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With less than half of the worldʼs urban population having safely managed sanitation due to the high cost and difficulty of building sewers and treatment plants, many rely on off-grid options like pit latrines and septic tanks, which are hard to empty and often lead to illegal waste dumping; this research focuses on container-based sanitation (CBS) as an emerging off-grid solution. Off-grid sanitation refers to waste management systems that operate independently of centralized infrastructure and CBS is a service providing toilets that collect human waste in sealable containers, which are regularly emptied and safely disposed of. These data relate to a project investigating CBS in Kenya, Peru, and South Africa, focusing on how different user groups access and utilize sanitation – contrasting CBS with other types. Participants, acting as citizen scientists, collected confidential data through a dedicated smartphone app designed by the authors and external contractors. This project aimed to explore the effective scaling, management, and regulation of off-grid sanitation systems, relevant to academics in urban planning, water and sanitation services, institutional capability, policy and governance, and those addressing inequality and poverty reduction.The 12-month data collection period offered participants small incentives for weekly engagement, in a micro payment for micro tasks approach. Participants were randomly selected, attended a training workshop, and (where needed) were given a smartphone which they could keep at the end of the project. We conducted weekly smartphone surveys in over 300 households across informal settlements. These surveys aimed to understand human-environment interactions by capturing daily life, wellbeing, income, infrastructural service use, and socioeconomic variables at a weekly resolution, contributing to more informed analyses and decision-making.The smartphone-based approach offers efficient, cost-effective, and flexible data collection, enabling extensive geographical coverage, broad subject areas, and frequent engagement. The Open Data Kit (ODK) tools were used to support data collection in the resource-constrained environment with limited or intermittent connectivity.

Summary: Resistance to chemotherapies such as temozolomide is a major hurdle to effectively treat therapy-resistant glioblastoma. This challenge arises from the activation of phosphatidylinositol 3-kinase (PI3K), which makes it an appealing therapeutic target. However, non-selectively blocking PI3K kinases PI3Kα/β/δ/γ has yielded undesired clinical outcomes. It is, therefore, imperative to investigate individual kinases in glioblastoma’s chemosensitivity. Here, we report that PI3K kinases were unequally expressed in glioblastoma, with levels of PI3Kβ being the highest. Patients deficient of O6-methylguanine-DNA-methyltransferase (MGMT) and expressing elevated levels of PI3Kβ, defined as MGMT-deficient/PI3Kβ-high, were less responsive to temozolomide and experienced poor prognosis. Consistently, MGMT-deficient/PI3Kβ-high glioblastoma cells were resistant to temozolomide. Perturbation of PI3Kβ, but not other kinases, sensitized MGMT-deficient/PI3Kβ-high glioblastoma cells or tumors to temozolomide. Moreover, PI3Kβ-selective inhibitors and temozolomide synergistically mitigated the growth of glioblastoma stem cells. Our results have demonstrated an essential role of PI3Kβ in chemoresistance, making PI3Kβ-selective blockade an effective chemosensitizer for glioblastoma.

A study was implemented to determine whether stormwater from Oscar 1 Pier outfall is a contributing source of polychlorinated biphenyls (PCBs) to Decision Unit (DU) N-2, Pearl Harbor Sediment Site, Honolulu, Hawaii USA. Results suggested that PCBs were discharged from the outfall, remained in suspension, and dispersed elsewhere before settling. Stormwater PCBs were characterized by heavier congeners, likely associated with particles. Surface water PCB samples collected throughout DU N-2 exhibited heavier congeners and lighter congeners that are typically associated with the dissolved phase. These lighter congeners could have originated from a different source(s) and/or partitioned from the suspended phase.

We propose a new gauge prepotential ϒi describing the four-dimensional N=2 superconformal gravitino multiplet. The former naturally arises via a superspace reduction of the N=3 conformal supergravity multiplet. A locally superconformal chiral action for ϒi, which is gauge-invariant in arbitrary conformally flat backgrounds, is derived. This construction readily yields a new superprojector, which maps an isospinor superfield Ψi to a multiplet characterised by the properties of a conformal supercurrent associated with ϒi. Our main results are also specialised to N=2 anti-de Sitter superspace.

ABSTRACT: Background: Naproxen is an established, effective treatment for pain management in acute musculoskeletal disorders and traumatic sports injuries. Reckitt Benckiser Health Limited have developed a naproxen sodium tablet with the same pharmacokinetic and pharmacodynamic properties as existing marketed naproxen products with the intention of increasing the number of naproxen products available for prescribers and pharmacies. Objective: This study aimed to assess comparative bioavailability between a test medicinal product developed by Reckitt Benckiser Health Limited (RB, 103-105 Bath Rd, Slough, SL1 3UH, United Kingdom; RB naproxen sodium 220 mg tablets), and a reference medicinal product, Aleve naproxen sodium 220 mg (Bayer B.V., Energieweg 1, 3641 RT Mijdrecht, Netherlands), in the fasted state. Methods: This was a randomized, single-dose, 2-way crossover, open-label, comparative bioavailability, pharmacokinetic study in 18 healthy male and female volunteers with a 5- to 8-day washout permitted between doses (based on the anticipated minimum washout period for naproxen determined from the known terminal elimination half-life of up to 17 hours). Blood samples were taken periodically over a 72-hour period following dosing and analyzed for plasma naproxen concentration using a validated LC-MS method. Noncompartmental pharmacokinetic analysis was used to derive pharmacokinetic parameters for naproxen; safety and tolerability were evaluated throughout the study. Results: Following a single-dose administration of naproxen sodium tablets (2 × 220 mg), the Cmax and AUC0–t (geometric least squares mean) for the test product was 65.88 µg/mL and 893.37 h * µg/mL, respectively; and for the reference product was 64.59 µg/mL and 890.60 h * µg/mL. The geometric least squares mean test/reference ratio 90% CI for both Cmax (93.98–110.70) and AUC0–t (98.04–102.63) was contained entirely within the predefined 80.00% to 125.00% lower and upper limits; additionally, there was no statistically significant difference in Tmax (P = 0.9878) following fasted administration of the test and reference product. There was 1 treatment-emergent adverse event reported during the study; there were no serious adverse events, no suspected unexpected serious adverse events, and no clinically significant changes in laboratory safety, vital signs, or 12-lead ECG measurements reported. Conclusions: This single-dose study found that the test product (RB naproxen sodium tablets) and reference product (Aleve naproxen sodium tablets) met the regulatory criteria for bioequivalence in these fasted male and female volunteers; both test and reference products were found to be safe and well tolerated. Key words: Anti-inflammatory drug, Bioequivalence, Naproxen, Nonsteroidal, Pain management, Classification: pharmacokinetics, pain management

Available point mutation tests have shown inconsistent results with various acrylates. Most of those tests were performed prior to OECD guidelines and appropriate data regarding cytotoxicity are not given. Data from three current OECD guideline compliant experiments conducted under GLP are provided. They include (a) an in vitro mouse lymphoma (TK+/−) assay (OECD 490) [3], (b) an in vitro HPRT locus gene mutation assay utilizing cultures of Chinese hamster V79 cells (OECD 476) [1], and (c) an in vitro micronucleus test in human lymphocytes (OECD 487) [2]. Test materials were not mutagenic under these experimental conditions, adding to the weight-of-evidence of non-genotoxicity for this group of chemicals.

Summary: The induction and maintenance of T cell memory is critical to the success of vaccines. A recently described subset of memory CD8+ T cells defined by intermediate expression of the chemokine receptor CX3CR1 was shown to have self-renewal, proliferative, and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells when memory is sustained at high levels: memory inflation induced by cytomegalovirus (CMV) and adenovirus-vectored vaccines. In mice, both CMV and vaccine-induced inflationary T cells showed sustained high levels of CX3R1int cells exhibiting an effector-memory phenotype, characteristic of inflationary pools, in early memory. In humans, CX3CR1int CD8+ T cells were strongly induced following adenovirus-vectored vaccination for hepatitis C virus (HCV) (ChAd3-NSmut) and during natural CMV infection and were associated with a memory phenotype similar to that in mice. These data indicate that CX3CR1int cells form an important component of the memory pool in response to persistent viruses and vaccines in both mice and humans. : Gordon et al. demonstrate that CX3CR1int peripheral memory T cells are a substantial component of memory inflation induced by persistent CMVs and adenoviral vaccination. They are characterized by sustained proliferation and an effector-memory phenotype linked to these expanded CD8+ T cell memory responses. Core phenotypic features are shared by humans and mice. Keywords: cytomegalovirus, T cells, memory, adenovirus, vaccination, CX3CR1, memory inflation, mouse, human

Purpose: To establish a relationship between the diameter and depth position of vessels in the superior and inferior corneo-scleral limbus using ultra-high resolution optical coherence tomography (UHR-OCT). Methods: Volumetric OCT images of the superior and inferior limbus were acquired from 14 healthy subjects with a research-grade UHR-OCT system. Differences in vessel diameter and depth between superior and inferior limbus were analyzed using repeated measured ANOVA in SPSS and R. Results: The mean (± SD) superior and inferior diameters were 29 ± 18 μm and 24 ± 18 μm respectively, and the mean (± SD) superior and inferior depths were 177 ± 109 μm and 207 ± 132 μm respectively. The superior limbal vessels were larger than the inferior ones (RM-ANOVA, p = 0.004), and the inferior limbal vessels were deeper than the superior vessels (RM-ANOVA, p = 0.041). There was a positive linear association between limbal vessel depth and size within the superior and inferior limbus with Pearson correlation coefficients of 0.803 and 0.754, respectively. Conclusion: This study demonstrated that the UHR-OCT was capable of imaging morphometric characteristics such as the size and depth of vessels in the limbus. The results of this study suggest a difference in the size and depth of vessels across different positions of the limbus, which may be indicative of adaptations to chronic hypoxia caused by the covering of the superior limbus by the upper eyelid. UHR-OCT may be a useful tool to evaluate the effect of contact lenses on the microvascular properties within the limbus.

Background Our knowledge of allergen structure and function continues to rise and new scientific data on the homology and cross-reactivity of allergen sources should be considered to extend the work of Lorenz et al., 2009 (Int Arch Allergy Immunol. 148(1):1–1, 2009) and the concept of homologous groups. In addition to this, sophisticated techniques such as mass spectrometry (MS) are increasingly utilised to better characterise the complex mix and nature of allergen extracts.Methods Homology models were used of Fag s 1 (Beech) and Cyn d 1 (Bermuda grass) and compared with template crystal structures of Bet v 1 and Phl p 1 from the ‘exemplar’ species of Birch and Timothy grass, respectively. ELISA experiments were performed to assess cross-reactivity of Beech (tree) and Bermuda (grass) extracts to rabbit sera raised to either “3-Tree” (Birch, Alder and Hazel) extract or “Grass” (12-grass mix extract), respectively. The comparability of biochemical stability of different allergen sources was assessed through statistical methods for a range of tree and grass species.Results Allergen cross-reactivity and/or structural homology have been described providing justification for inclusion of Beech within the Birch homologous tree group. Data from Bermuda grass (Cyn d 1) provides further justification for the inclusion of this species into the homologous group of the sweet grasses. However, further characterisation of relevant allergens from Bermuda grass and, in particular, comparison of cross-reactive patterns between subjects specifically in areas with high abundance of both Pooideae and Chloridoideae is sought.Conclusion MS allows the possibility to identify individual proteins or allergens from complex mixes by mass and/or sequence, and this has been extensively applied to the allergen field. New data on the homology, cross-reactivity and biological parameters of allergen sources have been considered to extend the work of Lorenz et al., 2009 in the context of tree and grass species. The concept of homologous groups is certainly dynamic allowing the flexibility and potential in streamlining quality parameters, such as stability profiles, due to extrapolation of exemplar data to a wider range of allergens. Keywords: Homology, Allergens, Grass, Tree, Structure, Cross-reactivity

Background: Most patients with SARS-CoV-2 are non-infectious within 2 weeks, though viral RNA may remain detectable for weeks. However there are reports of persistent SARS-CoV-2 infection, with viable virus and ongoing infectivity months after initial detection. Beyond individuals, viral evolution during persistent infections may be accelerated, driving emergence of mutations associated with viral variants of concern. These patients often do not meet inclusion criteria for clinical trials, meaning clinical and virologic characteristics, and optimal management strategies are poorly evidence-based. Methods: We analysed cases of SARS-CoV-2 infection from a regional testing laboratory in South-West England between March 2020 and December 2021, with at least two SARS-CoV-2 positive samples separated by ≥ 56 days were identified. Excluding those with confirmed or likely re-infection, we identified patients with persistent infection, characterised by an ongoing clinical syndrome consistent with COVID-19 alongside monophyletic viral lineage of SARS-CoV-2. We examined clinical and virologic characteristics, treatment, and outcome. We further performed a literature review investigating cases of persistent SARS-CoV-2 infection, reviewing patient characteristics and treatment. Results: We identified six patients with persistent SARS-CoV-2 infection. All were hypogammaglobulinaemic and had underlying haematological malignancy, with four having received B-cell depleting therapy. Evidence of viral evolution, including accrual of mutations associated with variants of concern, was demonstrated in five cases. Four patients ultimately cleared SARS-CoV-2. In two patients, clearance followed treatment with casirivimab/imdevimab. Both survived beyond thirty days following viral clearance, having experienced infections of 305- and 269-days duration respectively, after failed attempts at clearance with alternative therapies. We found 60 cases of confirmed persistent infection in the literature, with a further 31 probable cases. Of those, 80% of patients treated with monoclonal antibodies cleared SARS-CoV-2, and none died. Conclusion: Haematological malignancy and patients receiving B-cell depleting therapies represent key groups at risk of persistent SARS-CoV-2 infection. Throughout persistent infection, SARS-CoV-2 can evolve rapidly, giving rise to significant mutations, including those implicated in variants of concern. Monoclonal antibodies appear to be a promising therapeutic option, potentially in combination with antivirals, crucial for individuals, and for public health.

Treatment and subsequent re-use of wastewater from shale gas extraction is a feasible strategy to ensure sustainability and reduce the environmental impact of the process. Here we demonstrate the photocatalytic benefits of improved three-dimensional graphitic carbon nitride (3D g-C3N4) during the degradation of organic contaminants. We show that precursor ratio (melamine to cyanuric acid) affects both the properties of 3D g-C3N4 as well as catalytic performance. When optimized, 3D g-C3N4 displayed the highest organics removal rate in brine-free solutions, achieving 99% conversion within 240 min. Significantly, the 3D g-C3N4 materials improved photocatalytic activity even in simulated shale gas brine solutions.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic in 2020, high rates of acute kidney injury (AKI) in critically unwell patients are being reported, leading to an increased demand for renal replacement therapy (RRT). Providing RRT for this large number of patients is proving challenging, and so alternatives to continuous renal replacement therapies (CRRT) in the intensive care unit (ICU) are needed. Peritoneal dialysis (PD) can be initiated immediately after percutaneous insertion of the catheter, but there are concerns about impact on ventilation and RRT efficacy. We sought to describe our recent experience with percutaneous catheter insertion and peritoneal dialysis in patients in the ICU with COVID-19 infection. Method: Patients were selected according to local protocol, and catheters were inserted percutaneously by experienced operators using a Seldinger technique. Sequential Organ Failure Assessment (SOFA) score and ventilation requirements were recorded at the time of insertion and 24 hours later. Procedural complications, proportion of RRT provided by PD, renal recovery, and RRT parameters (serum potassium and maximum base excess) during PD were assessed. Results: Percutaneous PD catheters were successfully inserted in 37 of 44 patients (84.1%) after a median of 13.5 days (interquartile range [IQR] = 10.0, 20.3 days) in the ICU. No adverse events were reported; SOFA scores and ventilation requirements were comparable before and after insertion; and adequate RRT parameters were achieved. The median proportion of RRT provided by PD following catheter insertion was 94.6% (IQR = 75.0, 100%). Conclusion: Peritoneal dialysis provides a safe and effective alternative to CRRT in selected patients with AKI and COVID-19 infection requiring ventilation on intensive care.

Cu-ZrO2 is demonstrated to be a highly effective catalyst for the transfer hydrogenation of methyl levulinate to γ-valerolactone, using methanol as the hydrogen donor. The emergence of several new strategies for synthesising green methanol, underlines its potential as a sustainable hydrogen source for such transformations. Transfer hydrogenation of methyl levulinate over Cu-ZrO2 was determined to proceed through a two-step ‘hydrogen borrowing’ process. The first step involves methanol dehydrogenation (rate limiting) and the second, levulinate reduction. This proof-of-concept study demonstrates that methanol can be used effectively as a hydrogen source for such transformations when a suitable catalyst is employed.

The oxidative dehydrogenation of propane to propene using carbon dioxide is an attractive novel synthesis route to produce a key platform chemical. We investigated iron-chromia catalysts prepared by sol-gel. The mixed oxides showed improved specific surface area and a high concentration of acid and base sites and were found to be highly active catalysts. Although coking was observed over the catalysts, oxidative regeneration restored the majority of the initial activity over 5 consecutive cycles. The initial space time yield was amongst the most active Cr-based catalysts in the literature.

The direct synthesis of hydrogen peroxide from molecular H2 and O2 offers an attractive alternative to the current means of production of this powerful oxidant, on an industrial scale. Herein we investigate the role of nitric acid addition, during catalyst preparation as a means of improving catalytic performance, under reaction conditions that have previously been found to be optimal for H2O2 production. The addition of dilute nitric acid during catalyst preparation is found to lead to a significant improvement in H2O2 synthesis activity, through the modification of particle size and control of Pd oxidation state.

Background: Parenting interventions and conditional cash transfer (CCT) programmes are promising strategies to reduce the risk of violence against children, but evidence of the effectiveness of combining such programmes is lacking for families in low- and middle-income countries with children over two years of age. This study examined the effectiveness of a locally adapted parenting programme delivered as part of a government CCT system to low-income families with children aged two to six years in Metro Manila, Philippines. Methods: Participants were randomly assigned (1:1) to either a 12-session group-based parenting programme or treatment-as-usual services (N = 120). Participation in either service was required among the conditions for receiving cash grants. Baseline assessments were conducted in July 2017 with one-month post-intervention assessments in January-February 2018 and 12-month follow-up in January-February 2019. All assessments were parent-report (ClinicalTrials.gov: NCT03205449). Findings: One-month post-intervention assessments indicated moderate intervention effects for primary outcomes of reduced overall child maltreatment (d = -0.50 [-0.86, -0.13]), emotional abuse (d = -0.59 [-0.95; -0.22]), physical abuse (IRR = 0.51 [0.27; 0.74]), and neglect (IRR = 0.52 [0.18; 0.85]). There were also significant effects for reduced dysfunctional parenting, child behaviour problems, and intimate partner violence, and increased parental efficacy and positive parenting. Reduced overall maltreatment, emotional abuse, and neglect effects were sustained at one-year follow-up. Interpretation: Findings suggest that a culturally adapted parenting intervention delivered as part of a CCT programme may be effective in sustaining reductions in violence against children in low- and middle-income countries. Funding: This research was supported by UBS Optimus Foundation and UNICEF Philippines, and by the Complexity and Relationships in Health Improvement Programmes of the Medical Research Council MRC UK and Chief Scientist Office (Grant: MC_UU_00022/1 and CSO SPHSU16, MC_UU_00022/3 and CSO SPHSU18).

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Summary: In rodents, lower brown adipose tissue (BAT) activity is associated with greater liver steatosis and changes in the gut microbiome. However, little is known about these relationships in humans. In adults (n = 60), we assessed hepatic fat and cold-stimulated BAT activity using magnetic resonance imaging and the gut microbiota with 16S sequencing. We transplanted gnotobiotic mice with feces from humans to assess the transferability of BAT activity through the microbiota. Individuals with NAFLD (n = 29) have lower BAT activity than those without, and BAT activity is inversely related to hepatic fat content. BAT activity is not related to the characteristics of the fecal microbiota and is not transmissible through fecal transplantation to mice. Thus, low BAT activity is associated with higher hepatic fat accumulation in human adults, but this does not appear to have been mediated through the gut microbiota.

Summary: We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.

Summary: Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.

Improved animal health can reduce greenhouse gas (GHG) emissions intensity in livestock systems while increasing productivity. Integrated modelling of disease impacts on farm-scale emissions is important in identifying effective health strategies to reduce emissions. However, it requires that modellers understand the pathways linking animal health to emissions and how these might be incorporated into models. A key barrier to meeting this need has been the lack of a framework to facilitate effective exchange of knowledge and data between animal health experts and emissions modellers. Here, these two communities engaged in workshops, online exchanges and a survey to i) identify a comprehensive list of disease-related model parameters and ii) test its application to evaluating models. Fifty-six parameters were identified and proved effective in assessing the potential of farm-scale models to characterise livestock disease impacts on GHG emissions. Easy wins for the emissions models surveyed include characterising disease impacts related to feeding.

The European Union Effort Sharing Regulation (ESR) will require a 30% reduction in greenhouse gas (GHG) emissions by 2030 compared with 2005 from the sectors not included in the European Emissions Trading Scheme, including agriculture. This will require the estimation of current and future emissions from agriculture, including dairy cattle production systems. Using a farm-scale model as part of a Tier 3 method for farm to national scales provides a more holistic and informative approach than IPCC (2006) Tier 2 but requires independent quality control. Comparing the results of using models to simulate a range of scenarios that explore an appropriate range of biophysical and management situations can support this process by providing a framework for placing model results in context. To assess the variation between models and the process of understanding differences, estimates of GHG emissions from four farm-scale models (DairyWise, FarmAC, HolosNor and SFARMMOD) were calculated for eight dairy farming scenarios within a factorial design consisting of two climates (cool/dry and warm/wet)×two soil types (sandy and clayey)×two feeding systems (grass only and grass/maize). The milk yield per cow, follower:cow ratio, manure management system, nitrogen (N) fertilisation and land area were standardised for all scenarios in order to associate the differences in the results with the model structure and function. Potential yield and application of available N in fertiliser and manure were specified separately for grass and maize. Significant differences between models were found in GHG emissions at the farm-scale and for most contributory sources, although there was no difference in the ranking of source magnitudes. The farm-scale GHG emissions, averaged over the four models, was 10.6 t carbon dioxide equivalents (CO2e)/ha per year, with a range of 1.9 t CO2e/ha per year. Even though key production characteristics were specified in the scenarios, there were still significant differences between models in the annual milk production per ha and the amounts of N fertiliser and concentrate feed imported. This was because the models differed in their description of biophysical responses and feedback mechanisms, and in the extent to which management functions were internalised. We conclude that comparing the results of different farm-scale models when applied to a range of scenarios would build confidence in their use in achieving ESR targets, justifying further investment in the development of a wider range of scenarios and software tools.

Addressing the lack of sanitation globally is a major global challenge with 700 million people still practicing open defecation. Circular Economy (CE) in the context of sanitation focuses on the whole sanitation chain which includes the provision of toilets, the collection of waste, treatment and transformation into sanitation-derived products including fertiliser, fuel and clean water. After a qualitative study from five case studies across India, covering different treatment technologies, waste-derived products, markets and contexts; this research identifies the main barriers and enablers for circular sanitation business models to succeed. A framework assessing the technical and social system changes required to enable circular sanitation models was derived from the case studies. Some of these changes can be achieved with increased enforcement, policies and subsidies for fertilisers, and integration of sanitation with other waste streams to increase its viability. Major changes such as the cultural norms around re-use, demographic shifts and soil depletion would be outside the scope of a single project, policy or planning initiative. The move to CE sanitation may still be desirable from a policy perspective but we argue that shifting to CE models should not be seen as a panacea that can solve the global sanitation crisis. Delivering the public good of safe sanitation services for all, whether circular or not, will continue to be a difficult task., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

While introduced marine species have been arriving in Australia for centuries, it was the advent of container shipping and the discharge of ballast water into Australian ports that highlighted the problem. A summary is provided of how Australia responded to this challenge and continues to. More recently there has been an acceptance that hull fouling is also an important vector of introductions. A major problem in Australia is distinguishing introduced species from as yet undescribed native species. This is a particular problem in northern Australia where the native fauna is poorly documented. Despite the economic and environmental threats posed by introduced species, the impetus to undertake expensive comprehensive surveys has declined and attention is now focusing on targeted surveys especially of known marine pest species and molecular data to identify introductions. Ongoing research is still needed to monitor other species identified as being introduced and their potential to become pests., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

The components of bioerosion were investigated during ENCORE (The Effect of Nutrient Enrichment on Coral Reefs) over 2years of controlled additions of dissolved inorganic nitrogen and phosphorus. The study was carried out at One Tree Island, southern Great Barrier Reef, Australia. Rates of microbioerosion and external erosion by grazing were significantly higher at the enriched sites than at the control sites. Rates of accretion by coralline algae were also significantly higher at enriched sites. In contrast, rates of macroboring were not significantly different between enriched and control sites. This study highlights the importance of improving water quality on the reef to reduce rates of bioerosion given that quantities of dead coral substrates have recently substantially increased as a result of coral bleaching (Hughes et al., 2015) and several Crown of Thorns plagues (Fabricius et al., 2010; De'ath et al., 2012), on the Great Barrier Reef., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Monitoring surveys are an important tool for detecting new arrivals of exotic species, for documenting patterns of invasion, and exotic species impacts. Faced with time and cost constraints, these surveys are increasingly focused on lists of target pest species, identified as being most likely to arrive and cause significant harm. We used the national survey of Australian international ports for introduced marine pests as a case study to assess: (1) the taxonomic rigor of surveys focused on detection of target species; and (2) how the ability of port surveys to inform invasion patterns is dependent on taxonomic approach. Our analysis of the 46 available reports revealed common sub-optimal taxonomic practices that compromised their utility to identify abiotic conditions that are good predictors of biological invasion. Thus, although surveys for target species may provide information on the distribution of a handful of species, they may fail to do much else., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

In recent years, several sets of legislation worldwide (Oceans Act in USA, Australia or Canada; Water Framework Directive or Marine Strategy in Europe, National Water Act in South Africa, etc.) have been developed in order to address ecological quality or integrity, within estuarine and coastal systems. Most such legislation seeks to define quality in an integrative way, by using several biological elements, together with physico-chemical and pollution elements. Such an approach allows assessment of ecological status at the ecosystem level ('ecosystem approach' or 'holistic approach' methodologies), rather than at species level (e.g. mussel biomonitoring or Mussel Watch) or just at chemical level (i.e. quality objectives) alone. Increasing attention has been paid to the development of tools for different physico-chemical or biological (phytoplankton, zooplankton, benthos, algae, phanerogams, fishes) elements of the ecosystems. However, few methodologies integrate all the elements into a single evaluation of a water body. The need for such integrative tools to assess ecosystem quality is very important, both from a scientific and stakeholder point of view. Politicians and managers need information from simple and pragmatic, but scientifically sound methodologies, in order to show to society the evolution of a zone (estuary, coastal area, etc.), taking into account human pressures or recovery processes. These approaches include: (i) multidisciplinarity, inherent in the teams involved in their implementation; (ii) integration of biotic and abiotic factors; (iii) accurate and validated methods in determining ecological integrity; and (iv) adequate indicators to follow the evolution of the monitored ecosystems. While some countries increasingly use the establishment of marine parks to conserve marine biodiversity and ecological integrity, there is awareness (e.g. in Australia) that conservation and management of marine ecosystems cannot be restricted to Marine Protected Areas but must include areas outside such reserves. This contribution reviews the current situation of integrative ecological assessment worldwide, by presenting several examples from each of the continents: Africa, Asia, Australia, Europe and North America.

The long-term effects of marine aggregate dredging on near-shore benthic assemblages are still largely unknown, despite a global increase in demand for, and extraction of, marine aggregates. This study assessed the state of recovery of polychaete assemblages in Botany Bay, temperate NSW, Australia, at sites dredged for aggregate material more than 10 years previously. Sedimentary and faunal samples were collected from impact sites in Botany Bay, and from reference sites in nearby Pittwater estuary. This study was based on, and included data from, a study conducted by the Australian Museum at the same sites in the 2 years following cessation of dredging. Abundance, species richness and evenness of polychaetes, as well as overall polychaete assemblage structure, were compared between localities over time.

Annually large volumes of fresh water laden with sediment are washed down the Daintree River in North Queensland into the Great Barrier Reef lagoon. To investigate the effects of land runoff on bioerosion, samples of recently killed colonies of Porites were laid at 6 sites on a cross shelf transect from Snapper Island at the entrance to the river to Osprey Reef, approximately 328 km from the river mouth out in the Coral Sea. Rates and agents of bioerosion were determined over 4 years and inshore sites exhibited significantly lower rates of total bioerosion than the other sites. Offshore sites experienced high rates of bioerosion primarily due to grazing and internal bioerosion by macroborers such as sponges and bivalves was also important at some of these sites. Inshore sites were covered in heavy layers of silt which inhibited colonization and growth of microborers, primarily algae. This resulted in lower levels of grazing than at offshore sites. However the activity of macroborers (primarily sponges and bivalves) was often high at these sites. The macroboring communities differed between sites and over time and it is hypothesised that these site differences were due to different levels of terrestrial runoff. These results are compared with those from French Polynesia where contaminated terrestrial runoff greatly influenced rates and agents of bioerosion. However other factors such as overfishing may also play an important role in some locations.

Coral reef degradation resulting from nutrient enrichment of coastal waters is of increasing global concern. Although effects of nutrients on coral reef organisms have been demonstrated in the laboratory, there is little direct evidence of nutrient effects on coral reef biota in situ. The ENCORE experiment investigated responses of coral reef organisms and processes to controlled additions of dissolved inorganic nitrogen (N) and/or phosphorus (P) on an offshore reef (One Tree Island) at the southern end of the Great Barrier Reef, Australia. A multi-disciplinary team assessed a variety of factors focusing on nutrient dynamics and biotic responses. A controlled and replicated experiment was conducted over two years using twelve small patch reefs ponded at low tide by a coral rim. Treatments included three control reefs (no nutrient addition) and three + N reefs (NH4Cl added), three + P reefs (KH2PO4 added), and three + N + P reefs. Nutrients were added as pulses at each low tide (ca twice per day) by remotely operated units. There were two phases of nutrient additions. During the initial, low-loading phase of the experiment nutrient pulses (mean dose = 11.5 microM NH4+; 2.3 microM PO4(-3)) rapidly declined, reaching near-background levels (mean = 0.9 microM NH4+; 0.5 microM PO4(-3)) within 2-3 h. A variety of biotic processes, assessed over a year during this initial nutrient loading phase, were not significantly affected, with the exception of coral reproduction, which was affected in all nutrient treatments. In Acropora longicyathus and A. aspera, fewer successfully developed embryos were formed, and in A. longicyathus fertilization rates and lipid levels decreased. In the second, high-loading, phase of ENCORE an increased nutrient dosage (mean dose = 36.2 microM NH4+; 5.1 microM PO4(-3)) declining to means of 11.3 microM NH4+ and 2.4 microM PO4(-3) at the end of low tide) was used for a further year, and a variety of significant biotic responses occurred. Encrusting algae incorporated virtually none of the added nutrients. Organisms containing endosymbiotic zooxanthellae (corals and giant clams) assimilated dissolved nutrients rapidly and were responsive to added nutrients. Coral mortality, not detected during the initial low-loading phase, became evident with increased nutrient dosage, particularly in Pocillopora damicornis. Nitrogen additions stunted coral growth, and phosphorus additions had a variable effect. Coral calcification rate and linear extension increased in the presence of added phosphorus but skeletal density was reduced, making corals more susceptible to breakage. Settlement of all coral larvae was reduced in nitrogen treatments, yet settlement of larvae from brooded species was enhanced in phosphorus treatments. Recruitment of stomatopods, benthic crustaceans living in coral rubble, was reduced in nitrogen and nitrogen plus phosphorus treatments. Grazing rates and reproductive effort of various fish species were not affected by the nutrient treatments. Microbial nitrogen transformations in sediments were responsive to nutrient loading with nitrogen fixation significantly increased in phosphorus treatments and denitrification increased in all treatments to which nitrogen had been added. Rates of bioerosion and grazing showed no significant effects of added nutrients. ENCORE has shown that reef organisms and processes investigated in situ were impacted by elevated nutrients. Impacts were dependent on dose level, whether nitrogen and/or phosphorus were elevated and were often species-specific. The impacts were generally sub-lethal and subtle and the treated reefs at the end of the experiment were visually similar to control reefs. Rapid nutrient uptake indicates that nutrient concentrations alone are not adequate to assess nutrient condition of reefs. Sensitive and quantifiable biological indicators need to be developed for coral reef ecosystems. The potential bioindicators identified in ENCORE should be tested in future research on coral reef/nutrient interactions. Synergistic and cumulative effects of elevated nutrients and other environmental parameters, comparative studies of intact vs. disturbed reefs, offshore vs. inshore reefs, or the ability of a nutrient-stressed reef to respond to natural disturbances require elucidation. An expanded understanding of coral reef responses to anthropogenic impacts is necessary, particularly regarding the subtle, sub-lethal effects detected in the ENCORE studies.

The nonobese diabetic (NOD) mouse, a spontaneous animal model for insulin-dependent diabetes mellitus, displays a tendency in common with human diabetic populations to develop autoimmune thyroiditis although incidence and severity of thyroid lesions vary widely among different colonies around the world. A congenic strain of NOD mice bearing I-Ak on a NOD background (NOD-H2(h4)) has recently been derived and displays a much greater tendency to develop thyroiditis and autoantibodies to mouse thyroglobulin (MTg) although it is free of diabetes. Both thyroid infiltrates and autoantibody formation are accelerated and enhanced in NOD-H2(h4) mice by increased iodine intake. The effect of increased iodine intake on NOD mice themselves has not been directly investigated although a recent study of these animals given high or low doses of iodine showed no follicular destruction unless the mice were first rendered goitrous by iodine deprivation. We found that dietary iodine increased both the incidence and the severity of thyroid lesions in our NOD mice although autoantibodies to MTg were absent. NOD background genes appear to be essential for the development of these lesions, which were maximal after 4 weeks of iodine administration and showed no significant regression when the iodine was stopped. Furthermore, our studies show for the first time that both CD4(+) and CD8(+) T cells are necessary for the development of this accelerated but essentially spontaneous murine thyroid disease., (Copyright 1999 Academic Press.)

The current study examines associations between a history of sexual assault or abuse and severity of symptoms and diagnostic categories in an adult clinical outpatient sample. Twelve of 68 men (18%) and 71 of 120 women (59%) reported a history of sexual trauma. Abuse history was associated with mood and anxiety disorder diagnoses. Women were also more likely to receive these diagnoses; abused women were particularly likely to be diagnosed with an anxiety disorder. Abused subjects showed higher scores on every subscale of the SCL-90-R; there were no interactions between sex and history of abuse. Women scored higher than men on subscales indicating anxiety, phobia, and general distress. The results indicate an association between history of sexual trauma and symptom severity across a broad range of psychopathology, and with mood and anxiety disorders. There is no indication of differential gender effects of sexual assault.

An in vitro assay for the detection and enumeration of mouse and human cytokine-secreting cells is described and some ways in which it may be used diagnostically are indicated. The assay is an extension of the ELISA plaque assay or ELISPOT assay and uses pairs of antibodies to capture and then visually develop secreted lymphokines. In this way, it is possible to enumerate the specific cytokine-secreting cells. This assay may provide a valuable tool in the clinical investigation of the mechanisms of disease development and tissue destruction.

Mixed-lymphocyte culture-stimulated cells have been fractionated by their ability to bind the lectin Vicia villosa (Vv) and assessed for their cytolytic and suppressor activity in vitro. Vv positive and negative cells were separated either by cell affinity chromatography using Vv-Sepharose 6MB chromatography or by electronic cell sorting with FITC-Vv. Both populations expressed marked cytolytic and suppressor cell activity. Thus this lectin cannot be used to discriminate between these and other functional lymphoid cell population of blastoid cells binding the FITC-Vv appears following allogeneic stimulation; treatment with the immunosuppressive drug cyclosporin A, which affects cytotoxic cells preferentially, results in a considerable reduction of the Vv positive blastoid cells.