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The U.S. Environmental Protection Agency’s Endocrine Disruptor Screening Program (EDSP) is tasked with assessing chemicals for their potential to perturb endocrine pathways, including those controlled by androgen receptor (AR). To address challenges associated with traditional testing strategies, EDSP is considering in vitro high-throughput screening assays to screen and prioritize chemicals more efficiently. The ability of these assays to accurately reflect chemical interactions in nonmammalian species remains uncertain. Therefore, a goal of the EDSP is to evaluate how broadly results can be extrapolated across taxa. To assess the cross-species conservation of AR-modulated pathways, computational analyses and systematic literature review approaches were used to conduct a comprehensive analysis of existing in silico, in vitro, and in vivo data. First, molecular target conservation was assessed across 585 diverse species based on the structural similarity of ARs. These results indicate that ARs are conserved across vertebrates and are predicted to share similarly susceptibility to chemicals that interact with the human AR. Systematic analysis of over 5000 published manuscripts was used to compile in vitro and in vivo cross-species toxicity data. Assessment of in vitro data indicates conservation of responses occurs across vertebrate ARs, with potential differences in sensitivity. Similarly, in vivo data indicate strong conservation of the AR signaling pathways across vertebrate species, although sensitivity may vary. Overall, this study demonstrates a framework for utilizing bioinformatics and existing data to build weight of evidence for cross-species extrapolation and provides a technical basis for extrapolating hAR-based data to prioritize hazard in nonmammalian vertebrate species.

Vaginal vault perforation and evisceration of abdominal contents is a rare but well recognised complication of hysterectomy. We presented a rare case of a 40-year-old female with isolated omental prolapse 10 months post open abdominal hysterectomy after penile-vaginal intercourse. Early identification, initiation of antibiotics and operative management are critical to sepsis source control.

This issue of ATR considers numerous instances in which economic historians and historians of capitalism have turned to architecture as evidence of the workings of economic and financial systems. This collective position paper stems from the attempt to engage more directly with these disciplines; an attempt that was first manifested in the symposium “Built Orders of Finance, Risk and Racial Capitalism,” held online in early 2022. How are built orders shaped by processes of financialization, actuarial calculations of risk and the conditions of racial capitalism? How do built orders mobilize specific economic regimes? What kinds of evidence can be enlisted to discern the constitutive relationships established and maintained between architecture and regimes of finance? What scales are implied in these relationships? What is involved in their historicization? This article invites future conversations between the fields of scholarship it canvases to more comprehensively apprehend the terms, conditions, and histories of financialized space.

Today Richard Rogers + Partners’ Underwriting Room at Lloyd’s of London—known as “the Room”—is recognized as an icon of the High Tech movement, its modernity aestheticized through intersecting banks of escalators and a soaring twelve-story atrium. Yet on closer inspection, this interior represents a less satisfactory compromise. The product of years of protracted negotiations with a three hundred-year-old institution, the Room was conceived at a moment when the concept of risk, and the foundations of the insurance market, were transformed due to environmental crises, technological innovations and global financial deregulation. This paper contends that the changing nature of risk was mitigated through complex consultations over the design of the Room, simultaneously demanding new architectural solutions, whilst preserving the institution’s spatial and object-oriented rituals and mythologies. It concludes that the new Room, and the design process underpinning it, was a mode of institutional risk management in an age of uncertainty.

Background Saliva is easily obtainable non-invasively and potentially suitable for detecting both current and previous SARS-CoV-2 infection, but there is limited evidence on the utility of salivary antibody testing for community surveillance. Methods We established 6 ELISAs detecting IgA and IgG antibodies to whole SARS-CoV-2 spike protein, to its receptor binding domain region and to nucleocapsid protein in saliva. We evaluated diagnostic performance, and using paired saliva and serum samples, correlated mucosal and systemic antibody responses. The best-performing assays were field-tested in 20 household outbreaks. Results We demonstrate in test accuracy (N = 320), spike IgG (ROC AUC: 95.0%, 92.8–97.3%) and spike IgA (ROC AUC: 89.9%, 86.5–93.2%) assays to discriminate best between pre-pandemic and post COVID-19 saliva samples. Specificity was 100% in younger age groups (0–19 years) for spike IgA and IgG. However, sensitivity was low for the best-performing assay (spike IgG: 50.6%, 39.8–61.4%). Using machine learning, diagnostic performance was improved when a combination of tests was used. As expected, salivary IgA was poorly correlated with serum, indicating an oral mucosal response whereas salivary IgG responses were predictive of those in serum. When deployed to household outbreaks, antibody responses were heterogeneous but remained a reliable indicator of recent infection. Intriguingly, unvaccinated children without confirmed infection showed evidence of exposure almost exclusively through specific IgA responses. Conclusions Through robust standardisation, evaluation and field-testing, this work provides a platform for further studies investigating SARS-CoV-2 transmission and mucosal immunity with the potential for expanding salivo-surveillance to other respiratory infections in hard-to-reach settings.

Background Predicting the likely size of future SARS-CoV-2 waves is necessary for public health planning. In England, voluntary “plan B” mitigation measures were introduced in December 2021 including increased home working and face coverings in shops but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown. Methods We developed a rapid online survey of risk mitigation behaviours ahead of the winter 2021 festive period and deployed in two longitudinal cohort studies in the UK (Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK/COVID Symptom Study (CSS) Biobank) in December 2021. Using an individual-based, probabilistic model of COVID-19 transmission between social contacts with SARS-CoV-2 Omicron variant parameters and realistic vaccine coverage in England, we predicted the potential impact of the SARS-CoV-2 Omicron wave in England in terms of the effective reproduction number and cumulative infections, hospital admissions and deaths. Using survey results, we estimated in real-time the impact of voluntary risk mitigation behaviours on the Omicron wave in England, if implemented for the entire epidemic wave. Results Over 95% of survey respondents (NALSPAC = 2686 and NTwins = 6155) reported some risk mitigation behaviours, with vaccination and using home testing kits reported most frequently. Less than half of those respondents reported that their behaviour was due to “plan B”. We estimate that without risk mitigation behaviours, the Omicron variant is consistent with an effective reproduction number between 2.5 and 3.5. Due to the reduced vaccine effectiveness against infection with the Omicron variant, our modelled estimates suggest that between 55% and 60% of the English population could be infected during the current wave, translating into between 12,000 and 46,000 cumulative deaths, depending on assumptions about severity and vaccine effectiveness. The actual number of deaths was 15,208 (26 November 2021–1 March 2022). We estimate that voluntary risk reduction measures could reduce the effective reproduction number to between 1.8 and 2.2 and reduce the cumulative number of deaths by up to 24%. Conclusions Predicting future infection burden is affected by uncertainty in disease severity and vaccine effectiveness estimates. In addition to biological uncertainty, we show that voluntary measures substantially reduce the projected impact of the SARS-CoV-2 Omicron variant but that voluntary measures alone would be unlikely to completely control transmission.

1. Pollinating insects provide economic value by improving crop yield. They are also functionally and culturally important across ecosystems outside of cropland. To understand landscape-level drivers of pollinator declines, and guide policy and intervention to reverse declines, studies must cover (a) multiple insect and plant taxa and (b) a range of agricultural and semi-natural land uses. Furthermore, in an era of woodland restoration initiatives and rewilding ideologies, the contribution of woodland and woody linear features (WLFs; e.g. hedgerows) to pollinator abundance demands further investigation. 2. We demonstrate fine-scale analysis of high-quality, co-located measurements from a national environmental survey. We relate pollinator transect counts to ground-truth habitat and WLF maps across 300 1 km squares in Wales, UK. We look at effects of habitat type, flower cover, WLF density and habitat diversity on summer abundance (July and August) of eight insect groups, representing three insect orders (Lepidoptera, Hymenoptera and Diptera). 3. Compared with improved grassland (the dominant habitat in Wales), pollinator abundance is consistently higher in cropland and woodland—especially broadleaved woodland. For mining bees and two hoverfly groups, abundance is predicted to be at least 1.5× higher in woodland ecosystems than elsewhere. Furthermore, we estimate contributions of WLFs to abundance in agriculturally improved habitats to be up to 14% for honeybees and up to 21% for hoverflies. 4. The abundance of all insect groups increases with flower cover, which is a key mechanism through which woodland, cropland and grassland support pollinators. Importantly, we observe diminishing returns of increasing flower cover for abundance of non-Apis pollinator groups, expecting roughly twice the increase in abundance per % flower cover from 0% to 5%, as compared with 10% to 15%. However, the shape of the relationship was inverted for honeybees, which showed steeper increases in abundance at higher flower cover. 4. Synthesis and applications: We provide a holistic view of the drivers of pollinator abundance in Wales, in which flower cover, woodland, hedgerows and cropland are critical. We propose a key role for woodland creation, hedge-laying and farmland heterogeneity within future land management incentive schemes. Finally, we suggest targeting of interventions to maximise benefits for non-Apis pollinators. Specifically, increasing floral provision in areas where existing flower cover is low—for example, in flower-poor improved grasslands—could effectively increase pollinator abundance and diversity while prioritising wild over managed species.

ObjectivesTo explore public reactions to the COVID-19 pandemic across diverse ethnic groups.DesignRemote qualitative interviews and focus groups in English or Punjabi. Data were transcribed and analysed through inductive thematic analysis.SettingEngland and Wales, June to October 2020.Participants100 participants from 19 diverse ‘self-identified’ ethnic groups.ResultsDismay, frustration and altruism were reported across all ethnic groups during the first 6–9 months of the COVID-19 pandemic. Dismay was caused by participants’ reported individual, family and community risks, and loss of support networks. Frustration was caused by reported lack of recognition of the efforts of ethnic minority groups (EMGs), inaction by government to address COVID-19 and inequalities, rule breaking by government advisors, changing government rules around: border controls, personal protective equipment, social distancing, eating out, and perceived poor communication around COVID-19 and the Public Health England COVID-19 disparities report (leading to reported increased racism and social isolation). Altruism was felt by all, in the resilience of National Health Service (NHS) staff and their communities and families pulling together. Data, participants’ suggested actions and the behaviour change wheel informed suggested interventions and policies to help control COVID-19.ConclusionTo improve trust and compliance future reports or guidance should clearly explain any stated differences in health outcomes by ethnicity or other risk group, including specific messages for these groups and concrete actions to minimise any risks. Messaging should reflect the uncertainty in data or advice and how guidance may change going forward as new evidence becomes available. A contingency plan is needed to mitigate the impact of COVID-19 across all communities including EMGs, the vulnerable and socially disadvantaged individuals, in preparation for any rise in cases and for future pandemics. Equality across ethnicities for healthcare is essential, and the NHS and local communities will need to be supported to attain this.

Herein we present the synthesis, structure and NMR and mass spectroscopic analyses of the antioxidant 2-(3,5-dimethoxyphenyl)-2,3-dihydroquinolin-4(1H)-one (1), a member of the 2-aryl-2,3-dihydroquinolin-4(1H)-one family of molecules that have been shown to display a range of potent biological properties. The title molecule, prepared by an alternative methodology to that recently reported, crystallizes in the centrosymmetric space group P21/c with unit cell dimensions a = 11.775(17) A, b = 5.3592(8) A, c = 22.462(3) A and β = 96.576(11)°. Close analysis of the solid state structure reveals an array of weak N–H∙∙∙O hydrogen bonding as well as C–H∙∙∙O, and C–H∙∙∙π interactions between the neighboring molecules. The presence of 1 was also confirmed via NMR and mass spectroscopic analyses. Herein we present the solid state structure and results of mass spectroscopic and nuclear magnetic resonance analyses of the powerful antitumor compound 2-(3,5-dimethoxyphenyl)-2,3-dihydroquinolin-4(1H)-one prepared by an alternative synthetic avenue.

Tumor Associated Macrophages (TAMs), copiously found in the Tumor Microenvironment (TME) are key players in creating an immunosuppressive environment, increasing angiogenesis and metastasis in prostate cancer (PCa). They are plastic in nature and usually exist as, M1 (anti-tumorigenic) or M2 (pro-tumorigenic) phenotype, with relative abundance of M2. In this study, we aimed to explore the phenotypic effects of TAMs on PCa and investigate the potential of glycyrrhizin, a natural compound, to reprogram M2 TAMs, as a feasible treatment approach against PCa. THP-1 monocytes and RAW 264.7 were used to study macrophage differentiation and glycyrrhizin-mediated repolarization. THP-1 cells were cultured in conditioned media (CM) of LNCaP and BPH-Cd to obtain PCa associated macrophages. Flow cytometric analysis revealed increase in expression of surface markers CD32, CD64, CD206 and CD163 confirming M1/M2 differentiation. qPCR analysis also demonstrated upregulation of CD80, CD86, CD68, TGF-β and IL10. M2 markers such as CD68, CD163, CCL2, CCL5 and TGF-β were expressed in BPH-Cd TAMs. LNCaP TAMs also co-expressed CD68 and CD163. In spheroid assay on BPH-Cd cells, treatment with BPH-Cd TAM resulted in abnormally shaped, enlarged spheroids. Furthermore, the CM enhanced migration of BPH-Cd cells in transwell migration assay and downregulated P21 in western blot analysis, thus confirming its tumor-promoting role. MTT assay performed prior to studying the polarization potential of glycyrrhizin showed an increase in viability of glycyrrhizin-treated THP-1 and RAW 264.7 and selectively promoted viability in M1. The M1-polarizing properties of glycyrrhizin was revealed in the qPCR analysis of glycyrrhizin-treated M0 macrophages. The reduction in the size of the spheroids and decreased migration of BPH-Cd upon treatment with glycyrrhizin-treated M0 CM confirmed the same. Differentiation media (DM) of glycyrrhizin-treated M2 TAMs resulted in smaller, disintegrated BPH-Cd spheroids indicating possible reprogramming effect. Interestingly, glycyrrhizin-treated M2 CM downregulated the gene expression of stemness-associated markers such as NANOG, SNAIL, OCT3/4 and COX2 with concurrent suppression of EMT marker, N-Cadherin in LNCaP cells. Cell cycle analysis on LNCaP revealed a decrease in the percentage of cells in S phase compared to glycyrrhizin-treated M2 CM, suggesting hindered proliferation. A notable observation to help understand the plausible mechanism of M2 TAM suppression was the decrease in Reactive Oxygen Species (ROS) levels in glycyrrhizin-treated M1 and M2 TAMs derived from THP-1 cells. The glycyrrhizin-mediated inhibition of ROS was also confirmed in RAW 264.7. In conclusion, our findings suggest that glycyrrhizin could potentially reprogram TAMs to intercept proliferation, metastasis and stemness characteristics in PCa. Citation Format: Amy Thomas, Gnanasekar Munirathinam. Reprogramming M2-like tumor associated macrophages using a natural compound, glycyrrhizin, as a potential therapeutic strategy against prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2334.

The ACROBAT pilot trial of early cryoprecipitate for severe postpartum haemorrhage used deferred consent procedures. Pretrial discussions with a patient and public involvement group found mixed views towards deferred consent. This study aimed to build an understanding of how the deferred consent procedures worked in practice, to inform plans for a full-scale trial.Qualitative interview study within a cluster-randomised pilot trial, involving four London maternity services.Individual interviews were conducted postnatally with 10 women who had received blood transfusion for severe postpartum haemorrhage and had consented to the trial. We also interviewed four 'recruiters'-two research midwives and two clinical trials practitioners who conducted trial recruitment.Consent procedures in the ACROBAT pilot trial were generally acceptable and the intervention was viewed as low risk, but most women did not remember much about the consent conversation. As per trial protocol, recruiters sought to consent women before hospital discharge, but this time pressure had to be balanced against the need to ensure women were not approached when distressed or very unwell. Extra efforts had to be made to communicate trial information to women due to the exhaustion of their recovery and competing demands for their attention. Participant information was further complicated by explanations about the cluster design and change in transfusion process, even though the consent sought was for access to medical data.Our findings indicate that deferred consent procedures raise similar concerns as taking consent when emergency obstetric research is occurring-that is, the risk that participants may conflate research with clinical care, and that their ability to process trial information may be impacted by the stressful nature of recovery and newborn care. A future trial may support more meaningful informed consent by extending the window of consent discussion and ensuring trial information is minimal and easy to understand.ISRCTN12146519.

ObjectivesTo explore attitudes and intentions towards COVID-19 vaccination, and influences and sources of information about COVID-19 across diverse ethnic groups (EGs) in the UK.DesignRemote qualitative interviews and focus groups (FGs) conducted June-October 2020 before UK COVID-19 vaccine approval. Data were transcribed and analysed through inductive thematic analysis.SettingGeneral public in the community across England and Wales.Participants100 participants from 19 self-identified EGs with spoken English or Punjabi.ResultsMistrust and doubt were common themes across all EGs including white British and minority EGs, but more pronounced amongst Bangladeshi, Pakistani, Black ethnicities and Travellers. Many participants shared concerns about perceived lack of information about COVID-19 vaccine safety, efficacy and potential unknown adverse effects. Across EGs participants stated occupations with public contact, older adults and vulnerable groups should be prioritised for vaccination. Perceived risk, social influences, occupation, age, co-morbidities and engagement with healthcare influenced participants’ intentions to accept vaccination once available; all Jewish FG participants intended to accept, while all Traveller FG participants indicated they probably would not.Facilitators to COVID-19 vaccine uptake across all EGs included: desire to return to normality and protect health and wellbeing; perceived higher risk of infection; evidence of vaccine safety and efficacy; vaccine availability and accessibility.COVID-19 information sources were influenced by social factors, culture and religion and included: friends, family; media and news outlets; and research literature. Participants across most different EGs were concerned about misinformation or had negative attitudes towards the media.ConclusionsDuring vaccination programme roll-out, including boosters, commissioners and vaccine providers should provide accurate information, authentic community outreach, and use appropriate channels to disseminate information and counter misinformation. Adopting a context-specific approach to vaccine resources, interventions and policies and empowering communities has potential to increase trust in the programme.Article summary: strengths and limitationsThis is amongst the largest qualitative studies on attitudes to the COVID-19 pandemic in the UK general public across ethnic groups (EGs), ages and religions, adding insights from a broader range of participants.Qualitative methodology enabled discussion of participants’ responses around COVID-19 vaccination, probing to collect rich data to inform recommendations across EGs.Most data collection was undertaken in English, possibly excluding sectors of the population who may access COVID-19 information through different sources due to language.Data collection was June-October 2020 before COVID-19 vaccines were licensed. Attitudes are highly responsive to current information around a COVID-19 vaccine, as well as the state of the pandemic and perceived risk. Data were collected prior to much of the intervention work, putting the attitudes and intentions expressed in this study in a context of minimal community engagement and support. This provides a baseline snapshot of attitudes, providing the option to explore and assess the impact of such interventions.Socioeconomic data and index of multiple deprivation were not collected, limiting the ability to determine a possible accumulative effect of factors such as socioeconomic status, ethnicity and age.

ObjectivesTo explore public reactions to the COVID-19 pandemic across diverse ethnic groups.DesignRemote qualitative interviews and focus groups in English or Punjabi. Data were transcribed and analysed through inductive thematic analysis.SettingEngland and Wales June-October 2020.Participants100 participants from 19 diverse ‘self-identified’ ethnic groups.ResultsDismay, frustration and altruism were reported across all ethnic groups during the first six to nine months of the COVID-19 pandemic. Dismay was caused by participants’ reported individual, family and community risks, and loss of support networks. Frustration was caused by reported lack of recognition of the efforts of minority ethnic groups (MEGs), inaction by government to address COVID-19 and inequalities, rule breaking by government advisors, changing government rules around: border controls, personal protective equipment, social distancing, eating out, and perceived poor communication around COVID-19 and the Public Health England (PHE) COVID-19 disparities report (leading to reported increased racism and social isolation). Altruism was felt by all, in the resilience of NHS staff and their communities and families pulling together. Data, participants suggested actions, and the Behaviour Change Wheel informed suggested interventions and policies to help control COVID-19.ConclusionTo maintain public trust, it is imperative that governmental bodies consider vulnerable groups, producing clear COVID-19 control guidance with contingency, fiscal, service provision and communication policies for the next rise in COVID-19 cases. This needs to be combined with public interventions including information, education, modelling and enablement of infection prevention through local community involvement and persuasion techniques or incentivisation. Government policy needs to review and include town and social planning leading to environmental restructuring that facilitates infection prevention control. This includes easy access to hand-washing facilities in homes, work, all food providers and shopping centres; toilet facilities as our Travellers mentioned, and adequate living accommodation and work environment facilitating IPC for all.Strengths and limitationsThis is amongst the largest qualitative studies on attitudes to the COVID-19 pandemic in the UK general public across ethnic groups, ages and religions, adding insights to previous smaller qualitative studies, from a broader range of participants.The qualitative methodology allowed us to discuss participants’ responses around the COVID-19 pandemic, probing their answers to obtain detailed data to inform needs across ethnic groups.Most data collection was undertaken in English and therefore excludes non-English speaking sectors of the population who may have experienced the COVID-19 pandemic differently.We did not obtain the views of older members of the population over 70 years, who were most at risk.The data reflect public perceptions six to nine months into the pandemic when some of the social distancing rules had been relaxed in England; as the pandemic progresses attitudes and needs may well change.

BackgroundSocial contact survey data forms a core component of modern epidemic models: however, there has been little assessment of the potential biases in such data.MethodsWe conducted focus groups with university students who had (n=13) and had not (n=14) completed a social contact survey during the COVID-19 pandemic. Qualitative findings were explored quantitatively by analysing participation data.ResultsThe opportunity to contribute to COVID-19 research, to be heard and feel useful were frequently reported motivators for participating in the contact survey. Reductions in survey engagement following lifting of COVID-19 restrictions may have occurred because the research was perceived to be less critical and/ or because the participants were busier and had more contacts. Having a high number of contacts to report, uncertainty around how to report each contact, and concerns around confidentiality were identified as factors leading to inaccurate reporting. Focus groups participants thought that financial incentives or provision of study results would encourage participation.ConclusionsIncentives could improve engagement with social contact surveys. Qualitative research can inform the format, timing, and wording of surveys to optimise completion and accuracy.Graphical abstract

HighlightsSocial contact survey data inform epidemic models, but may have associated biases.We held focus groups of COVID-19 contact survey participants and non-participants.Motivators for participation were “being heard” and “feeling useful”.High contact numbers and uncertainty in reporting led to inaccuracies.Financial incentives and provision of survey results may encourage participation.AbstractBackgroundSocial contact survey data forms a core component of modern epidemic models: however, there has been little assessment of the potential biases in such data.MethodsWe conducted focus groups with university students who had (n = 13) and had never (n = 14) completed a social contact survey during the COVID-19 pandemic. Qualitative findings were explored quantitatively by analysing participation data.ResultsThe opportunity to contribute to COVID-19 research, to be heard and feel useful were frequently reported motivators for participating in the contact survey. Reductions in survey engagement following lifting of COVID-19 restrictions may have occurred because the research was perceived to be less critical and/or because the participants were busier and had more contacts. Having a high number of contacts to report, uncertainty around how to report each contact, and concerns around confidentiality were identified as factors leading to inaccurate reporting. Focus groups participants thought that financial incentives or provision of study results would encourage participation.ConclusionsIncentives could improve engagement with social contact surveys. Qualitative research can inform the format, timing, and wording of surveys to optimise completion and accuracy.

BackgroundThe Omicron variant of SARS-CoV-2 infection poses substantial challenges to public health. In England, “plan B” mitigation measures were introduced in December 2021 including increased home working and face coverings in shops, but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown.MethodsWe developed a rapid online survey of risk mitigation behaviours during the winter 2021 festive period and deployed in two longitudinal cohort studies in the UK (Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK/Covid Symptom Study (CSS) Biobank) in December 2021. Using an individual-based, probabilistic model of COVID-19 transmission between social contacts with SARS-CoV-2 Omicron variant parameters and realistic vaccine coverage in England, we describe the potential impact of the SARS-CoV-2 Omicron wave in England in terms of the effective reproduction number and cumulative infections, hospital admissions and deaths. Using survey results, we estimated in real-time the impact of voluntary risk mitigation behaviours on the Omicron wave in England, if implemented for the entire epidemic wave.ResultsOver 95% of survey respondents (NALSPAC=2,686 and NTwins=6,155) reported some risk mitigation behaviours, with vaccination and using home testing kits reported most frequently. Less than half of those respondents reported that their behaviour was due to “plan B”. We estimate that without risk mitigation behaviours, the Omicron variant is consistent with an effective reproduction number between 2.5 and 3.5. Due to the reduced vaccine effectiveness against infection with the Omicron variant, our modelled estimates suggest that between 55% and 60% of the English population could be infected during the current wave, translating into between 15,000 and 46,000 cumulative deaths, depending on assumptions about vaccine effectiveness. We estimate that voluntary risk reduction measures could reduce the effective reproduction number to between 1.8 and 2.2 and reduce the cumulative number of deaths by up to 24%.ConclusionsWe conclude that voluntary measures substantially reduce the projected impact of the SARS-CoV-2 Omicron variant, but that voluntary measures alone would be unlikely to completely control transmission.

We investigate the impact of vaccination and asymptomatic testing uptake on SARS-CoV-2 transmission in a university student population using a stochastic compartmental model. We find that the magnitude and timing of outbreaks is highly variable depending on the transmissibility of the most dominant strain of SARS CoV-2 and under different vaccine uptake levels and efficacies. When delta is the dominant strain, low level interventions (no asymptomatic testing, 30% vaccinated with a vaccine that is 80% effective at reducing infection) lead to 53-71% of students become infected during the first term. Asymptomatic testing is most useful when vaccine uptake is low: when 30% of students are vaccinated, 90% uptake of asymptomatic testing leads to almost half the case numbers. With high interventions (90% using asymptomatic testing, 90% vaccinated) cumulative incidence is 7-9%, with around 80% of these cases estimated to be asymptomatic. However, under emergence of a new variant that is at least twice as transmissible as delta and with the vaccine efficacy against infection reduced to 55%, large outbreaks are likely in universities, even with very high (90%) uptake of vaccination and 100% uptake of asymptomatic testing. If vaccine efficacy against infection against this new variant is higher (70%), then outbreaks can be mitigated if there is least 50% uptake of asymptomatic testing additional to 90% uptake of vaccination. Our findings suggest that effective vaccination is critical for controlling SARS-CoV-2 transmission in university settings with asymptomatic testing ranging from additionally useful to critical, depending on effectiveness and uptake of vaccination. Other measures may be necessary to control outbreaks under the emergence of a more transmissible variant with vaccine escape.

In many countries, an extensive vaccination programme has substantially reduced the public-health impact of SARS-CoV-2, limiting the number of hospital admissions and deaths compared to an unmitigated epidemic. Ensuring a low-risk transition from the current situation to one in which SARS-CoV-2 is endemic requires maintenance of high levels of population immunity. The observed waning of vaccine efficacy over time suggests that booster doses may be required to maintain population immunity especially in the most vulnerable groups. Here, using data and models for England, we consider the dynamics of COVID-19 over a two-year time-frame, and the role that booster vaccinations can play in mitigating the worst effects. We find that boosters are necessary to suppress the imminent wave of infections that would be generated by waning vaccine efficacy. Projecting further into the future, the optimal deployment of boosters is highly sensitive to their long-term action. If protection from boosters wanes slowly (akin to protection following infection) then a single booster dose to the over 50s may be all that is needed over the next two-years. However, if protection wanes more rapidly (akin to protection following second dose vaccination) then annual or even biannual boosters are required to limit subsequent epidemic peaks an reduce the pressure on public health services.

Background: Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background. AS is caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system. Disparities in the management of AS are a major problem in preparing for precision therapies and occur even in patients with access to experts and recognized clinics. AS patients receive care based on collective provider experience due to limited evidence-based literature. We present a consensus statement and comprehensive literature review that proposes a standard of care practices for the management of AS at a critical time when therapeutics to alter the natural history of the disease are on the horizon. Methods: We compiled the key recognized clinical features of AS based on consensus from a team of specialists managing patients with AS. Working groups were established to address each focus area with committees comprised of providers who manage >5 individuals. Committees developed management guidelines for their area of expertise. These were compiled into a final document to provide a framework for standardizing management. Evidence from the medical literature was also comprehensively reviewed. Results: Areas covered by working groups in the consensus document include genetics, developmental medicine, psychology, general health concerns, neurology (including movement disorders), sleep, psychiatry, orthopedics, ophthalmology, communication, early intervention and therapies, and caregiver health. Working groups created frameworks, including flowcharts and tables, to help with quick access for providers. Data from the literature were incorporated to ensure providers had review of experiential versus evidence-based care guidelines. Conclusion: Standards of care in the management of AS are keys to ensure optimal care at a critical time when new disease-modifying therapies are emerging. This document is a framework for providers of all familiarity levels.

Amy Thomas share her experience of mentoring dental nurses, as well as masterminding training days for dentists and their teams

The community pharmacy antimicrobial stewardship intervention (PAMSI) is multi-faceted and underpinned by behavioural science, consisting of the TARGET Antibiotic Checklist, staff e-Learning, and patient-facing materials. This mixed-method study evaluated the effect of PAMSI on community pharmacy staffs’ self-reported antimicrobial stewardship (AMS) behaviours. Data collection included staff pre- and post-intervention questionnaires, qualitative interviews, and TARGET Antibiotic Checklists. Quantitative data were analysed by a multivariate ordinal linear mixed effect model; qualitative data were analysed thematically. A total of 101 staff participated from 66 pharmacies, and six completed semi-structured interviews. The statistical model indicated very strong evidence (p < 0.001) that post-intervention, staff increased their antibiotic appropriateness checks and patient advice, covering antibiotic adherence, antibiotic resistance, infection self-care, and safety-netting. Staff reported feeling empowered to query antibiotic appropriateness with prescribing clinicians. The TARGET Antibiotic Checklist was completed with 2043 patients. Topics patients identified as requiring advice from the pharmacy team included symptom duration, alcohol and food consumption guidance, antibiotic side-effects, and returning unused antibiotics to pharmacies. Pharmacy staff acknowledged the need for improved communication across the primary care pathway to optimise antimicrobial use, and PAMSI has potential to support this ambition if implemented nationally. To support patients not attending a pharmacy in person, an online information tool will be developed.

University students have unique living, learning and social arrangements which may have implications for infectious disease transmission. To address this data gap, we created CONQUEST (COroNavirus QUESTionnaire), a longitudinal online survey of contacts, behaviour, and COVID-19 symptoms for University of Bristol (UoB) staff/students. Here, we analyse results from 740 students providing 1261 unique records from the start of the 2020/2021 academic year (14/09/2020–01/11/2020), where COVID-19 outbreaks led to the self-isolation of all students in some halls of residences. Although most students reported lower daily contacts than in pre-COVID-19 studies, there was heterogeneity, with some reporting many (median = 2, mean = 6.1, standard deviation = 15.0; 8% had ≥ 20 contacts). Around 40% of students’ contacts were with individuals external to the university, indicating potential for transmission to non-students/staff. Only 61% of those reporting cardinal symptoms in the past week self-isolated, although 99% with a positive COVID-19 test during the 2 weeks before survey completion had self-isolated within the last week. Some students who self-isolated had many contacts (mean = 4.3, standard deviation = 10.6). Our results provide context to the COVID-19 outbreaks seen in universities and are available for modelling future outbreaks and informing policy.

Soil porosity controls the flow of mass and energy through soil, and thus plays a fundamental role in regulating hydrological and biochemical cycling at the land surface. Global land surface and earth system models commonly derive porosity from soil texture using pedotransfer functions. This does not allow for response to change in environment or management, or potentially important climate feedbacks. Furthermore, the approach does not fully represent the baseline spatial variation in this important soil property. Here we show that porosity, and bulk density (BD), depend on SOM in temperate soils, using two comprehensive national data sets, covering the full range of soil organic matter (SOM) (n=1385 & n=2570). Our novel use of analytical models with machine learning (ML) algorithms opens up new physical insight into controls on porosity and BD, while generalized additive mixed models (GAMMs) provide further insights and opportunities for prediction. Our models allow us to consider influence of management on soil compaction and recent observations that soil porosity responds to climate change. The dependence of soil porosity on SOM, more so than texture, indicates the need for a paradigm shift in the conceptualization and modelling of these soil physical properties. Broad habitat was also an important control, and explained some of the variance in the relationship between SOM and porosity. This highlights that changes in soil porosity may occur due to land use or climate change, and will create feedbacks to hydrological and biogeochemical cycling which should be represented in Global land surface models. This will also be important for other pedotransfer functions, e.g. the use of BD to determine carbon stock from concentration. In addition, we found opportunities for improved representation of the spatial pattern of porosity, even in the absence of measured data on SOM, based on climate and earth observation data.

IntroductionUK universities re-opened in September 2020, despite the on-going coronavirus epidemic. During the first term, various national social distancing measures were introduced, including banning groups of >6 people and the second lockdown in November. COVID-19 can spread rapidly in university-settings, and students’ adherence to social distancing measures is critical for controlling transmission.MethodsWe measured university staff and student contact patterns via an online, longitudinal survey capturing self-reported contacts on the previous day. We investigated the change in contacts associated with COVID-19 guidance periods: post-first lockdown (23/06/2020-03/07/2020), relaxed guidance period (04/07/2020-13/09/2020), “rule-of-six” period (14/09/2020-04/11/2020), and the second lockdown (05/11/2020-25/11/2020).Results722 staff (4199 responses) (mean household size: 2.6) and 738 students (1906 responses) (mean household size: 4.5) were included in the study. Contact number decreased with age. Staff in single-person households reported fewer contacts than individuals in 2-and 3-person households, and individuals in 4-and 5-person households reported more contacts.For staff, daily contacts were higher in the relaxed guidance and “rule-of-six” periods (means: 3.2 and 3.5, respectively; medians: 3) than the post-first lockdown and second lockdown periods (means: 4.5 and 5.4, respectively; medians: 2). Few students responded until 05/10/2020, after which the median student contacts was 2 and the mean was 5.7, until the second lockdown when it dropped to 3.1.DiscussionUniversity staff and students responded to national guidance by altering their social contacts. The response in staff and students was similar, suggesting that students are able to adhere to social distancing guidance while at university.

Severe COVID-19 appears rare in children. This is unexpected, especially in young infants, who are vulnerable to severe disease caused by other respiratory viruses. We evaluate convalescent immune responses in 4 infants under 3 months old with confirmed COVID-19 who presented with mild febrile illness, alongside their parents, and adult controls recovered from confirmed COVID-19. Although not statistically significant, compared to seropositive adults, infants have high serum levels of IgG and IgA to SARS-CoV-2 spike protein, with a corresponding functional ability to block SARS-CoV-2 cellular entry. Infants also exhibit robust saliva anti-spike IgG and IgA responses. Spike-specific IFN-γ production by infant peripheral blood mononuclear cells appears restrained, but the frequency of spike-specific IFN-γ- and/or TNF-α-producing T cells is comparable between infants and adults. On principal-component analysis, infant immune responses appear distinct from their parents. Robust functional antibody responses alongside restrained IFN-γ production may help protect infants from severe COVID-19., Graphical abstract, Goenka et al. demonstrate that the SARS-CoV-2 immune response of young infants appears distinct compared with their parents. They show that infants exhibit relatively high serum (and saliva) levels of anti-spike IgG associated with robust SARS-CoV-2 neutralization but restrained cellular spike-specific IFN-γ production.

Current immunotherapy approaches aim to mitigate or reverse CD8+ T cell exhaustion to generate meaningful anti-tumor immune responses. However, the multi-step process of exhaustion fixes epigenetic programs that permanently scar T cells, limiting immunotherapeutic efficacy. Rather than reversing T cell exhaustion, we hypothesize that exploiting tumor-specific T cells from protected niches could yield therapies with improved anti-tumor benefit. A subset of TCF1-expressing precursor exhausted CD8+ T cells (TPEX) drives the anti-tumor immune response. The tumor draining lymph nodes (dLN) maintain a reservoir of TPEX cells which replenishes intra-tumoral effector T cells. Similarly, the bone marrow (BM) houses long-lived memory T cells with specificity against a broad spectrum of antigens, including tumor-associated antigens. Unlike T cells from the dLN or tumor infiltrating lymphocytes (TILs), BM T cells can be easily acquired from all patients at any disease stage. We used the B16.OVA-OT-I model to delineate how exhaustion affects tumor-specific T cells within the BM, dLN, spleen (SP), and tumor (TUM) during tumor progression. This model uses adoptively transferred transgenic, OVA-specific OT-I cells as a source of tumor-specific CD8+ T cells. High-dimensional immune profiling using spectral flow cytometry enabled us to characterize in vitro and in vivo anti-tumor functionality and the phenotype of OT-I cells derived from different compartments. Interestingly, upon adoptive transfer, OT-I cells resident in the TUM, dLN, BM, and SP or found in circulation were heterogenous in terms of function, persistence, and stemness. These findings suggest that discrete tissues impart location-specific T cell adaptations, and that tissue microenvironment markedly influences the exhaustion profile of tumor-specific T cells. OT-I cells derived from distinct lymphoid organs exhibited differential capacity for cytokine production and response to cognate antigen, especially compared to their TIL counterparts. Importantly, we identified BM- and dLN-derived CD8+ T cells as less exhausted and more functional than TILs. Moreover, BM resident T cells appear phenotypically more stem-like and similar to TPEX. Further studies to characterize this population are ongoing. This work implies that, in the context of localized disease, the kinetics of T cell exhaustion differ in lymphoid organs as compared to TILs. Leveraging a less-exhausted pool of tumor-specific cells may lead to greater anti-tumor benefit with new approaches to adoptive cell therapy. As the BM is accessible in all patients, understanding where tumor-specific BM T cells fall on the spectrum of exhaustion and memory could justify their use for such applications. Ongoing work aims to transcriptionally characterize tumor specific BM CD8+ T cells and evaluate their role in anti-tumor immunity. Citation Format: Elizabeth Maria Zawidzka, Luca Biavati, Amy Thomas, Megan Heimann, Ervin Griffin, Ivan Borrello. Microenvironment begets phenotype: Tumor specific CD8+ T cells derived from bone marrow and other lymphoid sites exhibit differential exhaustion profiles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6290.

ObjectiveThe ACROBAT pilot trial of early cryoprecipitate for severe postpartum haemorrhage used deferred consent procedures. Pretrial discussions with a patient and public involvement group found mixed views towards deferred consent. This study aimed to build an understanding of how the deferred consent procedures worked in practice, to inform plans for a full-scale trial.SettingQualitative interview study within a cluster-randomised pilot trial, involving four London maternity services.ParticipantsIndividual interviews were conducted postnatally with 10 women who had received blood transfusion for severe postpartum haemorrhage and had consented to the trial. We also interviewed four ‘recruiters’—two research midwives and two clinical trials practitioners who conducted trial recruitment.ResultsConsent procedures in the ACROBAT pilot trial were generally acceptable and the intervention was viewed as low risk, but most women did not remember much about the consent conversation. As per trial protocol, recruiters sought to consent women before hospital discharge, but this time pressure had to be balanced against the need to ensure women were not approached when distressed or very unwell. Extra efforts had to be made to communicate trial information to women due to the exhaustion of their recovery and competing demands for their attention. Participant information was further complicated by explanations about the cluster design and change in transfusion process, even though the consent sought was for access to medical data.ConclusionOur findings indicate that deferred consent procedures raise similar concerns as taking consent when emergency obstetric research is occurring—that is, the risk that participants may conflate research with clinical care, and that their ability to process trial information may be impacted by the stressful nature of recovery and newborn care. A future trial may support more meaningful informed consent by extending the window of consent discussion and ensuring trial information is minimal and easy to understand.Trial registration numberISRCTN12146519.

CONQUEST (COroNavirus QUESTionnaire) is an online survey of contacts, behaviour, and COVID-19 symptoms for University of Bristol (UoB) staff/students. We analysed survey results from the start of the 2020/2021 academic year, prior to the second national lockdown (14/09/2020-01/11/2020), where COVID-19 outbreaks led to lockdown of some student halls of residence. The aim of these analyses was to enhance knowledge of student contact patterns to inform infection disease mathematical modelling approaches.Responses captured information on demographics, contacts on the previous day, symptoms and self-isolation during the prior week, and COVID-19 status.740 students provided 1261 unique records. Of 42 (3%) students testing positive in the prior fortnight, 99% had been self-isolating. The median number of contacts on the previous day was 2 (interquartile range: 1-5), mode: 1, mean: 6.1; 8% had ≥20 contacts. 57% of student contacts were other UoB students/staff.Most students reported few daily contacts but there was heterogeneity, and some reported many. Around 40% of student contacts were with individuals not affiliated with UoB, indicating potential for transmission to non-students/staff.

We have used the pig, a large natural host animal for influenza with many physiological similarities to humans, to characterize αβ, γδ T cell and antibody (Ab) immune responses to the 2009 pandemic H1N1 virus infection. We evaluated the kinetic of virus infection and associated response in inbred Babraham pigs with identical MHC (Swine Leucocyte Antigen) and compared them to commercial outbred animals. High level of nasal virus shedding continued up to day 4-5 post infection followed by a steep decline and clearance of virus by day 9. Adaptive T cell and Ab responses were detectable from day 5-6 post infection reaching a peak at 9-14 days. γδ cells produced cytokines ex vivo at day 2 post infection, while virus specific IFNγ producing γδ T cells were detected from day 7 post infection. Analysis of NP tetramer specific and virus specific CD8 and CD4 T cells in blood, lung, lung draining lymph nodes and broncho-alveolar lavage (BAL) showed clear differences in cytokine production between these tissues. BAL contained the most highly activated CD8, CD4 and γδ cells producing large amounts of cytokines, which likely contribute to elimination of virus. The weak response in blood did not reflect the powerful local lung immune responses. The immune response in the Babraham pig following H1N1pdm09 influenza infection was comparable to that of outbred animals. The ability to utilize these two swine models together will provide unparalleled power to analyse immune responses to influenza.

Controlling COVID-19 transmission in universities poses challenges due to the complex social networks and potential for asymptomatic spread. We developed a stochastic transmission model based on realistic mixing patterns and evaluated alternative mitigation strategies. We predict, for plausible model parameters, that if asymptomatic cases are half as infectious as symptomatic cases, then 15% (98% Prediction Interval: 6–35%) of students could be infected during the first term without additional control measures. First year students are the main drivers of transmission with the highest infection rates, largely due to communal residences. In isolation, reducing face-to-face teaching is the most effective intervention considered, however layering multiple interventions could reduce infection rates by 75%. Fortnightly or more frequent mass testing is required to impact transmission and was not the most effective option considered. Our findings suggest that additional outbreak control measures should be considered for university settings., Reopening of universities to students following COVID-19 restrictions risks increased transmission due to high numbers of social contacts and the potential for asymptomatic transmission. Here, the authors use a mathematical model with social contact data to estimate the impacts of reopening a typical non-campus based university in the UK.

SummaryAlternative splicing plays important role in brain development, however its global contribution to human neurodevelopmental diseases (NDD) has not been fully investigated. Here, we examined the relationships between full-length splicing isoforms expression in the brain and de novo loss-of-function mutations identified in the patients with NDDs. We analyzed the full-length isoform transcriptome of the developing human brain and observed differentially expressed isoforms and isoform co-expression modules undetectable by gene-level analyses. These isoforms were enriched in loss-of-function mutations and microexons, co-expressed with a unique set of partners, and had higher prenatal expression. We experimentally tested the impact of splice site mutations in five NDD risk genes, including SCN2A, DYRK1A and BTRC, and demonstrated exon skipping. Furthermore, our results suggest that the splice site mutation in BTRC reduces translational efficiency, likely impacting Wnt signaling through impaired degradation of β-catenin. We propose that functional effect of mutations associated with human diseases should be investigated at the isoform-rather than the gene-level resolution.HighlightsDifferential isoform expression analysis of the human brain transcriptome reveals neurodevelopmental processes and pathways undetectable by differential gene expression analyses.Splicing isoforms impacted by neurodevelopmental disease (NDD) risk mutations exhibit higher prenatal expression, are enriched in microexons and are involved in neuronal-related functions.Isoform co-expression network analysis identifies modules with splicing and synaptic functions that are enriched in NDD mutations.Splice site mutations impacting NDD risk genes cause exon skipping and produce novel isoforms with altered biological properties.Functional impact of mutations should be investigated at the full-length isoform-level rather than the gene-level resolution

Background The number of people managing chronic conditions is growing with the rapidly aging population. Visits to the emergency department are steadily rising, but little is known about the rationale of those seeking emergent care. Aims The goal of this study was to better understand, from the patients' perspective, the reasons for seeking care in an emergency department setting. Design A qualitative descriptive design was used to interview aging adults with at least two chronic conditions who made three or more visits to the emergency department within a year. Participants/Subjects The eight-person sample was 88% female and 75% white, with an average age of 54 years. Methods Participant interviews were conducted with a semistructured interview guide. Conventional content analysis was used to examine words and phrases in professionally transcribed documents. Qualitative methods for testing and confirming conclusions were performed. Results We discovered that aging adults visit the emergency department to seek relief from unrelenting pain and to overcome barriers to receiving treatment for pain in ambulatory settings. Participants reported feeling judged when seeking emergency department care for pain management. Conclusions Participants described emergency department care as the only option in response to several barriers to healthcare access. Most commonly, emergency department care was sought when relief from persistent or acute pain was required. One way to reduce strain on EDs from pain-related visits is to manage patients with persistent pain more proactively in their community environment.

Alternative splicing plays important role in brain development, however its global contribution to human neurodevelopmental diseases (NDD) has not been fully investigated. Here, we examined the relationships between splicing isoforms expression in the brain and de novo loss-of-function mutations identified in the patients with NDDs. We constructed isoform transcriptome of the developing human brain, and observed differentially expressed isoforms and isoform co-expression modules undetectable by the gene-level analyses. These isoforms were enriched in loss-of-function mutations and microexons, co-expressed with a unique set of partners, and had higher prenatal expression. We experimentally tested the impact of splice site mutations in five NDD risk genes, including SCN2A, DYRK1A and BTRC, and demonstrated exon skipping. Furthermore, our results suggest that the splice site mutation in BTRC reduces translational efficiency, likely impacting Wnt signaling through impaired degradation of β-catenin. We propose that functional effect of mutations associated with human diseases should be investigated at isoform- rather than gene-level resolution.

The EMmY trial is sponsored by Queen Mary University of London and funded by Barts Charity, grant number MGU0373. EP and AH are also supported by the NIHR Collaboration for Leadership in Applied Health Research at Barts Health NHS Foundation Trust (NIHR ARC North Thames). KSK is distinguished investigator funded by the Beatriz Galindo (senior modality) grant to the University of Granada by the Spanish Ministry of Education., Objectives To determine the feasibility and acceptability of conducting a randomised trial on the effects of myo-inositol in preventing gestational diabetes in high-risk pregnant women. Design A multicentre, double-blind, placebo-controlled, pilot randomised trial with nested qualitative evaluation. Setting Five inner city UK National Health Service hospitals Participants Multiethnic pregnant women at 12+0 and 15+6 weeks’ gestation with risk factors for gestational diabetes. Interventions 2 g of myo-inositol or placebo, both included 200 μg folic acid, twice daily until delivery. Primary outcome measures Rates of recruitment, randomisation, adherence and follow-up. Secondary outcome measures Glycaemic indices (including homoeostatic model assessment-insulin resistance HOMA-IR), gestational diabetes (diagnosed using oral glucose tolerance test at 28 weeks and by delivery), maternal, perinatal outcomes, acceptability of intervention and costs. Results Of the 1326 women screened, 58% (773/1326) were potentially eligible, and 27% (205/773) were recruited. We randomised 97% (198/205) of all recruited women (99 each in intervention and placebo arms) and ascertained outcomes in 90% of women (178/198) by delivery. The mean adherence was 52% (SD 44) at 28 weeks’ and 34% (SD 41) at 36 weeks’ gestation. HOMA-IR and serum insulin levels were lower in the myo-inositol vs placebo arm (mean difference −0.6, 95% CI −1.2 to 0.0 and −2.69, 95% CI −5.26 to −0.18, respectively). The study procedures were acceptable to women and healthcare professionals. Women who perceived themselves at high risk of gestational diabetes were more likely to participate and adhere to the intervention. The powder form of myo-inositol and placebo, along with nausea in pregnancy were key barriers to adherence. Conclusions A future trial on myo-inositol versus placebo to prevent gestational diabetes is feasible. The intervention will need to be delivered in a non-powder form to improve adherence. There is a signal for efficacy in reducing insulin resistance in pregnancy with myo-inositol., Queen Mary University of London, Barts Charity MGU0373, NIHR Collaboration for Leadership in Applied Health Research at Barts Health NHS Foundation Trust (NIHR ARC North Thames), University of Granada by the Spanish Ministry of Education

Child psychologist Jean Piaget argued in the 1960s that children enter into a developmental stage of sensorimotor development between birth and two years old. In this stage, children learn to posit their bodies in their environment and rely on their senses to gain information about the world around them. The combination of sensory perceptions and motor skills creates the earliest form of intelligence.

In order to effectively manage natural resources at national scales national decision makers require data on the natural capital which supports the delivery of Ecosystem Services (ES). Key data sources used for the provision of national natural capital metrics include Satellite Remote Sensing (SRS), which provides information on land cover at an increasing range of resolutions, and field survey, which can provide very high resolution data on ecosystem components, but is constrained in its potential coverage by resource requirements. Here we combine spatially representative field data from a historic national survey of Great Britain (Countryside Survey (CS)) with concurrent low resolution SRS data land cover map within modelling frameworks to produce national natural capital metrics. We present three examples of natural capital metrics; top soil carbon, headwater stream quality and nectar species plant richness which show how highly resolved, but spatially representative field data can be used to significantly enhance the potential of low resolution SRS land cover data for providing national spatial data on natural capital metrics which have been linked to Ecosystem Services (ES). We discuss the role of such metrics in evaluations of ecosystem service provision and areas of further development to improve their utility for stakeholders.

Background Functional Restorative Programmes (FRP) for persistent non-specific lower back pain have been shown to be effective, but they often lack sufficient detailed reporting of the intervention components to allow for accurate replication. Objectives This study used the Behaviour Change Technique Taxonomy (v1) (BCTi) [1] to identify the main components of one such programme and interviewed patients to identify the most effective programme components and areas for improvement. Design A mixed methods design was used. Methods Intervention data were coded using the BCT Taxonomy (v1) to identify the BCTs utilised. Following this, semi-structured interviews with nine patients evaluated the BCTs included using thematic analysis and identified possible techniques for inclusion in future developments of the programme. Results Forty-one different BCTs were identified in the coding phase with frequency of occurrence in the programme ranging from forty-nine to one. Four main themes emerged from the interviews: Social Support, Shaping Knowledge, Repetition and Substitution and Changes in Mindset. Conclusion The results of this study identify the key ingredients in a programme for persistent, non-specific lower back pain, which facilitates the replication of this intervention and identified areas patients appreciated most as well as areas for improvement.

Water-borne pathogen contamination from untreated sewage effluent and runoff from farms is a serious threat to the use of river water for drinking and commercial purposes, such as downstream estuarine shellfish industries. In this study, the impact of climate change and land-use change on the presence of faecal indicator bacteria in freshwater was evaluated, through the use of a recently-developed catchment-scale pathogen model. The River Conwy in Wales has been used as a case-study, because of the large presence of livestock in the catchment and the importance of the shellfish harvesting activities in its estuary. The INCA-Pathogens catchment model has been calibrated through the use of a Monte-Carlo-based technique, based on faecal indicator bacteria measurements, and then driven by an ensemble of climate projections obtained from the HadRM3-PPE model (Future Flow Climate) plus four land-use scenarios (current land use, managed ecosystem, abandonment and agricultural intensification). The results show that climate change is not expected to have a very large impact on average river flow, although it might alter its seasonality. The abundance of faecal indicator bacteria is expected to decrease in response to climate change, especially during the summer months, due to reduced precipitation, causing reduced runoff, and increased temperature, which enhances the bacterial die-off processes. Land-use change can also have a potentially large impact on pathogens. The “managed ecosystems” scenario proposed in this study can cause a reduction of 15% in average water faecal indicator bacteria and up to 30% in the 90th percentile of water faecal indicator bacteria, mainly due to the conversion of pasture land into grassland and the expansion of forest land. This study provides an example of how to assess the impacts of human interventions on the landscape, and what may be the extent of their effects, for other catchments where the human use of the natural resources in the uplands can jeopardise the use of natural resources downstream.

We investigated three bovine respiratory pathobionts in healthy cattle using qPCR optimised and validated to quantify Histophilus somni, Mannheimia haemolytica and Pasteurella multocida over a wide dynamic range. A longitudinal study was conducted to investigate the carriage and density of these bacteria in the nasal passages of healthy beef calves (N = 60) housed over winter in an experimental farm setting. The three pathobiont species exhibited remarkably different carriage rates and density profiles. At housing, high carriage rates were observed for P. multocida (95%), and H. somni (75%), while fewer calves were positive for M. haemolytica (13%). Carriage rates for all three bacterial species declined over the 75-day study, but not all individuals became colonised despite sharing of environment and airspace. Colonisation patterns ranged from continuous to intermittent and were different among pathobiont species. Interval-censored exponential survival models estimated the median duration of H. somni and P. multocida carriage at 14.8 (CI

In this review paper, the authors identify priority areas, and opportunities for electric utilities in developing and emerging economies to incorporate Earth observation (EO) data into rural electrification planning, renewable energy resource assessment, distributed generation, grid operation and reliability, and disaster risk reduction and recovery efforts. Using a methodological framework, the authors conducted a comprehensive literature review of primary and gray literature. This paper reviews the many existing applications for EO data, such as the use of nighttime lights imagery for estimations of rural electrification, EO-derived normalized difference vegetation index (NDVI) products for vegetation monitoring for overhead transmission line management, solar radiance data for renewable energy project planning, and nowcasting for extreme weather events and other disaster monitoring. These and other applications can enhance energy security through improved governance of and access to modern and reliable electricity, renewable energy management, and disaster risk assessment in developing nations, paving the way for more sustainable social and economic development. Real-world examples of EO data use by utilities in developing and emerging economies, as well as barriers and opportunities for EO technology transfer, are discussed. Recommendations for stakeholder engagement, future EO training opportunities, and human capacity building are also presented.

Understanding the role of virulence loci within pathogenic organisms can be vital in exploring the evolution of disease. Streptomyces species are generally non-pathogenic soil saprophytes, yet within their genome we can find macrophage infectivity potentiator-like proteins (MIPs) (Clark et al., 2013). MIPs are a subset of immunophilins associated with virulence in a range of micro-organisms (Norville et al., 2011). It is unknown the role they possess in non-pathogenic strains such as Streptomyces coelicolor M145. This project will identify the role of MIPs in a non-pathogenic strain through cloning, overexpression and knock out of three genes encoding putative MIP-like proteins (SCO1638, SCO1639 and SCO2620). The phenotypes will then be characterised by growth under contrasting conditions. Antibiotic production will also be measured and compared to the wild-type M145 strain. The overexpression and mutant strains will also be tested for the ability to infect amoeba using amoeba infection assays compared to a wild-type control. The results from this study will contribute to the understanding of the role of MIPs and therefore the evolution of virulence within Streptomyces species.

Loss and fragmentation of natural land cover due to expansion of agricultural areas is a global issue. These changes alter the configuration and composition of the landscape, particularly affecting those ecosystem services (benefits people receive from ecosystems) that depend on interactions between landscape components. Hydrological mitigation describes the bundle of ecosystem services provided by landscape features such as woodland that interrupt the flow of runoff to rivers. These services include sediment retention, nutrient retention and mitigation of overland water flow. The position of woodland in the landscape and the landscape topography are both important for hydrological mitigation. Therefore, it is crucial to consider landscape configuration and flow pathways in a spatially explicit manner when examining the impacts of fragmentation. Here we test the effects of landscape configuration using a large number (>7,000) of virtual landscape configurations. We created virtual landscapes of woodland patches within grassland, superimposed onto real topography and stream networks. Woodland patches were generated with user‐defined combinations of patch number and total woodland area, placed randomly in the landscape. The Ecosystem Service model used hydrological routing to map the “mitigated area” upslope of each woodland patch. We found that more fragmented woodland mitigated a greater proportion of the catchment. Larger woodland area also increased mitigation, however, this increase was nonlinear, with a threshold at 50% coverage, above which there was a decline in service provision. This nonlinearity suggests that the benefit of any additional woodland depends on two factors: the level of fragmentation and the existing area of woodland. Edge density (total edge of patches divided by area of catchment) was the best single metric in predicting mitigated area. Distance from woodland to stream was not a significant predictor of mitigation, suggesting that agri‐environment schemes planting riparian woodland should consider additional controls such as the amount of fragmentation in the landscape. These findings highlight the potential benefits of fragmentation to hydrological mitigation services. However, benefits for hydrological services must be balanced against any negative effects of fragmentation or habitat loss on biodiversity and other services.

Soil carbon storage and sequestration provides an ecosystem service (ES) through regulation of atmospheric carbon concentration, and associated climate conditions. Landscape planning to enhance this function can be most efficient through spatial assessment, followed by targeting of mitigation efforts to locations where soil carbon (C) stores are high, currently degrading, or there is good potential for sequestration. Direct measurement of C storage in the landscape is complicated by spatial variation in C storage in soil and biomass, hence in order to evaluate GHG storage and sequestration, calculations can be made based on available data for key factors influencing the offering of this ES. Complex process based models are available for prediction, however landscape planning approaches tend to favour simpler approaches utilising inventory figures and emission factors associated with soil type and vegetation. Inventory figures may include significant uncertainty, and represent average values for the relevant land use and soil, however there is an assumption that errors will balance out at larger regional, and certainly at national scale. If soil data on finer scale is available as well, such as in the case of well-defined wetlands, the certainty of results seems to be good enough for deducing measures. This chapter includes a case study on the application of a simple landscape scale model for assessment of potential placement of agri-environmental measures to enhance or protect soil C storage and sequestration in the landscape, as well as description of other models which may be preferred under different application requirements.