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This chapter comprises the following sections: names, taxonomy, subspecies and distribution, descriptive notes, habitat, movements and home range, activity patterns, feeding ecology, reproduction and growth, behavior, parasites and diseases, status in the wild, and status in captivity.
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.
Drawing on both Statius’s Thebaid and Boccaccio’s Teseida, TheKnight’s Tale uncomfortably sutures the horrors of epic tragedy to the idealism of chivalric romance, inflecting both with the philosophical ambitions of Boethius’s Consolation. This chapter traces the modern engagement with the tale as a history of attempts to understand the tensions produced by its multiple sources, genres, and rhetorical registers, and explores how accounts of its form inflect and are inflected by accounts of its politics. Politics here, as in other Canterbury Tales, is as much a matter of gender and sexuality as it is of class, rule, and social order. Moreover, the problems posed by aesthetic and political form become problems of how to understand the relations among the text, its pilgrim narrator, and the author. Beginning with the high formalist moment of postwar criticism, the chapter follows the development of ideology critique and of feminist and psychoanalytic criticism, each of which remains attuned to earlier formalist questions. TheKnight’s Tale that emerges from this history is a text of great aesthetic ambition, whose aims are as much reflected in its incoherences as in its formalist impulses.
OBJECTIVES/GOALS: Neuroblastoma (NB) is an embryonal cancer of the sympathetic nervous system that affects mostly infants and young children. The complex genetic background present across NB patients results in diverse clinical response and difficulty in individualizing therapy. Currently, NB patients undergo a regimen of genotoxic chemotherapeutics, radiation therapy, and new immunotherapy that, while effective, has significant side effects, including excruciating pain. One promising avenue for targeted therapy in neuroblastoma focuses on anaplastic lymphoma kinase (ALK), a cell surface neural receptor tyrosine kinase. We previously identified activating point mutations within the tyrosine kinase domain of ALK as the primary cause of hereditary NB, and we and others subsequently showed that these same alterations are the most common somatic single-nucleotide mutations in the sporadic forms of the disease. Crizotinib, a first-generation small molecule ATP-competitive inhibitor of the ALK tyrosine kinase, showed limited anti-tumor activity in patients with relapsed NB harboring ALK F1174 and F1245 mutations. We have demonstrated that lorlatinib, a novel ATP-competitive ALK inhibitor, overcomes this de novo resistance in preclinical models of ALK-driven NB. Recent clinical trials with lorlatinib in patients with non-small cell lung cancer harboring an ALK fusion, and in patients with NB harboring ALK mutations show the emergence of multiple or compound ALK mutations as a mechanism of resistance. We postulate that these compound mutations disrupt the interaction between and ALK and cause resistance. In this study, we employ a computational approach to model mutated ALK in complex with lorlatinib as well as ATP to understand whether the new mutations alter the affinity or mode of lorlatinib/ATP binding to ALK, and thus cause suboptimal ALK inhibition. METHODS/STUDY POPULATION: We employ methods in computational structural biology and drug design, primarily based on molecular modeling, molecular dynamics (MD), and molecular docking. Based on existing crystal structures of wildtype ALK, we model the mutations and perform MD simulations in order to characterize the activation state of the protein as well as perform ensemble docking calculations to assess the binding affinities and modes in ALK-lorlatinib and ALK-ATP complexes. RESULTS/ANTICIPATED RESULTS: We expect that the compound mutations cause resistance to lorlatinib either by lowering protein affinity for the drug or increasing the affinity for ATP. Alternatively, the compound mutations may disrupt the protein activation state, in which case ALK may no longer be active, and another protein/pathway could be driving the resistance. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study will enable the understanding of the mechanism of resistance to lorlatinib and facilitate the design of new ALK inhibitors, or help develop more optimal and mechanism-guided therapies aimed to overcome the resistance.
Restless legs syndrome (RLS) is a neurological disorder characterized by an urge to move and uncomfortable sensations. Genetic studies have identified polymorphisms in up to 19 risk loci, including MEIS1 and BTBD9. Rodents deficient in either homolog show RLS-like phenotypes. However, whether MEIS1 and BTBD9 interact in vivo is unclear. Here, with C. elegans, we observed that the hyperactive egg-laying behavior caused by loss of BTBD9 homolog was counteracted by knockdown of MEIS1 homolog. This was further investigated in mutant mice with Btbd9, Meis1, or both knocked out. The double knockout mice showed an earlier onset of the motor deficit in a wheel running test but did not have increased sensitivity to heat stimuli as observed in single knock outs. Meis1 protein level was not influenced by Btbd9 deficiency, and Btbd9 transcription was not affected by Meis1 haploinsufficiency. Our results demonstrate that MEIS1 and BTBD9 do not regulate each other.
Field trials were conducted in North Carolina in 2017 and Louisiana and Mississippi in 2018 to determine the effect of pretransplanting applications of diquat on sweetpotato crop tolerance, yield, and storage root quality. In North Carolina treatments consisted of two rates of diquat (560 or 1,120 g ai ha−1) alone or mixed with 107 g ai ha−1 flumioxazin and applied 1 d before transplanting (DBP), sequential applications of diquat (560 or 1,120 g ha−1) 1 and 17 DBP, 107 g ha−1 flumioxazin alone, and a nontreated check. In Louisiana and Mississippi treatments consisted of diquat (560 or 1,120 g ha−1) applied 1 DBP either alone or followed by (fb) rehipping rows or 107 g ha−1 flumioxazin immediately prior to transplanting. Additional treatments included 546 g ha−1 paraquat applied 1 DBP and a nontreated check. In North Carolina injury was ≤3% for all treatments through 23 d after transplanting (DAP), and no injury was observed after 23 DAP. Visual sweetpotato stunting pooled across the Mississippi and Louisiana trials ranged from 1% to 14%, 0% to 6%, and 0% to 3% at 2, 4, and 6 wk after planting (WAP), respectively, and no crop injury was observed after 6 WAP. Diquat applied 1 DBP and not fb rehipping resulted in greater crop injury (12%) than comparable treatments that were rehipped (2%). In North Carolina single and sequential diquat applications resulted in reduced No. 1 sweetpotato yield (24,230 and 24,280 kg ha−1, respectively) compared with the nontreated check, but No. 1 yield when diquat plus flumioxazin (26,330 kg ha−1) was used was similar to that of the nontreated check. No. 1 yield did not differ by treatment in Louisiana and Mississippi.
Challenges faced by older people include losses of loved ones through death; declining health, mobility, and function of the five senses; loss of independence; diminishing cognitive ability; and the struggle with Erik Erikson’s final two stages of life, namely generativity versus stagnation and ego integrity versus despair. Those who dedicate their energies to helping the elderly meet these challenges will be well served by the toolbox of techniques within the rubric of interpersonal psychotherapy (IPT). This chapter will serve as a brief overview of IPT principles, a review of the extant scientific literature on its efficacy in late life, and case vignettes to illustrate how it was used for each of the four foci of IPT, namely, role transition, grief, role disputes, and interpersonal deficit.
There is robust evidence that compromised parenting, stemming from persistently high stress, mediates the impact of war and displacement on children's mental health and psychosocial wellbeing. Parenting interventions generally prioritize the acquisition of parenting knowledge and skills, while under-attending to parental stress and distress. This paper describes the development of the Caregiver Support Intervention (CSI), a nine-session group intervention for conflict-affected parents of children aged 3–13, that aims to strengthen parenting both indirectly, by lowering stress and improving psychosocial wellbeing among parents, and directly, by increasing knowledge and skill related to positive parenting.
We describe the multi-phase, iterative process by which we developed the CSI, and illustrate the essential role of community input in shaping the intervention and strengthening its cultural fit and perceived usefulness. We used focus group data from participants in successive cycles of implementation, feedback, and revision, as well as quantitative data and expert consultation to develop a culturally and empirically grounded intervention.
This mixed-method, iterative approach to intervention development enabled us to develop a psychosocial intervention for conflict-affected caregivers that is feasible, acceptable, and perceived by participants as useful in addressing their own wellbeing and their parenting. Focus group data support the underlying model in which caregiver wellbeing powerfully influences parenting.
Programs aimed at strengthening parenting in conflict-affected communities should substantively address caregiver wellbeing. An iterative approach incorporating community feedback can help ensure intervention acceptability and feasibility. We also illustrate the feasibility of involving men in parenting interventions.
Field trials were conducted near Pontotoc, Mississippi; Chase, Louisiana; and Clinton, North Carolina, in 2017 and 2018 to determine the effect of pendimethalin rate and timing application on sweetpotato crop tolerance, yield, and storage root quality. Treatments consisted of five pendimethalin rates (266, 532, 1,065, 1,597, and 2,130 g ai ha−1) by two application timings (0 to 1 or 10 to 14 d after transplanting). Additionally, a nontreated check was included for comparison. Crop injury (stunting) was minimal (≤4%) through 6 wk after transplanting (WAP) and no injury was observed from 8 to 14 WAP, regardless of application timing or rate. The nontreated check yielded 6.6, 17.6, 5.5, and 32.1 × 103 kg ha−1 of canner, no. 1, jumbo, and total grades, respectively. Neither pendimethalin application timing nor rate influenced jumbo, no. 1, marketable, or total sweetpotato yield. Overall, these results indicate that pendimethalin will be a valuable addition to the toolkit of sweetpotato growers.
The Japanese Murrelet Synthliboramphus wumizusume is a rare, globally ‘Vulnerable’ seabird, endemic to Japan and South Korea. However, little is known of its at-sea distribution, habitat or threats. We conducted several years of at-sea surveys around Japan to model Japanese Murrelet density in relation to habitat parameters, and make spatial predictions to assess the adequacy of the current Japanese marine Important Bird and Biodiversity Area (IBA) network for the species. During a five-year period, 3,485 km of at-sea surveys recorded 3,161 Japanese Murrelets around four breeding locations. Maximum murrelet group size was 90 individuals with a mean group size of 2.9 ± 4.2 individuals. Models of Japanese Murrelet at-sea density around the two largest breeding locations predicted that almost all murrelets occur within 30 km of the breeding colony and most within 10 km. Murrelets were predicted closer to the colony in May than in April and closer to the colony at a neritic colony than at an offshore island colony. Additionally, murrelets breeding on an offshore island colony also commuted to mainland neritic habitat for foraging. The marine habitat used by Japanese Murrelets differed between each of the four surveyed colonies, however oceanographic variables offered little explanatory power in models. Models with colony, month and year generated four foraging radii (9–39 km wide) containing murrelet densities of > 0.5 birds/km2. Using these radii the Japanese marine IBA network was found to capture between 95% and 25% of Japanese Murrelet at-sea habitat while breeding and appears appropriately configured to protect near-colony murrelet distributions. Given the range of marine habitats that breeding murrelets inhabit, our simple models offer an applicable method for predicting to unsampled colonies and generating ecologically-informed seaward extension radii. However, data on colony populations and further at-sea surveys are necessary to refine models and improve predictions.
Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes associated with genomic vulnerability for externalizing disorders.
One-hundred fifty-five White, non-Hispanic veterans were genotyped using a genome-wide array and underwent resting-state functional magnetic resonance imaging. Genetic susceptibility was assessed using an independently developed polygenic score (PS) for externalizing, and functional neural networks were identified using graph theory based network analysis. Tasks of inhibitory control and psychiatric diagnosis (alcohol/substance use disorders) were used to measure externalizing phenotypes.
A polygenic externalizing disorder score (PS) predicted connectivity in a brain circuit (10 nodes, nine links) centered on left amygdala that included several cortical [bilateral inferior frontal gyrus (IFG) pars triangularis, left rostral anterior cingulate cortex (rACC)] and subcortical (bilateral amygdala, hippocampus, and striatum) regions. Directional analyses revealed that bilateral amygdala influenced left prefrontal cortex (IFG) in participants scoring higher on the externalizing PS, whereas the opposite direction of influence was observed for those scoring lower on the PS. Polygenic variation was also associated with higher Participation Coefficient for bilateral amygdala and left rACC, suggesting that genes related to externalizing modulated the extent to which these nodes functioned as communication hubs.
Findings suggest that externalizing polygenic risk is associated with disrupted connectivity in a neural network implicated in emotion regulation, impulse control, and reinforcement learning. Results provide evidence that this network represents a genetically associated neurobiological vulnerability for externalizing disorders.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
To determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.
Individual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.
We searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.
Probiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.
Moderate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.
Laboratory experiments were performed on a geometrically scaled vertical-axis wind turbine model over an unprecedented range of Reynolds numbers, including and exceeding those of the full-scale turbine. The study was performed in the high-pressure environment of the Princeton High Reynolds number Test Facility (HRTF). Utilizing highly compressed air as the working fluid enabled extremely high Reynolds numbers while still maintaining dynamic similarity by matching the tip speed ratio (defined as the ratio of tip velocity to free stream,
) and Mach number (defined at the turbine tip,
). Preliminary comparisons are made with measurements from the full-scale field turbine. Peak power for both the field data and experiments resides around
. In addition, a systematic investigation of trends with Reynolds number was performed in the laboratory, which revealed details about the asymptotic behaviour. It was shown that the parameter that characterizes invariance in the power coefficient was the Reynolds number based on blade chord conditions (
). The power coefficient reaches its asymptotic value when
, which is higher than what the field turbine experiences. The asymptotic power curve is found, which is invariant to further increases in Reynolds number.
In this investigation, we reported the increase in emergency department and inpatient admission cases during the month of November 2012 post Hurricane Sandy as compared with baseline (November 2010, 2011, and 2013) for elderly patients aged 65 and up.
Medical claims data for patients aged 65 and over treated at emergency department and inpatient health care facilities in New Jersey were analyzed to examine the surge in frequencies of diagnoses treated immediately following Hurricane Sandy. The differences were quantified using gap analysis for 2 years before and 1 year after the event.
There was an average increase of 1700 cases for the month of November 2012 relative to baseline for the top 15 most frequently diagnosed emergency department medical conditions. On a daily basis, a volume increase by an average 57 cases could be expected, including significant numbers of limb fractures and other trauma cases for these most frequently encountered medical conditions.
Understanding the surge level in medical services needed in emergency departments and inpatient facilities during a natural disaster aftermath is critical for effective emergency preparation and response for the elderly population. (Disaster Med Public Health Preparedness. 2018;12:730-738)
On August 25, 2017, Hurricane Harvey made landfall near Corpus Christi, Texas. The ensuing unprecedented flooding throughout the Texas coastal region affected millions of individuals.1 The statewide response in Texas included the sheltering of thousands of individuals at considerable distances from their homes. The Dallas area established large-scale general population sheltering as the number of evacuees to the area began to amass. Historically, the Dallas area is one familiar with “mega-sheltering,” beginning with the response to Hurricane Katrina in 2005.2 Through continued efforts and development, the Dallas area had been readying a plan for the largest general population shelter in Texas. (Disaster Med Public Health Preparedness. 2019;13:33–37)
The seventh meeting of the World Congress of Pediatric Cardiology and Cardiac Surgery was an opportunity for healthcare professionals from around the world to meet and discuss current issues affecting patients with acquired and CHD. A dedicated anaesthesia track facilitated the exchange of ideas and fostered many new friendships. This review highlights the congenital cardiac anaesthesia track and the involvement of the Congenital Cardiac Anesthesia Society in the congress.