Salmonella Persist in Activated Macrophages in T Cell-Sparse Granulomas but Are Contained by Surrounding CXCR3 Ligand-Positioned Th1 Cells.

Salmonella enterica (Se) bacteria cause persistent intracellular infections while stimulating a robust interferon-γ-producing CD4+ T (Th1) cell response. We addressed this paradox of concomitant infection and immunity by tracking fluorescent Se organisms in mice. Se bacteria persisted in nitric oxide synthase (iNOS)-producing resident and recruited macrophages while inducing genes related to protection from nitric oxide. Se-infected cells occupied iNOS+ splenic granulomas that excluded T cells but were surrounded by mononuclear phagocytes producing the chemokines CXCL9 and CXCL10, and Se epitope-specific Th1 cells expressing CXCR3, the receptor for these chemokines. Blockade of CXCR3 inhibited Th1 occupancy of CXCL9/10-dense regions, reduced activation of the Th1 cells, and led to increased Se growth. Thus, intracellular Se bacteria survive in their hosts by counteracting toxic products of the innate immune response and by residing in T cell-sparse granulomas, away from abundant Th1 cells positioned via CXCR3 in a bordering region that act to limit infection.

Surveillance of Naegleria fowleri in Louisiana's public water systems.

The free-living amoeba Naegleria fowleri (Nf) inhabits soil and natural waters worldwide: it is thermophilic and thrives at temperatures up to 45 °C and in a multitude of environments. Three deaths in Louisiana were attributed to primary amoebic meningoencephalitis (PAM) caused by Nf infection in 2011 and 2013. Following these incidents, public water systems are now monitored for the presence of Nf in Louisiana. From 2014 to 2018, 29% (27/93) of samples collected showed positive for Nf and 68% (63/93) showed all thermophilic amoeba culture. Ten raw water sources and 17 distribution water systems tested positive. The year 2017 showed the highest number of samples with Nf (n = 10) followed by nine samples in 2015. As climate change increases surface water temperatures, continued testing for Nf prevalence will be an important facet of water monitoring and will need to extend into locations farther north than the current most common range.

HABs Karenia brevis and Pseudo-nitzschia pre- and post-Hurricane Michael.

Increased occurrences of harmful algal blooms (HAB) in the Gulf of Mexico, and even worldwide, yield concern for increases in brevetoxin exposure leading to respiratory illness or even death, highlighting the need for extensive scientific research and human health monitoring. It is known that major events such as tropical storms and hurricanes are followed by periods of increased red tides caused by HABs; however, the nature by which phytoplankton blooms proliferate following major events remains a topic of great interest and research. The impact of Hurricane Michael on October 10, 2018 on HABs in the Florida panhandle was examined by analyzing data from the Florida Fish and Wildlife Conservation Commission in coordination with Normalized Fluorescence Line Height (nFLH) data from the University of South Florida College of Marine Science. Results presented here demonstrate four phases of HABs during storm events: 1. Pre-storm concentrations, 2. Decreased concentration during the storm, 3. Elevated concentrations following the storm and 4. Recovery period. This time frame can serve to be important in understanding the health dynamics of coastal systems following major storm events.

Genomic erosion in a demographically recovered bird species during conservation rescue.

The pink pigeon (Nesoenas mayeri) is an endemic species of Mauritius that has made a remarkable recovery after a severe population bottleneck in the 1970s to early 1990s. Prior to this bottleneck, an ex situ population was established from which captive-bred individuals were released into free-living subpopulations to increase population size and genetic variation. This conservation rescue led to rapid population recovery to 400-480 individuals, and the species was twice downlisted on the International Union for the Conservation of Nature (IUCN) Red List. We analyzed the impacts of the bottleneck and genetic rescue on neutral genetic variation during and after population recovery (1993-2008) with restriction site-associated sequencing, microsatellite analyses, and quantitative genetic analysis of studbook data of 1112 birds from zoos in Europe and the United States. We used computer simulations to study the predicted changes in genetic variation and population viability from the past into the future. Genetic variation declined rapidly, despite the population rebound, and the effective population size was approximately an order of magnitude smaller than census size. The species carried a high genetic load of circa 15 lethal equivalents for longevity. Our computer simulations predicted continued inbreeding will likely result in increased expression of deleterious mutations (i.e., a high realized load) and severe inbreeding depression. Without continued conservation actions, it is likely that the pink pigeon will go extinct in the wild within 100 years. Conservation rescue of the pink pigeon has been instrumental in the recovery of the free-living population. However, further genetic rescue with captive-bred birds from zoos is required to recover lost variation, reduce expression of harmful deleterious variation, and prevent extinction. The use of genomics and modeling data can inform IUCN assessments of the viability and extinction risk of species, and it helps in assessments of the conservation dependency of populations.

La paloma rosada (Nesoenas mayeri) es una especie endémica de Mauricio que se ha recuperado impresionantemente después de un grave cuello de botella poblacional a principios de la década de 1970 que duró hasta inicios de la década de 1990. Antes de este cuello de botella se había establecido una población ex situ de la cual se liberaban individuos reproducidos en cautiverio a las subpoblaciones en libertad para incrementar la variación genética y el tamaño poblacional. Este rescate de conservación derivó en una recuperación rápida de la población (400-480 individuos) y la especie cambió positivamente de categoría dos veces en la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza (UICN). Analizamos los impactos del cuello de botella y el rescate genético sobre la variación genética neutral durante y después de la recuperación poblacional (de 1993 a 2008) mediante secuenciación RAD, análisis de microsatélites y análisis genéticos cuantitativos de los datos del libro genealógico de 1112 aves ubicadas en zoológicos de Europa y los Estados Unidos. Usamos simulaciones por computadora para estudiar los cambios pronosticados en la variación genética y en la viabilidad poblacional del pasado hacia el futuro. La variación genética declinó rápidamente, a pesar de la recuperación poblacional, y el tamaño efectivo de la población fue aproximadamente un orden de magnitud más pequeño que el tamaño del censo. La especie contó con una carga genética elevada de casi 15 equivalentes letales para la longevidad. Nuestras simulaciones pronostican que la endogamia continua probablemente resultará en un incremento en la expresión de mutaciones deletéreas (es decir, una carga realizada elevada) y en una depresión endogámica severa. Sin acciones continuas para la conservación, es probable que la paloma rosada esté extinta en vida libre dentro de cien años. El rescate de conservación de la paloma rosada ha sido fundamental en la recuperación de la población silvestre; sin embargo, se requiere de un rescate genético adicional con las aves de reproducción en cautiverio de los zoológicos para recuperar la variación perdida, reducir la expresión de la variación deletérea dañina y prevenir la extinción. El uso de la genómica y los datos modelados puede orientar las valoraciones de la UICN sobre la viabilidad y el riesgo de extinción de las especies, además de que ayuda en la evaluación de la dependencia que tienen las poblaciones de la conservación.

1-Propyl-4(5)-Methylimidazole Isomers for Temperature Swing Solvent Extraction.

Temperature swing solvent extraction (TSSE) utilizes an amine solvent with temperature-dependent water solubility to dissolve water at a lower temperature to concentrate or crystallize the brine and the phases are separated. Then, the water in solvent mixture is heated to reduce water solubility and cause phase separation between the solvent and water. The solvent and de-salted water phases are separated, and the regenerated solvent can be recycled. Issues with current TSSE solvents include the high solvent in water solubility and the high solvent volatility. This project used the highly tunable platform molecule imidazole to create two 1-butylimidazole isomers, specifically 1-propyl-4(5)-methylimidazole, to test their effectiveness for TSSE. The imidazoles take in more water than their current state-of-the-art counterparts, but do not desalinate the product water and dissolve in water at higher concentrations. Thus, while imidazoles make intriguing candidates for TSSE, further work is needed to understand how to design imidazoles that will be useful for TSSE applications.

Safety and Feasibility of Rehabilitation Interventions in Children Undergoing Hematopoietic Stem Cell Transplant With Thrombocytopenia.

OBJECTIVE: To analyze the relation between platelet counts, intensities of physical therapy (PT) and occupational therapy (OT) services received, and frequencies of bleeding complications in children undergoing hematopoietic stem cell transplant (HSCT) during a period of severe thrombocytopenia. DESIGN: Retrospective review study. SETTING: Tertiary care hospital. PARTICIPANTS: Children (N=63; age, <18y) hospitalized for HSCT in 2010 and 2011 who received PT and OT services while markedly thrombocytopenic (platelet count, ≤50K/mcL). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Intensities of PT and OT interventions, patients' platelet counts on specific therapy days, and any bleeding events (minor or major) that occurred during or shortly after rehabilitation interventions. RESULTS: Sixty-two patients (accounting for 63 HSCTs) met the criteria for analysis. Fifty-six of these patients (57 HSCTs) underwent PT and/or OT while markedly thrombocytopenic. There was no correlation between platelet counts and intensities of rehabilitation interventions. There were no major bleeding events. There was no association between minor bleeding events and intensities of PT or OT interventions and no association between minor bleeding events and platelet counts. Only 5 minor bleeding events occurred during or after moderate or intensive therapy out of 346 PT and OT sessions (1.5%). CONCLUSIONS: The results of our study suggest that bleeding complications during or after mobilization and supervised exercise during PT and OT in children with severe thrombocytopenia undergoing HSCT are minor and relatively rare. These are encouraging results for both patients and rehabilitation specialists treating this population who is at high risk of developing immobility-related complications.

Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.

Alternatively activated macrophages (AAM) that accumulate during chronic T helper 2 inflammatory conditions may arise through proliferation of resident macrophages or recruitment of monocyte-derived cells. Liver granulomas that form around eggs of the helminth parasite Schistosoma mansoni require AAM to limit tissue damage. Here, we characterized monocyte and macrophage dynamics in the livers of infected CX3CR1(GFP/+) mice. CX3CR1-GFP⁺ monocytes and macrophages accumulated around eggs and in granulomas during infection and upregulated PD-L2 expression, indicating differentiation into AAM. Intravital imaging of CX3CR1-GFP⁺ Ly6C(low) monocytes revealed alterations in patrolling behavior including arrest around eggs that were not encased in granulomas. Differential labeling of CX3CR1-GFP⁺ cells in the blood and the tissue showed CD4⁺ T cell dependent accumulation of PD-L2⁺ CX3CR1-GFP⁺ AAM in the tissues as granulomas form. By adoptive transfer of Ly6C(high) and Ly6C(low) monocytes into infected mice, we found that AAM originate primarily from transferred Ly6C(high) monocytes, but that these cells may transition through a Ly6C(low) state and adopt patrolling behavior in the vasculature. Thus, during chronic helminth infection AAM can arise from recruited Ly6C(high) monocytes via help from CD4⁺ T cells.

Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct.

Macrophages adopt an alternatively activated phenotype (AAMs) when activated by the interleukin-4receptor(R)α. AAMs can be derived either from proliferation of tissue resident macrophages or recruited inflammatory monocytes, but it is not known whether these different sources generate AAMs that are phenotypically and functionally distinct. By transcriptional profiling analysis, we show here that, although both monocyte and tissue-derived AAMs expressed high levels of Arg1, Chi3l3, and Retnla, only monocyte-derived AAMs up-regulated Raldh2 and PD-L2. Monocyte-derived AAMs were also CX3CR1-green fluorescent protein (GFP)(high) and expressed CD206, whereas tissue-derived AAMs were CX3CR1-GFP and CD206 negative. Monocyte-derived AAMs had high levels of aldehyde dehydrogenase activity and promoted the differentiation of FoxP3(+) cells from naïve CD4(+) cells via production of retinoic acid. In contrast, tissue-derived AAMs expressed high levels of uncoupling protein 1. Hence monocyte-derived AAM have properties associated with immune regulation, and the different physiological properties associated with AAM function may depend on the distinct lineage of these cells.

Social Norms for Cannabis Use After Nonmedical Legalization in Canada.

INTRODUCTION: Social norms play an important role in cannabis use; however, there is little evidence on how social norms change in jurisdictions that legalize cannabis. This study examined trends in social norms before and after legalization of nonmedical cannabis in Canada in 2018. METHODS: Data are from the International Cannabis Policy Study, a series of cross-sectional surveys conducted annually with Canadian respondents aged 16-65 years. Analyses were conducted in 2023 and included data from 58,045 respondents across 4 waves: the year immediately before legalization (2018) and 3 post-legalization waves (2019-2021). Regression models examined trends in injunctive norms (perceived approval of cannabis) and comfort in using cannabis in six different social contexts, adjusting for cannabis use frequency, medical authorization, and sociodemographic covariates. RESULTS: Perceived social approval of cannabis use and comfort using cannabis in different social contexts was highest among males, frequent cannabis consumers, and those who reported medical authorization (p<0.05 in all cases). No changes in perceived approval were observed across years, except a temporary decrease in 2020 versus 2018 (OR=0.87, 95% CI=0.80, 0.95). Modest increases in comfort of using cannabis in 6 different social contexts were observed in 2019 (ß=0.10, p=0.001), 2020 (ß=0.10, p=0.001), and 2021 (ß=0.12, p<0.001) versus in 2018. CONCLUSIONS: Social norms have remained relatively stable after nonmedical legalization in Canada, with only modest increases in comfort of using cannabis in different social settings. The findings may reflect widespread cannabis use in Canada prior to nonmedical legalization in 2018 as well as comprehensive restrictions on promotion and advertising.

Criteria for distinguishing heterogeneous from homogeneous conditions for aromatic diisocyanates in water.

Environmental fate and toxicity testing typically requires knowledge of the water solubility of the test substances. Determining the solubility of aromatic diisocyanates in water poses great challenges because of their hydrophobic nature and water-reactivity. The reactive dissolution process is dynamic and the establishment of a steady-state equilibrium cannot readily be observed. In preparation of experimental work, computer simulation was used to derive and evaluate criteria that enable distinguishing homogeneous (i.e., substances would be fully dissolved in water) from heterogeneous (i.e., a separate organic phase would be present) conditions. The simulation utilized available kinetic information and models representing the main physical and chemical processes taking place. It was found that the transition to heterogeneous conditions (i.e., the exceedance of the solubility limit with increasing loading) can be identified by observing either a rapid decline in ultimate yield of the diamine hydrolysis product from near-stoichiometric to much lower values, or a decrease in rate of formation of the diamine hydrolysis product relative to its ultimate yield. The latter criterion is expected to be the more powerful indicator. These criteria can be used in future work to define and interpret an experimental program for determining solubility limits for aromatic diisocyanates or other poorly-soluble, water-reactive substances.

Risk factors for Ascaris lumbricoides infection and its association with nutritional status and IQ in 14-Year old adolescents in Chitwan, Nepal.

Inconsistent results have been obtained from studies investigating the association between soil-transmitted helminths (STHs) and nutritional status and cognitive outcomes. This study aimed to investigate the influence of STHs and nutritional status on the intelligence quotient (IQ) of adolescents in the Chitwan Valley, Nepal. In this birth cohort study from the Chitwan district of Nepal, 74 cohort participants were followed up after 14 years. The presence and egg density of the STHs were investigated following the Kato-Katz method. Full-scale IQ was evaluated using the Wechsler Abbreviated Scale of Intelligence-II (WASI-II). Multivariate regression analysis was also conducted to examine the associations of STHs and nutritional status with IQ scores, adjusting for adverse childhood experiences (ACE) and demographic and socioeconomic factors. The only STHs detected was for Ascaris lumbricoides, which was detected in 16% (12/74) of the study participants. Similarly, 16% (12/73) of participants reported undernutrition (body mass index (BMI) Z score<-2SD), and 33% (25/74) of participants had a developmental deficit (WASI II FSIQ < 69). There were no significant associations between the presence of A. lumbricoides or egg density and IQ scores. However, undernutrition (BMIZ<-2SD) increased the odds of a developmental deficit according to both univariate and adjusted multivariate models [i.e., adjusted odds ratio (aOR) 9.41; 95% CI (2.23 to 39.80)]. While the study primarily examines the association of STHs and nutritional status with IQ, it is important to note that adolescents with educated mothers or higher incomes also showed better cognitive development. The prevalence of undernutrition and associated developmental deficits characterized by an IQ < 69 was alarmingly high in this cohort of adolescents from Chitwan, Nepal. Despite the high prevalence of A. lumbricoides, its infection was not identified as significantly associated with cognition. However, it is noteworthy that a consistent favorable impact of an enriching postnatal environment, approximated by maternal education and family income, may improve neurodevelopmental indicators.

Health-related quality of life in people with different diabetes-related foot ulcer health states: A cross-sectional study of healed, non-infected, infected, hospitalised and amputated ulcer states.

AIMS: Diabetes-related foot ulcers (DFU) are a leading cause of infection, hospitalisation and amputation. However, to our knowledge no studies have compared the health-related quality of life (HRQoL) of people with DFU that were infected, hospitalised or amputated. This study aimed to investigate and compare the HRQoL of different groups of people with healed, non-infected, infected, hospitalised, or amputated DFU. METHODS: This was a multi-centre cross-sectional study measuring the HRQoL of patients, attending one of 18 Diabetic Foot Services across Queensland, Australia, with one of five DFU health states: healed, non-infected, infected, hospitalised, amputated. HRQoL was measured using the EQ-5D-5L to estimate age-sex adjusted utility values. RESULTS: Of 376 included patients (mean age 63 (12) years, 75% male), age-sex adjusted HRQoL utility estimates (95% CIs) were: healed DFU 0.57 (0.51-0.64), non-infected DFU 0.55 (0.49-0.62), infected DFU 0.45 (0.36-0.55), hospitalised DFU 0.53 (0.42-0.64), and amputated DFU 0.55 (0.46-0.63). CONCLUSION: People in any DFU health state have considerably reduced HRQoL, with greatest reductions in those with infected DFU. These findings provide valuable HRQoL estimates and comparisons for several different important DFU health states, adding to our understanding of the impact of DFU on HRQoL and facilitating future economic evaluations.

Implant dynamics, inner structure, and their impact on drug release of in situ forming implants uncovered through CT imaging.

In situ forming implants (ISFIs) composed of biodegradable polymers and biocompatible solvents are generally designed for sustained drug release. In this study, a non-invasive computed tomography (CT) imaging approach is used to achieve real time imaging of ISFIs in vivo and in vitro using leuprolide acetate in situ forming implant as a model drug product. The process of implant formation, inner structure change and their impact on drug release were elucidated. Real-time drug distribution was unveiled by the CT contrast agent, iohexol, where it shows a core-shell structure of the deposition. The incorporation of leuprolide acetate (LA) led to a reduced extent of burst release, prolongated release profile, and extended implant size expansion. LA was found to interact with the solvent and slowed down the polymer phase inversion, thus significantly changed the drug distribution in the implant and reduced the drug release. The implant inner structure identified through SEM, implant size change, and polymer degradation along with the CT real time imaging all consistently support the implant formation differences and their implant on the drug release. Similar patterns of implant size expansion and iohexol distribution in the implants were observed both in vitro and in vivo for the implants with and without LA. The comprehensive understanding of the impact of implant formation on drug release through real time CT imaging facilitates the ISFI product development and evaluation.

Model-Assisted Interpretation of 4,4'-Methylene Dianiline Adsorption on Soils at Micromolar Concentrations.

Adsorption kinetics and isotherms were determined for 4,4'-methylene dianiline (MDA) on five diverse soils at nominal concentrations of 0.01-1.0 mg L-1 (nominal soil loading 0.1-40 µg gs -1 ). The data were used to model the adsorption process based on the two-step mechanism that is characteristic of the adsorption of aromatic amines, consisting of a physical equilibrium between the aqueous phase and the soil organic matter and a chemical reaction between the adsorbed MDA and reactive sites in the soil organic matter. Generic parameters were determined that enabled application of the model to other soils, which was checked against previously published data for MDA adsorption. At the low concentrations evaluated, the adsorption process took place almost exclusively in the organic matter without the need to account for a separate ion exchange process with the soil mineral fraction. Physical adsorption was found to be mainly dependent on the protonation state of MDA and increased with decreasing pH of the soils. Because of the chemical reaction taking place, adsorption equilibrium constants (organic-carbon partition coefficient [KOC ]) normalized to the organic carbon content in the soil gradually increased with time; and it was demonstrated that, at steady-state conditions, values of log KOC > 3.5 can be expected for most any soil at conservatively estimated potential environmental MDA concentrations. Environ Toxicol Chem 2023;42:2580-2588. © 2023 SETAC.

Interventions Targeting Health and Wellbeing among Nail Salon Workers: A Scoping Review.

OBJECTIVES: To identify existing interventions targeting the health and wellbeing of nail salon workers. METHODS: Arksey and O'Malley's framework on reviews guided this project. The databases MEDLINE, EMBASE, Scopus, CINAHL, and Web of Science were searched. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) chart was used to capture the inclusion protocol. RESULTS: Four interventions were identified, of which one was a randomized controlled trial. Across the four interventions, there were about 424 participants that were recruited through cosmetology schools and 34 from nail salons. Interventions varied from pamphlet distribution and inspections to full-day training sessions. Intervention effectiveness was determined via pre- and post-tests and infractions frequency. Maximum follow-up time was 8 months. Outcomes included increased knowledge on exposures, fewer infractions, increased adherence to infection control practices and use of personal protective equipment, and behavior and attitude changes. CONCLUSIONS: There is a need for further research on interventions targeting vulnerable workers in nail salons who face numerous hazards on the job. Two of the four interventions targeted nail technician trainees and their instructors, indicating the potential of early interventions before the workers officially enter the workforce.

Characteristics Associated With Consistent Handwashing and Satisfaction in the Workplace: A Pilot Survey of U.S. Workers.

BACKGROUND: This study seeks to determine what handwashing facilities are available to workers, predominantly in the manufacturing and service industries, to find out if their workplace has the appropriate resources to conduct proper handwashing and how that affects handwashing satisfaction. METHODS: This cross-sectional study surveyed U.S. adult workers (N = 241) on their workplace handwashing equipment and facilities. The associations between demographic characteristics, consistent handwashing, and handwashing satisfaction were evaluated using Fisher's exact test. FINDINGS: Eighty-eight percent of respondents reported consistent handwashing. Pulling a handle to exit the restroom was negatively associated with handwashing satisfaction (p = .004) and having difficulty with an automatic faucet or dispenser was negatively marginally significant in its association with handwashing consistency (p = .10). CONCLUSION/APPLICATIONS TO PRACTICE: Greater understanding of the available equipment in workplace restroom facilities and how to improve selection and use of that equipment may improve workers' handwashing experiences.

The Gold Coast Integrated Care Programme: The Perspectives of Patients, Carers, General Practitioners and Healthcare Staff.

INTRODUCTION: The Australian Gold Coast Integrated Care programme trialled an innovative model of care to proactively manage high risk patients with complex and chronic conditions in collaboration with general practitioners. The objective was to enhance coordination and continuity of care across primary and secondary health services from a single point-of-entry multidisciplinary coordination centre. This case study, embedded in the broader trial, analysed the perceptions of patients, healthcare staff and general practitioners on the adequacy, comprehensiveness, timeliness and acceptability of the new model of care to help inform the decision by the health service whether to adopt it beyond the trial. METHODS: This mixed method embedded, explanatory case study design included surveys of general practice staff and focus groups with patients, carers and coordination centre staff. Qualitative data were thematically analysed and findings merged with survey data in a narrative explanatory case report. DISCUSSION: Staff, patients, general practitioners and practice nurses were generally satisfied with services, coordination of care and information sharing but general practice staff satisfaction ratings declined over time. CONCLUSION: The programme enhanced care and coordination of services and was valued by patients and healthcare providers. Study results provide a rationale for adopting the model for those with chronic and complex conditions.

Effect of Nanopatterning on Concentration Polarization during Nanofiltration.

Membranes used for desalination still face challenges during operation. One of these challenges is the buildup of salt ions at the membrane surface. This is known as concentration polarization, and it has a negative effect on membrane water permeance and salt rejection. In an attempt to decrease concentration polarization, a line-and-groove nanopattern was applied to a nanofiltration (NF) membrane. Aqueous sodium sulfate (Na2SO4) solutions were used to test the rejection and permeance of both pristine and patterned membranes. It was found that the nanopatterns did not reduce but increased the concentration polarization at the membrane surface. Based on these studies, different pattern shapes and sizes should be investigated to gain a fundamental understanding of the influence of pattern size and shape on concentration polarization.

The Cost Consequences of the Gold Coast Integrated Care Programme.

INTRODUCTION: The Australian Gold Coast Integrated Care programme trialled a model of care targeting those with chronic and complex conditions at highest risk of hospitalisation with the goal of producing the best patient outcomes at no additional cost to the healthcare system. This paper reports the economic findings of the trial. METHODS: A pragmatic non-randomised controlled study assessed differences between patients enrolled in the programme (intervention group) and patients who received usual care (control group), in health service utilisation, including Medicare Benefits Schedule and Pharmaceutical Benefits Scheme claims, patient-reported outcome measures, including health-related quality of life, mortality risk, and cost. RESULTS: A total of 1,549 intervention participants were enrolled and matched on the basis of patient level data to 3,042 controls. We found no difference in quality of life between groups, but a greater decrease in capability, social support and satisfaction with care scores and higher hospital service use for the intervention group, leading to a greater cost to the healthcare system of AUD$6,400 per person per year. In addition, the per person per year cost of being in the GCIC programme was AUD$8,700 equating to total healthcare expenditures of AUD$15,100 more for the intervention group than the control group. CONCLUSION: The GCIC programme did not show value for money, incurring additional costs to the health system and demonstrating no significant improvements in health-related quality of life. Because patient recruitment was gradual throughout the trial, we had only one year of complete data for analysis which may be too short a period to determine the true cost-consequences of the program.

Occurrence of SARS-CoV-2 RNA in Six Municipal Wastewater Treatment Plants at the Early Stage of COVID-19 Pandemic in The United States.

In this study, we investigated the occurrence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) RNA in primary influent (n = 42), secondary effluent (n = 24) and tertiary treated effluent (n = 34) collected from six wastewater treatment plants (WWTPs A-F) in Virginia (WWTP A), Florida (WWTPs B, C, and D), and Georgia (WWTPs E and F) in the United States during April-July 2020. Of the 100 wastewater samples analyzed, eight (19%) untreated wastewater samples collected from the primary influents contained SARS-CoV-2 RNA as measured by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assays. SARS-CoV-2 RNA were detected in influent wastewater samples collected from WWTP A (Virginia), WWTPs E and F (Georgia) and WWTP D (Florida). Secondary and tertiary effluent samples were not positive for SARS-CoV-2 RNA indicating the treatment processes in these WWTPs potentially removed SARS-CoV-2 RNA during the secondary and tertiary treatment processes. However, further studies are needed to understand the log removal values (LRVs) and transmission risks of SARS-CoV-2 RNA through analyzing wastewater samples from a wider range of WWTPs.