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The current study argues that population prevalence estimates for mental health disorders, or changes in mean scores over time, may not adequately reflect the heterogeneity in mental health response to the COVID-19 pandemic within the population.
The COVID-19 Psychological Research Consortium (C19PRC) Study is a longitudinal, nationally representative, online survey of UK adults. The current study analysed data from its first three waves of data collection: Wave 1 (March 2020, N = 2025), Wave 2 (April 2020, N = 1406) and Wave 3 (July 2020, N = 1166). Anxiety-depression was measured using the Patient Health Questionnaire Anxiety and Depression Scale (a composite measure of the PHQ-9 and GAD-7) and COVID-19-related posttraumatic stress disorder (PTSD) with the International Trauma Questionnaire. Changes in mental health outcomes were modelled across the three waves. Latent class growth analysis was used to identify subgroups of individuals with different trajectories of change in anxiety-depression and COVID-19 PTSD. Latent class membership was regressed on baseline characteristics.
Overall prevalence of anxiety-depression remained stable, while COVID-19 PTSD reduced between Waves 2 and 3. Heterogeneity in mental health response was found, and hypothesised classes reflecting (i) stability, (ii) improvement and (iii) deterioration in mental health were identified. Psychological factors were most likely to differentiate the improving, deteriorating and high-stable classes from the low-stable mental health trajectories.
A low-stable profile characterised by little-to-no psychological distress (‘resilient’ class) was the most common trajectory for both anxiety-depression and COVID-19 PTSD. Monitoring these trajectories is necessary moving forward, in particular for the ~30% of individuals with increasing anxiety-depression levels.
The coronavirus disease 2019 (COVID-19) emergency has led to numerous attempts to assess the impact of the pandemic on population mental health. The findings indicate an increase in depression and anxiety but have been limited by the lack of specificity about which aspects of the pandemic (e.g. viral exposure or economic threats) have led to adverse mental health outcomes.
Network analyses were conducted on data from wave 1 (N = 2025, recruited 23 March–28 March 2020) and wave 2 (N = 1406, recontacts 22 April–1 May 2020) of the COVID-19 Psychological Research Consortium Study, an online longitudinal survey of a representative sample of the UK adult population. Our models included depression (PHQ-9), generalized anxiety (GAD-7) and trauma symptoms (ITQ); and measures of COVID-specific anxiety, exposure to the virus in self and close others, as well as economic loss due to the pandemic.
A mixed graphical model at wave 1 identified a potential pathway from economic adversity to anxiety symptoms via COVID-specific anxiety. There was no association between viral exposure and symptoms. Ising network models using clinical cut-offs for symptom scores at each wave yielded similar findings, with the exception of a modest effect of viral exposure on trauma symptoms at wave 1 only. Anxiety and depression symptoms formed separate clusters at wave 1 but not wave 2.
The psychological impact of the pandemic evolved in the early phase of lockdown. COVID-related anxiety may represent the mechanism through which economic consequences of the pandemic are associated with psychiatric symptoms.
Infectious disease emergencies are increasingly becoming part of the health care delivery landscape, having implications to not only individuals and the public, but also on those expected to respond to these emergencies. Health care workers (HCWs) are perhaps the most important asset in an infectious disease emergency, yet these individuals have their own barriers and facilitators to them being willing or able to respond.
The purpose of this review was to identify factors affecting HCW willingness to respond (WTR) to duty during infectious disease outbreaks and/or bioterrorist events.
An integrative literature review methodology was utilized to conduct a structured search of the literature including CINAHL, Medline, Embase, and PubMed databases using key terms and phrases. PRISMA guidelines were used to report the search outcomes and all eligible literature was screened with those included in the final review collated and appraised using a quality assessment tool.
A total of 149 papers were identified from the database search. Forty papers were relevant following screening, which highlighted facilitators of WTR to include: availability of personal protective equipment (PPE)/vaccine, level of training, professional ethics, family and personal safety, and worker support systems. A number of barriers were reported to prevent WTR for HCWs, such as: concern and perceived risk, interpersonal factors, job-level factors, and outbreak characteristics.
By comprehensively identifying the facilitators and barriers to HCWs’ WTR during infectious disease outbreaks and/or bioterrorist events, strategies can be identified and implemented to improve WTR and thus improve HCW and public safety.
The COVID-19 pandemic has created an unprecedented global crisis, necessitating drastic changes to living conditions, social life, personal freedom and economic activity. No study has yet examined the presence of psychiatric symptoms in the UK population under similar conditions.
We investigated the prevalence of COVID-19-related anxiety, generalised anxiety, depression and trauma symptoms in the UK population during an early phase of the pandemic, and estimated associations with variables likely to influence these symptoms.
Between 23 and 28 March 2020, a quota sample of 2025 UK adults aged 18 years and older, stratified by age, gender and household income, was recruited by online survey company Qualtrics. Participants completed standardised measures of depression, generalised anxiety and trauma symptoms relating to the pandemic. Bivariate and multivariate associations were calculated for demographic and health-related variables.
Higher levels of anxiety, depression and trauma symptoms were reported compared with previous population studies, but not dramatically so. Anxiety or depression and trauma symptoms were predicted by young age, presence of children in the home, and high estimates of personal risk. Anxiety and depression were also predicted by low income, loss of income and pre-existing health conditions in self and others. Specific anxiety about COVID-19 was greater in older participants.
This study showed a modest increase in the prevalence of mental health problems in the early stages of the pandemic, and these problems were predicted by several specific COVID-related variables. Further similar surveys, particularly of those with children at home, are required as the pandemic progresses.
OBJECTIVES/GOALS: It has been previously shown that pediatric high-grade glioma (pHGG) survival is different between sexes. We set out to find out whether there are sex-specific differences in the genomic landscapes of pHGG that may underlie this sex disparity. METHODS/STUDY POPULATION: We downloaded Illumina 450k DNAm data from ArrayExpress and GeneExpressionOmnibus. The minfi package was used to process raw DNAm data. Sex chromosomes and CpGs that are common SNPs were removed. Surrogate variables (SVs) were estimated via the sva Bioconductor package. Differentially methylated CpGs were identified by fitting a multiple linear regression model for the DNAm level at each CpG, with independent variables being sex (a binary variable) and the estimated SVs. RNAseq data was downloaded from Cavatica, and differential gene expression analysis was carried out via the DESeq2 package. RESULTS/ANTICIPATED RESULTS: In the pediatric glioblastoma (GBM) DNAm data [58 female & 91 male IDH wt samples; ages 0.1–21 yrs;], we found 7,371 differentially methylated cytosines (DMCs) at FDR≤0.05. Of the DMCs, 289 had DNAm differences between male and female samples ≥10%. The majority of probes (68%) were in CpG islands, shelves, or shores. We also found 4 differentially methylated regions (DMRs) between sexes (FWER≤0.1). In the adult GBM DNAm samples [32 F & 32 M IDH wt samples; ages 22–75 yrs], we found only 117 DMCs at FDR≤0.05, and no DMRs. In the RNAseq dataset [68 F & 54 M pHGG samples, ages 0.08–30.6 yrs], we found 383 differentially expressed genes (at FDR≤0.05), and 16 of them (4%) overlapped a DMC. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings demonstrate that pHGG exhibits sex-specific methylome differences. Interestingly, this difference is greater in the pediatric population as compared to adults. The pHGG transcriptome also differs by sex, which may be related to differential DNAm in a minority of cases.
Solar coronal dimmings have been observed extensively in the past two decades and are believed to have close association with coronal mass ejections (CMEs). Recent study found that coronal dimming is the only signature that could differentiate powerful flares that have CMEs from those that do not. Therefore, dimming might be one of the best candidates to observe the stellar CMEs on distant Sun-like stars. In this study, we investigate the possibility of using coronal dimming as a proxy to diagnose stellar CMEs. By simulating a realistic solar CME event and corresponding coronal dimming using a global magnetohydrodynamics model (AWSoM: Alfvén-wave Solar Model), we first demonstrate the capability of the model to reproduce solar observations. We then extend the model for simulating stellar CMEs by modifying the input magnetic flux density as well as the initial magnetic energy of the CME flux rope. Our result suggests that with improved instrument sensitivity, it is possible to detect the coronal dimming signals induced by the stellar CMEs.
Neospora caninum is a commonly diagnosed cause of reproductive losses in farmed ruminants worldwide. This study examined 495 and 308 samples (brain, heart and placenta) which were collected from 455 and 119 aborted cattle and sheep fetuses, respectively. DNA was extracted and a nested Neospora ITS1 PCR was performed on all samples. The results showed that for bovine fetuses 79/449 brain [17.6% (14.2–21.4)], 7/25 heart [28.0% (12.1–49.4)] and 5/21 placenta [23.8% (8.2–47.2)] were PCR positive for the presence of Neospora DNA. Overall 82/455 [18.0% (14.6–21.7)] of the bovine fetuses tested positive for the presence of N. caninum DNA in at least one sample. None (0/308) of the ovine fetal samples tested positive for the presence of Neospora DNA in any of the tissues tested. The results show that N. caninum was associated with fetal losses in cattle (distributed across South-West Scotland), compared to sheep in the same geographical areas where no parasite DNA was found. Neospora is well distributed amongst cattle in South-West Scotland and is the potential cause of serious economic losses to the Scottish cattle farming community; however, it does not appear to be a problem amongst the Scottish sheep flocks.
Atypical Teratoid Rhabdoid Tumors (AT/RTs) often affect children under the age of 3 and are the most common malignant CNS tumors in children younger than 6 months. It is very rare to see these tumors in patients older than 6 years of age. We discuss the case of a 14 year old male with AT/RT of the right insula. He had a prior diagnosis of Dysembryoplastic Neuroectodermal Tumor (DNET) at the age of 10, after two years of intermittent headaches, nausea, and seizures, which was treated with conformal radiation and chemotherapy for a year. Following the diagnosis of AT/RT, he underwent radiotherapy, multiple lines of chemotherapy, and two additional debulking surgeries of the left temporal lobe due to continuing progression. He was then treated with Alisertib (an Aurora-A kinase inhibitor) with good response on sequential MRIs after the first three cycles. He progressed after nine cycles of Alisertib and required further debulking surgery. Six years after his AT/RT diagnosis (and 10 years after his DNET diagnosis), the patient expired at the age of 20 due to ongoing progression. To our knowledge, this is only the second reported case of Alisertib use in a non-pediatric AT/RT case. We also performed a literature review of all reported cases of AT/RT in adults between the years 2000 – 2017 and discuss treatment options, patient demographics, and survival.
Background: Brain tumors present unique challenges to patient and family quality of life (QOL). Cognitive dysfunction is common and functionally limiting, with no established treatments. These studies evaluate feasibility and preliminary efficacy of behavioral interventions developed for neuro-oncology patients. Study 1: A randomized controlled trial (N=25 primary brain tumor patients) compared an adapted version of Goal Management Training (GMT, a neuroscience-based integration of mindfulness and strategy training) and a newly-designed supportive psychoeducational intervention (Brain Health Program, BHP) to standard of care. Each intervention comprised 8 individual sessions and at-home practice between sessions. GMT patients’ executive functions improved immediately (p=.077, d=1.13), with maintenance at 4-month follow-up (p=.046, d=1.09). Both intervention groups reported improvements in everyday cognitive functioning immediately (p=.049; d’s GMT=0.43, BHP=0.79) and at follow-up (p=.001; d’s GMT=0.22, BHP=1.01). BHP patients also reported improved mood (p’s=.026 & .012, d’s=0.61 & 0.62). Study 2: Following a needs assessment about cognitive concerns and QOL in brain metastases patients (N=109) and caregivers (N=31), we developed a novel, brief (3 sessions + homework) Cognitive Support Program to provide education and strategy-training in key areas of concern: executive functions, memory, and communication. Options include caregiver co-training, and in-person or web-based delivery. Preliminary data from a pilot trial in progress demonstrate objective and subjective improvements. Conclusions: Cognitive rehabilitation may be a feasible and effective option for primary or metastatic brain tumor patients, addressing a need that is largely unmet in standard cancer care. Further development and larger trials appear warranted, with capacity for remote delivery recommended.
Background: Bevacizumab has been used in recurrent glioblastoma (rGBM) since 2010 in Canada. Given its cost, potential toxicities, and unclear efficacy, further studies are required to better define suitable candidates for therapy. Methods: A single-center retrospective review of patients started on bevacizumab for rGBM from 2012 to 2015 was performed. Patient demographics, tumor characteristics, treatment regimen, and dates of clinical progression and death were collected. Overall survival (OS) and progression-free survival (PFS) were used as clinical outcomes and estimates. Radiological response was assessed using modified Response Assessment in Neuro-Oncology criteria. Results: A total of 80 patients were included. There were 67 reported deaths, and the median OS was 9.2 months (95% confidence interval [CI95%]=7.0-10.1 months), with a 12-month OS of 31% (CI95%=21.9-43.5%). Some 79 patients were included for analysis of clinical progression, among whom 61 had documented clinical progression. The median clinical PFS was 4.6 months (CI95%=3.8-6.4 months), and the 6-month clinical PFS was 39% (CI95%=29.0-52.9%). Addition of chemotherapy did not improve clinical outcomes. A total of 68 patients were included for radiological progression analysis, with 58 radiological progressions. The median radiological PFS was 5.8 months (CI95%=4.2-6.7 months), and the 6-month radiological PFS was 46% (CI95%=35.6-60.0%). Conclusions: This is the first reported Canadian experience with bevacizumab for rGBM. Our clinical outcomes are consistent with published data from multicenter phase II and III trials on bevacizumab in rGBM. More research is required to determine which subtype(s) of patients with rGBM could benefit from bevacizumab upon recurrence.
Drug use during pregnancy and lactation remain underdeveloped areas of clinical pharmacology and drug research. Pregnancy risk factors together with an increased incidence of chronic diseases and a rise in the average maternal age predict medication use will continue to rise during gestation. Common exposure categories include over-the-counter (OTC) medication, psychiatric agents, gastrointestinal medications, herbals, vitamins, antibiotics, and topical products. Only a few medications have been tested specifically for safety and efficacy during human gestation. Profound physiologic changes occur during both normal and pathologic pregnancy that may dramatically alter drug clearance, efficacy, and safety. Under such circumstances, the danger of a drug to mothers, their fetuses, and nursing infants cannot be determined with any confidence until it has been widely used. It is important that women with medical disorders such as diabetes, hypertension, epilepsy, and inflammatory bowel disease continue necessary therapy while pregnant. Unfortunately, many physicians stop or delay medically important agents precisely because of the lack of information.
Late Pregnancy – Maternal Problems
Carl P. Weiner, Center for Advanced Fetal Care, Department of Obstetrics & Gynecology, The University of Kansas Medical Center, Kansas City, KS, USA,
Clifford W. Mason, Department of Obstetrics & Gynecology, University of Kansas Medical Center, Kansas City, KS, USA
Drug use during pregnancy and lactation remain underdeveloped areas of clinical pharmacology and drug research. Pregnancy risk factors together with an increased incidence of chronic diseases and a rise in the average maternal age predict medication use will continue to rise during gestation. Common exposure categories include over-the-counter (OTC) medication, psychiatric agents, gastrointestinal medications, herbals, vitamins, antibiotics, and topical products. Only a few medications have been tested specifically for safety and efficacy during human gestation. Profound physiologic changes occur during both normal and pathologic pregnancy that may dramatically alter drug clearance, efficacy, and safety. Under such circumstances, the danger of a drug to mothers, their fetuses, and nursing infants cannot be determined with any confidence until it has been widely used. It is important that women with medical disorders such as diabetes, hypertension, epilepsy, and inflammatory bowel disease continue necessary therapy while pregnant. Unfortunately, many physicians stop or delay medically important agents precisely because of the lack of information. Innovative research in genomics and proteomics should facilitate the development of medications exponentially as part of the new scientific field of “theranostics” – an amalgam of diagnostics and therapeutics whereby diagnosis and treatment are personalized for individual patients. Theranostics holds great potential for personalized medicine, especially in pregnant women who are in desperate need of tailored medical treatments. In this chapter, we seek to provide a general but concise resource of drugs commonly used during pregnancy and lactation. It is important clinicians become familiar with all the aspects of the drugs they recommend and consult with a maternal–fetal medicine specialist, when appropriate, so that the best possible evidence-based counseling and treatments are provided.
Maternal Physiologic Adaptation to Pregnancy
Pregnancy is characterized by profound changes in cardiovascular, respiratory, renal, gastrointestinal, and endocrine systems. These changes begin early and evolve steadily. By 6–8 weeks’ gestation, the plasma volume begins to rise, reaching 50% above the nonpregnant level by the end of the third trimester. Given this increase in the extracellular space and total body water, physiologic dilution occurs, which may explain some loss of drug efficacy during pregnancy.
The Neogene was a time of transition both in the development of the present vegetation and the palynological study of it. The vegetation cover changed from one dominated by rainforest, which is traditionally regarded as ‘Tertiary’, to one in which rainforest became very reduced in extent. The nature of this change has been difficult to document due to an increasingly arid landscape with a concomitant reduction in suitable pollen preservation sites. The difficulty has been compounded by a relative lack of palynological study on the period. Stratigraphic palynologists have focussed on the earlier part of the Tertiary and there is no formal or well dated biostratigraphy, for much of the period under consideration, that is applicable to Australian terrestrial environments. Palynologists concerned with vegetation reconstruction have largely restricted their attention to the later part of the Quaternary period and have had variable success when venturing back into the Tertiary, as the vegetation then was frequently very different from that of today. Consequently, the database from which we piece together this critical period in Australia's vegetation history is very fragmentary and of varying quality.
In keeping with the problematic documentation of vegetation, there are difficulties in defining the period itself. There is general agreement on its beginning - the Miocene began about 25 million years (Ma) ago, although this does not necessarily hold any palynostratigraphic or biogeographical significance - but there are different views on the best location of the end of the period, i.e. the Pliocene/Pleistocene boundary. Conventionally this boundary is placed at the top of the Olduvai palaeomagnetic event dated to 1.6 Ma (Berggren et aL, 1985) but there is increasing pressure to reposition this close to the Gauss/Matuyama palaeomagnetic reversal boundary, around 2.4 Ma, as this reflects more closely the beginning of the substantial cooling and climatic fluctuations that characterise the Pleistocene period (Zagwin, 1985; Kukla, 1989).
Major factors influencing the whole of Australia during the Neogene include global climatic changes and the northward movement of the continent. The build up of ice on Antarctica, partly a result of the northward movement of Australia, which allowed the development of a circum-Antarctic ocean current, caused a steepening of the temperature gradient from equator to pole and development of the present atmospheric circulation pattern (Kemp, 1978).
Background: Radiotherapy with procarbazine, lomustine, and vincristine improves overall survival (OS) in patients with 1p19q co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma. Methods: This retrospective analysis investigated outcomes in patients with 1p19q co-deleted/partially deleted oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma. OS and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and prognostic factors using the Cox proportional hazard model. Results: A total of 106 patients (between December 1997 and December 2013) were included. Median age was 40 years (19-66), 58 were male (55%), Eastern Cooperative Oncology Group performance status was 0 in 80 patients (75%). 1p19q status was co-deleted in 66 (62%), incompletely co-deleted in 27 (25%), and 1p or 19q loss alone in four (4%) and nine (8%) patients, respectively. Isocitrate dehydrogenase-1 R132H mutation was found in 67 of 85 patients with sufficient material. Upfront treatment was given in 72 (68%) patients and temozolomide alone in 52 (49%). Median time to radiotherapy in 47 patients (44%) was 34.7 months and 41.2 months in 9 patients with co-deleted/incompletely co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma who received upfront temozolomide alone. Median OS was not reached and 5-year OS was 91% for all groups (median follow-up, 5.1 years). On multivariable analysis for all patients, receipt of therapy upfront versus none (p=0.04), PS 1 versus 0 (p<0.001) and 1p19q co-deletion/incomplete deletion versus 1p or 19q loss alone (p=0.005) were prognostic for PFS. Isocitrate dehydrogenase-1 status was not prognostic for PFS. Conclusions: With similar survival patterns in low-grade/anaplastic gliomas, molecular characteristics may be more important than histological grade. Longer follow-up and results of prospective trials are needed for definitive guidance on treatment of these patients.
Neighboring tidewater glaciers often exhibit asynchronous dynamic behavior, despite relatively uniform regional atmospheric and oceanic forcings. This variability may be controlled by a combination of local factors, including glacier and fjord geometry, fjord heat content and circulation, and glacier surface melt. In order to characterize and understand contrasts in adjacent tidewater glacier and fjord dynamics, we made coincident ice-ocean-atmosphere observations at high temporal resolution (minutes to weeks) within a 10 000 km2 area near Uummannaq, Greenland. Water column velocity, temperature and salinity measurements reveal systematic differences in neighboring fjords that imply contrasting circulation patterns. The observed ocean velocity and hydrography, combined with numerical modeling, suggest that subglacial discharge plays a major role in setting fjord conditions. In addition, satellite remote sensing of seasonal ice flow speed and terminus position reveal both speedup and slow-down in response to melt, as well as differences in calving style among the neighboring glaciers. Glacier force budgets and modeling also point toward subglacial discharge as a key factor in glacier behavior. For the studied region, individual glacier and fjord geometry modulate subglacial discharge, which leads to contrasts in both fjord and glacier dynamics.
In support of the Radioactive Waste Management (RWM) safety case for a geological disposal facility (GDF) in the UK, there is a regulatory requirement to consider the likelihood and consequences of nuclear criticality. Waste packages are designed to ensure that criticality is not possible during the transport and operational phases of a GDF and for a significant period post-closure. However, over longer post-closure timescales, conditions in the GDF will evolve.
For waste packages containing spent fuel, it can be shown that, under certain conditions, package flooding could result in a type of criticality event referred to as 'quasi-steady-state' (QSS). Although unlikely, this defines a 'what-if' scenario for understanding the potential consequences of post-closure criticality. This paper provides an overview of a methodology to understand QSS criticality and its application to a spent fuel waste package.
The power of such a hypothetical criticality event is typically estimated to be a few kilowatts: comparable with international studies of similar systems and the decay heat for which waste packages are designed. This work has built confidence in the methodology and supports RWM's demonstration that post-closure criticality is not a significant concern.
A geological disposal facility (GDF) will include fissile materials that could, under certain conditions, lead to criticality. Demonstration of criticality safety therefore forms an important part of a GDF's safety case.
Containment provided by the waste package will contribute to criticality safety during package transport and the GDF operational phase. The GDF multiple-barrier system will ensure that criticality is prevented for some time after facility closure. However, on longer post-closure timescales, conditions in the GDF will evolve and it is necessary to demonstrate: an understanding of the conditions under which criticality could occur; the likelihood of such conditions occurring; and the consequences of criticality should it occur.
Work has addressed disposal of all of the UK's higher-activity wastes in three illustrative geologies. This paper, however, focuses on presenting results to support safe disposal of spent fuel, plutonium and highlyenriched uranium in higher-strength rock.
The results support a safety case assertion that post-closure criticality is of low likelihood and, if it was to occur, the consequences would be tolerable.