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UK Biobank is an intensively characterised prospective cohort of 500,000 adults aged 40–69 years when recruited between 2006 and 2010. The study was established to enable researchers worldwide to undertake health-related research in the public interest. The existence of such a large, detailed prospective cohort with a high degree of participant engagement enabled its rapid repurposing for coronavirus disease-2019 (COVID-19) research. In response to the pandemic, the frequency of updates on hospitalisations and deaths among participants was immediately increased, and new data linkages were established to national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and primary care health records to facilitate research into the determinants of severe COVID-19. UK Biobank also instigated several sub-studies on COVID-19. In 2020, monthly blood samples were collected from approximately 20,000 individuals to investigate the distribution and determinants of SARS-CoV-2 infection, and to assess the persistence of antibodies following infection with another blood sample collected after 12 months. UK Biobank also performed repeat imaging of approximately 2,000 participants (half of whom had evidence of previous SARS-CoV-2 infection and half did not) to investigate the impact of the virus on changes in measures of internal organ structure and function. In addition, approximately 200,000 UK Biobank participants took part in a self-test SARS-CoV-2 antibody sub-study (between February and November 2021) to collect objective data on previous SARS-CoV-2 infection. These studies are enabling unique research into the genetic, lifestyle and environmental determinants of SARS-CoV-2 infection and severe COVID-19, as well as their long-term health effects. UK Biobank’s contribution to the national and international response to the pandemic represents a case study for its broader value, now and in the future, to precision medicine research.
This collection profiles understudied figures in the book and print trades of the seventeenth century. With an equal balance between women and men, it intervenes in the history of the trades, emphasising the broad range of material, cultural, and ideological work these people undertook. It offers a biographical introduction to each figure, placing them in their social, professional, and institutional settings. The collection considers varied print trade roles including that of the printer, publisher, paper-maker, and bookseller, as well as several specific trade networks and numerous textual forms. The biographies draw on extensive new archival research, with details of key sources for further study on each figure. Chronologically organised, this Element offers a primer both on numerous individual figures, and on the tribulations and innovations of the print trade in the century of revolution.
OBJECTIVES/GOALS: There is increasing evidence that cannabidiol (CBD) has promising potential to treat PTSD. However, more research is warranted to fully understand the benefits of CBD for PTSD. This poster will describe the design and methodology of one of the first ever pilot RCTs examining CBD (vs. placebo) combined with prolonged exposure therapy for PTSD. METHODS/STUDY POPULATION: This study is an early Phase II double-blind, pilot RCT. Participants are 24 individuals 18-65 years old who meet DSM-5 criteria for PTSD on the CAPS-5 and were recruited from local hospitals and the community. Individuals complete a standardized baseline assessment with an independent evaluator to assess study eligibility. Participants who meet study inclusion are randomized to 18 days of CBD 250mg (BID) or placebo delivered in combination with 10-sessions Prolonged Exposure (PE) psychotherapy over 2 weeks. Individuals begin medication 3 days prior to beginning PE to ensure steady state. Participants complete self-report and biomarker outcomes at select timepoints during study participation, and are also asked to complete a 1-month follow-up assessment following treatment. RESULTS/ANTICIPATED RESULTS: This aims of this study are to: 1) examine the safety, feasibility, and PTSD symptom reductions associated with the combined intervention; 2) evaluate biomarkers associated with the endocannabinoid system and stress response; 3) determine the association between changes in biomarkers and PTSD symptoms following treatment. It is expected that CBD+PE will be safe and feasible, and that there will be a detectable signal of CBD vs. placebo in the reduction of PTSD symptoms. It is also anticipated that CBD will have higher levels of endocannabinoids and lower stress response levels compared to placebo. Lastly, we expect that greater changes in biomarkers will be associated with lower levels of PTSD severity following treatment. DISCUSSION/SIGNIFICANCE: Although there is growing interest in cannabinoids for psychiatric conditions, such as PTSD, controlled trials are limited and have yet to examine the proposed intervention for PTSD. If successful, this study will enhance the feasibility of a larger, adequately powered RCT to address immediate and long-term improvements for PTSD treatments.
OBJECTIVES/GOALS: Cognitive Processing Therapy (CPT) is a cognitive behavioral treatment for posttraumatic stress disorder (PTSD). CPT is effective in treating combat-related PTSD among Veterans and active duty service members. It is unknown whether improvement in PTSD is related to accommodation of patient preference of the modality of therapy, such as in-office, telehealth, and in-home settings. An equipoise-stratified randomization design allows for complete randomization of participants who are interested and eligible for all three treatment arms. It also allows participants to reject one treatment arm if they are not interested or eligible. Participants who elect to opt out of one arm are randomized to one of the two remaining treatment arms. The primary aim of this study was to evaluate differences in patient satisfaction, treatment stigma beliefs, and credibility beliefs based on patient treatment modality preference. The second aim of this study was to examine if baseline satisfaction, stigma beliefs, and credibility beliefs predicted PTSD treatment outcomes. METHODS/STUDY POPULATION: Active duty service members and veterans with PTSD (N = 123) were randomized to one of three arms using an equipoise stratified randomization. Participants underwent diagnostic interviews for PTSD at baseline and post-treatment and completed self-report measures of satisfaction, stigma, credibility and expectancies of therapy. RESULTS/ANTICIPATED RESULTS: A series of ANOVAs indicated that there were group differences on patient stigma beliefs regarding mental health, F = 5.61, p = .001, and therapist credibility, F = 5.11, p = .002. Post hoc analyses revealed that participants who did not opt of any treatment arm demonstrated lower levels of stigma beliefs compared to participants who opted-out of in-office, p = .001. Participants who opted out of in-home viewed the therapist as less credible compared to participants who did not opt of any arm, p = .004. Multiple regression analysis found that baseline patient satisfaction, stigma beliefs, and credibility beliefs were not predictive of PTSD treatment outcomes, p > .05. DISCUSSION/SIGNIFICANCE OF IMPACT: Combat PTSD patients may opt out of in-office therapy due to mental health stigma beliefs, and visibility in mental health clinics may be a concern. For patients who opted out of in-home therapy, lack of credibility may have decreased participants’ desire for therapists to enter their home. Despite concerns of mental health stigma and the credibility of the therapy in certain treatment arms, patients in each treatment arm significantly improved in PTSD symptomotology. Moreover, patient characteristics, including satisfaction, stigma, and credibility of the therapy, did not significantly predict treatment outcomes, which demonstrates the robustness of Cognitive Processing Therapy.
The Foothills Erratics Train consists of large quartzite blocks of Rocky Mountains origin deposited on the eastern slopes of the Rocky Mountain Foothills in Alberta between ~53.5°N and 49°N. The blocks were deposited in their present locations when the western margin of the Laurentide Ice Sheet (LIS) detached from the local ice masses of the Rocky Mountains, which initiated the opening of the southern end of the ice-free corridor between the Cordilleran Ice Sheet and the LIS. We use 10Be exposure dating to constrain the beginning of this decoupling. Based on a group of 12 samples well-clustered in time, we date the detachment of the western LIS margin from the Rocky Mountain front to ~14.9 ± 0.9 ka. This is ~1000 years later than previously assumed, but a lack of a latitudinal trend in the ages over a distance of ~500 km is consistent with the rapid opening of a long wedge of unglaciated terrain portrayed in existing ice-retreat reconstructions. A later separation of the western LIS margin from the mountain front implies higher ice margin–retreat rates in order to meet the Younger Dryas ice margin position near the boundary of the Canadian Shield ~2000 years later.
Few studies have investigated the patterns of posttraumatic stress disorder (PTSD) symptom change in prolonged exposure (PE) therapy. In this study, we aimed to understand the patterns of PTSD symptom change in both PE and present-centered therapy (PCT).
Methods
Participants were active duty military personnel (N = 326, 89.3% male, 61.2% white, 32.5 years old) randomized to spaced-PE (S-PE; 10 sessions over 8 weeks), PCT (10 sessions over 8 weeks), or massed-PE (M-PE; 10 sessions over 2 weeks). Using latent profile analysis, we determined the optimal number of PTSD symptom change classes over time and analyzed whether baseline and follow-up variables were associated with class membership.
Results
Five classes, namely rapid responder (7–17%), steep linear responder (14–22%), gradual responder (30–34%), non-responder (27–33%), and symptom exacerbation (7–13%) classes, characterized each treatment. No baseline clinical characteristics predicted class membership for S-PE and M-PE; in PCT, more negative baseline trauma cognitions predicted membership in the non-responder v. gradual responder class. Class membership was robustly associated with PTSD, trauma cognitions, and depression up to 6 months after treatment for both S-PE and M-PE but not for PCT.
Conclusions
Distinct profiles of treatment response emerged that were similar across interventions. By and large, no baseline variables predicted responder class. Responder status was a strong predictor of future symptom severity for PE, whereas response to PCT was not as strongly associated with future symptoms.
An animal egg such as amphibian, mammalian or sea urchin egg receives only a single sperm at fertilisation. After binding of the first sperm, the egg is prevented from allowing the entry of additional sperm. In fact, polyspermy results in aborted development of the zygote. It has been generally accepted that a molecule(s) released from cortical granules participates in the block to polyspermy. As one such molecule, a cortical granule lectin has been isolated from unfertilised Xenopus eggs (Xenopus cortical granule lectin; XCGL). XCGL is released into the perivitelline space after fertilisation, and forms a complex with J1 jelly molecules to form an F layer, resulting in a block to additional sperm penetration.
A lectin molecule has also been purified from the eggs of several species of fish. The fish egg lectin is located in the cortical alveoli and is released from them after fertilisation. However, its biological function is unclear. We isolated cortical alveolar lectin from unfertilised eggs of Chinook salmon through affinity column chromatography (salmon egg lectin; SEL). The lectin activity was estimated by haemagglutination. The activity of the purified SEL was most strongly inhibited by L-rhamnose and D-galactose, but not by EDTA. Further analysis by C4 reverse-phase column chromatography using HPLC revealed that the lectin was composed of three subunit proteins: 24K, 26Ka and 26Kb proteins. In addition, we cloned cDNAs for them by RT-PCR. The deduced amino acid sequence of the 26Ka protein was homologous with that of the 26Kb protein (identity, 96.4%). Identities of the 24K with the 26Ka and the 26Kb proteins were 55.9% and 66.7%, respectively. A database search revealed that a lectin molecule similar to the SEL had been identified in Anthocidaris crassispina egg (sea urchin egg lectin; SUEL). The SUEL is composed of 105 amino acids, and is similar to both amino-terminal and carboxyl-terminal halves of the SELs. Thus, the SEL molecule is composed of two repeats of such SUEL-like domains, suggesting that the SEL gene was produced by gene duplication.
The extended production of allelochemicals from a living mulch cover crop may potentially enhance weed management and crop productivity compared with traditional zucchini squash production systems. However, the efficacy of a living mulch cover crop in no-tillage (NT) systems with herbicides has not been determined for many vegetable crops. The objective of this research was to evaluate weed management and zucchini squash production using the combination of NT and a herbicide-suppressed winter rye cover crop with or without PRE herbicides. When used in combination with herbicides, the winter rye living mulch reduced the biomass of redroot pigweed compared to the herbicides applied alone, but did not influence the biomass of smooth crabgrass for any herbicide treatment. Visual estimates of weed control were similar for each herbicide treatment with and without the winter rye living mulch. The herbicide-suppressed winter rye resulted in excessive stunting of zucchini squash at 56 d after treatment which correlated with 20 and 50% squash yield reductions for the 2004 and 2005 growing seasons, respectively. Although some squash yield loss may have resulted from direct competition with the winter rye living mulch, yield reductions most likely resulted from allelopathy. The winter rye living mulch was the primary contributing factor for reduced squash yield and did not interact with herbicide treatment. All treatments containing herbicides resulted in yields similar to the weed-free treatment. Because of excessive zucchini injury, this research suggests that the use of herbicide-suppressed winter rye living mulch does not appear to be a feasible option for increased weed control in zucchini squash production regardless of the herbicide treatment.
Volunteer horseradish plants that emerged from root segments remaining after harvest can reduce yields of rotational crops as well as provide a host for pathogens and insects, thus reducing the benefits of crop rotation. POST applications of halosulfuron in corn can be an effective component to improve management of volunteer horseradish, but the replant interval from application to safe planting of commercial horseradish has not been determined. Fall herbicide applications are another possible volunteer horseradish management strategy than can be implemented once crops are harvested. Therefore, field experiments were conducted to evaluate the safe replant interval of horseradish following halosulfuron applications and to determine the efficacy of fall herbicide applications for volunteer horseradish control. Visual estimates of horseradish injury were greatest (85%) in plantings made zero months after halosulfuron applied at two times the approved rate; moreover, for all rates, injury decreased as the time after halosulfuron application increased. No herbicide injury or root biomass reduction occurred on horseradish at any halosulfuron rate from replanting beyond 4 mo after halosulfuron application. Control of volunteer horseradish was 91% or greater for all fall herbicide applications that included 2,4-D. Furthermore, volunteer horseradish shoot density was the lowest following combinations of 2,4-D tank-mixed with halosulfuron or rimsulfuron : thifensulfuron (0.2 and 0.4 shoots m−2, respectively) compared with the nontreated control (5.1 shoots m−2). This research demonstrates the effectiveness of both halosulfuron and 2,4-D as components of an integrated management strategy for volunteer horseradish control and the potential for halosulfuron applications without soil persistence beyond 4 mo affecting subsequent commercial horseradish production.
Greenhouse experiments were conducted to evaluate pumpkin cultivar injury and control of three grass species from tank-mixtures of halosulfuron with either clethodim or sethoxydim in combination with nonionic surfactant (NIS), crop-oil concentrate (COC), methylated seed oil (MSO), and high-surfactant oil concentrate (HSOC). Pumpkin injury, in the form of chlorosis and visual growth reduction, was 13 to 21% by 7 d after treatment (DAT) for all pumpkin cultivars. The specific adjuvant used with halosulfuron did not influence pumpkin injury or final plant dry weight. Pumpkin growth reduction at 21 DAT from halosulfuron was less than 9% for all pumpkin cultivars with the least growth reduction (5% or less) observed with Cucurbita pepo ‘Howden’, C. pepo ‘Appalachian’, and Cucurbita moschata ‘Libby's Select’. The efficacy of sethoxydim or clethodim on large crabgrass was antagonized by the addition of halosulfuron with NIS or COC. However, only combinations of sethoxydim and halosulfuron with COC or MSO were antagonistic on smooth crabgrass. Giant foxtail dry weight reduction was decreased 4 to 24% by the addition of halosulfuron to sethoxydim with NIS and clethodim regardless of adjuvant. Although the frequency and magnitude of grass antagonism was variable, the use of clethodim and MSO with halosulfuron most often provided the greatest level of grass control compared with sethoxydim or other adjuvants.
Viable horseradish roots of various sizes remain in the soil after harvest and can develop into volunteer plants in subsequent crops. Experiments were conducted to evaluate POST herbicides on volunteer horseradish control and to determine if efficacy is dependent upon horseradish root segment size, herbicide rate, horseradish cultivar, or horseradish shoot size at application. In the greenhouse, horseradish root segment size did not affect herbicide efficacy. Chlorimuron, cloransulam, imazamox, (2,4-dichlorophenoxy)acetic acid (2,4-D) amine, halosulfuron, and imazethapyr plus imazapyr provided greater than 95% foliar control of volunteer horseradish. Chlorimuron, halosulfuron, and 2,4-D amine were also among the herbicides that provided the greatest reduction in horseradish root biomass (69% or greater). Glyphosate provided little foliar control (76%) and root biomass reduction (57%) after one application. The efficacy of 2,4-D amine on horseradish foliage and root biomass increased with increasing herbicide rate; however, the response of horseradish to halosulfuron was similar for all rates evaluated. Root biomass reduction of the horseradish cultivar ‘1573’ was less responsive to 2,4-D amine and halosulfuron applications compared with ‘1038’ and ‘1722’. However, foliar injury from 2,4-D amine and halosulfuron was less for the horseradish cultivar ‘1038’ compared with ‘1573’ and ‘1722’. In field studies, 2,4-D amine applied to 15- and 30-cm-tall horseradish and halosulfuron applied to 15-cm-tall horseradish resulted in the greatest foliar and root biomass reduction. This study indicated that in-season control of volunteer horseradish in rotational crops may be achieved through proper herbicide selection.
A 2-yr study was conducted to evaluate bell pepper response and honeyvine milkweed control from PRE herbicides, clomazone and trifluralin, applied under polyethylene mulch. Clomazone (0.8 and 1.4 kg ai ha−1) and trifluralin (0.7 and 1.1 kg ai ha−1) were applied alone or in combination. Herbicides were applied after beds were made and before polyethylene mulch was laid, followed by transplanting pepper within hours of herbicide application. In both years, initial bleaching of lower leaves was observed; the injury was observed in some treatments, but not others. Honeyvine milkweed, growing in the planting hole, exhibited significant bleaching and stunting in most herbicide treatments. Both clomazone and trifluralin resulted in season-long honeyvine milkweed control in both years. However, the use of clomazone and trifluralin together for control of honeyvine milkweed does not seem justified due to the potential for herbicide antagonism, as indicated in this study. The total number and fresh weight of harvested bell pepper were not affected by the herbicides or rates. All herbicide treatments resulted in about twice the yield (average of 8.8 kg) of the hand-weeded control (4.6 kg) in both years. This study strongly supports the safety and effectiveness of clomazone and/or trifluralin applied pretransplant under polyethylene mulch in bell pepper production for control of honeyvine milkweed.
Objectives: The headroom approach to medical device development relies on the estimation of a value-based price ceiling at different stages of the development cycle. Such price-ceilings delineate the commercial opportunities for new products in many healthcare systems. We apply a simple model to obtain critical business information as the product proceeds along a development pathway, and indicate some future directions for the development of the approach.
Methods: Health economic modelling in the supply-side development cycle for new products.
Results: The headroom can be used: initially as a ‘reality check’ on the viability of the device in the healthcare market; to support product development decisions using a real options approach; and to contribute to a pricing policy which respects uncertainties in the reimbursement outlook.
Conclusions: The headroom provides a unifying thread for business decisions along the development cycle for a new product. Over the course of the cycle attitudes to uncertainty will evolve, based on the timing and manner in which new information accrues. Within this framework the developmental value of new information can justify the costs of clinical trials and other evidence-gathering activities. Headroom can function as a simple shared tool to parties in commercial negotiations around individual products or groups of products. The development of similar approaches in other contexts holds promise for more rational planning of service provision.
Although dietary intake over a single 24-h period may be atypical of an individual’s habitual pattern, multiple 24-h dietary assessments can be representative of habitual intake and help in assessing seasonal variation. Web-based questionnaires are convenient for the participant and result in automatic data capture for study investigators. This study reports on the acceptability of repeated web-based administration of the Oxford WebQ – a 24-h recall of frequency from a set food list suitable for self-completion from which energy and nutrient values can be automatically generated. As part of the UK Biobank study, four invitations to complete the Oxford WebQ were sent by email over a 16-month period. Overall, 176 012 (53 % of those invited) participants completed the online version of the Oxford WebQ at least once and 66 % completed it more than once, although only 16 % completed it on all four occasions. The response rate for any one round of invitations varied between 34 and 26 %. On most occasions, the Oxford WebQ was completed on the same day that they received the invitation, although this was less likely if sent on a weekend. Participants who completed the Oxford WebQ tended to be white, female, slightly older, less deprived and more educated, which is typical of health-conscious volunteer-based studies. These findings provide preliminary evidence to suggest that repeated 24-h dietary assessment via the Internet is acceptable to the public and a feasible strategy for large population-based studies.
Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.