Background: Despite the utility of administrative health data, there remains a lack of patient-centered outcome measures to meaningfully capture morbidity after traumatic brain injury (TBI). We sought to characterize and validate days at home (DAH) as a feasible measure to assess population-level moderate to severe TBI (msTBI) outcomes and health resource utilization. Methods: We utilized linked health administrative data sources to identify adults with msTBI patients presenting to trauma centers in Ontario injured between 2009-2021. DAH at 180 days reflects the total number of days spent alive and at home excluding the days spent institutionalized in acute care, rehabilitation, inpatient mental health settings or post-acute readmissions. Construct and predictive validity were determined; we additionally estimated minimally important difference (MID) in DAH180days. Results: There were 6340 patients that met inclusion criteria. Median DAH180days were 70 days (interquartile range 0-144). Increased health resource utilization at baseline, older age, increasing cranial injury severity and major extracranial injuries were significantly associated with fewer DAH180days. DAH180days was correlated to DAH counts at 1-3 years. The average MID estimate from anchor-based and distribution-based methods was 18 days. Conclusions: We introduce DAH180days as a feasible and sufficiently responsive patient-centered outcome measure with construct, predictive and face validity in an msTBI population.

Background: Employment and personal income loss after traumatic brain injury (TBI) is a major source of post-injury stress and barrier to societal reintegration for affected patients. We sought to quantify the labor market implications for tax-filing adult TBI survivors. Methods: We performed a matched difference-in-difference analysis using a national retrospective cohort of working adult TBI survivors injured between 2007-2017. Linear and logistic mixed effects regressions were used to estimate the magnitude of personal income loss and proportion of patients displaced from the workforce in the three post-injury years (Y+1 to Y+3). Results: Among 18,050 patients identified with TBI, the adjusted average loss of personal annual income was $-7,635 dollars in Y+1 and $-5,000 in Y+3. An additional -7.8% individuals were newly unemployed compared to the pre-injury baseline. For mild, moderate, and severe TBI subgroups, income loss was $-3354, $-6750, and $-17375 respectively in Y+3; the proportion of newly unemployed individuals in Y+3 was 5.8%, 9.2%, and 20% lower than baseline. We estimated 500 million dollars of incurred labor markets losses related to TBI in Canada. Conclusions: This work represents the first national cohort data quantifying the labor market implications of TBI. These results may be used to inform post-injury care pathways and vocational rehabilitation.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

OBJECTIVES/GOALS: Silicosis is a highly fatal progressive fibrotic disease of the lungs characterized by accumulation and persistence of fibroblasts that excessively deposit Collagen1a1. We sought to eliminate Collagen1a1-expressing fibroblasts through a targeted genetic ablation strategy and hypothesized that this would arrest the progression of Silicosis. METHODS/STUDY POPULATION: Silicosis was induced with a single intratracheal (i.t.) instillation of silica particles ( RESULTS/ANTICIPATED RESULTS: Targeted ablation of Col1a1+ fibroblast in established Silicosis resulted in a decrease in: 1) Col1a1+ fibroblasts by flow cytometry and within fibrotic nodules by immunofluorescent staining, 2) total lung collagen content by histology and hydroxyproline assay, 3) tissue-associated disease by microCT and an increase in arterial oxygen saturation by pulse oximetry. Cessation of targeted Col1a1+ fibroblast ablation resulted in a rebound effect in Silicosis disease progression. Following ablation, Col1a1+ fibroblasts expanded by proliferation (Ki67+) and total lung collagen levels returned to pre-ablation levels. DISCUSSION/SIGNIFICANCE: Silicosis is a often fatal disease with no FDA approved therapies. These results suggest that targeted loss of Col1a1+ fibroblasts in Silicosis is sufficient to arrest disease progression. Thus, it is essential to understand how targeted loss of pro-fibrotic fibroblasts can alter disease progression as a tool to develop novel therapeutic strategies.

Using an ensemble of close- and long-range remote sensing, lake bathymetry and regional meteorological data, we present a detailed assessment of the geometric changes of El Morado Glacier in the Central Andes of Chile and its adjacent proglacial lake between 1932 and 2019. Overall, the results revealed a period of marked glacier down wasting, with a mean geodetic glacier mass balance of −0.39 ± 0.15 m w.e.a−1 observed for the entire glacier between 1955 and 2015 with an area loss of 40% between 1955 and 2019. We estimate an ice elevation change of −1.00 ± 0.17 m a−1 for the glacier tongue between 1932 and 2019. The increase in the ice thinning rates and area loss during the last decade is coincident with the severe drought in this region (2010–present), which our minimal surface mass-balance model is able to reproduce. As a result of the glacier changes observed, the proglacial lake increased in area substantially between 1955 and 2019, with bathymetry data suggesting a water volume of 3.6 million m3 in 2017. This study highlights the need for further monitoring of glacierised areas in the Central Andes. Such efforts would facilitate a better understanding of the downstream impacts of glacier downwasting.

At Guy's King's and St Thomas’ School of Medicine, a unique initiative is the Psychiatry Early Experience Programme (PEEP), which allows students to shadow psychiatry trainees at work several times a year. The students’ attitudes towards psychiatry and the scheme are regularly assessed and initial results are already available.

Though theory suggests that individual differences in neuroticism (a tendency to experience negative emotions) would be associated with altered functioning of the amygdala (which has been linked with emotionality and emotion dysregulation in childhood, adolescence, and adulthood), results of functional neuroimaging studies have been contradictory and inconclusive. We aimed to clarify the relationship between neuroticism and three hypothesized neural markers derived from functional magnetic resonance imaging during negative emotion face processing: amygdala activation, amygdala habituation, and amygdala-prefrontal connectivity, each of which plays an important role in the experience and regulation of emotions. We used general linear models to examine the relationship between trait neuroticism and the hypothesized neural markers in a large sample of over 500 young adults. Although neuroticism was not significantly associated with magnitude of amygdala activation or amygdala habituation, it was associated with amygdala–ventromedial prefrontal cortex connectivity, which has been implicated in emotion regulation. Results suggest that trait neuroticism may represent a failure in top-down control and regulation of emotional reactions, rather than overactive emotion generation processes, per se. These findings suggest that neuroticism, which has been associated with increased rates of transdiagnostic psychopathology, may represent a failure in the inhibitory neurocircuitry associated with emotion regulation.

The evaporation of sessile droplets is analysed when the influence of the thermal properties of the system is strong. We obtain asymptotic solutions for the evolution, and hence explicit expressions for the lifetimes, of droplets when the substrate has a high thermal resistance relative to the droplet and when the saturation concentration of the vapour depends strongly on temperature. In both situations we find that the lifetimes of the droplets are significantly extended relative to those when thermal effects are weak.

Children reared in impoverished environments are at risk for enduring psychological and physical health problems. Mechanisms by which poverty affects development, however, remain unclear. To explore one potential mechanism of poverty's impact on social–emotional and cognitive development, an experimental examination of a rodent model of scarcity-adversity was conducted and compared to results from a longitudinal study of human infants and families followed from birth (N = 1,292) who faced high levels of poverty-related scarcity-adversity. Cross-species results supported the hypothesis that altered caregiving is one pathway by which poverty adversely impacts development. Rodent mothers assigned to the scarcity-adversity condition exhibited decreased sensitive parenting and increased negative parenting relative to mothers assigned to the control condition. Furthermore, scarcity-adversity reared pups exhibited decreased developmental competence as indicated by disrupted nipple attachment, distress vocalization when in physical contact with an anesthetized mother, and reduced preference for maternal odor with corresponding changes in brain activation. Human results indicated that scarcity-adversity was inversely correlated with sensitive parenting and positively correlated with negative parenting, and that parenting fully mediated the association of poverty-related risk with infant indicators of developmental competence. Findings are discussed from the perspective of the usefulness of bidirectional–translational research to inform interventions for at-risk families.

Six herbicides were applied at 3, 9, and 27 lb/A to the soil in forests of three types in Puerto Rico. The forests differed in soil type, amount and pattern of rainfall, and species composition. Defoliation occurred slowly, but the correlation between percentage defoliation and plants killed was significant at the 1% level of probability. Some defoliation was evident 1 month after treatment and increased slowly during the next 6 to 8 months. The most effective herbicide was 4-amino-3,5,6-trichloropicolinic acid (picloram). Generally, 2-methoxy-3,6-dichlorobenzoic acid (dicamba), 2-methoxy-4,6-bis(isopropylamino)-s-triazine (prometone), and 5-bromo-3-sec-butyl-6-methyluracil (bromacil) were less effective than picloram. Both 2,3,6-trichlorophenylacetic acid (fenac) and 3-(3,4-dichlorophenyl)-l,l-dimethylurea (diuron) were ineffective. Defoliation was greatest and more plants were killed in the driest site.

One year after treatment, fenac was the most persistent herbicide in the soil. Herbicides were found to a 36 to 48-in depth within 3 months after application.

Herbaceous and woody seedlings were present at all sites within 18 months after herbicide application. There was no definite relationship between herbicidal treatment and secondary succession, except that the number and frequency of successional species were greater on plots having the highest percentage of defoliation.

Tomato (Lycopersicon esculentum Mill. ‘Campbell 17’) plant height and dry weight of tops decreased with increasing rates of α,α,α-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine (trifluralin) and increased with increasing rates of phosphorus. Trifluralin and phosphorus interacted in their effects on root growth; phosphorus was less effective in promoting root growth as the rate of trifluralin increased. Phosphorus content of plant tops increased with each increment of soil-applied phosphorus at 0 and 0.84 kg/ha of trifluralin, but each increment of applied phosphorus did not significantly increase plant phosphorus content at higher rates of trifluralin. The inhibitory effect of trifluralin on phosphorus uptake diminished with time in 1969. Interactions between trifluralin and phosphorus did not occur in 1970.

Effects of temperature on response of transplanted tomatoes (Lycopersicon esculentum Mill. ‘Campbell 17′) to trifluralin (α,α,α-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine), nitralin [4-(methylsulfonyl)-2,6-dinitro-N,N-dipropylaniline], profluralin [N-(cyclopropylmethyl)-α,α,α-trifluoro-2,6-dinitro-N-propyl-p-toluidine], and isopropalin (2,6-dinitro-N,N-dipropylcumidine) were investigated in field studies. Trifluralin and nitralin caused greater reductions in growth and yields of tomatoes transplanted early in April than to tomatoes transplanted around May 1. Responses to profluralin were similar but total yields of early transplanted tomatoes were not reduced although initial yields were below those of tomatoes treated with isopropalin. In controlled environment chamber studies, percent phosphorus of plant tops was reduced by trifluralin at low temperatures but was not influenced by trifluralin at high temperatures. Tomoto responses to phosphorus as reflected by plant fresh weight, dry weight and phosphorus content (mg/plant) were reduced by trifluralin at low and high temperatures.

In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.

Children with cancer are potentially at a high risk of plasma 25-hydroxyvitamin D (25(OH)D) inadequacy, and despite UK vitamin D supplementation guidelines their implementation remains inconsistent. Thus, we aimed to investigate 25(OH)D concentration and factors contributing to 25(OH)D inadequacy in paediatric cancer patients. A prospective cohort study of Scottish children aged <18 years diagnosed with, and treated for, cancer (patients) between August 2010 and January 2014 was performed, with control data from Scottish healthy children (controls). Clinical and nutritional data were collected at defined periods up to 24 months. 25(OH)D status was defined by the Royal College of Paediatrics and Child Health as inadequacy (<50 nmol/l: deficiency (<25 nmol/l), insufficiency (25–50 nmol/l)), sufficiency (51–75 nmol/l) and optimal (>75 nmol/l). In all, eighty-two patients (median age 3·9, interquartile ranges (IQR) 1·9–8·8; 56 % males) and thirty-five controls (median age 6·2, IQR 4·8–9·1; 49 % males) were recruited. 25(OH)D inadequacy was highly prevalent in the controls (63 %; 22/35) and in the patients (64 %; 42/65) at both baseline and during treatment (33–50 %). Non-supplemented children had the highest prevalence of 25(OH)D inadequacy at every stage with 25(OH)D median ranging from 32·0 (IQR 21·0–46·5) to 45·0 (28·0–64·5) nmol/l. Older age at baseline (R −0·46; P<0·001), overnutrition (BMI≥85th centile) at 3 months (P=0·005; relative risk=3·1) and not being supplemented at 6 months (P=0·04; relative risk=4·3) may have contributed to lower plasma 25(OH)D. Paediatric cancer patients are not at a higher risk of 25(OH)D inadequacy than healthy children at diagnosis; however, prevalence of 25(OH)D inadequacy is still high and non-supplemented children have a higher risk. Appropriate monitoring and therapeutic supplementation should be implemented.

Experiments on the National Ignition Facility show that multi-dimensional effects currently dominate the implosion performance. Low mode implosion symmetry and hydrodynamic instabilities seeded by capsule mounting features appear to be two key limiting factors for implosion performance. One reason these factors have a large impact on the performance of inertial confinement fusion implosions is the high convergence required to achieve high fusion gains. To tackle these problems, a predictable implosion platform is needed meaning experiments must trade-off high gain for performance. LANL has adopted three main approaches to develop a one-dimensional (1D) implosion platform where 1D means measured yield over the 1D clean calculation. A high adiabat, low convergence platform is being developed using beryllium capsules enabling larger case-to-capsule ratios to improve symmetry. The second approach is liquid fuel layers using wetted foam targets. With liquid fuel layers, the implosion convergence can be controlled via the initial vapor pressure set by the target fielding temperature. The last method is double shell targets. For double shells, the smaller inner shell houses the DT fuel and the convergence of this cavity is relatively small compared to hot spot ignition. However, double shell targets have a different set of trade-off versus advantages. Details for each of these approaches are described.

The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.

This paper describes the current status of knowledge regarding the impact of aviation on the atmosphere. The growth of the aviation industry is likely to continue in the future and at present there are significant concerns that this will adversely affect climate and local air quality in the vicinity of airports. Indeed, it is possible that air quality may become a constraint to increased capacity of some large hub airports. Currently the radiative forcing impact from aircraft emissions, other than CO2, are not accounted for in the International Civil Aviation Organization emission trading scheme proposals. Taking only this approach, emissions trading could, in theory, increase the radiative forcing, rather than decrease it. The study of improved ‘environmentally friendly’ flight is still in its infancy, however any proposed and actual new developments, in terms of technology and operational practice, should include an environmental assessment.

A developmental model, based upon murine rodents, has been proposed by Kavanagh et al. (2007) to explain lower molar proportions in mammals. We produce a clade-wide macroevolutionary test of the model using the dental evolutionary trends in a unique radiation of extinct mammals endemic to South America (“Meridiungulata”) that comprise a diverse array of molar morphologies. All of the South American ungulate groups examined follow the inhibitory cascade model with the exception of two groups: Interatheriidae (Notoungulata) and Astrapotheria. For most taxa studied, ratios between lower molar areas are greater than 1.0, indicating a weak inhibition by m1 on the subsequent molars in the tooth row, and a trend to greater absolute size of the posterior molars. Comparisons of mean ratios between clades indicate that a significant phylogenetic signal can be detected, particularly between the two groups within Notoungulata— Typotheria and Toxodontia. Body mass estimates were found to be significantly correlated with both m3/m1 and m2/m1 ratios, suggesting that the larger body size achieved the weaker inhibition between the lower molars. Molar ratio patterns are examined and discussed in relation to the independent and numerous acquisitions of hypsodonty that are characteristic of dental evolution in “Meridiungulata.”