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Objectives/Goals: Here, we utilize deep learning to automate the analysis of dual X-ray absorptiometry (DEXA) scans in the UK Biobank (UKB) imaging dataset to enable a large-scale assessment of lumbar spine disc degeneration, low back pain, and socioeconomic status. Methods/Study Population: Study Population: The UKB is a biomedical database that includes lateral spine DEXA imaging for 50,000 participants. Deep Learning Model Development: A computer vision model was developed that receives a DEXA scan as input and outputs a quadrilateral that corresponds to the corners of 5 lumbar vertebral bodies. The model is a deep, fully convolutional, encoder–decoder network using DeepLabV3. Statistical Analysis: To determine our preliminary model accuracy, we used the intersection over union (IoU) metric.We analyzed data using an ordinal regression model to determine the relationship between income/ neighborhood level multiple deprivation index (MDI) and low back pain (LBP), as well as a mixed effects model to estimate the relationship between income/MDI and disc height index (DHI). Results/Anticipated Results: Our model predicted vertebral body quadrilaterals in training and unseen test data (train IoU = 0.96, test IoU = .91) and was used to infer data for 10,440 participants. Confirming previous studies, there were significant relationships (p0.05) between income or MDI and DHI (Figure 2). Discussion/Significance of Impact: Low back pain is the world’s leading cause of disability, and socioeconomic factors play an important role. We found no relationship between disc height index and socioeconomic status. Thus, disc degeneration may not be a factor in this low back pain phenotype.
As part of a broad survey of the trematodes of damselfishes (Pomacentridae) in the tropical Indo-West Pacific, zoogonids were collected from multiple localities in Australia, New Caledonia, and French Polynesia. All zoogonid specimens collected were consistent with the subfamily Lecithostaphylinae, and morphological and molecular data (ITS2 and 28S rDNA, and cox1 mtDNA) were generated for most host-locality combinations to enable an integrative species delimitation. The collection comprised three species: Deretrema stratiotes n. sp. from four species of Abudefduf Forsskål from Ningaloo Reef in Western Australia, and two species consistent with the genus Lecithostaphylus Odhner, 1911 for which Innuptacola n. gen. is proposed based on phylogenetic and morphological distinction, the type-species I. gibsoni (Cribb, Bray & Barker, 1992) n. comb. (= L. gibsoni) from six species of Abudefduf in Ningaloo Reef, Queensland and New Caledonia, and I. torquata n. sp. from 12 pomacentrid species in Ningaloo Reef, the Great Barrier Reef in Queensland, and the Gambier Islands in French Polynesia. The new collection demonstrates that some zoogonid species are geographically widespread (from the Pacific Ocean to the Indian Ocean) and can infect a broad range of hosts (multiple genera within a family), whereas others are apparently geographically restricted and exhibit higher host-specificity (fishes within a single genus).
We provide a complete classification of Teichmüller curves occurring in hyperelliptic components of the meromorphic strata of differentials. Using a non-existence criterion based on how Teichmüller curves intersect the boundary of the moduli space we derive a contradiction to the algebraicity of any candidate outside of Hurwitz covers of strata with projective dimension one, and Hurwitz covers of zero residue loci in strata with projective dimension two.
The economic burden of migraine is substantial; determining the cost that migraine imposes on the Canadian healthcare system is needed.
Methods:
Administrative data were used to identify adults living with migraine, including chronic migraine (CM) and episodic migraine (EM), and matched controls in Alberta, Canada. One- and two-part generalized linear models with gamma distribution were used to estimate direct healthcare costs (hospitalization, emergency department, ambulatory care, physician visit, prescription medication; reported in 2022 Canadian dollars) of migraine during a 1-year observation period (2017/2018).
Results:
The fully adjusted total mean healthcare cost of migraine (n = 100,502) was 1.5 times (cost ratio: 1.53 [95% CI: 1.50, 1.55]) higher versus matched controls (n = 301,506), with a predicted annual incremental cost of $2,806 (95% CI: $2,664, $2,948) per person. The predicted annual incremental cost of CM and EM was $5,059 (95% CI: $4,836, $5,283) and $669 (95% CI: $512, $827) per person, respectively, compared with matched controls. All healthcare cost categories were greater for migraine (overall, CM and EM) compared with matched controls, with prescription medication the primary cost driver (incremental cost – overall: $1,381 [95% CI: $1,234, $1,529]; CM: $2,057 [95% CI: %1,891, $2,223]; EM: $414 [95% CI: $245, $583] per person per year).
Conclusion:
Persons living with migraine had greater direct healthcare costs than those without. With an estimated migraine prevalence of 8.3%–10.2%, this condition may account for an additional $1.05–1.29 billion in healthcare costs per year in Alberta. Strategies to prevent and effectively manage migraine and associated healthcare costs are needed.
Increasing daylight exposure might be a simple way to improve mental health. However, little is known about daylight-symptom associations in depressive disorders.
Methods
In a subset of the Australian Genetics of Depression Study (N = 13,480; 75% female), we explored associations between self-reported number of hours spent in daylight on a typical workday and free day and seven symptom dimensions: depressive (overall, somatic, psychological); hypo-manic-like; psychotic-like; insomnia; and daytime sleepiness. Polygenic scores for major depressive disorder (MDD); bipolar disorder (BD); and schizophrenia (SCZ) were calculated. Models were adjusted for age, sex, shift work status, employment status, season, and educational attainment. Exploratory analyses examined age-stratified associations (18–24 years; 25–34 years; 35–64 years; 65 and older). Bonferroni-corrected associations (p < 0.004) are discussed.
Results
Adults with depression reported spending a median of one hour in daylight on workdays and three hours on free days. More daylight exposure on workdays and free days was associated with lower depressive (overall, psychological, somatic) and insomnia symptoms (p’s<0.001), but higher hypo-manic-like symptoms (p’s<0.002). Genetic loading for MDD and SCZ were associated with less daylight exposure in unadjusted correlational analyses (effect sizes were not meaningful). Exploratory analyses revealed age-related heterogeneity. Among 18–24-year-olds, no symptom dimensions were associated with daylight. By contrast, for the older age groups, there was a pattern of more daylight exposure and lower insomnia symptoms (p < 0.003) (except for 25–34-year-olds on free days, p = 0.019); and lower depressive symptoms with more daylight on free days, and to some extent workdays (depending on the age-group).
Conclusions
Exploration of the causal status of daylight in depression is warranted.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Recent reports suggest the ON and OFF pathways are differentially susceptible to selective vision loss in glaucoma. Thus, perimetric assessment of ON- and OFF-pathway function may serve as a useful diagnostic. However, this necessitates a developed understanding of normal ON/OFF pathway function around the visual field and as a function of input intensity. Here, using electroencephalography, we measured ON- and OFF-pathway biased contrast response functions in the upper and lower visual fields. Using the steady-state visually evoked potential paradigm, we flickered achromatic luminance probes according to a saw-tooth waveform, the fast phase of which biased responses towards the ON or OFF pathways. Neural responses from the upper and lower visual fields were simultaneously measured using frequency tagging - probes in the upper visual field modulated at 3.75 Hz, while those in the lower visual field modulated at 3 Hz. We find that responses to OFF/decrements are larger than ON/increments, especially in the lower visual field. In the lower visual field, both ON and OFF responses were well described by a sigmoidal non-linearity. In the upper visual field, the ON pathway function was very similar to that of the lower, but the OFF pathway function showed reduced saturation and more cross-subject variability. Overall, this demonstrates that the relationship between the ON and OFF pathways depends on the visual field location and contrast level, potentially reflective of natural scene statistics.
Weeds are one of the greatest challenges to snap bean (Phaseolus vulgaris L.) production. Anecdotal observation posits certain species frequently escape the weed management system by the time of crop harvest, hereafter called residual weeds. The objectives of this work were to (1) quantify the residual weed community in snap bean grown for processing across the major growing regions in the United States and (2) investigate linkages between the density of residual weeds and their contributions to weed canopy cover. In surveys of 358 fields across the Northwest (NW), Midwest (MW), and Northeast (NE), residual weeds were observed in 95% of the fields. While a total of 109 species or species-groups were identified, one to three species dominated the residual weed community of individual fields in most cases. It was not uncommon to have >10 weeds m−2 with a weed canopy covering >5% of the field’s surface area. Some of the most abundant and problematic species or species-groups escaping control included amaranth species such as smooth pigweed (Amaranthus hybridus L.), Palmer amaranth (Amaranthus palmeri S. Watson), redroot pigweed (Amaranthus retroflexus L.), and waterhemp [Amaranthus tuberculatus (Moq.) Sauer]; common lambsquarters (Chenopodium album L.); large crabgrass [Digitaria sanguinalis (L.) Scop.]; and ivyleaf morningglory (Ipomoea hederacea Jacq.). Emerging threats include hophornbeam copperleaf (Acalypha ostryifolia Riddell) in the MW and sharppoint fluvellin [Kickxia elatine (L.) Dumort.] in the NW. Beyond crop losses due to weed interference, the weed canopy at harvest poses a risk to contaminating snap bean products with foreign material. Random forest modeling predicts the residual weed canopy is dominated by C. album, D. sanguinalis, carpetweed (Mollugo verticillata L.), I. hederacea, amaranth species, and A. ostryifolia. This is the first quantitative report on the weed community escaping control in U.S. snap bean production.
Understanding post-stroke spasticity (PSS) treatment in everyday clinical practice may guide improvements in patient care.
Methods:
This was a retrospective cohort study that used population-level administrative data. Adults (aged ≥18 years) who initiated PSS treatment (defined by the first PSS clinic visit, focal botulinum toxin injection, or anti-spasticity medication dispensation [baclofen, dantrolene and tizanidine] with none of these treatments occurring during the 2 years before the stroke) were identified between 2012 and 2019 in Alberta, Canada. Spasticity treatment use, time to treatment start and type of prescribing/treating physician were measured. Descriptive statistics were performed.
Results:
Within the cohort (n = 1,079), the most common PSS treatment was oral baclofen (initial treatment: 60.9%; received on/after the initial treatment date up to March 31, 2020: 69.0%), largely prescribed by primary care physicians (77.6%) and started a median of 348 (IQR 741) days after the stroke. Focal botulinum toxin (23.3%; 37.7%) was largely prescribed by physiatrists (72.2%) and started 311 (IQR 446) days after the stroke; spasticity clinic visits (18.6%; 23.8%) were also common.
Conclusions:
We found evidence of gaps in provision of spasticity management in persons with PSS including overuse of systemic oral baclofen (that has common adverse side effects and lacks evidence of effectiveness in PSS) and potential underuse of focal botulinum toxin injections. Further investigation and strategies should be pursued to improve alignment of PSS treatment with guideline recommendations that in turn will support better outcomes for those with PSS.
Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25–26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs. Prominent themes surfaced, including competing research priorities and incentives, inadequate representation of patient population in clinical trials, opportunities to better leverage existing technology and infrastructure in trial design, and a need for heightened transparency and accountability in research practices. The group determined that together these elements contribute to an inefficient and costly clinical research enterprise, amplifying disparities in population health and sustaining gaps in evidence that impede advancements in equitable healthcare delivery and outcomes. The goal of addressing the identified challenges is to ultimately make clinical trials faster, more inclusive, and more efficient across diverse communities and settings.
It is well established that there is a substantial genetic component to eating disorders (EDs). Polygenic risk scores (PRSs) can be used to quantify cumulative genetic risk for a trait at an individual level. Recent studies suggest PRSs for anorexia nervosa (AN) may also predict risk for other disordered eating behaviors, but no study has examined if PRS for AN can predict disordered eating as a global continuous measure. This study aimed to investigate whether PRS for AN predicted overall levels of disordered eating, or specific lifetime disordered eating behaviors, in an Australian adolescent female population.
Methods
PRSs were calculated based on summary statistics from the largest Psychiatric Genomics Consortium AN genome-wide association study to date. Analyses were performed using genome-wide complex trait analysis to test the associations between AN PRS and disordered eating global scores, avoidance of eating, objective bulimic episodes, self-induced vomiting, and driven exercise in a sample of Australian adolescent female twins recruited from the Australian Twin Registry (N = 383).
Results
After applying the false-discovery rate correction, the AN PRS was significantly associated with all disordered eating outcomes.
Conclusions
Findings suggest shared genetic etiology across disordered eating presentations and provide insight into the utility of AN PRS for predicting disordered eating behaviors in the general population. In the future, PRSs for EDs may have clinical utility in early disordered eating risk identification, prevention, and intervention.
We aimed to (1) report updated estimates of direct healthcare costs for people living with MS (pwMS), (2) contrast costs to a control population and (3) explore differences between disability levels among pwMS.
Methods:
Administrative data were used to identify adult pwMS (MS cohort) and without (control cohort) in Alberta, Canada; disability level (based on the Expanded Disability Status Scale) among pwMS was estimated. One- and two-part generalized linear models with gamma distribution were used to estimate the incremental direct healthcare cost (2021 $CDN) of MS during a 1-year observation period.
Results:
Adjusting for confounders, the total healthcare cost ratio was higher in the MS cohort (n = 13,089) versus control (n = 150,080) (5.24 [95% CI: 5.08, 5.41]) with a predicted incremental cost of $15,016 (95% CI: $14,497, $15,535) per person-year. Among the MS cohort, total predicted direct healthcare costs were higher with greater disability, $14,430 (95% CI: $13,980, $14,880) to $58,697 ($51,514, $65,879) per person-year in mild and severe disability, respectively. The primary health resource cost component shifted from disease-modifying therapies in mild disability to supportive care in moderate and severe disability.
Conclusion:
Adult pwMS had greater direct healthcare costs than those without. Extrapolating to the population level (where 14,485 adult pwMS were identified in the study), it is estimated that $218 million per year in healthcare costs may be attributable to MS in Alberta. The significantly larger economic impact associated with greater disability underscores the importance of preventing or delaying disease progression and functional impairment in MS.
Rift propagation, rather than basal melt, drives the destabilization and disintegration of the Thwaites Eastern Ice Shelf. Since 2016, rifts have episodically advanced throughout the central ice-shelf area, with rapid propagation events occurring during austral spring. The ice shelf's speed has increased by ~70% during this period, transitioning from a rate of 1.65 m d−1 in 2019 to 2.85 m d−1 by early 2023 in the central area. The increase in longitudinal strain rates near the grounding zone has led to full-thickness rifts and melange-filled gaps since 2020. A recent sea-ice break out has accelerated retreat at the western calving front, effectively separating the ice shelf from what remained of its northwestern pinning point. Meanwhile, a distributed set of phase-sensitive radar measurements indicates that the basal melting rate is generally small, likely due to a widespread robust ocean stratification beneath the ice–ocean interface that suppresses basal melt despite the presence of substantial oceanic heat at depth. These observations in combination with damage modeling show that, while ocean forcing is responsible for triggering the current West Antarctic ice retreat, the Thwaites Eastern Ice Shelf is experiencing dynamic feedbacks over decadal timescales that are driving ice-shelf disintegration, now independent of basal melt.
The moderation of user-generated content on online platforms remains a key solution to protecting people online, but also remains a perpetual challenge as the appropriateness of content moderation guidelines depends on the online community that they aim to govern. This challenge affects marginalized groups in particular, as they more frequently experience online abuse but also end up falsely being the target of content-moderation guidelines. While there have been calls for democratic, community-moderation, there has so far been little research into how to implement such approaches. Here, we present the co-creation of content moderation strategies with the users of an online platform to address some of these challenges. Within the context of AutSPACEs—an online citizen science platform that aims to allow autistic people to share their own sensory processing experiences publicly—we used a community-based and participatory approach to co-design a content moderation solution that would fit the preferences, priorities, and needs of its autistic user community. We outline how this approach helped us discover context-specific moderation dilemmas around participant safety and well-being and how we addressed those. These trade-offs have resulted in a moderation design that differs from more general social networks in aspects such as how to contribute, when to moderate, and what to moderate. While these dilemmas, processes, and solutions are specific to the context of AutSPACEs, we highlight how the co-design approach itself could be applied and useful for other communities to uncover challenges and help other online spaces to embed safety and empowerment.
Understanding disease-modifying therapy (DMT) use and healthcare resource utilization by different geographical areas among people living with multiple sclerosis (pwMS) may identify care gaps that can be used to inform policies and practice to ensure equitable care.
Methods:
Administrative data was used to identify pwMS on April 1, 2017 (index date) in Alberta. DMT use and healthcare resource utilization were compared between those who resided in various geographical areas over a 2-year post-index period; simple logistic regression was applied.
Results:
Among the cohort (n = 12,338), a higher proportion of pwMS who resided in urban areas (versus rural) received ≥ 1 DMT dispensation (32.3% versus 27.4%), had a neurologist (67.7% versus 63.9%), non-neurologist specialist (88.3% versus 82.9%), ambulatory care visit (87.4% versus 85.3%), and MS tertiary clinic visit (59.2% versus 51.7%), and a lower proportion had an emergency department (ED) visit (46.3% versus 62.4%), and hospitalization (20.4% versus 23.0%). Across the provincial health zones, there were variations in DMT selection, and a higher proportion of pwMS who resided in the Calgary health zone, where care is managed by MS tertiary clinic neurologists, had an outpatient visit to a neurologist or MS tertiary clinic versus those who resided in other zones where delivery of MS-related care is more varied.
Conclusions:
Urban/rural inequalities in DMT use and healthcare resource utilization appear to exist among pwMS in Alberta. Findings suggest the exploration of barriers with consequent strategies to increase access to DMTs and provide timely outpatient MS care management, particularly for those pwMS residing in rural areas.
Limited evidence exists regarding care pathways for stroke survivors who do and do not receive poststroke spasticity (PSS) treatment.
Methods:
Administrative data was used to identify adults who experienced a stroke and sought acute care between 2012 and 2017 in Alberta, Canada. Pathways of stroke care within the health care system were determined among those who initiated PSS treatment (PSS treatment group: outpatient pharmacy dispensation of an anti-spastic medication, focal chemo-denervation injection, or a spasticity tertiary clinic visit) and those who did not (non-PSS treatment group). Time from the stroke event until spasticity treatment initiation, and setting where treatment was initiated were reported. Descriptive statistics were performed.
Results:
Health care settings within the pathways of stroke care that the PSS (n = 1,079) and non-PSS (n = 22,922) treatment groups encountered were the emergency department (86 and 84%), acute inpatient care (80 and 69%), inpatient rehabilitation (40 and 12%), and long-term care (19 and 13%), respectively. PSS treatment was initiated a median of 291 (interquartile range 625) days after the stroke event, and most often in the community when patients were residing at home (45%), followed by “other” settings (22%), inpatient rehabilitation (18%), long-term care (11%), and acute inpatient care (4%).
Conclusions:
To our knowledge, this is the first population based cohort study describing pathways of care among adults with stroke who subsequently did or did not initiate spasticity treatment. Areas for improvement in care may include strategies for earlier identification and treatment of PSS.
The rapid growth of cultural evolutionary science, its expansion into numerous fields, its use of diverse methods, and several conceptual problems have outpaced corollary developments in theory and philosophy of science. This has led to concern, exemplified in results from a recent survey conducted with members of the Cultural Evolution Society, that the field lacks ‘knowledge synthesis’, is poorly supported by ‘theory’, has an ambiguous relation to biological evolution and uses key terms (e.g. ‘culture’, ‘social learning’, ‘cumulative culture’) in ways that hamper operationalization in models, experiments and field studies. Although numerous review papers in the field represent and categorize its empirical findings, the field's theoretical challenges receive less critical attention even though challenges of a theoretical or conceptual nature underlie most of the problems identified by Cultural Evolution Society members. Guided by the heterogeneous ‘grand challenges’ emergent in this survey, this paper restates those challenges and adopts an organizational style requisite to discussion of them. The paper's goal is to contribute to increasing conceptual clarity and theoretical discernment around the most pressing challenges facing the field of cultural evolutionary science. It will be of most interest to cultural evolutionary scientists, theoreticians, philosophers of science and interdisciplinary researchers.
Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).