The lived experience of severe mental illness and long-term conditions: a qualitative exploration of service user, carer, and healthcare professional perspectives on self-managing co-existing mental and physical conditions.

BACKGROUND: People with severe mental illness (SMI), such as schizophrenia, have higher rates of physical long-term conditions (LTCs), poorer health outcomes, and shorter life expectancy compared with the general population. Previous research exploring SMI and diabetes highlights that people with SMI experience barriers to self-management, a key component of care in long-term conditions; however, this has not been investigated in the context of other LTCs. The aim of this study was to explore the lived experience of co-existing SMI and LTCs for service users, carers, and healthcare professionals. METHODS: A qualitative study with people with SMI and LTCs, their carers, and healthcare professionals, using semi-structured interviews, focused observations, and focus groups across the UK. Forty-one interviews and five focus groups were conducted between December 2018 and April 2019. Transcripts were coded by two authors and analysed thematically. RESULTS: Three themes were identified, 1) the precarious nature of living with SMI, 2) the circularity of life with SMI and LTCs, and 3) the constellation of support for self-management. People with co-existing SMI and LTCs often experience substantial difficulties with self-management of their health due to the competing demands of their psychiatric symptoms and treatment, social circumstances, and access to support. Multiple long-term conditions add to the burden of self-management. Social support, alongside person-centred professional care, is a key facilitator for managing health. An integrated approach to both mental and physical healthcare was suggested to meet service user and carer needs. CONCLUSION: The demands of living with SMI present a substantial barrier to self-management for multiple co-existing LTCs. It is important that people with SMI can access person-centred, tailored support for their LTCs that takes into consideration individual circumstances and priorities.

Sources of non-methane hydrocarbons in surface air in Delhi, India.

Rapid economic growth and development have exacerbated air quality problems across India, driven by many poorly understood pollution sources and understanding their relative importance remains critical to characterising the key drivers of air pollution. A comprehensive suite of measurements of 90 non-methane hydrocarbons (NMHCs) (C2-C14), including 12 speciated monoterpenes and higher molecular weight monoaromatics, were made at an urban site in Old Delhi during the pre-monsoon (28-May to 05-Jun 2018) and post-monsoon (11 to 27-Oct 2018) seasons using dual-channel gas chromatography (DC-GC-FID) and two-dimensional gas chromatography (GC×GC-FID). Significantly higher mixing ratios of NMHCs were measured during the post-monsoon campaign, with a mean night-time enhancement of around 6. Like with NOx and CO, strong diurnal profiles were observed for all NMHCs, except isoprene, with very high NMHC mixing ratios between 35-1485 ppbv. The sum of mixing ratios of benzene, toluene, ethylbenzene and xylenes (BTEX) routinely exceeded 100 ppbv at night during the post-monsoon period, with a maximum measured mixing ratio of monoaromatic species of 370 ppbv. The mixing ratio of highly reactive monoterpenes peaked at around 6 ppbv in the post-monsoon campaign and correlated strongly with anthropogenic NMHCs, suggesting a strong non-biogenic source in Delhi. A detailed source apportionment study was conducted which included regression analysis to CO, acetylene and other NMHCs, hierarchical cluster analysis, EPA UNMIX 6.0, principal component analysis/absolute principal component scores (PCA/APCS) and comparison with NMHC ratios (benzene/toluene and i-/n-pentane) in ambient samples to liquid and solid fuels. These analyses suggested the primary source of anthropogenic NMHCs in Delhi was from traffic emissions (petrol and diesel), with average mixing ratio contributions from Unmix and PCA/APCS models of 38% from petrol, 14% from diesel and 32% from liquified petroleum gas (LPG) with a smaller contribution (16%) from solid fuel combustion. Detailed consideration of the underlying meteorology during the campaigns showed that the extreme night-time mixing ratios of NMHCs during the post-monsoon campaign were the result of emissions into a very shallow and stagnant boundary layer. The results of this study suggest that despite widespread open burning in India, traffic-related petrol and diesel emissions remain the key drivers of gas-phase urban air pollution in Delhi.

Avoiding high ozone pollution in Delhi, India.

Surface ozone is a major pollutant threatening public health, agricultural production and natural ecosystems. While measures to improve air quality in megacities such as Delhi are typically aimed at reducing levels of particulate matter (PM), ozone could become a greater threat if these measures focus on PM alone, as some air pollution mitigation steps can actually lead to an increase in surface ozone. A better understanding of the factors controlling ozone production in Delhi and the impact that PM mitigation measures have on ozone is therefore critical for improving air quality. Here, we combine in situ observations and model analysis to investigate the impact of PM reduction on the non-linear relationship between volatile organic compounds (VOC), nitrogen oxides (NOx) and ozone. In situ measurements of NOx, VOC, and ozone were conducted in Delhi during the APHH-India programme in summer (June) and winter (November) 2018. We observed hourly averaged ozone concentrations in the city of up to 100 ppbv in both seasons. We performed sensitivity simulations with a chemical box model to explore the impacts of PM on the non-linear VOC-NOx-ozone relationship in each season through its effect on aerosol optical depth (AOD). We find that ozone production is limited by VOC in both seasons, and is particularly sensitive to solar radiation in winter. Reducing NOx alone increases ozone, such that a 50% reduction in NOx emissions leads to 10-50% increase in surface ozone. In contrast, reducing VOC emissions can reduce ozone efficiently, such that a 50% reduction in VOC emissions leads to ∼60% reduction in ozone. Reducing PM alone also increases ozone, especially in winter, by reducing its dimming effects on photolysis, such that a 50% reduction in AOD can increase ozone by 25% and it also enhances VOC-limitation. Our results highlight the importance of reducing VOC emissions alongside PM to limit ozone pollution, as well as benefitting control of PM pollution through reducing secondary organic aerosol. This will greatly benefit the health of citizens and the local ecosystem in Delhi, and could have broader application for other megacities characterized by severe PM pollution and VOC-limited ozone production.

Using highly time-resolved online mass spectrometry to examine biogenic and anthropogenic contributions to organic aerosol in Beijing.

Organic aerosols, a major constituent of fine particulate mass in megacities, can be directly emitted or formed from secondary processing of biogenic and anthropogenic volatile organic compound emissions. The complexity of volatile organic compound emission sources, speciation and oxidation pathways leads to uncertainties in the key sources and chemistry leading to formation of organic aerosol in urban areas. Historically, online measurements of organic aerosol composition have been unable to resolve specific markers of volatile organic compound oxidation, while offline analysis of markers focus on a small proportion of organic aerosol and lack the time resolution to carry out detailed statistical analysis required to study the dynamic changes in aerosol sources and chemistry. Here we use data collected as part of the joint UK-China Air Pollution and Human Health (APHH-Beijing) collaboration during a field campaign in urban Beijing in the summer of 2017 alongside laboratory measurements of secondary organic aerosol from oxidation of key aromatic precursors (1,3,5-trimethyl benzene, 1,2,4-trimethyl benzene, propyl benzene, isopropyl benzene and 1-methyl naphthalene) to study the anthropogenic and biogenic contributions to organic aerosol. For the first time in Beijing, this study applies positive matrix factorisation to online measurements of organic aerosol composition from a time-of-flight iodide chemical ionisation mass spectrometer fitted with a filter inlet for gases and aerosols (FIGAERO-ToF-I-CIMS). This approach identifies the real-time variations in sources and oxidation processes influencing aerosol composition at a near-molecular level. We identify eight factors with distinct temporal variability, highlighting episodic differences in OA composition attributed to regional influences and in situ formation. These have average carbon numbers ranging from C5-C9 and can be associated with oxidation of anthropogenic aromatic hydrocarbons alongside biogenic emissions of isoprene, α-pinene and sesquiterpenes.

Exploring what is important to patients with regards to quality of life after experiencing a lower limb reconstructive procedure: a qualitative evidence synthesis.

BACKGROUND: Patient reported outcome measures (PROMs) are used to understand the impact of lower limb reconstruction surgery on patients' quality of life (QOL). Existing measures have not been developed to specifically capture patient experiences amongst adults with lower limb conditions that require reconstruction surgery. This review aimed to synthesise qualitative evidence to identify what is important to patients requiring, undergoing, or following reconstructive surgery for lower limb conditions. METHODS: MEDLINE, Embase, PsychINFO and Cinahl were searched from inception until November 2020. Studies were included if they employed qualitative research methods, involved patients requiring, undergoing or following lower limb reconstruction and explored patients' experiences of care, treatment, recovery and QOL. Mixed methods studies that did not separately report qualitative findings, mixed population studies that were not separately reported and studies in languages other than English were excluded. Included studies were analysed using thematic synthesis. The Critical Appraisal Skills Programme qualitative studies checklist was used to undertake quality assessment. RESULTS: Nine studies met the inclusion criteria. The thematic synthesis identified two overarching themes: (1) areas of living key to QOL for lower limb reconstruction patients and (2) moving towards a new normal. The way in which lower limb reconstruction affects an individual's QOL and their recovery is complex and is influenced by a range of inter-related factors, which will affect patients to varying degrees depending on their individual circumstances. We identified these factors as: pain, daily functioning and lifestyle, identity, income, emotional wellbeing, support, the ability to adapt and adjust and the ability to move forwards. CONCLUSIONS: The way patients' QOL is affected after a lower limb reconstruction is complex, may change over time and is strongly linked to their recovery. These findings will aid us in developing a conceptual framework which identifies the outcomes important to patients and those that should be included in a PROM. Further research is then required to establish whether the range of factors we identified are captured by existing PROMs. Depending on the outcome of this work, a new PROM for patients following lower limb reconstruction may be required.

Dietary protein and bone health across the life-course: an updated systematic review and meta-analysis over 40 years.

We undertook a systematic review and meta-analysis of published papers assessing dietary protein and bone health. We found little benefit of increasing protein intake for bone health in healthy adults but no indication of any detrimental effect, at least within the protein intakes of the populations studied. This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. The PubMed database was searched for all relevant human studies from the 1st January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0-4% of areal BMC and areal BMD variance in adults and 0-14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR(random) = 0.94; 0.72 to 1.23, I2 = 32%), animal (RR (random) = 0.98; 0.76 to 1.27, I2 = 46%) or vegetable protein (RR (fixed) = 0.97 (0.89 to 1.09, I2 = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n = 255, MD(fixed) = 0.04 g/cm2 (0.00 to 0.08, P = 0.07), I2 = 0%) or FNBMD (total n = 435, MD(random) = 0.01 g/cm2 (-0.03 to 0.05, P = 0.59), I2 = 68%). There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8-1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents.

Effectiveness of interventions to support the early detection of skin cancer through skin self-examination: a systematic review and meta-analysis.

BACKGROUND: As skin cancer incidence rises, there is a need to evaluate early detection interventions by the public using skin self-examination (SSE); however, the literature focuses on primary prevention. No systematic reviews have evaluated the effectiveness of such SSE interventions. OBJECTIVES: To systematically examine, map, appraise and synthesize, qualitatively and quantitatively, studies evaluating the early detection of skin cancer, using SSE interventions. METHODS: This is a systematic review (narrative synthesis and meta-analysis) examining randomized controlled trials (RCTs) and quasiexperimental, observational and qualitative studies, published in English, using PRISMA and National Institute for Health and Care Excellence guidance. The MEDLINE, Embase and PsycINFO databases were searched through to April 2015 (updated in April 2018 using MEDLINE). Risk-of-bias assessment was conducted. RESULTS: Included studies (n = 18), totalling 6836 participants, were derived from 22 papers; these included 12 RCTs and five quasiexperiments and one complex-intervention development. More studies (n = 10) focused on targeting high-risk groups (surveillance) than those at no higher risk (screening) (n = 8). Ten (45%) study interventions were theoretically underpinned. All of the study outcomes were self-reported, behaviour related and nonclinical in nature. Meta-analysis demonstrated the impact of the intervention on the degree of SSE activity from five studies, especially in the short term (up to 4 months) (odds ratio 2·31, 95% confidence interval 1·90-2·82), but with small effect sizes. Risk-of-bias assessment indicated that 61% of the studies (n = 11) were of weak quality. CONCLUSIONS: Four RCTs and a quasiexperimental study indicate that some interventions can enhance SSE activity and so are more likely to aid early detection of skin cancer. However, the actual clinical impact remains unclear, and this is based on overall weak study (evidence) quality.

Automation in cell and gene therapy manufacturing: from past to future.

As more and more cell and gene therapies are being developed and with the increasing number of regulatory approvals being obtained, there is an emerging and pressing need for industrial translation. Process efficiency, associated cost drivers and regulatory requirements are issues that need to be addressed before industrialisation of cell and gene therapies can be established. Automation has the potential to address these issues and pave the way towards commercialisation and mass production as it has been the case for 'classical' production industries. This review provides an insight into how automation can help address the manufacturing issues arising from the development of large-scale manufacturing processes for modern cell and gene therapy. The existing automated technologies with applicability in cell and gene therapy manufacturing are summarized and evaluated here.

Associations between Theileria orientalis Ikeda type infection and the growth rates and haematocrit of suckled beef calves in the North Island of New Zealand.

AIMS: The principle aim of this study was to examine the association between infection with Theileria orientalis Ikeda type and growth rates of suckled beef calves on four beef farms. In addition, associations between calf sex, sampling time, and individual farm and T. orientalis Ikeda type infection intensity and haematocrit (HCT) were investigated. METHODS: The study was a prospective longitudinal study in which 240 calves from four purposively selected beef farms in the North Island of New Zealand were blood sampled and weighed in late spring, mid-summer and early autumn. Two farms were from high-risk (A and B) and two from low-risk (C and D) tick areas. Blood samples were analysed to determine HCT, and the number of T. orientalis Ikeda type organisms/µL of blood (infection intensity) using a quantitative PCR assay. A calf was defined as infected if >415 organisms/µL were detected in a blood sample. Linear mixed models were used to examine associations between infection intensity, mean daily liveweight gain (MDG), HCT, calf sex and time of sampling on the four farms. RESULTS: On Farms A and B nearly all calves were infected at each sampling time, on Farm C <30% were infected at any sampling and on Farm D infection prevalence increased from 32 to 79% between late spring and early autumn. On Farms C and D, from mid-summer to early autumn, mean MDG was 0.127 (95% CI=0.072-0.183) kg/day less for infected than uninfected calves (p<0.001). On all farms MDG was negatively associated with infection intensity for mid-summer and early autumn sampling times (p=0.037). The relationship between time of sampling and infection intensity varied between farms (p<0.001), and between male and female calves (p=0.018). Females had a higher infection intensity than males at the mid-summer and early autumn samplings. The association between HCT and infection intensity varied with sampling time and farm (p=0.018). There was a strong negative association between infection intensity and HCT at the late spring sampling, but in mid-summer there was no association, and in early autumn only a weak association. CONCLUSIONS AND CLINICAL RELEVANCE: This study has shown that beef farmers in the North Island of New Zealand should be concerned about the welfare effects and economic impacts of T. orientalis Ikeda type infection in suckled beef calves.

Whole-Genome Characterization of Bacillus cereus Associated with Specific Disease Manifestations.

Bacillus cereus remains an important cause of infections, particularly in immunocompromised hosts. While typically associated with enteric infections, disease manifestations can be quite diverse and include skin infections, bacteremia, pneumonia, and meningitis. Whether there are any genetic correlates of bacterial strains with particular clinical manifestations remains unknown. To address this gap in understanding, we undertook whole-genome analysis of B. cereus strains isolated from patients with a range of disease manifestations, including noninvasive colonizing disease, superficial skin infections, and invasive bacteremia. Interestingly, strains involved in skin infection tended to form a distinct genetic cluster compared to isolates associated with invasive disease. Other disease manifestations, despite not being exclusively clustered, nonetheless had unique genetic features. The unique features associated with the specific types of infections ranged from traditional virulence determinants to metabolic pathways and gene regulators. These data represent the largest genetic analysis to date of pathogenic B. cereus isolates with associated clinical parameters.

Cost-effectiveness of computerized cognitive-behavioural therapy for the treatment of depression in primary care: findings from the Randomised Evaluation of the Effectiveness and Acceptability of Computerised Therapy (REEACT) trial.

BACKGROUND: Computerized cognitive-behavioural therapy (cCBT) forms a core component of stepped psychological care for depression. Existing evidence for cCBT has been informed by developer-led trials. This is the first study based on a large independent pragmatic trial to assess the cost-effectiveness of cCBT as an adjunct to usual general practitioner (GP) care compared with usual GP care alone and to establish the differential cost-effectiveness of a free-to-use cCBT programme (MoodGYM) in comparison with a commercial programme (Beating the Blues) in primary care. METHOD: Costs were estimated from a healthcare perspective and outcomes measured using quality-adjusted life years (QALYs) over 2 years. The incremental cost-effectiveness of each cCBT programme was compared with usual GP care. Uncertainty was estimated using probabilistic sensitivity analysis and scenario analyses were performed to assess the robustness of results. RESULTS: Neither cCBT programme was found to be cost-effective compared with usual GP care alone. At a £20 000 per QALY threshold, usual GP care alone had the highest probability of being cost-effective (0.55) followed by MoodGYM (0.42) and Beating the Blues (0.04). Usual GP care alone was also the cost-effective intervention in the majority of scenario analyses. However, the magnitude of the differences in costs and QALYs between all groups appeared minor (and non-significant). CONCLUSIONS: Technically supported cCBT programmes do not appear any more cost-effective than usual GP care alone. No cost-effective advantage of the commercially developed cCBT programme was evident compared with the free-to-use cCBT programme. Current UK practice recommendations for cCBT may need to be reconsidered in the light of the results.

VOC emission rates over London and South East England obtained by airborne eddy covariance.

Volatile organic compounds (VOCs) originate from a variety of sources, and play an intrinsic role in influencing air quality. Some VOCs, including benzene, are carcinogens and so directly affect human health, while others, such as isoprene, are very reactive in the atmosphere and play an important role in the formation of secondary pollutants such as ozone and particles. Here we report spatially-resolved measurements of the surface-to-atmosphere fluxes of VOCs across London and SE England made in 2013 and 2014. High-frequency 3-D wind velocities and VOC volume mixing ratios (made by proton transfer reaction - mass spectrometry) were obtained from a low-flying aircraft and used to calculate fluxes using the technique of eddy covariance. A footprint model was then used to quantify the flux contribution from the ground surface at spatial resolution of 100 m, averaged to 1 km. Measured fluxes of benzene over Greater London showed positive agreement with the UK's National Atmospheric Emissions Inventory, with the highest fluxes originating from central London. Comparison of MTBE and toluene fluxes suggest that petroleum evaporation is an important emission source of toluene in central London. Outside London, increased isoprene emissions were observed over wooded areas, at rates greater than those predicted by a UK regional application of the European Monitoring and Evaluation Programme model (EMEP4UK). This work demonstrates the applicability of the airborne eddy covariance method to the determination of anthropogenic and biogenic VOC fluxes and the possibility of validating emission inventories through measurements.

Joint instability leads to long-term alterations to knee synovium and osteoarthritis in a rabbit model.

OBJECTIVES: Joint instability is believed to promote early osteoarthritic changes in the knee. Inflammatory reactions are associated with cartilage degradation in osteoarthritis (OA) but their possible synergistic or additive effects remain largely unexplored. The goal of the present study was to investigate the in vivo effects of Botulinum Toxin A (BTX-A) induced joint instability on intraarticular alterations in an otherwise intact rabbit knee joint model. METHODS: Ten 1-year-old female New Zealand White rabbits (average 5.7 kg, range 4.8-6.6 kg) were randomly assigned to receive three monthly unilateral intramuscular injections of BTX-A (experimental group), or no treatment (control group). After 90 days, all knees were analyzed for specific mRNA levels using RT-qPCR. The synovium and cartilage tissue was assessed for histological alterations using the OARSI scoring system. RESULTS: Cartilage and synovial histology showed significant higher OARSI scores in the BTX-A group animals compared to the untreated controls and contralateral limbs. There were no differences between the untreated control and the contralateral experimental limbs. Gene expression showed significant elevations for collagen I, collagen III, nitric oxide, TGF-ß, IL-1 and IL-6 compared to the healthy controls. CONCLUSION: BTX-A induced joint instability in a muscle weakness model uniquely leads to alterations in gene expression and histological changes in the synovial membranes and cartilage in otherwise intact knee joints. These results lead to the conclusion that joint instability may promote an inflammatory intraarticular milieu, thereby contributing to the development of OA.

Spatially resolved flux measurements of NOx from London suggest significantly higher emissions than predicted by inventories.

To date, direct validation of city-wide emissions inventories for air pollutants has been difficult or impossible. However, recent technological innovations now allow direct measurement of pollutant fluxes from cities, for comparison with emissions inventories, which are themselves commonly used for prediction of current and future air quality and to help guide abatement strategies. Fluxes of NOx were measured using the eddy-covariance technique from an aircraft flying at low altitude over London. The highest fluxes were observed over central London, with lower fluxes measured in suburban areas. A footprint model was used to estimate the spatial area from which the measured emissions occurred. This allowed comparison of the flux measurements to the UK's National Atmospheric Emissions Inventory (NAEI) for NOx, with scaling factors used to account for the actual time of day, day of week and month of year of the measurement. The comparison suggests significant underestimation of NOx emissions in London by the NAEI, mainly due to its under-representation of real world road traffic emissions. A comparison was also carried out with an enhanced version of the inventory using real world driving emission factors and road measurement data taken from the London Atmospheric Emissions Inventory (LAEI). The measurement to inventory agreement was substantially improved using the enhanced version, showing the importance of fully accounting for road traffic, which is the dominant NOx emission source in London. In central London there was still an underestimation by the inventory of 30-40% compared with flux measurements, suggesting significant improvements are still required in the NOx emissions inventory.

A randomised trial of the cool pad pillow topper versus standard care for sleep disturbance and hot flushes in women on endocrine therapy for breast cancer.

PURPOSE: Quality of life in women receiving adjuvant endocrine therapy for breast cancer (BC) may be impaired by hot flushes and night sweats. The cool pad pillow topper (CPPT) is a commercial product, promoted to improve quality of sleep disrupted by hot flushes. This study aimed to identify if the CPPT reduces severity of sleep disturbance by minimising effects of hot flushes. METHODS: This randomised phase II trial, recruited women with BC, on adjuvant endocrine therapy, experiencing hot flushes and insomnia. Participants were randomised (stratified by baseline sleep efficiency score (SES) and menopausal status) to the intervention arm (CPPT + standard care) or control arm (standard care). Participants completed Hospital Anxiety and Depression Scale and Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaires and fortnightly sleep/hot flush diaries (where responses were averaged over 2-week periods). The primary endpoint was change in average SES from -2 to 0 weeks to 2 to 4 weeks. RESULTS: Seventy-four pre- (68.9 %) and post-menopausal (31.1 %) women were recruited. Median age was 49.5 years. Endocrine therapies included tamoxifen (93.2 %). Median SES at weeks 2 to 4 improved in both arms but the increase on the intervention arm was almost twice that on the control arm (p = 0.024). There were significantly greater reductions in hot flushes and HADS depression in the intervention arm (p = 0.09 and p = 0.036, respectively). There were no significant differences in FACT-B or HADS anxiety. CONCLUSION: This study supports the use of the CPPT as an aid to reduce sleep disturbance and the frequency/severity of hot flushes.

Impact of Biofuel Poplar Cultivation on Ground-Level Ozone and Premature Human Mortality Depends on Cultivar Selection and Planting Location.

Isoprene and other volatile organic compounds emitted from vegetation play a key role in governing the formation of ground-level ozone. Emission rates of such compounds depend critically on the plant species. The cultivation of biofuel feedstocks will contribute to future land use change, altering the distribution of plant species and hence the magnitude and distribution of emissions. Here we use relationships between biomass yield and isoprene emissions derived from experimental data for 29 commercially available poplar hybrids to assess the impact that the large-scale cultivation of poplar for use as a biofuel feedstock will have on air quality, specifically ground-level ozone concentrations, in Europe. We show that the increases in ground-level ozone across Europe will increase the number of premature deaths attributable to ozone pollution each year by up to 6%. Substantial crop losses (up to ∼9 Mt y(-1) of wheat and maize) are also projected. We further demonstrate that these impacts are strongly dependent on the location of the poplar plantations, due to the prevailing meteorology, the population density, and the dominant crop type of the region. Our findings indicate the need for a concerted and centralized decision-making process that considers all aspects of future land use change in Europe, and not just the effect on greenhouse gas emissions.

Isoprene emission protects photosynthesis but reduces plant productivity during drought in transgenic tobacco (Nicotiana tabacum) plants.

Isoprene protects the photosynthetic apparatus of isoprene-emitting plants from oxidative stress. The role of isoprene in the response of plants to drought is less clear. Water was withheld from transgenic isoprene-emitting and non-emitting tobacco (Nicotiana tabacum) plants, to examine: the response of isoprene emission to plant water deficit; a possible relationship between concentrations of the drought-induced phytohormone abscisic acid (ABA) and isoprene; and whether isoprene affected foliar reactive oxygen species (ROS) and lipid peroxidation levels. Isoprene emission did not affect whole-plant water use, foliar ABA concentration or leaf water potential under water deficit. Compared with well-watered controls, droughted non-emitting plants significantly increased ROS content (31-46%) and lipid peroxidation (30-47%), concomitant with decreased operating and maximum efficiencies of photosystem II photochemistry and lower leaf and whole-plant water use efficiency (WUE). Droughted isoprene-emitting plants showed no increase in ROS content or lipid peroxidation relative to well-watered controls, despite isoprene emission decreasing before leaf wilting. Although isoprene emission protected the photosynthetic apparatus and enhanced leaf and whole-plant WUE, non-emitting plants had 8-24% more biomass under drought, implying that isoprene emission incurred a yield penalty.

Trial Forge Guidance 4: a guideline for reporting the results of randomised Studies Within A Trial (SWATs).

BACKGROUND: Evidence to support decisions on trial processes is minimal. One way to generate this evidence is to use a Study Within A Trial (SWAT) to test trial processes or explore methodological uncertainties. SWAT evidence relies on replication to ensure sufficient power and broad applicability of findings. Prompt reporting is therefore essential; however, SWAT publications are often the first to be abandoned in the face of other time pressures. Reporting guidance for embedded methodology trials does exist but is not widely used. We sought therefore to build on these guidelines to develop a straightforward, concise reporting standard, which remains adherent to the CONSORT guideline. METHODS: An iterative process was used to develop the guideline. This included initial meetings with key stakeholders, development of an initial guideline, pilot testing of draft guidelines, further iteration and pilot testing, and finalisation of the guideline. RESULTS: We developed a reporting guideline applicable to randomised SWATs, including replications of previous evaluations. The guideline follows the Consolidated Standards for Reporting Trials (CONSORT) statement and provides example text to ensure ease and clarity of reporting across all domains. CONCLUSIONS: The SWAT reporting guideline will aid authors, reviewers, and journal editors to produce and review clear, structured reports of randomised SWATs, whilst also adhering to the CONSORT guideline. TRIAL REGISTRATION: EQUATOR Network - Guidelines Under Development ( https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-clinical-trials/#SWAT ). Registered on 25 March 2021.