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Team development and idea generation are key intertwined steps in translational science that need a framework to accommodate unstructured, participatory interactions. To this end, we introduced Un-Meetings to the Clinical and Translational Science Awards (CTSA) Program, innovative events that facilitate cross-disciplinary idea generation and informal discussions between translational scientists, policy makers, community members, advocates, and public health professionals. Here we describe a mixed methods study to characterize the conceptual diversity and clusterization of ideas generated through an Opioid Crisis Un-Meeting.
Methods:
An Un-Meeting targeting translation science approaches to the opioid crisis were hosted at the University of Rochester Center for Leading Innovation and Collaboration (CLIC). We used semantic analysis and conceptual mapping of keywords to analyze how attendee-led idea generation sessions identified topics for breakout discussions.
Results:
One hundred and two individuals from 40 institutions proposed 150 unique ideas that were grouped into 23 breakout sessions. Network analysis showed that diverse pools of experts were bridged by topics addressing the complexities of the opioid crisis. Two clusters emerged: (1) systems, contexts, and community engagement, and (2) technologies, innovations, and treatment advancements.
Conclusions:
The cross-disciplinary nature of topic areas that bridge across thematic communities provide opportunities for CTSA programs to engage and support development of diverse translational teams. Potential opportunities for team building include technological advancements of opioid prevention, treatment, surveillance, systems approaches, and studies focusing on special populations and health disparities. The analysis method here may be useful in identifying naturally emerging teams of experts and community gaps when addressing large problems.
In 2019 the present authors, along with our colleague Mic Spencer, began work on a project funded by the Leeds Institute for Teaching Excellence, designed to look at the ways in which we taught composition at the University of Leeds and how we might change them. Mic has focused on postgraduate teaching, and we have considered the earliest parts of the undergraduate curriculum, particularly the first two years of study, when the largest numbers of students with the least experience of the study of composition at tertiary level might be in a classroom (50 or so, in our case).
Bustards comprise a highly threatened family of birds and, being relatively fast, heavy fliers with very limited frontal visual fields, are particularly susceptible to mortality at powerlines. These infrastructures can also displace them from immediately adjacent habitat and act as barriers, fragmenting their ranges. With geographically ever wider energy transmission and distribution grids, the powerline threat to bustards is constantly growing. Reviewing the published and unpublished literature up to January 2021, we found 2,774 records of bustard collision with powerlines, involving 14 species. Some studies associate powerline collisions with population declines. To avoid mortalities, the most effective solution is to bury the lines; otherwise they should be either routed away from bustard-frequented areas, or made redundant by local energy generation. When possible, new lines should run parallel to existing structures and wires should preferably be as low and thick as possible, with minimal conductor obstruction of vertical airspace, although it should be noted that these measures require additional testing. A review of studies finds limited evidence that ‘bird flight diverters’ (BFDs; devices fitted to wires to induce evasive action) achieve significant reductions in mortality for some bustard species. Nevertheless, dynamic BFDs are preferable to static ones as they are thought to perform more effectively. Rigorous evaluation of powerline mortalities, and effectiveness of mitigation measures, need systematic carcass surveys and bias corrections. Whenever feasible, assessments of displacement and barrier effects should be undertaken. Following best practice guidelines proposed with this review paper to monitor impacts and mitigation could help build a reliable body of evidence on best ways to prevent bustard mortality at powerlines. Research should focus on validating mitigation measures and quantifying, particularly for threatened bustards, the population effects of powerline grids at the national scale, to account for cumulative impacts on bustards and establish an equitable basis for compensation measures.
The UK's relationship with the European Union (EU) is now embodied in two principal legal instruments: the EU–UK Trade and Cooperation Agreement, which formally entered into force on 1 May 2021; and the Withdrawal Agreement, with its Protocol on Ireland/Northern Ireland, which continues to apply. Using a ‘building blocks’ framework for analysis of national health systems derived from the World Health Organisation, this article examines the likely impacts in the UK of this legal settlement on the National Health Service (NHS), health and social care. Specifically, we determine the extent to which the trade, cooperation and regulatory aspects of those legal measures support positive impacts for the NHS and social care. We show that, as there is clear support for positive health and care outcomes in only one of the 17 NHS ‘building blocks’, unless mitigating action is taken, the likely outcomes will be detrimental. However, as the legal settlement gives the UK a great deal of regulatory freedom, especially in Great Britain, we argue that it is crucial to track the effects of proposed new health and social care-related policy choices in the months and years ahead.
Cultivation of lowbush blueberry (Vaccinium angustifolium Aiton), an important crop in the eastern part of North America, is unique, as it is carried out over the course of two consecutive growing seasons. Pest management, particularly weed management, is impacted by this biennial cultural practice. The choice of methods to control weeds is narrow, and such a system relies heavily on herbicides for weed management. Availability of unique herbicide active ingredients for weed management is limited, and available herbicides are used repeatedly, so the risk of developing resistance is acute. Hair fescue (Festuca filiformis Pourr.), a perennial grass weed, has evolved resistance to hexazinone, a photosystem II inhibitor frequently used in lowbush blueberry production. We show that substitution of phenylalanine to isoleucine at position 255 is responsible for a decreased sensitivity to hexazinone by a factor of 6.12. Early diagnosis of resistance based on the detection of the mutation will alert growers to use alternative control methods and thus help to increase the sustainability of the cropping system.
Following indirect-drive experiments which demonstrated promising performance for low convergence ratios (below 17), previous direct-drive simulations identified a fusion-relevant regime which is expected to be robust to hydrodynamic instability growth. This paper expands these results with simulated implosions at lower energies of 100 and 270 kJ, and ‘hydrodynamic equivalent’ capsules which demonstrate comparable convergence ratio, implosion velocity and in-flight aspect ratio without the need for cryogenic cooling, which would allow the assumptions of one-dimensional-like performance to be tested on current facilities. A range of techniques to improve performance within this regime are then investigated, including the use of two-colour and deep ultraviolet laser pulses. Finally, further simulations demonstrate that the deposition of electron energy into the hotspot of a low convergence ratio implosion through auxiliary heating also leads to significant increases in yield. Results include break even for 1.1 MJ of total energy input (including an estimated 370 kJ of short-pulse laser energy to produce electron beams for the auxiliary heating), but are found to be highly dependent upon the efficiency with which electron beams can be created and transported to the hotspot to drive the heating mechanism.
Subthreshold/attenuated syndromes are established precursors of full-threshold mood and psychotic disorders. Less is known about the individual symptoms that may precede the development of subthreshold syndromes and associated social/functional outcomes among emerging adults.
Methods
We modeled two dynamic Bayesian networks (DBN) to investigate associations among self-rated phenomenology and personal/lifestyle factors (role impairment, low social support, and alcohol and substance use) across the 19Up and 25Up waves of the Brisbane Longitudinal Twin Study. We examined whether symptoms and personal/lifestyle factors at 19Up were associated with (a) themselves or different items at 25Up, and (b) onset of a depression-like, hypo-manic-like, or psychotic-like subthreshold syndrome (STS) at 25Up.
Results
The first DBN identified 11 items that when endorsed at 19Up were more likely to be reendorsed at 25Up (e.g., hypersomnia, impaired concentration, impaired sleep quality) and seven items that when endorsed at 19Up were associated with different items being endorsed at 25Up (e.g., earlier fatigue and later role impairment; earlier anergia and later somatic pain). In the second DBN, no arcs met our a priori threshold for inclusion. In an exploratory model with no threshold, >20 items at 19Up were associated with progression to an STS at 25Up (with lower statistical confidence); the top five arcs were: feeling threatened by others and a later psychotic-like STS; increased activity and a later hypo-manic-like STS; and anergia, impaired sleep quality, and/or hypersomnia and a later depression-like STS.
Conclusions
These probabilistic models identify symptoms and personal/lifestyle factors that might prove useful targets for indicated preventative strategies.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Multiple micronutrient deficiencies are widespread in Ethiopia. However, the distribution of Se and Zn deficiency risks has previously shown evidence of spatially dependent variability, warranting the need to explore this aspect for wider micronutrients. Here, blood serum concentrations for Ca, Mg, Co, Cu and Mo were measured (n 3102) on samples from the Ethiopian National Micronutrient Survey. Geostatistical modelling was used to test spatial variation of these micronutrients for women of reproductive age, who represent the largest demographic group surveyed (n 1290). Median serum concentrations were 8·6 mg dl−1 for Ca, 1·9 mg dl−1 for Mg, 0·4 µg l−1 for Co, 98·8 µg dl−1 for Cu and 0·2 µg dl−1 for Mo. The prevalence of Ca, Mg and Co deficiency was 41·6 %, 29·2 % and 15·9 %, respectively; Cu and Mo deficiency prevalence was 7·6 % and 0·3 %, respectively. A higher prevalence of Ca, Cu and Mo deficiency was observed in north western, Co deficiency in central and Mg deficiency in north eastern parts of Ethiopia. Serum Ca, Mg and Mo concentrations show spatial dependencies up to 140–500 km; however, there was no evidence of spatial correlations for serum Co and Cu concentrations. These new data indicate the scale of multiple mineral micronutrient deficiency in Ethiopia and the geographical differences in the prevalence of deficiencies suggesting the need to consider targeted responses during the planning of nutrition intervention programmes.
Glyphosate’s efficacy is influenced by the amount absorbed and translocated throughout the plant to inhibit 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS). Glyphosate resistance can be due to target-site (TS) or non–target site (NTS) resistance mechanisms. TS resistance includes an altered target site and gene overexpression, while NTS resistance includes reduced absorption, reduced translocation, enhanced metabolism, and exclusion/sequestration. The goal of this research was to elucidate the mechanism(s) of glyphosate resistance in common ragweed (Ambrosia artemisiifolia L.) from Ontario, Canada. The resistance factor for this glyphosate-resistant (GR) A. artemisiifolia biotype is 5.1. No amino acid substitutions were found at positions 102 or 106 of the EPSPS enzyme in this A. artemisiifolia biotype. Based on [14C]glyphosate studies, there was no difference in glyphosate absorption or translocation between glyphosate-susceptible (GS) and GR A. artemisiifolia biotypes. Radio-labeled glyphosate metabolites were similar for GS and GR A. artemisiifolia 96 h after application. Glyphosate resistance in this A. artemisiifolia biotype is not due to an altered target site due to amino acid substitutions at positions 102 and 106 in the EPSPS and is not due to the NTS mechanisms of reduced absorption, reduced translocation, or enhanced metabolism.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.
Vulture populations are in severe decline across Africa and prioritization of geographic areas for their conservation is urgently needed. To do so, we compiled three independent datasets on vulture occurrence from road-surveys, GPS-tracking, and citizen science (eBird), and used maximum entropy to build ensemble species distribution models (SDMs). We then identified spatial vulture conservation priorities in Ethiopia, a stronghold for vultures in Africa, while accounting for uncertainty in our predictions. We were able to build robust distribution models for five vulture species across the entirety of Ethiopia, including three Critically Endangered, one Endangered, and one Near Threatened species. We show that priorities occur in the highlands of Ethiopia, which provide particularly important habitat for Bearded Gypaetus barbatus, Hooded Necrosyrtes monachus, Rüppell’s Gyps rüppelli and White-backed Gyps africanus Vultures, as well as the lowlands of north-eastern Ethiopia, which are particularly valuable for the Egyptian Vulture Neophron percnopterus. One-third of the core distribution of the Egyptian Vulture was protected, followed by the White-backed Vulture at one-sixth, and all other species at one-tenth. Overall, only about one-fifth of vulture priority areas were protected. Given that there is limited protection of priority areas and that vultures range widely, we argue that measures of broad spatial and legislative scope will be necessary to address drivers of vulture declines, including poisoning, energy infrastructure, and climate change, while considering the local social context and aiding sustainable development.
To understand the long-term climate and glaciological evolution of the ice sheet in the region bordering the Weddell Sea, the British Antarctic Survey has undertaken a series of successful ice core projects drilling to bedrock on Berkner Island, James Ross Island and the Fletcher Promontory. A new project, WACSWAIN, seeks to increase this knowledge by further drilling to bedrock on two further ice rises in this region. In a single-season project, an ice core was recovered to bedrock at 651 m on Skytrain Ice Rise using an ice core drill in a fluid-filled borehole. In a second season, a rapid access drill was used to recover ice chips to 323 m on Sherman Island in a dry borehole, though failing to reach the bedrock which was at an estimated depth of 428 m.
Migraine, including episodic migraine (EM) and chronic migraine (CM), is a common neurological disorder that imparts a substantial health burden.
Objective:
Understand the characteristics and treatment of EM and CM from a population-based perspective.
Methods:
This retrospective population-based cross-sectional study utilized administrative data from Alberta. Among those with a migraine diagnostic code, CM and EM were identified by an algorithm and through exclusion, respectively; characteristics and migraine medication use were examined with descriptive statistics.
Results:
From 79,076 adults with a migraine diagnostic code, 12,700 met the criteria for CM and 54,686 were considered to have EM. The majority of migraineurs were female, the most common comorbidity was depression, and individuals with CM had more comorbidities than EM. A larger proportion of individuals with CM versus EM were dispensed acute (80.6%: CM; 63.4%: EM) and preventative (58.0%: CM; 28.9%: EM) migraine medications over 1 year. Among those with a dispensation, individuals with CM had more acute (13.6 ± 32.2 vs. 4.6 ± 10.9 [mean ± standard deviation], 95% confidence interval [CI] 7.7-8.3), and preventative (12.6 ± 43.5 vs. 5.0 ± 12.6, 95% CI 6.9-8.4) migraine medication dispensations than EM, over 1-year. Opioids were commonly used in both groups (proportion of individuals dispensed an opioid over 1-year: 53.1%: CM; 25.7%: EM).
Conclusions:
Individuals with EM and CM displayed characteristics and medication use patterns consistent with other reports. Application of this algorithm for CM may be a useful and efficient means of identifying subgroups of migraine using routinely collected health data in Canada.
The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.