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Carboxylic ester hydrolases with the capacity to degrade polyesters are currently highly sought after for their potential use in the biological degradation of PET and other chemically synthesized polymers. Here, we describe MarCE, a carboxylesterase family protein identified via genome mining of a Maribacter sp. isolate from the marine sponge Stelligera stuposa. Based on phylogenetic analysis, MarCE and its closest relatives belong to marine‐associated genera from the Cytophaga–Flavobacterium–Bacteroides taxonomic group and appear evolutionarily distinct to any homologous carboxylesterases that have been studied to date in terms of structure or function. Molecular docking revealed putative binding of BHET, a short‐chain PET derivative, onto the predicted MarCE three‐dimensional structure. The synthetic ester‐degrading activity of MarCE was subsequently confirmed by MarCE‐mediated hydrolysis of 2 mM BHET substrate, indicated by the release of its breakdown products MHET and TPA, which were measured, respectively, as 1.28 and 0.12 mM following 2‐h incubation at 30°C. The findings of this study provide further insight into marine carboxylic ester hydrolases, which have the potential to display unique functional plasticity resulting from their adaptation to complex and fluctuating marine environmentsw. [ABSTRACT FROM AUTHOR]

The demand for more efficient gas turbines relies heavily on the development of new environmental‐thermal barrier coatings (ETBCs). However, there is still uncertainty about which alloys and composites will be used for the next generation of turbine blades, as well as the most promising coating materials. Herein, an ETBCs development strategy is presented by integrating the coating design, synthesis, and screening using an ultrafast high temperature sintering (UHS) technique to accelerate coating improvements. The initial basis for composition selection is their thermal expansion mismatch with the substrate alloys; for which a temperature‐dependent coefficient of thermal expansion database is created. By combining tape casting method with the UHS technique a high‐throughput synthesis of single and multi‐layer coatings are realized with different compositions, layer stacking sequences, and layer thicknesses. To evaluate the coatings, thermal cycling tests from room temperature to 1300 °C are conducted. The approach enabled coatings on objects with complex geometries, multi‐layer ETBCs, and porosity tailoring by using staged UHS that runs with different temperatures and durations. The fast iteration strategy is more cost‐effective for the screening of ETBCs compared to conventional methods and greater throughput which can be further extended for rapid optimization of other materials systems. [ABSTRACT FROM AUTHOR]

The Kunming‐Montreal Global Biodiversity Framework (GBF) calls for a 50% reduction in rates of invasive alien species establishment by 2030. However, estimating changes in rates of introduction and establishment is far from straightforward, particularly on a national scale. Variation in survey effort over time, the absence of data on survey effort, and aspects of the invasion process itself interact in ways that make rate estimates from naive models of invasion trends inaccurate. To support progress toward robust global and national reporting against the GBF invasions target, we illustrate this problem using a combination of simulations, and global and national scale case studies. We provide recommendations and a clear set of steps that are needed for progress. These include routine collection of survey effort data as part of surveillance and monitoring protocols and working closely with researchers to develop meaningful estimates of change in biological invasions. Better awareness of this challenge and investment in developing robust approaches will be required from Parties if progress on Target 6 of the GBF is to be tracked and achieved. [ABSTRACT FROM AUTHOR]

Background: People with serious mental illness (SMI) are underserved from a hepatitis C virus (HCV) screening and treatment perspective. Aims: To examine the HCV care cascade in people with SMI and to pilot a supported HCV treatment integration programme. Methods: HCV prevalence was retrospectively analysed from 4492 consecutive individuals admitted to a tertiary hospital mental health service between January 2017 and December 2018. Subcohort analysis of screening patterns and predictors of seropositive infection was performed. Referral pathways and community care integration were analysed for HCV‐positive individuals, and a prospective community‐based 'identify and treat' HCV programme was assessed. Results: Screening for HCV had been performed in 18.6% (835/4492) of the cohort. Seroprevalence was 4.6% (207/4492). HCV seropositivity was associated with age >40 years (odds ratio (OR) = 9.30; confidence interval (CI) 3.69–23.45; P < 0.01), injecting drug use (OR = 24.26; CI 8.99–65.43; P < 0.01) and previous incarceration (OR = 12.26; CI 4.51–33.31; P < 0.01). In a cohort of treatment‐eligible individuals, 43.3% (90/208) had neither been referred to specialist services or general practitioners for HCV management. Amongst those referred to specialist services, 64.7% (57/88) did not attend scheduled follow up, and 48.3% (15/31) of attendees were lost to follow up. Through an intensified community access programme, 10 people were successfully treated for HCV, although 22 could not be engaged. Conclusion: People with SMI are underserved by traditional models of HCV healthcare. Intensified community‐based support can partially bolster the treatment cascade, although investment in innovative screening and management strategies are required to achieve healthcare parity. [ABSTRACT FROM AUTHOR]

Protein misfolding and aggregation into oligomeric and fibrillar structures is a common feature of many neurogenerative disorders. Single‐molecule techniques have enabled characterization of these lowly abundant, highly heterogeneous protein aggregates, previously inaccessible using ensemble averaging techniques. However, they usually rely on the use of recombinantly‐expressed labeled protein, or on the addition of amyloid stains that are not protein‐specific. To circumvent these challenges, we have made use of a high affinity antibody labeled with orthogonal fluorophores combined with fast‐flow microfluidics and single‐molecule confocal microscopy to specifically detect α‐synuclein, the protein associated with Parkinson's disease. We used this approach to determine the number and size of α‐synuclein aggregates down to picomolar concentrations in biologically relevant samples. [ABSTRACT FROM AUTHOR]

Multilayer dielectric elastomer actuators have a wide range of potential applications, but their development and commercial implementation have been hindered by existing manufacturing processes. Existing processes are low‐throughput, limited in area, and/or can only process a narrow range of elastomers. This study presents a novel fabrication paradigm that overcomes these challenges: instead of sequentially patterning electrodes directly onto successive elastomer layers, electrode stamps are patterned onto a carrier film in an independent batch‐spray process and the electrodes are then stamp‐transferred onto each elastomer layer. By modularizing the production and assembly of electrodes, a laboratory‐scale implementation of the process achieves a throughput of 15 layers h−1, a maximum electrode size of 300×300 mm, and tuning‐free compatibility with a wide range of elastomers. The batch‐spraying paradigm also provides the unique capability to evaluate and modify electrodes before they are assembled into a multilayer; a method of mechanically treating the electrodes is employed to increase the breakdown strength of Elastosil P7670 devices from 15.7 to 33.5 V µm−1. The electrodes are conductive up to a strain of more than 200% and add negligible stiffness to the multilayer structure. The capabilities of this process to produce useful devices are demonstrated with a large‐area loudspeaker and an actuator with 60 active layers. [ABSTRACT FROM AUTHOR]

Monitoring the progress parties have made toward meeting global biodiversity targets requires appropriate indicators. The recognition of invasive alien species (IAS) as a biodiversity threat has led to the development of specific targets aiming at reducing their prevalence and impact. However, indicators for adequately monitoring and reporting on the status of biological invasions have been slow to emerge, with those that exist being arguably insufficient. We performed a systematic review of the peer‐reviewed literature to assess the adequacy of existing IAS indicators against a range of policy‐relevant and scientifically valid properties. We found that very few indicators have most of the desirable properties and that existing indicators are unevenly spread across the components of the Driver‐Pressure‐State‐Response and Theory of Change frameworks. We provide three possible reasons for this: (i) inadequate attention paid to the requirements of an effective IAS indicator, (ii) insufficient data required to populate and inform policy‐relevant, scientifically robust indicators, or (iii) deficient investment in the development and maintenance of IAS indicators. This review includes an analysis of where current inadequacies in IAS indicators exist and provides a roadmap for the future development of indicators capable of measuring progress made toward mitigating and halting biological invasions. [ABSTRACT FROM AUTHOR]

Broadly, Höcke's response to the ZPS's action was characterized by seeking a victim role for himself and his family, from which position he sought to portray the ZPS activists as dangerous elements who themselves had no place in a democratic society. For example, on the ZPS's web pages dedicated to Bornhagen, comments by AfD politicians and supporters decrying the ZPS as terrorists are shown alongside criticism from the Christian Democrats, all under the banner "The AfD's praise for our action." The ZPS also attracted attention from the police, after a complaint that the group were subjecting Höcke to illegal coercion by insisting that they would only end the action if he kneeled before their memorial and asked for forgiveness (Reinsch, 2017).[1] From the point of view of agonistic politics, this approach on the part of the ZPS also has certain problematic aspects. While producing footage of ZPS members in camouflage gear and trench coats, the ZPS had collected publicly available information and images on Höcke and his property, montaging these together in their promotional films to create the impression that an observation had been underway. [Extracted from the article]

Various approaches to first‐in‐human (FIH) starting dose selection for new molecular entities (NMEs) are designed to minimize risk to trial subjects. One approach uses the minimum anticipated biological effect level (MABEL), which is a conservative method intended to maximize subject safety and designed primarily for NMEs having high perceived safety risks. However, there is concern that the MABEL approach is being inappropriately used for lower risk molecules with negative impacts on drug development and time to patient access. In addition, ambiguity exists in how MABEL is defined and the methods used to determine it. The International Consortium for Innovation and Quality in Pharmaceutical Development convened a working group to understand current use of MABEL and its impact on FIH starting dose selection, and to make recommendations for FIH dose selection going forward. An industry‐wide survey suggested the achieved or estimated maximum tolerated dose, efficacious dose, or recommended phase II dose was > 100‐fold higher than the MABEL‐based starting dose for approximately one third of NMEs, including trials in patients. A decision tree and key risk factor table were developed to provide a consistent, data driven‐based, and risk‐based approach for selecting FIH starting doses. [ABSTRACT FROM AUTHOR]

Active soft materials that change shape on demand are of interest for a myriad of applications, including soft robotics, biomedical devices, and adaptive systems. Despite recent advances, the ability to rapidly design and fabricate active matter in complex, reconfigurable layouts remains challenging. Here, the 3D printing of core‐sheath‐shell dielectric elastomer fibers (DEF) and fiber bundles with programmable actuation is reported. Complex shape morphing responses are achieved by printing individually addressable fibers within 3D architectures, including vertical coils and fiber bundles. These DEF devices exhibit resonance frequencies up to 700 Hz and lifetimes exceeding 2.6 million cycles. The multimaterial, multicore‐shell 3D printing method opens new avenues for creating active soft matter with fast programable actuation. [ABSTRACT FROM AUTHOR]

Change in global mean surface temperature (ΔGMST), based on a blend of land air and ocean water temperatures, is a widely cited climate change indicator that informs the Paris Agreement goal to limit global warming since preindustrial to "well below" 2°C. Assessment of current ΔGMST enables determination of remaining target‐consistent warming and therefore a relevant remaining carbon budget. In recent IPCC reports, ΔGMST was estimated via linear regression or differences between decade‐plus period means. We propose nonlinear continuous local regression (LOESS) using ±20 year windows to derive ΔGMST across all periods of interest. Using the three observational GMST data sets with almost complete interpolated spatial coverage since the 1950s, we evaluate 1850–1900 to 2019 ΔGMST as 1.14°C with a likely (17%–83%) range of 1.05°C–1.25°C, based on combined statistical and observational uncertainty, compared with linear regression of 1.05°C over 1880–2019. Performance tests in observational data sets and two model large ensembles demonstrate that LOESS, like period mean differences, is unbiased. However, LOESS also provides a statistical uncertainty estimate and gives warming through 2019, rather than the 1850–1900 to 2010–2019 period mean difference centered at the end of 2014. We derive historical global near‐surface air temperature change (ΔGSAT), using a subset of CMIP6 climate models to estimate the adjustment required to account for the difference between ocean water and ocean air temperatures. We find ΔGSAT of 1.21°C (1.11°C–1.32°C) and calculate remaining carbon budgets. We argue that continuous nonlinear trend estimation offers substantial advantages for assessment of long‐term observational ΔGMST. Key Points: Continuous local regression is an alternative to traditional IPCC temperature change estimation methodsGlobal warming, estimated from combined land and sea‐surface temperature observational series with enhanced surface coverage, reached 1.14°C in 2019 relative to 1850–1900 (likely range 1.05°C–1.25°C)Global surface air temperature anomalies reached 1.21°C in 2019 relative to 1850–1900 (1.11°C–1.32°C), implying a remaining carbon budget of ∼220 GtCO2 to limit warming to 1.5°C [ABSTRACT FROM AUTHOR]

Impact assessment is an important and cost‐effective tool for assisting in the identification and prioritization of invasive alien species. With the number of alien and invasive alien species expected to increase, reliance on impact assessment tools for the identification of species that pose the greatest threats will continue to grow. Given the importance of such assessments for management and resource allocation, it is critical to understand the uncertainty involved and what effect this may have on the outcome. Using an uncertainty typology and insects as a model taxon, we identified and classified the causes and types of uncertainty when performing impact assessments on alien species. We assessed 100 alien insect species across two rounds of assessments with each species independently assessed by two assessors. Agreement between assessors was relatively low for all three impact classification components (mechanism, severity, and confidence) after the first round of assessments. For the second round, we revised guidelines and gave assessors access to each other's assessments which improved agreement by between 20% and 30% for impact mechanism, severity, and confidence. Of the 12 potential reasons for assessment discrepancies identified a priori, 11 were found to occur. The most frequent causes (and types) of uncertainty (i.e., differences between assessment outcomes for the same species) were as follows: incomplete information searches (systematic error), unclear mechanism and/or extent of impact (subjective judgment due to a lack of knowledge), and limitations of the assessment framework (context dependence). In response to these findings, we identify actions that may reduce uncertainty in the impact assessment process, particularly for assessing speciose taxa with diverse life histories such as Insects. Evidence of environmental impact was available for most insect species, and (of the non‐random original subset of species assessed) 14 of those with evidence were identified as high impact species (with either major or massive impact). Although uncertainty in risk assessment, including impact assessments, can never be eliminated, identifying, and communicating its cause and variety is a first step toward its reduction and a more reliable assessment outcome, regardless of the taxa being assessed. [ABSTRACT FROM AUTHOR]

Objective: Common data elements (CDEs) are standardized questions and answer choices that allow aggregation, analysis, and comparison of observations from multiple sources. Clinical CDEs are foundational for learning health care systems, a data‐driven approach to health care focused on continuous improvement of outcomes. We aimed to create clinical CDEs for pediatric epilepsy. Methods: A multiple stakeholder group (clinicians, researchers, parents, caregivers, advocates, and electronic health record [EHR] vendors) developed clinical CDEs for routine care of children with epilepsy. Initial drafts drew from clinical epilepsy note templates, CDEs created for clinical research, items in existing registries, consensus documents and guidelines, quality metrics, and outcomes needed for demonstration projects. The CDEs were refined through discussion and field testing. We describe the development process, rationale for CDE selection, findings from piloting, and the CDEs themselves. We also describe early implementation, including experience with EHR systems and compatibility with the International League Against Epilepsy classification of seizure types. Results: Common data elements were drafted in August 2017 and finalized in January 2020. Prioritized outcomes included seizure control, seizure freedom, American Academy of Neurology quality measures, presence of common comorbidities, and quality of life. The CDEs were piloted at 224 visits at 10 centers. The final CDEs included 36 questions in nine sections (number of questions): diagnosis (1), seizure frequency (9), quality of life (2), epilepsy history (6), etiology (8), comorbidities (2), treatment (2), process measures (5), and longitudinal history notes (1). Seizures are categorized as generalized tonic‐clonic (regardless of onset), motor, nonmotor, and epileptic spasms. Focality is collected as epilepsy type rather than seizure type. Seizure frequency is measured in nine levels (all used during piloting). The CDEs were implemented in three vendor systems. Early clinical adoption included 1294 encounters at one center. Significance: We created, piloted, refined, finalized, and implemented a novel set of clinical CDEs for pediatric epilepsy. [ABSTRACT FROM AUTHOR]

Leupeptin is a bacterial small molecule that is used worldwide as a protease inhibitor. However, its biosynthesis and genetic distribution remain unknown. We identified a family of leupeptins in gammaproteobacterial pathogens, including Photorhabdus, Xenorhabdus, and Klebsiella species, amongst others. Through genetic, metabolomic, and heterologous expression analyses, we established their construction by discretely expressed ligases and accessory enzymes. In Photorhabdus species, a hypothetical protein required for colonizing nematode hosts was established as a new class of proteases. This enzyme cleaved the tripeptide aldehyde protease inhibitors, leading to the formation of "pro‐pyrazinones" featuring a hetero‐tricyclic architecture. In Klebsiella oxytoca, the pathway was enriched in clinical isolates associated with respiratory tract infections. Thus, the bacterial production and proteolytic degradation of leupeptins can be associated with animal colonization phenotypes. [ABSTRACT FROM AUTHOR]

Background: Self‐harm amongst young people is an increasing problem, with looked‐after young people at higher risk. Despite this, little research exists on what young people who self‐harm find helpful. Method: One hundred and twenty‐six 11–21 year olds (53 who had experience of the care system and 73 who did not) were recruited from the community and NHS. All participants had self‐harmed in the past 6 months. Participants completed an Audio Computer‐Assisted Self‐interview (ACASI) regarding their views about the support they had received, how helpful it was, and what further help they felt they needed. Results: Looked‐after young people reported the three most helpful sources of support were Child and Adolescent Mental Health Services (CAMHS), friends and pets and the least helpful were CAMHS, Accident and Emergency (A&E) and Social services. For non‐looked‐after young people, CAMHS, counselling and Harmless (user‐led support service for self‐harm) were most helpful and CAMHS, cognitive behavioural therapy (CBT) and general practitioner (GP) were the least. Compared with the other group, more looked‐after young people had received help from A&E and CAMHS, whereas more non‐looked‐after young people had accessed GPs, parents, psychological therapies, self‐help books and websites. More looked‐after young people found support groups helpful, and more non‐looked‐after young people reported that distraction techniques, medication and their siblings were helpful. Conclusion: Young people who self‐harm have mixed views about CAMHS. Differences in the pattern of access and preferences for support between looked‐after and non‐looked‐after young people should be reflected in service availability and commissioning. Key Practitioner Message: Little is known about what young people who self‐harm find helpful, particularly for looked‐after young people.CAMHS was named amongst the most helpful and the least helpful services by both looked‐after and non‐looked‐after young people.Social services and A&E were frequently cited amongst the least helpful sources of support.Young people report finding informal support helpful, including family and friends.There appears to be a need for explorations of the reasons behind the apparent negative perception of statutory services in young people, and what is required to shift that. [ABSTRACT FROM AUTHOR]

Issues Addressed: Although cannabis use is still illegal in most places around the world, it remains a widely used drug. The recreational use of cannabis has been linked to multiple mental wellbeing issues, including psychosis, depression and anxiety. The objective of this study was to investigate the temporal dynamics of cannabis use in relation to mental health issues.Methods: The current research uses a novel methodological approach, behaviour sequence analysis, to understand the temporal relationship between recreational cannabis use and surrounding issues related to mental wellbeing, in a sample of 61 participants who had written autobiographical accounts online.Results: The results indicated a bi-directional temporal ordering between cannabis use and mood disorders. Cannabis use preceded psychosis and can also exacerbate symptoms of psychosis, depression and anxiety. Findings also suggested that low self-esteem may be a predictor of future cannabis use.Conclusions: Research shows a link between mood disorders and recreational cannabis use. The BSA method can be used in applied settings to map pathways in individuals' life histories. SO WHAT?: The current study shows the sequential links between cannabis use and psychosis, depression and anxiety. Results show there is no single clear pathway and clinical practitioners should focus on a wider range of factors in individual's case histories. [ABSTRACT FROM AUTHOR]

Background: Interest in how stroke survivors might be better supported to manage life after stroke has grown rapidly in recent years, with a particular emphasis on enabling 'self‐management'. Post‐stroke communication difficulties may pose a unique barrier to longer term adaptation and adjustment. It is important to understand how stroke survivors with communication difficulties manage life after stroke and what support may be needed to facilitate this process. Aims: To explore how stroke survivors with communication difficulties manage life after stroke in the first year. Methods & Procedures: A cross‐sectional qualitative study involving in‐depth semi‐structured interviews with stroke survivors with communication difficulties (aphasia, dysarthria or apraxia of speech) and/or their family members at single time points during the first year post‐stroke. A total of 21 participants (14 stroke survivors and seven family members) took part in interviews for the study. Interview data were analysed using thematic analysis. Outcome & Results: A total of six themes were identified: (1) strategies to manage changes to communication; (2) testing communication outside of the home; (3) balancing support and independence; (4) hope for recovery; (5) obtaining support from healthcare professionals; and (6) adapting activities and keeping busy. Stroke survivors with communication difficulties and their family members undertook significant work (practical, relational, emotional) to manage their condition. Adaptation and adjustment was often facilitated by 'doing'; testing out which activities could be managed independently and which required additional support. Some stroke survivors and their family members demonstrated considerable resourcefulness and creativity in developing strategies to manage their communication difficulties. Despite the work undertaken, many expressed a lack of confidence in their ability and feelings of powerlessness and abandonment at the point of discharge from community services. Conclusions & Implications: Stroke survivors and their family members develop personally meaningful and context‐specific strategies to adjust to and manage life after stroke. Future interventions should recognize, support and build upon the active work already undertaken by stroke survivors with communication difficulties and their families. Further support before and around the point of discharge from community services may be needed to help build confidence and skills to manage in the longer term. The benefit of a supported self‐management approach for stroke survivors with communication difficulties should be further investigated. [ABSTRACT FROM AUTHOR]

Abstract: Oligopeptide‐based supramolecular hydrogels hold promise in a range of applications. The gelation of these systems is hard to control, with minor alterations in the peptide sequence significantly influencing the self‐assembly process. We explored three pentapeptide sequences with different charge distributions and discovered that they formed robust, pH‐responsive hydrogels. By altering the concentration and charge distribution of the peptide sequence, the stiffness of the hydrogels could be tuned across two orders of magnitude (2–200 kPa). Also, through reassembly of the β‐sheet interactions the hydrogels could self‐heal and they demonstrated shear‐thin behavior. Using spectroscopic and cryo‐imaging techniques, we investigated the relationship between peptide sequence and molecular structure, and how these influence the mechanical properties of the hydrogel. These pentapeptide hydrogels with tunable morphology and mechanical properties have promise in tissue engineering, injectable delivery vectors, and 3D printing applications. [ABSTRACT FROM AUTHOR]

Abstract: This article examines the process of training informal carers on stroke units using the lens of power. Care is usually assumed as a kinship obligation but the state has long had an interest in framing the carer and caring work. Training carers in healthcare settings raises questions about the power of the state and healthcare professionals as its agents to shape expectations and practices related to the caring role. Drawing on Foucault's notion of disciplinary power, we show how disciplinary forms of power exercised in interactions between healthcare professionals and carers shape the engagement and resistance of carers in the process of training. Interview and observational field note extracts are drawn from a multi‐sited study of a training programme on stroke units targeting family carers of people with stroke to consider the consequences of subjecting caring to this intervention. We found that the process of training informal carers on stroke units was not simply a matter of transferring skills from professional to lay person, but entailed disciplinary forms of power intended to shape the conduct of the carer. We interrogate the extent to which a specific kind of carer is produced through such an approach, and the wider implications for the participation of carers in training in healthcare settings and the empowerment of carers. [ABSTRACT FROM AUTHOR]

This essay introduces three 18th century Chinese visitors to Britain, analysing the important role they played in cross‐cultural intellectual and artistic contact between the two countries. Loum Kiqua, a merchant, arrived in London in 1756. He gave the first known performance on a Chinese musical instrument in the West. Chitqua, a portrait modeller who arrived in 1769, exhibited at the newly‐established Royal Academy (becoming the first named Chinese artist to have a work shown in an overseas exhibit). Whang at Tong (Whang Atong, Huang Yadong), was only in his early 20s at the time of his arrival in England in August 1774, but he played a significant role in the transfer of botanical knowledge from China to the West through his connections with John Bradby Blake in Canton and his father John Blake in London. [ABSTRACT FROM AUTHOR]

Objectives Young people in the public care system ('looked-after' young people) have high levels of self-harm. Design This paper reports the first detailed study of factors leading to self-harm over time in looked-after young people in England, using sequence analyses of the Card Sort Task for Self-harm (Ca TS). Methods Young people in care (looked-after group: n = 24; 14-21 years) and young people who had never been in care (contrast group: n = 21; 13-21 years) completed the Ca TS, describing sequences of factors leading to their first and most recent episodes of self-harm. Lag sequential analysis determined patterns of significant transitions between factors (thoughts, feelings, behaviours, events) leading to self-harm across 6 months. Results Young people in care reported feeling better immediately following their first episode of self-harm. However, fearlessness of death, impulsivity, and access to means were reported most proximal to recent self-harm. Although difficult negative emotions were salient to self-harm sequences in both groups, young people with no experience of being in care reported a greater range of negative emotions and transitions between them. For the contrast group, feelings of depression and sadness were a significant starting point of the self-harm sequence 6 months prior to most recent self-harm. Conclusions Sequences of factors leading to self-harm can change and evolve over time, so regular monitoring and assessment of each self-harm episode are needed. Support around easing and dealing with emotional distress is required. Restricting access to means to carry out potentially fatal self-harm attempts, particularly for the young persons with experience of being in care, is recommended. Practitioner points Self-harm (and factors associated with self-harm) can change and evolve over time; assessments need to reflect this., Looked-after young people reported feeling better after first self-harm; fearlessness of death, access to means, and impulsivity were reported as key in recent self-harm., Underlying emotional distress, particularly depression and self-hatred were important in both first and most recent self-harm., Looked-after young people should undergo regular monitoring and assessment of each self-harm episode and access to potentially fatal means should be restricted., The CaTS would have clinical utility as an assessment tool, Recruiting participants can be a significant challenge in studies with looked-after children and young people., Future research with larger clinical samples would be valuable. [ABSTRACT FROM AUTHOR]

We investigate a new proxy for ENSO climate variability based on particle-size data from long-term, coastal sediment records preserved in a barrier estuary setting. Corresponding ~4-8 year periodicities identified from Wavelet analysis of particle-size data from Pescadero Marsh in Central Coast California and rainfall data from San Francisco reflect established ENSO periodicity, as further evidenced in the Multivariate ENSO Index (MEI), and thus confirms an important ENSO control on both precipitation and barrier regime variability. Despite the fact that barrier estuary mean particle size is influenced by coastal erosion, precipitation and streamflow, balanced against barrier morphology and volume, it is encouraging that considerable correspondence can also be observed in the time series of MEI, regional rainfall and site-based mean particle size over the period 1871-2008. This correspondence is, however, weakened after c.1970 by temporal variation in sedimentation rate and event-based deposition. These confounding effects are more likely when: (i) accommodation space may be a limiting factor; and (ii) particularly strong El Niños, e.g. 1982/1983 and 1997/1998, deposit discrete >cm-thick units during winter storms. The efficacy of the sediment record of climate variability appears not to be compromised by location within the back-barrier setting, but it is limited to those El Niños that lead to barrier breakdown. For wider application of this particle size index of ENSO variability, it is important to establish a well-resolved chronology and to sample the record at the appropriate interval to characterize deposition at a sub-annual scale. Further, the sample site must be selected to limit the influence of decreasing accommodation space through time (infilling) and event-based deposition. It is concluded that particle-size data from back-barrier sediment records have proven potential for preserving evidence of sub-decadal climate variability, allowing researchers to explore temporal and spatial patterns in phenomena such as ENSO. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Lateral impact damage from over-height vehicle collisions with bridge superstructures is of increasing concern in the United States. However this issue is not fully addressed in current bridge specifications. Previous researchers have conducted a number of small-scale tests to study the impact process. Also, the finite element method has largely been used to analyze the complicated collision mechanism. This paper provides an opportunity for full-scale lateral impact testing of a prestressed concrete girder, which leads to a realistic level of damage and mechanism analysis. A full-scale lateral impact testing facility was designed and built on a construction site in Knoxville, Tennessee. The over-height vehicle impact was simulated by impacting the bottom of an AASHTO Type I prestressed concrete girder with an impact cart. This paper describes the details of the impact testing facility as well as the response of the prestressed concrete girder during lateral impact. The collected test data were calibrated by using finite element software ABAQUS. [ABSTRACT FROM AUTHOR]

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, plays a critical role in the orchestration of immune responses. S1P levels within the mammalian host are tightly regulated, in part through the activity of S1P lyase (S1PL) which catalyses its irreversible degradation. Herein, we describe the identification and characterization of secreted S1PL orthologues encoded by the facultative intracellular bacteria Burkholderia pseudomallei and Burkholderia thailandensis. These bacterial orthologues exhibited S1PL enzymatic activity, functionally complemented an S1PL-deficient yeast strain and conferred resistance to the antimicrobial sphingolipid D- erythro-sphingosine. We report that secretion of these bacterial S1PLs is pH-dependent, and is observed during intracellular infection. S1PL-deficient mutants displayed impaired intracellular replication in murine macrophages (associated with an inability to evade the maturing phagosome) and were significantly attenuated in murine and larval infection models. Furthermore, treatment of Burkholderia-infected macrophages with either S1P or a selective agonist of S1P receptor 1 enhanced bacterial colocalisation with LAMP-1 and reduced their intracellular survival. In summary, our studies confirm bacterial-encoded S1PL as a critical virulence determinant of B. pseudomallei and B. thailandensis, further highlighting the pivotal role of S1P in host-pathogen interactions. In addition, our data suggest that S1P pathway modulators have potential for the treatment of intracellular infection. [ABSTRACT FROM AUTHOR]

We demonstrate the preparation of surface-bound cucurbit[8]uril (CB[8]) catenanes on silica nanoparticles (NPs), where CB[8] was employed as a tethered supramolecular 'handcuff' to selectively capture target guest molecules. In this catenane, CB[8] was threaded onto a methyl viologen (MV2+) axle and immobilized onto silica NPs. The formation of CB[8] catenanes on NPs were confirmed by UV/Vis titration experiments and lithographic characterization, demonstrating a high density of CB[8] on the silica NPs surface, 0.56 nm−2. This CB[8] catenane system exhibits specific molecular recognition towards certain aromatic molecules such as perylene bis(diimide), naphthol and aromatic amino acids, and thus it can act as a nanoscale molecular receptor for target guests. Furthermore, we also demonstrate its use as an efficient and recyclable nano-platform for peptide separation. By embedding magnetic NPs inside silica NPs, separation could be achieved by simply applying an external magnetic field. Moreover, the peptides captured by the catenanes could be released by reversible single-electron reduction of MV2+. The entire process demonstrated high recoverability. [ABSTRACT FROM AUTHOR]

Background: The recently refined Demoralization Scale-II (DS-II) is a 16-item, self-report measure of demoralization. Its 2 factors-Meaning and Purpose and Distress and Coping Ability-demonstrate sound internal validity, including item fit, unidimensionality, internal consistency, and test-retest reliability. The convergent and discriminant validity of the DS-II with various measures is reported here.Methods: Patients who had cancer or other progressive diseases and were receiving palliative care (n = 211) completed a battery of questionnaires, including the DS-II and measures of symptom burden, quality of life, depression, and attitudes toward the end of life. Spearman ρ correlations were determined to assess convergent validity. Mann-Whitney U tests with calculated effect sizes were used to examine discriminant validity and establish the minimal clinically important difference (MCID). Cross-tabulation frequencies with chi-square analyses were used to examine discriminant validity with major depression.Results: The DS-II demonstrated convergent validity with measures of psychological distress, quality of life, and attitudes toward the end of life. It also demonstrated discriminant validity, as the DS-II differentiated patients who had different functional performance levels and high/low symptoms, with a difference of 2 points between groups on the DS-II considered clinically meaningful. Furthermore, discriminant validity was demonstrated, as comorbidity with depression was not observed at moderate levels of demoralization.Conclusions: The DS-II has sound psychometric properties and is an appropriate measure of demoralization. Given its structural simplicity and brevity, it is likely to be a useful tool in meaning-centered therapies. Cancer 2016;122:2260-7. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The Demoralization Scale (DS) was initially validated in 2004 to enable the measurement of demoralization in patients with advanced cancer. Subsequent shortcomings indicated the need for psychometric strengthening. Here, the authors report on the refinement and revalidation of the DS to form the DS-II, specifically reporting the scale's internal validity.Methods: Patients with cancer or other progressive diseases who were receiving palliative care (n = 211) completed a revised version of the 24-item DS and a measure of symptom burden (the Memorial Symptom Assessment Scale). Exploratory factor analysis and Rasch modeling were used to evaluate, modify, and revalidate the scale, providing information about dimensionality, suitability of response format, item fit, item bias, and item difficulty. Test-retest reliability was examined for 58 symptomatically stable patients at a 5-day follow-up.Results: Exploratory factor analysis supported a 22-item, 2-component model. Separate Rasch modeling of each component resulted in collapsing the response option categories and removing 3 items from each component. Both final 8-item subscales met Rasch model expectations and were appropriate to sum as a 16-item total score. The DS-II demonstrated internal consistency and test-retest reliability (Meaning and Purpose subscale: α = .84; intraclass correlation [ICC] = 0.68; Distress and Coping Ability subscale: α = .82; ICC = 0.82; total DS: α = .89; ICC = 0.80).Conclusions: The DS-II is a 3-point response, self-report scale comprising 16 items and 2 subscales. Given its revalidation, psychometric strengthening, and simplification, the DS-II is an improved and more practical measure of demoralization for research and clinical use. External validation of the DS-II will be reported subsequently. Cancer 2016;122:2251-9. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

The enteric gamma-proteobacterium Photorhabdus luminescens kills a wide range of insects, whilst also maintaining a mutualistic relationship with soil nematodes from the family Heterorhabditis. Pathogenicity is associated with bacterial exponential growth, whilst mutualism is associated with post-exponential (stationary) phase. During post-exponential growth, P. luminescens also elaborates an extensive secondary metabolism, including production of bioluminescence, antibiotics and pigment. However, the regulatory network that controls the expression of this secondary metabolism is not well understood. The stringent response is a well-described global regulatory system in bacteria and mediated by the alarmone (p)ppGpp. In this study, we disrupted the genes relA and spoT, encoding the two predicted (p)ppGpp synthases of P. luminescens TTO1, and we showed that (p)ppGpp is required for secondary metabolism. Moreover, we found the (p)ppGpp is not required for pathogenicity of P. luminescens, but is required for bacterial survival within the insect cadaver. Finally, we showed that (p)ppGpp is required for P. luminescens to support normal nematode growth and development. Therefore, the regulatory network that controls the transition from pathogenicity to mutualism in P. luminescens requires (p)ppGpp. This is the first report outlining a role for (p)ppGpp in controlling the outcome of an interaction between a bacteria and its host. [ABSTRACT FROM AUTHOR]

The amount of substance and its unit the mole is a basic concept in chemistry. However, previous research has shown that teaching and learning the concept are challenging tasks for both teachers and students. The purpose of this study was to pinpoint the problems which emerge in the teaching and learning process, and provide integrated suggestions for classroom instruction. By means of videotaping and interviews, the case studies explored how the mole is presented and conceptualized in two secondary classrooms in two different countries, Australia and Taiwan. Data analysis was based on a concept map and focused on how two key ideas were presented in the lessons and perceived by the students: (1) the definition of the mole, and (2) the concept of molar mass. The findings show that during the lessons on the mole, most of the time was spent on solving stoichiometric problems. Conceptually, the number aspect of the mole, that is, Avogadro's number, was emphasized; the concept of molar mass was introduced without meaningfully connecting it to the concept of relative atomic/molecular mass. Although the students were able to solve relevant problems, they could not coherently explain the relations among the concepts. Two critical components for a conceptual understanding of the mole emerged: (1) the number aspect of the mole needs to be justified by its mass aspect, and (2) the connection between molar mass and relative atomic/molecular mass needs to be explicitly explained. The two components provide one explanation for students' algorithmic learning and their confusion in learning about the mole, and serve as concrete suggestions for improving classroom instruction. The study once again manifested the significance of teaching for conceptual understanding in science education. It also exemplifies how a concept map of a specific scientific concept can also be a useful analytical tool in educational research. © 2015 Wiley Periodicals, Inc. J Res Sci Teach 53: 181-214, 2016. [ABSTRACT FROM AUTHOR]

Silicon oxycarbide glasses can be produced over a range of Si-O-C compositions by the controlled pyrolysis of polymer precursors. We present measurements of the thermal conductivity of a silicon oxycarbide glass after two different heat treatments and two Si-O-C nano-composites, hot-pressed at 1600°C, up to 1000°C and compare them to fused silica, amorphous carbon, and SiC. The temperature dependence of their thermal conductivities is similar to other amorphous materials. The presence of low volume fractions of nanoparticles of hafnia (4.5 v/o) or zirconia (7.4 v/o) dispersed within the amorphous matrix only modifies the conductivity slightly, consistent with a simple Maxwell model, and does not affect the temperature dependence of the thermal conductivity above room temperature. [ABSTRACT FROM AUTHOR]