneral G. morsitans morsitans were fed an infectious T. b. brucei-spiked bloodmeal. At 19 days post-infection, infected and naïve tsetse were caged together in the following ratios: (T1) 9:3, (T2) 6:6 (T3) 1:11 and a control (C0) 0:12 in triplicate. Following 24-hour incubation, DNA was extracted from each fly and screened for parasite DNA presence using PCR and qPCR. All insectary-reared infected flies were positive for T. brucei DNA using TBR-qPCR. However, naïve tsetse also tested positive. Even at a ratio of 1 infected to 11 naïve flies, 91% of naïve tsetse gave positive TBR-qPCR results. Furthermore, the quantity of T. brucei DNA detected in naïve tsetse was significantly correlated with cage infection ratio. With evidence of cross-contamination, field-caught tsetse from Tanzania were then assessed using the same screening protocol. End-point TBR-PCR predicted a sample population prevalence of 24.8%. Using qPCR and Cq cut-offs optimised on insectary-reared flies, we estimated that prevalence was 0.5% (95% confidence interval [0.36, 0.73]).Conclusions/significanceOur results show that infected tsetse can contaminate naïve flies with T. brucei DNA when co-caged, and that the level of contamination can be extensive. Whilst simple PCR may overestimate infection prevalence, quantitative PCR offers a means of eliminating false positives.

Bifacial photovoltaics (bPV) provide an advantage over their traditional monofacial counterparts as they can utilise solar radiation incident on both the front and rear side of the module, allowing for increased energy production. While this is an advantage on the side of bPV, the amount of energy produced by the rear side of the bPV panel can vary greatly depending on the inclination and azimuth of the panel as well as external climatic and ground albedo conditions. This paper aims to analyse the electrical and thermal performance of bPV under varying albedo conditions, using two different materials: grass, and a reflective material. It also contains an example of bifaciality testing under real-world conditions. Several experiments were conducted to evaluate the electrical performance and the temperature distribution of the bPV panel under different weather conditions at the UK location and then the results were compared with the single diode model of bPV. Furthermore, a bPV panel temperature model has been developed for the temperate climate condition of UK. The results show that the open circuit voltage of the system increases with irradiance up to around 800 W/m2, at which point it decreased due to the increased PV system temperature. The normalised efficiency for the PV system under different conditions were also evaluated, which showed that the bPV module was most efficient under diffuse irradiance conditions, encouraging the use of the bPV technology in the UK.

In recent years, floating photovoltaic (FPV) systems have emerged as a promising technology for generating renewable energy using the surface of water bodies such as reservoirs, lakes, and oceans. FPV systems offer several advantages over traditional land-based solar arrays, including increased land-use efficiency, reduced water evaporation, and improved cooling and maintenance. However, like all solar power systems, FPVs are subject to variability and intermittency due to changes in weather, seasons, and time of day. The environmental impact is discussed along with the deployment consideration and the feasibility for a better understanding of the system. Challenges associated with this are addressed by progressed research suggesting the integration of FPVs with various energy storage and hybrid systems. The most promising areas researched in this paper look at hybrid FPV hydropower plants (HPP), in parts of the world experiencing droughts HPP is not working to its optimum capacity. A review of available literature has been conducted on the topic of offshore and onshore floating solar electricity generation using floating solar photovoltaics to identify the challenges and opportunities presented. This work looks at a variety of other hybrid FPV energy sources with varying technology readiness levels. This paper concludes with the possibility of integrating different renewable technologies with existing FPVs and highlights the boons of doing so with some examples. Ultimately, current as well as future perspectives have been provided which consolidate the current research being done and give recommendations for future research work.

Literature review papers are highly influential in directing academic discourse, not only because they map the state of the art in a subject area, but also because they show future research prospects by identifying weaknesses, limitations, and gaps in the extant body of knowledge on a particular subject [...]

Abstract Background Overdose-associated deaths and morbidity related to substance use is a global public health emergency with devastating social and economic costs. Complications of substance use are most pronounced among people who inject drugs (PWID), particularly infections, resulting in increased risk of hospitalization. PWID often require intravenous access for medical treatments such as antibiotics; however, vascular access may be limited due to the impacts of long-term self-venipuncture. While vascular access devices including peripherally inserted central catheters (PICCs) allow reliable and sustained routes of administration for indicated therapies, the use of PICCs among PWID presents unique challenges. The incidence and risks associated with self-injecting non-prescribed substances into vascular access devices (SIVAD) is one such concern for which there is limited evidence and absence of formal practice guidance. Case presentation We report the experience of a multidisciplinary team at a health organization in Vancouver, Canada, working to characterize the incidence, patient and healthcare provider perspectives, and overall impact of SIVAD. The case study of SIVAD begins with a patient’s perspective, including patient rationale for SIVAD, understanding of risks and the varying responses given by healthcare providers following disclosure of SIVAD. Using the limited literature available on the subject, we summarize the intersection of SIVAD and substance use and outline known and anticipated health risks. The case study is further contextualized by experience from a Vancouver in-hospital Overdose Prevention Site (OPS), where 37% of all individual visits involve SIVAD. The case study concludes by describing the systematic process by which local clinical guidance for SIVAD harm reduction was developed with stakeholder engagement, medical ethics consultation, expert consensus guideline development and implementation with staff education and planned research evaluation. Conclusion SIVAD is encountered with enough frequency in an urban healthcare setting in Vancouver, Canada, to warrant an organizational approach. This case study aims to enhance appreciation of SIVAD as a common and complex clinical issue with anticipated health risks. The authors conclude that using a harm reduction lens for SIVAD policy and research can provide benefit to clinicians and patients by offering a clear and a consistent healthcare response to this common issue.

Academic journals rely crucially upon the willingness of academics to review papers and for them to provide high-quality review reports. The purpose of this Editorial is to assist reviewers for Tourism and Hospitality in providing review reports that will be helpful to the journal editors in making decisions about whether to accept, reject or require revisions to papers that are submitted to the journal. It provides reviewers with a ‘peep behind the curtain’ of what can sometimes seem a rather opaque paper review process, with the aim of clarifying the purpose and format of the review process, and thereby to gain a greater appreciation of what it required of them. Several tips for writing high-quality review reports are also presented.

Background: Hospitals were affected by COVID-19, with significant concern regarding transmission from unidentified cases. Fraser Health, a Canadian regional health authority, implemented universal testing along with screening questions for emergency department (ED) admissions. We sought to determine which factors were associated with SARS-CoV-2–positive test on admission as well as patient outcome, stratified by screening question responses. Methods: This retrospective analysis included patients aged ≥6 years admitted through 12 hospital EDs between November 1, 2020, and June 30, 2022. Admission, laboratory, and screening data were extracted from electronic health records. Patients who had a first SARS-CoV-2 PCR–positive test in the prior 60 days collected within 48 hours of admission were classified as positive. Covariates included age, geographical region, and SARS-CoV-2 variant era. All questions were modeled using multinomial logistic regression, with components informed through crude analysis in R Studio software. Results: There were 88,511 unique eligible admissions, with 7,642 positive tests (8.6%). The positivity rate over the study period ranged from 0.6% to 21.8%, with a mean of 6.5%. Patients meeting screening criteria were 4.7 times (95% CI, 4.43–4.92) as likely to test positive as those who did not. Patients in the SARS-CoV-2 omicron variant era were 3.2 times (95% CI, 2.98–3.47) as likely to test positive as those in the earlier era of the pandemic. Patients later in the pandemic were less likely to be identified by screening questions than those in earlier eras, with patients in the SARS-CoV-2 omicron variant era only 14% (95% CI, 12%–17%) as likely as in the earlier stages of the pandemic to be identified by screening questions. Patients who tested positive were 1.5 (95% CI, 1.37–1.64) times as likely to die as patients who tested negative, whereas patients in later stages of the pandemic were less likely to die overall. Discussion: Patients who tested positive on admission were more likely to meet screening criteria; however, screening missed half of all positive cases. It is not known whether patients who tested positive without meeting screening criteria would have resulted in transmission. Conclusions: Due to changes in COVID-19 epidemiology, Fraser Health has discontinued universal admission screening. Although universal testing increased resource needs, more than half of patients who tested positive during the study period would not have been identified based on screening criteria alone, allowing for implementation of precaution measures to prevent possible transmission. Ultimately, the decision to conduct universal testing must be a balance of the resources required, community prevalence, and patient population.

Background: Some hospitals continue to struggle with nosocomial transmission of Clostridioides difficile infection (CDI) and methicillin-resistant Staphylococcus aureus (MRSA) despite years of infection control efforts. We investigated the relationship between unit infrastructural–organizational risk factors and nosocomial transmission of CDI and MRSA. Methods: This retrospective observational study included 100 eligible acute-care inpatient units from 12 hospitals in British Columbia, Canada, from April 1, 2020, to September 16, 2021. The outcome variables included whether a unit was on the CDI or MRSA vulnerable unit list (ie, defined as having ≥5 CDI cases or ≥6 MRSA cases being attributed to the unit in the last 6 fiscal periods), the average CDI/MRSA rate, as well as the average CDI/MRSA standardized infection ratio (SIR). Independent variables included, but were not limited to, infection control factors (eg hand hygiene rate), infrastructural factors (eg, unit age, total beds on unit), and organizational factors (eg, hallway bed utilization, nursing overtime). Multivariable regression was performed to identify statistically significant risk factors using SAS, R Studio, and Stata software. Results: For CDI, older units were associated with higher odds of being on the CDI vulnerable unit list (aOR, 1.086; 95% CI, 1.024–1.175), higher CDI rate (adjusted relative risk [aRR], 0.012; 95% CI, 0.004–0.020), and higher CDI SIR (aRR, 0.011; 95% CI, 0.003–0.020). Larger unit size was associated with higher odds of being on the CDI vulnerable unit list (aOR, 1.210; 95% CI, 1.095–1.400) and higher CDI SIR (aRR, 0.013; 95% CI, 0.001–0.026). For MRSA, an increase in hand hygiene rate was associated with lower odds of being on the MRSA vulnerable unit list (aOR, 0.71; 95% CI, 0.53–0.897), lower MRSA rate (aRR, −0.035; 95% CI, −0.063 to −0.008), and lower MRSA SIR (aRR, −0.039; 95% CI, −0.069 to −0.008). Higher MRSA bioburden was associated with higher odds of being on the MRSA vulnerable unit list (aOR, >999; 95% CI, >999 to >999), higher MRSA rate (aRR, 9.008; 95% CI, 5.586–12.429), and higher MRSA SIR (aRR, 4.964; 95% CI, 1.971–7.958). Additionally, higher MRSA rates were associated increased utilization of hallway beds (aRR, 0.680; 95% CI, 0.094–1.267), increased nursing overtime rate (aRR, 5.018; 95% CI, 1.210–8.826), and not having a clean supply room with the door consistently closed (aRR, −0.283; 95% CI, −0.536 to −0.03). Conclusions: Several infrastructural and organizational factors were associated with nosocomial transmissions of CDI and MRSA. Further research is needed to investigate the mechanisms by which these factors are associated.

We present James Webb Space Telescope (JWST) Mid-InfraRed Instrument (MIRI) observations of warm CO and H _2 O gas in emission toward the low-mass protostar IRAS 15398-3359, observed as part of the CORINOS program. The CO is detected via the rovibrational fundamental band and hot band near 5 μ m, whereas the H _2 O is detected in the rovibrational bending mode at 6–8 μ m. Rotational analysis indicates that the CO originates in a hot reservoir with an excitation temperature of 1598 ± 118 K, while the water is much cooler at 204 ± 7 K. Neither the CO nor the H _2 O line images are significantly spatially extended, constraining the emission to within ∼40 au of the protostar. The compactness and high temperature of the CO are consistent with an origin in the embedded protostellar disk, or in a compact disk wind. In contrast, the water must arise from a cooler region and requires a larger emitting area (compared to the CO) to produce the observed fluxes. The water may arise from a more extended part of the disk, or from the inner portion of the outflow cavity. Thus, the origin of the molecular emission observed with JWST remains ambiguous. Better constraints on the overall extinction, comparison with realistic disk models, and future kinematically resolved observations may all help to pinpoint the true emitting reservoirs.

Gas-phase abundance ratios between C _2 H _4 O _2 isomers methyl formate (MF), glycolaldehyde (GA), and acetic acid (AA) are typically on the order of 100:10:1 in star-forming regions. However, an unexplained divergence from this neat relationship was recently observed toward a collection of sources in the massive protocluster NGC 6334I; some sources exhibited extreme MF:GA ratios, producing a bimodal behavior between different sources, while the MF:AA ratio remained stable. Here, we use a three-phase gas-grain hot-core chemical model to study the effects of a large parameter space on the simulated C _2 H _4 O _2 abundances. A combination of high gas densities and long timescales during ice-mantle desorption (∼125–160 K) appears to be the physical cause of the high MF:GA ratios. The main chemical mechanism for GA destruction occurring under these conditions is the rapid adsorption and reaction of atomic H with GA on the ice surfaces before it has time to desorb. The different binding energies of MF and GA on water ice are crucial to the selectivity of the surface destruction mechanism; individual MF molecules rapidly escape the surface when exposed by water loss, while GA lingers and is destroyed by H. Moderately elevated cosmic-ray ionization rates can increase absolute levels of “complex organic molecule” (COM) production in the ices and increase the MF:GA ratio, but extreme values are destructive for gas-phase COMs. We speculate that the high densities required for extreme MF:GA ratios could be evidence of COM emission dominated by COMs desorbing within a circumstellar disk.

Abstract Chagas disease vector control relies on prompt, accurate identification of houses infested with triatomine bugs for targeted insecticide spraying. However, most current detection methods are laborious, lack standardization, have substantial operational costs and limited sensitivity, especially when triatomine bug densities are low or highly focal. We evaluated the use of FTA cards or cotton-tipped swabs to develop a low-technology, non-invasive method of detecting environmental DNA (eDNA) from both triatomine bugs and Trypanosoma cruzi for use in household surveillance in eastern Colombia, an endemic region for Chagas disease. Study findings demonstrated that Rhodnius prolixus eDNA, collected on FTA cards, can be detected at temperatures between 21 and 32 °C, when deposited by individual, recently blood-fed nymphs. Additionally, cotton-tipped swabs are a feasible tool for field sampling of both T. cruzi and R. prolixus eDNA in infested households and may be preferable due to their lower cost. eDNA detection should not yet replace current surveillance tools, but instead be evaluated in parallel as a more sensitive, higher-throughput, lower cost alternative. eDNA collection requires virtually no skills or resources in situ and therefore has the potential to be implemented in endemic communities as part of citizen science initiatives to control Chagas disease transmission.

GATA3 has been considered to be primarily associated with CD4+ Th2 cell function. Using CD4+ effector memory that re-express CD45RA (EMRA) T cells the authors show that in response to DNA damage GATA3 can regulate increase of mitochondrial mass and biogenesis involving AMPK.

Since taking up the post of Editor-in-Chief of Tourism and Hospitality in 2020, it has been a real pleasure for me to see the journal grow in so many ways [...]

Background: Many healthcare facilities have faced the decision of conducting point prevalence testing (PPT) of healthcare workers (HCW) during COVID-19 outbreaks. As a containment strategy, PPT can identify asymptomatic or presymptomatic cases for isolation. It is less clear how useful testing asymptomatic HCW is in understanding the spread and possible routes of transmission in an outbreak. This study investigated HCW cases identified through PPT during acute-care outbreaks in Fraser Health (FH), British Columbia, incorporating both epidemiological and whole-genome sequencing (WGS) data to determine their epidemiological source. Methods: This study was a retrospective review of cases associated with COVID-19 acute-care outbreaks in FH occurring between December 2020 and June 2021, when most of these infections were of the alpha and gamma lineages. All patients and HCWs with a positive COVID-19 test and epidemiologically linked to the outbreaks were included in the study. WGS results supported determination of epidemiological source for cases. The proportion of patient and HCW cases related to the outbreak was compared. All analyses were conducted using SAS version 4.3 software with the PROC GLM package. Results: Between December 2020 and June 2021, 49 acute-care COVID-19 outbreaks were declared. Point-prevalence testing of HCWs, in addition to routine patient PPT, was conducted in 28 outbreaks (57%), with 2,167 eligible HCWs (63%) tested. Testing identified 14 previously unknown HCW cases, representing 12.96% of all HCW cases epidemiologically linked to the outbreaks. None of these HCWs were determined to be the index case for their associated outbreak. There was no statistically significant difference between HCWs and patients regarding WGS failure rate, and all failed samples were removed from further analysis. Patients were 3.8 times as likely as HCWs to present as symptomatic when testing positive. HCWs were 2.2 times as likely as patients to have WGS results unrelated to the outbreak. Discussion: Although point-prevalence testing of HCW identified previously unknown cases, these cases were more likely than patients to be unrelated to the outbreak and therefore less useful in understanding the epidemiology of the outbreak. It is difficult to determine whether HCW PPT was effective at preventing transmission, especially with robust infection prevention measures already in place. Patients were more likely than HCWs to present as asymptomatic, however this may be due to the attribution of symptoms to other conditions. Conclusions: Point prevalence testing of HCWs during COVID-19 outbreaks may assist with preventing transmission but is less likely to contribute meaningful information to the investigation.

Background: Transmission of SARS-CoV-2 in acute-care settings affects patients, healthcare workers, and the already-burdened healthcare system. An analysis of risk factors associated with outbreak severity was conducted to inform prevention strategies. Methods: This study was a cross-sectional analysis of COVID-19 outbreaks at Fraser Health (FH) acute-care sites between March 2020 and March 2021. Outbreak severity measures included COVID-19 attack rate, outbreak duration, and 30-day case mortality. Covariates at patient, outbreak, unit level, and facility level were included (Table 1). Generalized linear models with generalized estimation equations were used for all outcome measures, with outbreak duration and 30-day case mortality using multivariate negative binomial distributions, and attack rate using Gaussian distribution. A P value of .05 indicated statistical significance. Analyses

BackgroundTsetse flies (Glossina) transmit Trypanosoma brucei gambiense which causes Gambian human African trypanosomiasis (gHAT) in Central and West Africa. Several countries use Tiny Targets, comprising insecticide-treated panels of material which attract and kill tsetse, as part of their national programmes to eliminate gHAT. We studied how the scale and arrangement of target deployment affected the efficacy of control.Methodology and principal findingsBetween 2012 and 2016, Tiny Targets were deployed biannually along the larger rivers of Arua, Maracha, Koboko and Yumbe districts in North West Uganda with the aim of reducing the abundance of tsetse to interrupt transmission. The extent of these deployments increased from ~250 km2 in 2012 to ~1600 km2 in 2015. The impact of Tiny Targets on tsetse populations was assessed by analysing catches of tsetse from a network of monitoring traps; sub-samples of captured tsetse were dissected to estimate their age and infection status. In addition, the condition of 780 targets (~195/district) was assessed for up to six months after deployment. In each district, mean daily catches of tsetse (G. fuscipes fuscipes) from monitoring traps declined significantly by >80% following the deployment of targets. The reduction was apparent for several kilometres on adjacent lengths of the same river but not in other rivers a kilometre or so away. Expansion of the operational area did not always produce higher levels of suppression or detectable change in the age structure or infection rates of the population, perhaps due to the failure to treat the smaller streams and/or invasion from adjacent untreated areas. The median effective life of a Tiny Target was 61 (41.8-80.2, 95% CI) days.ConclusionsScaling-up of tsetse control reduced the population of tsetse by >80% across the intervention area. Even better control might be achievable by tackling invasion of flies from infested areas within and outside the current intervention area. This might involve deploying more targets, especially along smaller rivers, and extending the effective life of Tiny Targets.

Abstract Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture, and the limited sensitivity of lateral flow tests. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty eight out of thirty nine participants were able to self-collect an adequate sample of capillary blood (≥ 50 µl). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen’s kappa coefficient of > 0.88 (near-perfect agreement, 95% CI 0.738–1.000). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.

We investigated the dynamics of seroconversion in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During March 29–May 22, 2020, we collected serum samples and associated clinical data from 177 persons in London, UK, who had SARS-CoV-2 infection. We measured IgG against SARS-CoV-2 and compared antibody levels with patient outcomes, demographic information, and laboratory characteristics. We found that 2.0%–8.5% of persons did not seroconvert 3–6 weeks after infection. Persons who seroconverted were older, were more likely to have concurrent conditions, and had higher levels of inflammatory markers. Non-White persons had higher antibody concentrations than those who identified as White; these concentrations did not decline during follow-up. Serologic assay results correlated with disease outcome, race, and other risk factors for severe SARS-CoV-2 infection. Serologic assays can be used in surveillance to clarify the duration and protective nature of humoral responses to SARS-CoV-2 infection.

Purpose: To examine outcomes in COVID-19 positive acute care patients and the differential impact of the presence of COVID-19 Variants of Concern (VOCs). Methods & Materials: This study was a cross-sectional analysis using patient data from the patient's electronic medical records. Inclusion criteria were COVID-19-positive patients hospitalized within acute care sites in Fraser Health (British Columbia) between January 1 and April 30, 2021. Data analysis was conducted using SAS Studio 3.8 and STATA 17.0. Results: Of the patients included in the study, 934 (33%) were classified as having a VOC. The proportion of VOC-related COVID-19 cases steadily increased from 0.6% of all COVID-19 admissions in January 2021 to 67.2% in April 2021. Males were more likely to have VOCs than females (36% vs. 30%). The age groups with the highest proportion of VOCs were 40-49 (51%), 50-59 (44%), and 60-69 (40%). After controlling for sex and age, it was shown that patients with VOCs were more than twice as likely to require critical care admission than those without VOCs (OR=2.04, 95%CI:1.67, 2.48; p

Abstract Background Managed alcohol programs are a harm reduction approach for people with severe alcohol use disorder that provide alcohol in a structured setting. We examined the patient experience of receiving alcohol after the implementation of a hospital-based managed alcohol program. Methods Using an interpretative descriptive methodology, we conducted interviews with five patients. The criteria for enrollment included continuation of community managed alcohol program or provision of alcohol for stabilization in hospital and ability to provide consent. Results Five themes emerged in the analysis: (1) Reasons for alcohol use highlighting factors leading to alcohol consumption; (2) I’m very appreciative indicating participant’s perception of hospital-based managed alcohol program; (3) From just vibrating to calm and It’s kinda like a pacifier for me recognizing the impact of hospital-based managed alcohol program on managing withdrawal and on psychological health; (4) I have no need to go anywhere at all demonstrating engagement in healthcare; and (5) Might be nice to have a selection for other people indicating the need for a broader selection of alcohol. Conclusions This study helped to explore the effectiveness of a hospital-based managed alcohol program as experienced by the patients. Overall, participants had a positive experience on hospital-based managed alcohol program. Their perceptions can be used to inform implementation of managed alcohol programs in other hospital settings.

Abstract Persistent insecticides sprayed onto house walls, and incorporated into insecticide‐treated bednets, provide long‐acting, cost‐effective control of vector‐borne diseases such as malaria and leishmaniasis. The high concentrations that occur immediately postdeployment may kill both resistant and susceptible insects. However, insecticide concentration, and therefore killing ability, declines in the months after deployment. As concentrations decline, resistant insects start to survive, while susceptible insects are still killed. The period of time after deployment, within which the mortality of resistant individuals is lower than that of susceptible ones, has been termed the “window of selection” in other contexts. It is recognized as driving resistance in bacteria and malaria parasites, both of which are predominantly haploid. We argue that paying more attention to these mortality differences can help understand the evolution of insecticide resistance. Because insects are diploid, resistance encoded by single genes generates heterozygotes. This gives the potential for a narrower “window of dominance,” within the window of selection, where heterozygote mortality is lower than that of susceptible homozygotes. We explore the general properties of windows of selection and dominance in driving resistance. We quantify their likely effect using data from new laboratory experiments and published data from the laboratory and field. These windows can persist months or years after insecticide deployments. Differential mortalities of resistant, susceptible and heterozygous genotypes, after public health deployments, constitute a major challenge to controlling resistance. Greater attention to mortality differences by genotype would inform strategies to reduce the evolution of resistance to existing and new insecticides.

IntroductionIn December 2019, a novel coronavirus, SARS-CoV-2, was identified. Whilst pregnant women appear to be at risk of severe infection, pre-term birth, and stillbirth, it is unclear whether placental dysfunction is a consistent feature of maternal SARS-CoV-2 infection during pregnancy. We aim to describe the immune response in placentas of women who had COVID-19 infection during pregnancy and investigate whether there are any associated morphological changes.MethodsThe placentas of women testing positive for COVID-19 during their pregnancy were compared to contemporaneous controls who were not known to have had COVID-19 during pregnancy. Samples of each placenta were sent for histopathological analysis or underwent immunohistochemical staining for CD163, CD20, CD3, CD31, and SARS-CoV-2 spike protein. A subset of samples were sent for transmission electron microscopy.ResultsThere was a significant increase in the number of CD163+ macrophages in the Post COVID group (p = 0.0020). There was no difference in the percentage of CD3+, CD20+ cells, but there was an increase in placental vascularity in the Post COVID group compared to controls (p = 0.026).There were no structural differences observed between the samples sent for EM analysis. However, one of the placentas from the Post COVID group was seen to have several large sub-apical vacuoles in the syncytiotrophoblast. We did not observe any virions within the vacuoles and SARS-CoV-2 spike protein staining was negative for the sample. Histopathological investigations indicated that there was no specific placental pathology caused by maternal COVID-19 infection in this cohort of samples.ConclusionsThis study did not confirm previous studies which describe a possible increase in cases of both maternal and fetal vascular malperfusion, and placentitis in women who had COVID-19, which were seen in association with adverse pregnancy outcomes. It remains unclear whether observed abnormalities are caused by maternal infection, or whether maternal infection exacerbates existing placental pathology; understanding why some placentas generate these abnormalities is a key goal.

The origin of complex organic molecules (COMs) in young Class 0 protostars has been one of the major questions in astrochemistry and star formation. While COMs are thought to form on icy dust grains via gas-grain chemistry, observational constraints on their formation pathways have been limited to gas-phase detection. Sensitive mid-infrared spectroscopy with JWST enables unprecedented investigation of COM formation by measuring their ice absorption features. Mid-infrared emission from disks and outflows provide complementary constraints on the protostellar systems. We present an overview of JWST/Mid-Infrared Instrument (MIRI) Medium Resolution Spectroscopy (MRS) and imaging of a young Class 0 protostar, IRAS 15398−3359, and identify several major solid-state absorption features in the 4.9–28 μ m wavelength range. These can be attributed to common ice species, such as H _2 O, CH _3 OH, NH _3 , and CH _4 , and may have contributions from more complex organic species, such as C _2 H _5 OH and CH _3 CHO. In addition to ice features, the MRS spectra show many weaker emission lines at 6–8 μ m, which are due to warm CO gas and water vapor, possibly from a young embedded disk previously unseen. Finally, we detect emission lines from [Fe ii ], [Ne ii ], [S i ], and H _2 , tracing a bipolar jet and outflow cavities. MIRI imaging serendipitously covers the southwestern (blueshifted) outflow lobe of IRAS 15398−3359, showing four shell-like structures similar to the outflows traced by molecular emission at submillimeter wavelengths. This overview analysis highlights the vast potential of JWST/MIRI observations and previews scientific discoveries in the coming years.

The observation and synthesis of organic molecules in interstellar space is one of the most exciting and rapidly growing topics in astrochemistry. Spectroscopic observations especially with millimeter and submillimeter waves have resulted in the detection of more than 250 molecules in the interstellar clouds from which stars and planets are ultimately formed. In this review, we focus on the diverse suggestions made to explain the formation of Complex Organic Molecules (COMs) in the low-temperature interstellar medium. The dominant mechanisms at such low temperatures are still a matter of dispute, with both gas-phase and granular processes, occurring on and in ice mantles, thought to play a role. Granular mechanisms include both diffusive and nondiffusive processes. A granular explanation is strengthened by experiments at 10 K that indicate that the synthesis of large molecules on granular ice mantles under space-like conditions is exceedingly efficient, with and without external radiation. In addition, the bombardment of carbon-containing ice mantles in the laboratory by cosmic rays, which are mainly high-energy protons, can lead to organic species even at low temperatures. For processes on dust grains to be competitive at low temperatures, however, non-thermal desorption mechanisms must be invoked to explain why the organic molecules are detected in the gas phase. Although much remains to be learned, a better understanding of low-temperature organic syntheses in space will add both to our understanding of unusual chemical processes and the role of molecules in stellar evolution.

In this reflective essay we examined the experiences of a group of students from a small liberal arts college in the United States on a study abroad program to the Marshall Islands to intern as preservice teachers in Marshallese schools. Specifically, we examined 32 students’ critical reflections written once they returned from their programs. We interrogated their understanding of themselves regarding their privilege as American students and the inequality between the two nations. Through their teaching of Marshallese students, they deeply questioned the meaning of privilege, culture, identity, and community. We interpreted these experiences through the lens of transformative learning theory and the notion of constructive disequilibrium. When critical-transformative pedagogies inform these experiences, they nudge students out of their comfort zone and offer them opportunities to consider new possibilities that widen their life trajectories and develop global citizenship. We conclude with advocating for the importance of study abroad experiences.

This article explores the problems and potential of funded short-term cross-sector partnerships to address technological deficits in the nonprofit sector by engaging with the partners of a concluded project. The partnership case study that forms the backbone of this article was a three-year nationally funded nonprofit-industry-academic partnership. The ob- jective of the partnership was to increase the data collection capacity of a national nonprofit organization and its affiliate centres through the development of a web-based app. This article highlights the challenges and differing experiences of nonprofit-industry-academic partnerships more generally, and technology-development partnerships more specifically.

Triatomine bugs of the genera Triatoma and Rhodnius are vectors of Chagas disease, a neglected tropical disease of humans in South America caused by Trypanosoma cruzi. Triatoma virus (TrV), a natural pathogen of Triatoma infestans, has been proposed as a possible tool for the bio-control of triatomine bugs, but research into this virus has been hampered by a lack of suitable host cells for in vitro propagation. Here we report establishment and partial characterisation of continuous cell lines from embryos of T. infestans (TIE/LULS54) and Rhodnius prolixus (RPE/LULS53 and RPE/LULS57). RNAseq screening by a sequence-independent, single primer amplification approach confirmed the absence of TrV and other RNA viruses known to infect R. prolixus, indicating that these new cell lines could be used for propagation of TrV.

Mitochondrial health and cellular metabolism can heavily influence the onset of senescence in T cells. CD8+ EMRA T cells exhibit mitochondrial dysfunction and alterations to oxidative phosphorylation, however, the metabolic properties of senescent CD8+ T cells from people living with type 2 diabetes (T2D) are not known. We show here that mitochondria from T2D CD8+ T cells had a higher oxidative capacity together with increased levels of mitochondrial reactive oxgen species (mtROS), compared to age-matched control cells. While fatty acid uptake was increased, fatty acid oxidation was impaired in T2D CD8+ EMRA T cells, which also showed an accumulation of lipid droplets and decreased AMPK activity. Increasing glucose and fatty acids in healthy CD8+ T cells resulted in increased p-p53 expression and a fragmented mitochondrial morphology, similar to that observed in T2D CD8+ EMRA T cells. The resulting mitochondrial changes are likely to have a profound effect on T cell function. Consequently, a better understanding of these metabolic abnormalities is crucial as metabolic manipulation of these cells may restore correct T cell function and help reduce the impact of T cell dysfunction in T2D.

BackgroundIn 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016.MethodsEight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS.ResultsComplete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019.ConclusionThrough effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets.

Abstract Background Psychosocial person-centred interventions are considered best practice for addressing complex behaviours and care needs such as agitation and anxiety, and for improving the quality of life of people with dementia in care homes. Dementia Care Mapping (DCM™) is an established practice development tool and process aimed to help care home staff deliver more person-centred care. To date, few studies have evaluated the efficacy of DCM™ and have found mixed results. These results are suggested to be the outcome of intervention implementation, which may be impacted by a range of factors. This study reports the barriers and facilitators to DCM™ implementation in care homes found during the process evaluation conducted as part of a randomized controlled trial. Methods Eighteen of the 31 DCM™ intervention care homes were recruited to participate in the embedded process evaluation. Semi-structured interviews were conducted with 83 participants, comprising care home managers, trained DCM™ users (mappers), expert external mappers, staff members, relatives, and residents. Results Barriers and facilitators to DCM™ implementation were found at the mapper level (e.g. motivation and confidence), the DCM™ intervention level (e.g. understanding of DCM™) and the care home level (e.g. staffing issues, manager support). Further barriers caused by the burden of trial participation were also identified (e.g. additional paperwork). Conclusions Implementing DCM™ is complex and a greater consideration of potential barriers and facilitators in planning future studies and in practice could help improve implementation. Trial registration Current Controlled Trials ISRCTN82288852, registered 16/01/2014.

The degree of porosity in interstellar dust-grain material is poorly defined, although recent work has suggested that the grains could be highly porous. Aside from influencing the optical properties of the dust, porosity has the potential to affect the chemistry occurring on dust-grain surfaces, via increased surface area, enhanced local binding energies, and the possibility of trapping of molecules within the pores as ice mantles build up on the grains. Through computational kinetics simulations, we investigate how interstellar grain-surface chemistry and ice composition are affected by the porosity of the underlying dust-grain material. Using a simple routine, idealized three-dimensional dust-grains are constructed, atom by atom, with varying degrees of porosity. Diffusive chemistry is then simulated on these surfaces using the off-lattice microscopic Monte Carlo chemical kinetics model, MIMICK, assuming physical conditions appropriate to dark interstellar clouds. On the porous grain surface, the build-up of ice mantles, mostly composed of water, leads to the covering over of the pores, leaving empty pockets. Once the pores are completely covered, the chemical and structural behavior is similar to non-porous grains of the same size. The most prominent chemical effect of the presence of grain porosity is the trapping of molecular hydrogen, formed on the grain surfaces, within the ices and voids inside the grain pores. Trapping of H2 in this way may indicate that other volatiles, such as inert gases not included in these models, could be trapped within dust-grain porous structures when ices begin to form.

Introduction The emergence and rapid spread of COVID-19 have caused widespread and catastrophic public health and economic impact, requiring governments to restrict societal activity to reduce the spread of the disease. The role of household transmission in the population spread of SARS-CoV-2, and of host immunity in limiting transmission, is poorly understood. This paper describes a protocol for a prospective observational study of a cohort of households in Liverpool City Region, UK, which addresses the transmission of SARS-CoV-2 between household members and how immunological response to the infection changes over time.Methods and analysis Households in the Liverpool City Region, in which members have not previously tested positive for SARS-CoV-2 with a nucleic acid amplification test, are followed up for an initial period of 12 weeks. Participants are asked to provide weekly self-throat and nasal swabs and record their activity and presence of symptoms. Incidence of infection and household secondary attack rates of COVID-19 are measured. Transmission of SARS-CoV-2 will be investigated against a range of demographic and behavioural variables. Blood and faecal samples are collected at several time points to evaluate immune responses to SARS-CoV-2 infection and prevalence and risk factors for faecal shedding of SARS-CoV-2, respectively.Ethics and dissemination The study has received approval from the National Health Service Research Ethics Committee; REC Reference: 20/HRA/2297, IRAS Number: 283 464. Results will be disseminated through scientific conferences and peer-reviewed open access publications. A report of the findings will also be shared with participants. The study will quantify the scale and determinants of household transmission of SARS-CoV-2. Additionally, immunological responses before and during the different stages of infection will be analysed, adding to the understanding of the range of immunological response by infection severity.

The study of seabird behaviour has largely relied on animal-borne tags to gather information, requiring interpretation to estimate at-sea behaviours. Details of shallow-diving birds' foraging are less known than deep-diving species due to difficulty in identifying shallow dives from biologging devices. Development of smaller video loggers allow a direct view of these birds' behaviours, at the cost of short battery capacity. However, recordings from video loggers combined with relatively low power usage accelerometers give a means to develop a reliable foraging detection method. Combined video and acceleration loggers were attached to streaked shearwaters in Funakoshi-Ohshima Island (39°24'N,141°59'E) during the breeding season in 2018. Video recordings were classified into behavioural categories (rest, transit, and foraging) and a detection method was generated from the acceleration signals. Two foraging behaviours, surface seizing and foraging dives, are reported with video recordings. Surface seizing was comprised of successive take-offs and landings (mean duration 0.6 and 1.5s, respectively), while foraging dives were shallow subsurface dives (3.2s mean duration) from the air and water surface. Birds were observed foraging close to marine predators, including dolphins and large fish. Results of the behaviour detection method were validated against video recordings, with mean true and false positive rates of 90% and 0%, 79% and 5%, and 66% and

AimTo capture pandemic experiences of people with opioid use disorder (OUD) to better inform the programs that serve them.DesignWe designed, conducted, and analyzed semi-structured qualitative interviews using grounded theory. We conducted interviews until theme saturation was reached and we iteratively developed a codebook of emerging themes. Individuals with lived experience of substance use provided feedback at all steps of the study.SettingWe conducted phone or in-person interviews in compliance with physical distancing and public health regulations in outdoor Vancouver parks or well-ventilated indoor spaces between June to September 2020.ParticipantsUsing purposive sampling, we recruited participants (n = 19) who were individuals with OUD enrolled in an intensive community outreach program, had visited one of two emergency departments, were over 18, lived within catchment, and were not already receiving opioid agonist therapy.MeasurementsWe audio-recorded interviews, which were later transcribed verbatim and checked for accuracy while removing all identifiers. Interviews explored participants' knowledge of COVID-19 and related safety measures, changes to drug use and healthcare services, and community impacts of COVID-19.ResultsOne third of participants were women, approximately two thirds had stable housing, and ages ranged between 23 and 59 years old. Participants were knowledgeable on COVID-19 public health measures. Some participants noted that fear decreased social connection and reluctance to help reverse overdoses; others expressed pride in community cohesion during crisis. Several participants mentioned decreased access to housing, harm reduction, and medical care services. Several participants reported using drugs alone more frequently, consuming different or fewer drugs because of supply shortages, or using more drugs to replace lost activities.ConclusionCOVID-19 had profound effects on the social lives, access to services, and risk-taking behaviour of people with opioid use disorder. Pandemic public health measures must include risk mitigation strategies to maintain access to critical opioid-related services.

Much of the Canadian population reports some level of difficulty in accessing health care services. Despite being a recognized determinant of health, the relationship between access to health care and overall health has not been examined extensively. This study is an analysis of the Canadian Community Health Survey 2016 database. A composite score for difficulty in accessing health care was constructed based on several survey questions. Self-rated health (SRH), the measure of general health status, was compared between individuals with and without difficulty in accessing health care services by estimating prevalence rate ratios adjusting for age, sex, education, income, urban/rural status, race, and Indigenous status. After adjustment for pertinent confounders, difficulty in accessing health care was not statistically significantly associated with SRH. However, in stratified models, difficulty accessing health care was associated with a 12% lower probability of reporting good SRH among non-white individuals. Test of interactions for other social determinants was not significant. For racial minorities, inequalities in access to health care are associated with lower self-rated health. Further research to investigate causes underlying difficulties in accessing health care could lead to public health programs ensuring all Canadians receive equal health care services.

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Human African Trypanosomiasis (HAT) is a potentially fatal parasitic infection caused by the trypanosome sub-species Trypanosoma brucei gambiense and T. b. rhodesiense transmitted by tsetse flies. Currently, global HAT case numbers are reaching less than 1 case per 10,000 people in many disease foci. As such, there is a need for simple screening tools and strategies to replace active screening of the human population which can be maintained post-elimination for Gambian HAT and long-term for Rhodesian HAT. Here, we describe the proof of principle application of a novel high-resolution melt assay for the xenomonitoring of Trypanosoma brucei gambiense and T. b. rhodesiense in tsetse. Both novel and previously described primers which target species-specific single copy genes were used as part of a multiplex qPCR. An additional primer set was included in the multiplex to determine if samples had sufficient genomic material for detecting genes present in low copy number. The assay was evaluated on 96 wild-caught tsetse previously identified to be positive for T. brucei s. l. of which two were known to be positive for T. b. rhodesiense. The assay was found to be highly specific with no cross-reactivity with non-target trypanosome species and the assay limit of detection was 104 tryps/mL. The qPCR successfully identified three T. b. rhodesiense positive flies, in agreement with the reference species-specific PCRs. This assay provides an alternative to running multiple PCRs when screening for pathogenic sub-species of T. brucei s. l. and produces results in less than 2 hours, avoiding gel electrophoresis and subjective analysis. This method could provide a component of a simple and efficient method of screening large numbers of tsetse flies in known HAT foci or in areas at risk of recrudescence or threatened by the changing distribution of both forms of HAT.

Background: The effective management of agitation and other neuropsychiatric and behavioural symptoms in people with dementia is a major challenge, particularly in care home settings, where dementia severity is higher and there is limited training and support for care staff. There is evidence for the value of staff training and the use of psychosocial approaches; however, no intervention currently exists that combines these elements into an intervention that is fit for purpose and effective in these settings based on evidence from a randomised controlled trial. Objective: The objective was to develop and evaluate a complex intervention to improve well-being, reduce antipsychotic use and improve quality of life in people with dementia in care homes through person-centred care, management of agitation and non-drug approaches. Design: This was a 5-year programme that consisted of six work packages. Work package 1 consisted of two systematic reviews of personalised psychosocial interventions for behavioural and psychological symptoms for people with dementia in care homes. Work package 2 consisted of a metasynthesis of studies examining implementation of psychosocial interventions, in addition to developing a draft Well-being and Health for people with Dementia (WHELD) programme. Work package 3 consisted of a factorial study of elements of the draft WHELD programme in 16 care homes. Work package 4 involved optimisation of the WHELD programme based on work package 3 data. Work package 5 involved a multicentre randomised controlled trial in 69 care homes, which evaluated the impact of the optimised WHELD programme on quality of life, agitation and overall neuropsychiatric symptoms in people with dementia. Work package 6 focused on dissemination of the programme. Setting: This programme was carried out in care homes in the UK. Participants: Participants of this programme were people with dementia living in care homes, and the health and care professionals providing treatment and care in these settings. Results: Work package 1: reviews identified randomised controlled trials and qualitative evidence supporting the use of psychosocial approaches to manage behavioural symptoms, but highlighted a concerning lack of evidence-based training manuals in current use. Work package 2: the meta-analysis identified key issues in promoting the use of interventions in care homes. The WHELD programme was developed through adaptation of published approaches. Work package 3: the factorial trial showed that antipsychotic review alone significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval 0.05 to 0.60). Antipsychotic review plus social interaction significantly reduced mortality (odds ratio 0.36, 95% confidence interval 0.23 to 0.57), but this group showed significantly worse outcomes in behavioural and psychological symptoms of dementia than the group receiving neither antipsychotic review nor social interaction (mean difference 7.37 symptoms, 95% confidence interval 1.53 to 13.22 symptoms). This detrimental impact was reduced when combined with social interaction (mean difference –0.44 points, 95% confidence interval –4.39 to 3.52 points), but with no significant benefits for agitation. The exercise intervention significantly improved neuropsychiatric symptoms (mean difference –3.58 symptoms, 95% confidence interval –7.08 to –0.09 symptoms) but not depression (mean difference –1.21 points, 95% confidence interval –4.35 to 1.93 points). Qualitative work with care staff provided additional insights into the acceptability and feasibility of the intervention. Work package 4: optimisation of the WHELD programme led to a final version that combined person-centred care training with social interaction and pleasant activities. The intervention was adapted for delivery through a ‘champion’ model. Work package 5: a large-scale, multicentre randomised controlled trial in 69 care homes showed significant benefit to quality of life, agitation and overall neuropsychiatric symptoms, at reduced overall cost compared with treatment as usual. The intervention conferred a statistically significant improvement in quality of life (Dementia Quality of Life Scale – Proxy z-score of 2.82, mean difference 2.54, standard error of measurement 0.88, 95% confidence interval 0.81 to 4.28, Cohen’s d effect size of 0.24; p = 0.0042). There were also statistically significant benefits in agitation (Cohen-Mansfield Agitation Inventory z-score of 2.68, mean difference –4.27, standard error of measurement 1.59, 95% confidence interval –7.39 to –1.15, Cohen’s d effect size of 0.23; p = 0.0076) and overall neuropsychiatric symptoms (Neuropsychiatric Inventory – Nursing Home version z-score of 3.52, mean difference –4.55, standard error of measurement 1.28, 95% confidence interval –7.07 to –2.02, Cohen’s d of 0.30; p

Background: The quality of care for people with dementia in care homes is of concern. Interventions that can improve care outcomes are required. Objective: To investigate the clinical effectiveness and cost-effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation and improving care outcomes for people living with dementia in care homes, versus usual care. Design: A pragmatic, cluster randomised controlled trial with an open-cohort design, follow-up at 6 and 16 months, integrated cost-effectiveness analysis and process evaluation. Clusters were not blinded to allocation. The primary end point was completed by staff proxy and independent assessors. Setting: Stratified randomisation of 50 care homes to the intervention and control groups on a 3 : 2 ratio by type, size, staff exposure to dementia training and recruiting hub. Participants: Fifty care homes were randomised (intervention, n = 31; control, n = 19), with 726 residents recruited at baseline and a further 261 recruited after 16 months. Care homes were eligible if they recruited a minimum of 10 residents, were not subject to improvement notices, had not used DCM in the previous 18 months and were not participating in conflicting research. Residents were eligible if they lived there permanently, had a formal diagnosis of dementia or a score of 4+ on the Functional Assessment Staging Test of Alzheimer’s Disease, were proficient in English and were not terminally ill or permanently cared for in bed. All homes were audited on the delivery of dementia and person-centred care awareness training. Those not reaching a minimum standard were provided training ahead of randomisation. Eighteen homes took part in the process evaluation. Intervention: Two staff members from each intervention home were trained to use DCM and were asked to carry out three DCM cycles; the first was supported by an external expert. Main outcome measures: The primary outcome was agitation (Cohen-Mansfield Agitation Inventory), measured at 16 months. Secondary outcomes included resident behaviours and quality of life. Results: There were 675 residents in the final analysis (intervention, n = 388; control, n = 287). There was no evidence of a difference in agitation levels between the treatment arms. The adjusted mean difference in Cohen-Mansfield Agitation Inventory score was –2.11 points, being lower in the intervention group than in the control (95% confidence interval –4.66 to 0.44; p = 0.104; adjusted intracluster correlation coefficient: control = 0, intervention = 0.001). The sensitivity analyses results supported the primary analysis. No differences were detected in any of the secondary outcomes. The health economic analyses indicated that DCM was not cost-effective. Intervention adherence was problematic; only 26% of homes completed more than their first DCM cycle. Impacts, barriers to and facilitators of DCM implementation were identified. Limitations: The primary completion of resident outcomes was by staff proxy, owing to self-report difficulties for residents with advanced dementia. Clusters were not blinded to allocation, although supportive analyses suggested that any reporting bias was not clinically important. Conclusions: There was no benefit of DCM over control for any outcomes. The implementation of DCM by care home staff was suboptimal compared with the protocol in the majority of homes. Future work: Alternative models of DCM implementation should be considered that do not rely solely on leadership by care home staff. Trial registration: Current Controlled Trials ISRCTN82288852. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 16. See the NIHR Journals Library website for further project information.

Bats are primary consumers of nocturnal insects, disperse nutrients across landscapes, and are excellent bioindicators of an ecosystem's health, however four of the seventeen Great British species are listed as declining. In this study we aim to investigate the link between bat guano morphology and diet, specifically looking at the ability to predict 1) species, 2) dietary guild, and 3) bat size, using guano morphology alone. Guano from 16 bat species sampled from across Great Britain were analysed to determine various morphological metrics. These data were coupled with diet data obtained by an extensive literature review. It was found that guano morphology overlapped too much to make predictions on the species of bat which deposited the guano, however, in some cases, it could be used to indicate the dietary guild to which the bat belonged. In general, guano morphology seems more correlated to diet than species. This enables the identification of the most important prey taxa within a local environment; a crucial step for informing conservation strategies.

A new, more comprehensive model of gas–grain chemistry in hot molecular cores is presented, in which nondiffusive reaction processes on dust-grain surfaces and in ice mantles are implemented alongside traditional diffusive surface/bulk-ice chemistry. We build on our nondiffusive treatments used for chemistry in cold sources, adopting a standard collapse/warm-up physical model for hot cores. A number of other new chemical model inputs and treatments are also explored in depth, culminating in a final model that demonstrates excellent agreement with gas-phase observational abundances for many molecules, including some (e.g., methoxymethanol) that could not be reproduced by conventional diffusive mechanisms. The observed ratios of structural isomers methyl formate, glycolaldehyde, and acetic acid are well reproduced by the models. The main temperature regimes in which various complex organic molecules (COMs) are formed are identified. Nondiffusive chemistry advances the production of many COMs to much earlier times and lower temperatures than in previous model implementations. Those species may form either as by-products of simple-ice production, or via early photochemistry within the ices while external UV photons can still penetrate. Cosmic ray-induced photochemistry is less important than in past models, although it affects some species strongly over long timescales. Another production regime occurs during the high-temperature desorption of solid water, whereby radicals trapped in the ice are released onto the grain/ice surface, where they rapidly react. Several recently proposed gas-phase COM-production mechanisms are also introduced, but they rarely dominate. New surface/ice reactions involving CH and CH _2 are found to contribute substantially to the formation of certain COMs.

Chemical models and experiments indicate that interstellar dust grains and their ice mantles play an important role in the production of complex organic molecules (COMs). To date, the most complex solid-phase molecule detected with certainty in the interstellar medium is methanol, but the James Webb Space Telescope (JWST) may be able to identify still larger organic species. In this study, we use a coupled chemodynamical model to predict new candidate species for JWST detection toward the young star-forming core Cha-MMS1, combining the gas–grain chemical kinetic code MAGICKAL with a 1D radiative hydrodynamics simulation using Athena++ . With this model, the relative abundances of the main ice constituents with respect to water toward the core center match well with typical observational values, providing a firm basis to explore the ice chemistry. Six oxygen-bearing COMs (ethanol, dimethyl ether, acetaldehyde, methyl formate, methoxy methanol, and acetic acid), as well as formic acid, show abundances as high as, or exceeding, 0.01% with respect to water ice. Based on the modeled ice composition, the infrared spectrum is synthesized to diagnose the detectability of the new ice species. The contribution of COMs to IR absorption bands is minor compared to the main ice constituents, and the identification of COM ice toward the core center of Cha-MMS1 with the JWST NIRCAM/Wide Field Slitless Spectroscopy (2.4–5.0 μ m) may be unlikely. However, MIRI observations (5–28 μ m) toward COM-rich environments where solid-phase COM abundances exceed 1% with respect to the column density of water ice might reveal the distinctive ice features of COMs.

PCR of upper respiratory specimens is the diagnostic standard for severe acute respiratory syndrome coronavirus 2 infection. However, saliva sampling is an easy alternative to nasal and throat swabbing. We found similar viral loads in saliva samples and in nasal and throat swab samples from 110 patients with coronavirus disease.

Background: Few interventions directly compare equivalent calcium and vitamin D from dairy vs. supplements on the same bone outcomes. The radioisotope calcium-41 (41Ca) holds promise as a tracer method to directly measure changes in bone resorption with differing dietary interventions. Objective: Using 41Ca tracer methodology, determine if 4 servings/day of dairy foods results in greater 41Ca retention than an equivalent amount of calcium and vitamin D from supplements. Secondary objective was to evaluate the time course for the change in 41Ca retention. Methods: In this crossover trial, postmenopausal women (n = 12) were dosed orally with 100 nCi of 41Ca and after a 180 day equilibration period received dairy (4 servings/day of milk or yogurt; ~1300 mg calcium, 400 IU cholecalciferol (vitamin D3/day)) or supplement treatments (1200 mg calcium carbonate/day and 400 IU vitamin D3/day) in random order. Treatments lasted 6 weeks separated by a 6 week washout (WO). Calcium was extracted from weekly 24 h urine collections; accelerator mass spectrometry (AMS) was used to determine the 41/40Ca ratio. Primary outcome was change in 41/40Ca excretion. Secondary outcome was the time course for change in 41Ca excretion during intervention and WO periods. Results: The 41/40Ca ratio decreased significantly over time during both treatments; there was no difference between treatments. Both treatments demonstrated a significant retention of 41Ca within 1–2 weeks (p = 0.0007 and p

BackgroundAgitation is a common, challenging symptom affecting large numbers of people with dementia and impacting on quality of life (QoL). There is an urgent need for evidence-based, cost-effective psychosocial interventions to improve these outcomes, particularly in the absence of safe, effective pharmacological therapies. This study aimed to evaluate the efficacy of a person-centred care and psychosocial intervention incorporating an antipsychotic review, WHELD, on QoL, agitation, and antipsychotic use in people with dementia living in nursing homes, and to determine its cost.Methods and findingsThis was a randomised controlled cluster trial conducted between 1 January 2013 and 30 September 2015 that compared the WHELD intervention with treatment as usual (TAU) in people with dementia living in 69 UK nursing homes, using an intention to treat analysis. All nursing homes allocated to the intervention received staff training in person-centred care and social interaction and education regarding antipsychotic medications (antipsychotic review), followed by ongoing delivery through a care staff champion model. The primary outcome measure was QoL (DEMQOL-Proxy). Secondary outcomes were agitation (Cohen-Mansfield Agitation Inventory [CMAI]), neuropsychiatric symptoms (Neuropsychiatric Inventory-Nursing Home Version [NPI-NH]), antipsychotic use, global deterioration (Clinical Dementia Rating), mood (Cornell Scale for Depression in Dementia), unmet needs (Camberwell Assessment of Need for the Elderly), mortality, quality of interactions (Quality of Interactions Scale [QUIS]), pain (Abbey Pain Scale), and cost. Costs were calculated using cost function figures compared with usual costs. In all, 847 people were randomised to WHELD or TAU, of whom 553 completed the 9-month randomised controlled trial. The intervention conferred a statistically significant improvement in QoL (DEMQOL-Proxy Z score 2.82, p = 0.0042; mean difference 2.54, SEM 0.88; 95% CI 0.81, 4.28; Cohen's D effect size 0.24). There were also statistically significant benefits in agitation (CMAI Z score 2.68, p = 0.0076; mean difference 4.27, SEM 1.59; 95% CI -7.39, -1.15; Cohen's D 0.23) and overall neuropsychiatric symptoms (NPI-NH Z score 3.52, p < 0.001; mean difference 4.55, SEM 1.28; 95% CI -7.07,-2.02; Cohen's D 0.30). Benefits were greatest in people with moderately severe dementia. There was a statistically significant benefit in positive care interactions as measured by QUIS (19.7% increase, SEM 8.94; 95% CI 2.12, 37.16, p = 0.03; Cohen's D 0.55). There were no statistically significant differences between WHELD and TAU for the other outcomes. A sensitivity analysis using a pre-specified imputation model confirmed statistically significant benefits in DEMQOL-Proxy, CMAI, and NPI-NH outcomes with the WHELD intervention. Antipsychotic drug use was at a low stable level in both treatment groups, and the intervention did not reduce use. The WHELD intervention reduced cost compared to TAU, and the benefits achieved were therefore associated with a cost saving. The main limitation was that antipsychotic review was based on augmenting processes within care homes to trigger medical review and did not in this study involve proactive primary care education. An additional limitation was the inherent challenge of assessing QoL in this patient group.ConclusionsThese findings suggest that the WHELD intervention confers benefits in terms of QoL, agitation, and neuropsychiatric symptoms, albeit with relatively small effect sizes, as well as cost saving in a model that can readily be implemented in nursing homes. Future work should consider how to facilitate sustainability of the intervention in this setting.Trial registrationISRCTN Registry ISRCTN62237498.

Traditionally, the bioavailability of vitamin B-12 (B12) from in vivo labeled foods was determined by labeling the vitamin with radiocobalt (57Co, 58Co or 60Co). This required use of penetrating radioactivity and sometimes used higher doses of B12 than the physiological limit of B12 absorption. The aim of this study was to determine the bioavailability and absorbed B12 from chicken eggs endogenously labeled with 14C-B12 using accelerator mass spectrometry (AMS). 14C-B12 was injected intramuscularly into hens to produce eggs enriched in vivo with the 14C labeled vitamin. The eggs, which provided 1.4 to 2.6 μg of B12 (~1.1 kBq) per serving, were scrambled, cooked and fed to 10 human volunteers. Baseline and post-ingestion blood, urine and stool samples were collected over a one-week period and assessed for 14C-B12 content using AMS. Bioavailability ranged from 13.2 to 57.7% (mean 30.2 ± 16.4%). Difference among subjects was explained by dose of B12, with percent bioavailability from 2.6 μg only half that from 1.4 μg. The total amount of B12 absorbed was limited to 0.5−0.8 μg (mean 0.55 ± 0.19 μg B12) and was relatively unaffected by the amount consumed. The use of 14C-B12 offers the only currently available method for quantifying B12 absorption in humans, including food cobalamin absorption. An egg is confirmed as a good source of B12, supplying approximately 20% of the average adult daily requirement (RDA for adults = 2.4 μg/day).