Multicolour lineage tracing reveals clonal dynamics of squamous carcinoma evolution from initiation to metastasis.

Tumour cells are subjected to evolutionary selection pressures during progression from initiation to metastasis. We analysed the clonal evolution of squamous skin carcinomas induced by DMBA/TPA treatment using the K5CreER-Confetti mouse and stage-specific lineage tracing. We show that benign tumours are polyclonal, but only one population contains the Hras driver mutation. Thus, benign papillomas are monoclonal in origin but recruit neighbouring epithelial cells during growth. Papillomas that never progress to malignancy retain several distinct clones, whereas progression to carcinoma is associated with a clonal sweep. Newly generated clones within carcinomas demonstrate intratumoural invasion and clonal intermixing, often giving rise to metastases containing two or more distinct clones derived from the matched primary tumour. These data demonstrate that late-stage tumour progression and dissemination are governed by evolutionary selection pressures that operate at a multicellular level and, therefore, differ from the clonal events that drive initiation and the benign-malignant transition

Pathways to care in at-risk mental states and first episode psychosis

Background: People with early psychotic symptoms often experience treatment delays, which can exacerbate distress and lead to poorer outcomes, with significant personal and financial costs. Delays can occur in both people with an At-Risk Mental State (ARMS) for psychosis and in First Episode Psychosis (FEP). The thesis aimed to explore treatment delays and help-seeking using the paradigm of Pathways to Care (PtC). Methods: A systematic review of PtC in ARMS was conducted which synthesised quantitative and qualitative studies. A qualitative study was carried out exploring PtC in participants with ARMS and FEP using semi-structured one-to-one interviews, analysed using thematic analysis. Results: Ten studies met inclusion criteria for the systematic review. There was significant heterogeneity, with varying countries, screening tools and PtC instruments adopted. Overall, mental health professionals and General Practitioners (GPs) were found to have a key role in PtC, with family also identified as important in several studies. In the empirical study, eleven participants were interviewed about their experiences of PtC and barriers and facilitators to earlier help-seeking. Many participants had complex PtC and difficult experiences. Themes identified for experiences of PtC were “onset” and “unheard”; for barriers and facilitators themes were “gate keepers”, “personal” and “societal”. Overall the empirical paper also identified the key role of GPs and family, as well as stigma and culture. Conclusions: The role of both GPs and family in help-seeking in both ARMS and FEP renders the need for service-level and public health interventions to raise awareness of psychotic experiences and available services. These may have the potential to shorten the PtC and improve outcomes. Clinical implications, including for GPs and Early Intervention in Psychosis services are given. Further research is required to triangulate and extend the findings

Service user interview panels for recruitment to UK child and adolescent mental health services: A questionnaire study exploring the experiences of young people, staff and candidates

Service user involvement is increasingly important in health and social care policy, including in Child and Adolescent Mental Health Services (CAMHS), but evidence evaluating involvement initiatives is lacking. This questionnaire study evaluated the use of young people’s (YP) interview panels in the recruitment of CAMHS staff, from the perspectives of YP, candidates and members of the staff interview panels. Self-report questionnaires were administered to YP, candidates and staff interview panel. This included quantitative and qualitative “free text” responses. YP’s panels were found to be important in hearing the voices of YP; participants all stated they would like YP to take part in future interviews. Qualitative analysis found YP provided added insight into the process, had a professional manner, were valued and important, gave clear feedback, and benefitted the YP involved. A number of changes to the process were identified. This evaluation found YP’s interview panels were feasible, and a valuable addition to the recruitment process, and should be considered in other CAMHS teams. Experience Framework This article is associated with the Patient, Family & Community Engagement lens of The Beryl Institute Experience Framework. (http://bit.ly/ExperienceFramework) Access other PXJ articles related to this lens. Access other resources related to this lens

Pathways to care in at-risk mental states: a systematic review

Aim: Pathways to care are well studied in the First Episode Psychosis field, but less attention has been given to At‐Risk Mental States or prodromal psychosis. This is important because accessing appropriate help at the earliest opportunity is likely to improve outcomes, particularly for those who make transition to psychosis. The present systematic review aimed to synthesize the available literature on pathways to care in ARMS or prodromal psychosis, and investigate the barriers and facilitators to receiving care for ARMS. Methods: The CINAHL Complete, EMBASE, Medline Complete, PsycINFO and PubMED databases were searched. Studies were included if they were published in English between 1985 and 2019, where reported data came exclusively from an At‐Risk Mental State population, and the study described or related to pathways to care. Results: Ten studies met the inclusion criteria, of which 8 were quantitative. Screening tools and pathways to care instruments varied. Mental health professionals, and general practitioners played a key role in help seeking. Family involvement was also found to be an important factor. Conclusions: Pathways to care research in At‐Risk Mental States are more scarce than in the field of First Episode Psychosis. More research is warranted, especially concerning the role of patient‐level characteristics on pathways to care. A validated measure of pathways to care may also be of benefit

Hand hygiene with hand sanitizer versus handwashing: what are the planetary health consequences?

In order to reduce the transmission of pathogens, and COVID-19, WHO and NHS England recommend hand washing (HW) and/or the use of hand sanitizer (HS). The planetary health consequences of these different methods of hand hygiene have not been quantified. A comparative life cycle assessment (LCA) was carried out to compare the environmental impact of the UK population practising increased levels of hand hygiene during the COVID-19 pandemic for 1 year. Washing hands with soap and water was compared to using hand sanitizer (both ethanol and isopropanol based sanitizers were studied). The isopropanol-based HS had the lowest environmental impact in 14 out of the 16 impact categories used in this study. For climate change, hand hygiene using isopropanol HS produced the equivalent of 1060 million kg CO2, compared to 1460 million for ethanol HS, 2300 million for bar soap HW, and 4240 million for liquid soap HW. For both the ethanol and isopropanol HS, the active ingredient was the greatest overall contributing factor to the environmental impact (83.24% and 68.68% respectively). For HW with liquid soap and bar soap, there were additional contributing factors other than the soap itself: for example tap water use (28.12% and 48.68% respectively) and the laundering of a hand towel to dry the hands (10.17% and 17.92% respectively). All forms of hand hygiene have an environmental cost, and this needs to be weighed up against the health benefits of preventing disease transmission. When comparing hand sanitizers to handwashing with soap and water, this study found that using isopropanol based hand sanitizer is better for planetary health. However, no method of hand hygiene was ideal; isopropanol had a greater fossil fuel resource use than ethanol based hand sanitizer. More research is needed to find hand hygiene sources which do not diminish planetary health, and environmental impact is a consideration for public health campaigns around hand hygiene

The over-35s: early intervention in psychosis services entering uncharted territory

Aims and method: Following the introduction of new standards for early intervention in psychosis (EIP) in England, EIP services are accepting referrals for people aged 35–65. The Cambridgeshire and Peterborough EIP service (CAMEO) aimed to explore the immediate implications for the service, especially with regards to referral numbers and sources. Data were collected from April 2016 to June 2017. Results: Referrals for over-35s represented 25.7% of all new referrals. Fifty per cent of referrals for over-35s were accepted onto caseload (40.2% for under-35s). The over-35s were more likely to be referred from acute and secondary mental health services (P < 0.01) and had longer durations of untreated psychosis than the under-35s (P = 0.02). Clinical implications: CAMEO has received a significantly higher number of referrals as a result of age inclusivity, with an increased proportion of patients suffering from severe, acute psychotic presentations and existing mental health difficulties. This has implications for service planning

Quantum Control of Two-Qubit Entanglement Dissipation

We investigate quantum control of the dissipation of entanglement under environmental decoherence. We show by means of a simple two-qubit model that standard control methods - coherent or open-loop control - will not in general prevent entanglement loss. However, we propose a control method utilising a Wiseman-Milburn feedback/measurement control scheme which will effectively negate environmental entanglement dissipation.Comment: 11 pages,4 figures, minor correctio

Modelling the variation of land surface temperature as determinant of risk of heat-related health events

<p>Abstract</p> <p>Background</p> <p>The evaluation of exposure to ambient temperatures in epidemiological studies has generally been based on records from meteorological stations which may not adequately represent local temperature variability. Here we propose a spatially explicit model to estimate local exposure to temperatures of large populations under various meteorological conditions based on satellite and meteorological data.</p> <p>Methods</p> <p>A general linear model was used to estimate surface temperatures using 15 LANDSAT 5 and LANDSAT 7 images for Quebec Province, Canada between 1987 and 2002 and spanning the months of June to August. The images encompassed both rural and urban landscapes and predictors included: meteorological records of temperature and wind speed, distance to major water bodies, Normalized Differential Vegetation Index (NDVI), land cover (built and bare land, water, or vegetation), latitude, longitude, and week of the year.</p> <p>Results</p> <p>The model explained 77% of the variance in surface temperature, accounting for both temporal and spatial variations. The standard error of estimates was 1.42°C. Land cover and NDVI were strong predictors of surface temperature.</p> <p>Conclusions</p> <p>This study suggests that a statistical approach to estimating surface temperature incorporating both spatially explicit satellite data and time-varying meteorological data may be relevant to assessing exposure to heat during the warm season in the Quebec. By allowing the estimation of space- and time-specific surface temperatures, this model may also be used to assess the possible impacts of land use changes under various meteorological conditions. It can be applied to assess heat exposure within a large population and at relatively fine-grained scale. It may be used to evaluate the acute health effect of heat exposure over long time frames. The method proposed here could be replicated in other areas around the globe for which satellite data and meteorological data is available.</p

Survival of the fittest: explanations for gadoid imbalance in heavily fished seas

1. Anthropogenic activities have caused the degradation of the world's ecosystems, accelerating the loss of biodiversity. In marine ecosystems, fishing has had strong impacts on fish populations and their habitats; however, not all species have responded equally to fishing pressure. 2. Atlantic cod (Gadus morhua), haddock (Melanogrammus aeglefinus), and whiting (Merlangius merlangus) are of high commercial value throughout the North Atlantic. Despite having relatively similar life cycles, the state of stocks of these three species varies enormously, with whiting faring better than cod. Within the Firth of Clyde (south‐west Scotland), this imbalance is especially accentuated, where small whiting now make up the greater proportion of the biomass. 3. In this study, cod, haddock, and whiting recruitment to coastal areas, growth, and bait attraction were explored within a marine protected area (MPA) in the Firth of Clyde. Over the course of the summers of 2013 and 2014, whiting and haddock arrived at coastal areas earlier than cod, and grew more quickly. Cod were on average the smallest gadoid observed, and whiting the largest. Whiting also had more predominant scavenging behaviour. 4. These results, in combination with other life‐history traits, indicate that whiting may be at a competitive advantage over cod, and this may partly explain the imbalance of gadoids in the Firth of Clyde. This study highlights the importance of considering life‐history differences in multi‐species fisheries management, and how appropriately managed MPAs could help to restore fish population and assemblage structure

Assessing the potential of autonomous submarine gliders for ecosystem monitoring across multiple trophic levels (plankton to cetaceans) and pollutants in shallow shelf seas

A combination of scientific, economic, technological and policy drivers is behind a recent upsurge in the use of marine autonomous systems (and accompanying miniaturized sensors) for environmental mapping and monitoring. Increased spatial–temporal resolution and coverage of data, at reduced cost, is particularly vital for effective spatial management of highly dynamic and heterogeneous shelf environments. This proof-of-concept study involves integration of a novel combination of sensors onto buoyancy-driven submarine gliders, in order to assess their suitability for ecosystem monitoring in shelf waters at a variety of trophic levels. Two shallow-water Slocum gliders were equipped with CTD and fluorometer to measure physical properties and chlorophyll, respectively. One glider was also equipped with a single-frequency echosounder to collect information on zooplankton and fish distribution. The other glider carried a Passive Acoustic Monitoring system to detect and record cetacean vocalizations, and a passive sampler to detect chemical contaminants in the water column. The two gliders were deployed together off southwest UK in autumn 2013, and targeted a known tidal-mixing front west of the Isles of Scilly. The gliders’ mission took about 40 days, with each glider travelling distances of &gt;1000 km and undertaking &gt;2500 dives to depths of up to 100 m. Controlling glider flight and alignment of the two glider trajectories proved to be particularly challenging due to strong tidal flows. However, the gliders continued to collect data in poor weather when an accompanying research vessel was unable to operate. In addition, all glider sensors generated useful data, with particularly interesting initial results relating to subsurface chlorophyll maxima and numerous fish/cetacean detections within the water column. The broader implications of this study for marine ecosystem monitoring with submarine gliders are discussed