Recent advances in biomedical, biosensor and clinical measurement devices for use in humans and the potential application of these technologies for the study of physiology and disease in wild animals

The goal of achieving enhanced diagnosis and continuous monitoring of human health has led to a vibrant, dynamic and well-funded field of research in medical sensing and biosensor technologies. The field has many sub-disciplines which focus on different aspects of sensor science; engaging engineers, chemists, biochemists and clinicians, often in interdisciplinary teams. The trends which dominate include the efforts to develop effective point of care tests and implantable/wearable technologies for early diagnosis and continuous monitoring. This review will outline the current state of the art in a number of relevant fields, including device engineering, chemistry, nanoscience and biomolecular detection, and suggest how these advances might be employed to develop effective systems for measuring physiology, detecting infection and monitoring biomarker status in wild animals. Special consideration is also given to the emerging threat of antimicrobial resistance and in the light of the current SARS-CoV-2 outbreak, zoonotic infections. Both of these areas involve significant crossover between animal and human health and are therefore well placed to seed technological developments with applicability to both human and animal health and, more generally, the reviewed technologies have significant potential to find use in the measurement of physiology in wild animals. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'

The Role of the Private Sector in Supporting Malaria Control in Resource Development Settings.

Industrial operations of the private sector, such as extraction, agriculture, and construction, can bring large numbers of people into new settlement areas and cause environmental change that promotes the transmission of vector-borne diseases. Industry-related workers and communities unduly exposed to infection risk typically lack the knowledge and means to protect themselves. However, there is a strong business rationale for protecting local resident employees through integrated vector control programs, as well as an ethical responsibility to care for these individuals and the affected communities. We discuss the role and challenges of the private sector in developing malaria control programs, which can include extensive collaborations with the public sector that go on to form the basis of national vector control programs or more broadly support local healthcare systems

Dealing with the deluge of historical weather data: the example of the TEMPEST database

People have long been interested in the history of weather, particularly extremes, and chronologies of past events drawing on information from written records, have been compiled and published throughout history. In recent years, concern over current and future weather and climate has triggered a new level of interest in past weather events and their impacts. This interest, alongside the development of digital humanities research methods has resulted in a rapid growth in the number of online databases relating to historic weather and climate around the world. This paper reviews this expansion with reference to a range of examples, before documenting the design and creation of one such database, TEMPEST, an online repository for extreme weather history in the UK. TEMPEST has been created as the major output of the AHRC funded project ?Spaces of Experience and Horizons of Expectation: Extreme Weather in the UK, Past, Present and Future? (2013-2016). Unlike the majority of existing databases that rely on published materials, TEMPEST?s records are drawn from primary research into original documentary sources held in archives around the UK. The c. 18,000 records that TEMPEST currently contains offer personalised and geo-referenced insights into the relationship between society and extreme weather in the UK spanning a period of over 400 years. We conclude this paper by outlining some potential applications for TEMPEST, and suggesting directions for future research and resources in historical weather. We also consider broader issues for the digital humanities.publishersversionPeer reviewe

Research Report for COVID-19 Public Inquiry

This report was commissioned by the Scottish Covid-19 Inquiryas introductory scoping research

Patients’ experiences of emergency hospital care following self-harm: Systematic review and thematic synthesis of qualitative research

Rates of hospital presentation for self-harm have increased in recent years and although clinical practice guidelines on clinical provision prioritise positive patient experiences, the quality of provision remains variable. This systematic review provides an updated and extended synthesis of qualitative research on: i) patients’ experiences of treatment following presentation to hospital; and ii) patients’ perceptions of the impact of treatment on recurrent self-harm and/or suicidal ideation, and future help-seeking. 26 studies were identified for inclusion in the final synthesis. Three meta-themes emerged: i) individuals undertake extensive identity work when presenting with self-harm, navigating the process of becoming a patient and negotiating the type of patient they want to be; ii) care ranges from gentle to hostile, with care at admission and discharge being particularly disorientating and iii) negative experiences of clinical treatment may increase future self-harm. Emerging research gaps include the need for further theoretically-informed qualitative research in this area

STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle.

Human papillomaviruses (HPV) activate a number of host factors to control their differentiation-dependent life cycles. The transcription factor signal transducer and activator of transcription (STAT)-3 is important for cell cycle progression and cell survival in response to cytokines and growth factors. STAT3 requires phosphorylation on Ser727, in addition to phosphorylation on Tyr705 to be transcriptionally active. In this study, we show that STAT3 is essential for the HPV life cycle in undifferentiated and differentiated keratinocytes. Primary human keratinocytes containing high-risk HPV18 genomes display enhanced STAT3 phosphorylation compared to normal keratinocytes. Expression of the E6 oncoprotein is sufficient to induce the dual phosphorylation of STAT3 at Ser727 and Tyr705 by a mechanism requiring Janus kinases and members of the MAPK family. E6-mediated activation of STAT3 induces the transcription of STAT3 responsive genes including cyclin D1 and Bcl-xL. Silencing of STAT3 protein expression by siRNA or inhibition of STAT3 activation by small molecule inhibitors, or by expression of dominant negative STAT3 phosphorylation site mutants, results in blockade of cell cycle progression. Loss of active STAT3 impairs HPV gene expression and prevents episome maintenance in undifferentiated keratinocytes and upon differentiation, lack of active STAT3 abolishes virus genome amplification and late gene expression. Organotypic raft cultures of HPV18 containing keratinocytes expressing a phosphorylation site STAT3 mutant display a profound reduction in suprabasal hyperplasia, which correlates with a loss of cyclin B1 expression and increased differentiation. Finally, increased STAT3 expression and phosphorylation is observed in HPV positive cervical disease biopsies compared to control samples, highlighting a role for STAT3 activation in cervical carcinogenesis. In summary, our data provides evidence of a critical role for STAT3 in the HPV18 life cycle

A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection

Dendritic cells (DCs) are the key initiators of T-helper (Th) 2 immune responses against the parasitic helminth Schistosoma mansoni. Although the liver is one of the main sites of antigen deposition during infection with this parasite, it is not yet clear how distinct DC subtypes in this tissue respond to S. mansoni antigens in vivo, or how the liver microenvironment might influence DC function during establishment of the Th2 response. In this study, we show that hepatic DC subsets undergo distinct activation processes in vivo following murine infection with S. mansoni. Conventional DCs (cDCs) from schistosome-infected mice upregulated expression of the costimulatory molecule CD40 and were capable of priming naive CD4+ T cells, whereas plasmacytoid DCs (pDCs) upregulated expression of MHC class II, CD86 and CD40 but were unable to support the expansion of either naive or effector/memory CD4+ T cells. Importantly, in vivo depletion of pDCs revealed that this subset was dispensable for either maintenance or regulation of the hepatic Th2 effector response during acute S. mansoni infection. Our data provides strong evidence that S. mansoni infection favors the establishment of an immunogenic, rather than tolerogenic, liver microenvironment that conditions cDCs to initiate and maintain Th2 immunity in the context of ongoing antigen exposure

CD11c depletion severely disrupts Th2 induction and development in vivo

Although dendritic cells (DCs) are adept initiators of CD4+ T cell responses, their fundamental importance in this regard in Th2 settings remains to be demonstrated. We have used CD11c–diphtheria toxin (DTx) receptor mice to deplete CD11c+ cells during the priming stage of the CD4+ Th2 response against the parasitic helminth Schistosoma mansoni. DTx treatment significantly depleted CD11c+ DCs from all tissues tested, with 70–80% efficacy. Even this incomplete depletion resulted in dramatically impaired CD4+ T cell production of Th2 cytokines, altering the balance of the immune response and causing a shift toward IFN-γ production. In contrast, basophil depletion using Mar-1 antibody had no measurable effect on Th2 induction in this system. These data underline the vital role that CD11c+ antigen-presenting cells can play in orchestrating Th2 development against helminth infection in vivo, a response that is ordinarily balanced so as to prevent the potentially damaging production of inflammatory cytokines

Measuring the timeliness of childhood vaccinations: Using cohort data and routine health records to evaluate quality of immunisation services

Background: To achieve full benefits of vaccination programmes, high uptake and timely receipt of vaccinations are required. Objectives: To examine uptake and timeliness of infant and pre-school booster vaccines using cohort study data linked to health records. Methods: We included 1782 children, born between 2000 and 2001, participating in the Millennium Cohort Study and resident in Wales, whose parents gave consent for linkage to National Community Child Health Database records at the age seven year contact. We examined age at receipt, timeliness of vaccination (early, on-time, delayed, or never), and intervals between vaccine doses, based on the recommended schedule for children at that time, of the following vaccines: primary (diphtheria, tetanus, pertussis (DTP), polio, Meningococcal C (Men C), Haemophilus influenzae type b (Hib)); first dose of measles, mumps and rubella (MMR); and pre-school childhood vaccinations (DTP, polio, MMR). We compared parental report with child health recorded MMR vaccination status at age three years. Results: While 94% of children received the first dose of primary vaccines early or on time, this was lower for subsequent doses (82%, 65% and 88% for second and third doses and pre-school booster respectively). Median intervals between doses exceeded the recommended schedule for all but the first dose with marked variation between children. There was high concordance (97%) between parental reported and child health recorded MMR status. Conclusions: Routine immunisation records provide useful information on timely receipt of vaccines and can be used to assess the quality of childhood vaccination programmes. Parental report of MMR vaccine status is reliable

Meta-analyses of cognitive functions in early-treated adults with phenylketonuria

Our study estimated size of impairment for different cognitive functions in early-treated adults with PKU (AwPKU) by combining literature results in a meta-analytic way. We analysed a large set of functions (N=19), each probed by different measures (average=12). Data were extracted from 26 PKU groups and matched controls, with 757 AwPKU contributing 220 measures. Effect sizes (ESs) were computed using Glass' ∆ where differences in performance between clinical/PKU and control groups are standardized using the mean and standard deviation of the control groups. Significance was assessed using 'measures nested within independent PKU groups' as a random factor. The weighted Glass' ∆ was -.44 for all functions taken together, and -.60 for IQ, both highly significant. Separate, significant impairments were found for most functions, but with great variability (ESs from -1.02 to -.18). The most severe impairments were in reasoning, visual-spatial attention speed, sustained attention, visuo-motor control, and flexibility. Effect sizes were larger with speed than accuracy measures, and with visuo-spatial than verbal stimuli. Results show a specific PKU profile that needs consideration when monitoring the disease