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Excited delirium, which has been defined as combativeness, agitation, and altered sensorium, requires immediate treatment in prehospital or emergency department (ED) settings for the safety of both patients and caregivers. Prehospital ketamine use is prevalent, although the evidence on safety and efficacy is limited. Many patients with excited delirium are intoxicated with illicit substances. This investigation explores whether patients treated with prehospital ketamine for excited delirium with concomitant substance intoxication have higher rates of subsequent intubation in the ED compared to those without confirmed substance usage.
Over 28 months at two large community hospitals, all medical records were retrospectively searched for all patients age 18 years or greater with prehospital ketamine intramuscular (IM) administration for excited delirium and identified illicit and prescription substance co-ingestions. Trained abstractors collected demographic characteristics, history of present illness (HPI), urine drug screens (UDS), alcohol levels, and noted additional sedative administrations. Substance intoxication was determined by UDS and alcohol positivity or negativity, as well as physician HPI. Patients without toxicological testing or documentation of substance intoxication, or who may have tested positive due to ED sedation, were excluded from relevant analyses. Subsequent ED intubation was the primary pre-specified outcome. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to compare variables.
Among 86 patients given prehospital ketamine IM for excited delirium, baseline characteristics including age, ketamine dose, and body mass index were similar between those who did or did not undergo intubation. Men had higher intubation rates. Patients testing positive for alcohol, amphetamines, barbiturates, benzodiazepines, ecstasy, marijuana, opiates, and synthetic cathinones, both bath salts and flakka, had similar rates of intubation compared to those negative for these substances. Of 27 patients with excited delirium and concomitant cocaine intoxication, nine (33%) were intubated compared with four of 50 (8%) without cocaine intoxication, yielding a 5.75 OR (95%, CI 1.57 to 21.05; P = .009).
Patients treated with ketamine IM for excited delirium with concomitant cocaine intoxication had a statistically significant 5.75-fold increased rate of subsequent intubation in the ED. Amongst other substances, no other trends with intubation were noted, but further study is warranted.
The classical model for studying one-phase Hele-Shaw flows is based on a highly nonlinear moving boundary problem with the fluid velocity related to pressure gradients via a Darcy-type law. In a standard configuration with the Hele-Shaw cell made up of two flat stationary plates, the pressure is harmonic. Therefore, conformal mapping techniques and boundary integral methods can be readily applied to study the key interfacial dynamics, including the Saffman–Taylor instability and viscous fingering patterns. As well as providing a brief review of these key issues, we present a flexible numerical scheme for studying both the standard and nonstandard Hele-Shaw flows. Our method consists of using a modified finite-difference stencil in conjunction with the level-set method to solve the governing equation for pressure on complicated domains and track the location of the moving boundary. Simulations show that our method is capable of reproducing the distinctive morphological features of the Saffman–Taylor instability on a uniform computational grid. By making straightforward adjustments, we show how our scheme can easily be adapted to solve for a wide variety of nonstandard configurations, including cases where the gap between the plates is linearly tapered, the plates are separated in time, and the entire Hele-Shaw cell is rotated at a given angular velocity.
This chapter analyzes the technology of human genome editing with a focus on the ethical issues involved and offers guidance as how best to regulate this technology. First, this chapter explains several common types of gene editing technologies and then analyzes the ethical implications of the two primary therapeutic uses of gene editing: somatic and germline. Primary ethical analysis will focus on the bioethical principles of autonomy, beneficence, non-maleficence, and social justice; analysis will then provide a weighing of these principles and likely consequences–noting the biologic differences between somatic versus germline treatments. Somatic gene editing is generally more confined to the individual, while germline editing changes the genes of cells that are passed sexually to offspring, thus having the power to shape the human genome generationally--the ultimate consequence of which is the influence and shaping of human evolution. In conclusion, the chapter argues the consequences of somatic vs. germline genome editing demand that, when considering the proper emphasis of a regulatory paradigm, somatic editing should be regulated under a nationally guided framework and germline editing should be regulated under both a nationally and globally guided framework.
Yellow-Flag Iris (Iris pseudacorus L.) is a non-native, invasive wetland plant that disrupts riparian ecosystem processes and is widely distributed across the US and Canada. Due to its physiological and morphological characteristics, I. pseudacorus has the capacity to exclude native vegetation and form extensive monocultures in both lotic and lentic wetland systems. Methods commonly used to manage I. pseudacorus include manual (e.g., hand-pulling, digging) and mechanical (e.g., mowing) treatments for small populations and herbicide applications for larger populations; however, herbicide applications near water may be prohibited due to label restrictions. The objective of this research was to evaluate cattle trampling as a non-chemical method to reduce I. pseudacorus in riparian habitats. A greenhouse study was conducted to investigate the effects of inundation and two different timings of simulated trampling on I. pseudacorus density, height, and soluble sugar concentrations in the rhizomes. A complementary field demonstration was established on a ranch in northwestern Nebraska to evaluate cattle trampling effects on I. pseudacorus density and height after two consecutive years. Simulated cattle trampling in the greenhouse had no effect on I. pseudacorus density or height of non-inundated samples. However, combining trampling with inundation reduced I. pseudacorus density from a median of 10 iris per pot to 0 iris per pot and median height from 0.35 m to 0 m by the conclusion of the study. Additionally, the field demonstration resulted in reductions of both density and height of I. pseudacorus after two consecutive years (72% and 67% reduction, respectively). Soluble sugar concentrations were not impacted by any treatment.
Our objective was to quantify the cross-sectional associations between dietary fatty acid (DFA) patterns and cognitive function among Hispanic/Latino adults. This study included data from 8,942 participants of the Hispanic Community Health Study/Study of Latinos, a population-based cohort study (weighted age 56.2 y and proportion female 55.2%). The NCI (National Cancer Institute) method was used to estimate dietary intake from two 24-hr recalls. We derived DFA patterns using principal components analysis with 26 fatty acid and total plant and animal monounsaturated fatty acid (MUFA) input variables. Global cognitive function was calculated as the average z-score of 4 neurocognitive tests. Survey linear regression models included multiple potential confounders such as age, sex, education, depressive symptoms, physical activity, energy intake, and cardiovascular disease. DFA patterns were characterized by consumption of long-chain saturated fatty acids (SFA), animal-based MUFA, and trans fatty acids (Factor 1); short to medium-chain SFA (Factor 2); very-long-chain omega-3 polyunsaturated fatty acids (PUFA) (Factor 3); very-long-chain SFA and plant-based MUFA and PUFA (Factor 4). Factor 2 was associated with greater scores for global cognitive function (β=0.037 ± 0.012) and the Digit Symbol Substitution (DSS) (β=0.56±0.17), Brief Spanish English Verbal Learning-Sum (B-SEVLT) (β=0.23 ± 0.11), and B-SEVLT-Recall (β=0.11 ± 0.05) tests (P<0.05 for all). Factors 1 (β=0.04 ± 0.01) and 4 (β=0.70 ± 0.18) were associated with the DSS test (P<0.05 for all). Consumption of short to medium-chain SFA may be associated with higher cognitive function among U.S.-residing Hispanic/Latino adults. Prospective studies are necessary to confirm these findings.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Of 100 patients discharged from short-stay units (SSUs) with antibiotics, 47 had a skin and soft-tissue infection, 22 had pneumonia, and 21 had a urinary tract infection. Among all discharge antibiotic prescriptions, 78% involved antibiotic overuse, most commonly excess duration (54 of 100) and guideline discordant selection (44 of 100).
Herbicide-resistant (HR) kochia is a growing problem in the Great Plains region of Canada and the United States (U.S.). Resistance to up to four herbicide sites of action, including photosystem II inhibitors, acetolactate synthase inhibitors, synthetic auxins, and the 5-enolpyruvylshikimate-3-phosphate synthase inhibitor glyphosate have been reported in many areas of this region. Despite being present in the U.S. since 1993/1994, auxinic-HR kochia is a recent and growing phenomenon in Canada. This study was designed to characterize (a) the level of resistance and (b) patterns of cross-resistance to dicamba and fluroxypyr in 12 putative auxinic-HR kochia populations from western Canada. The incidence of dicamba-resistant individuals ranged among populations from 0% to 85%, while fluroxypyr-resistant individuals ranged from 0% to 45%. In whole-plant dose-response bioassays, the populations exhibited up to 6.5-fold resistance to dicamba and up to 51.5-fold resistance to fluroxypyr based on visible injury 28 days after application. Based on plant survival estimates, the populations exhibited up to 3.7-fold resistance to dicamba and up to 72.5-fold resistance to fluroxypyr. Multiple patterns of synthetic auxin resistance were observed, where one population from Cypress County, Alberta was resistant to dicamba but not fluroxypyr, while another from Rocky View County, Alberta was resistant to fluroxypyr but not dicamba based on single-dose population screening and dose-response bioassays. These results suggest that multiple mechanisms may confer resistance to dicamba and/or fluroxypyr in Canadian kochia populations. Further research is warranted to determine these mechanisms. Farmers are urged to adopt proactive non-chemical weed management tools in an effort to preserve efficacy of the remaining herbicide options available for control of HR kochia.
There is evidence that maternal perinatal depression is associated with adverse neurodevelopmental and mental health outcomes in children. No study has yet examined the association between maternal depressive symptoms during pregnancy and the postpartum period and the risk of oppositional-defiant disorder (ODD) in children and adolescents.
This study aimed to investigate whether there is an association between perinatal depressive symptoms and the risk of ODD in offspring from age 7 to 15 years.
We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based prospective birth cohort study in the UK. Offspring ODD at the age of 7, 10, 13 and 15 years were assessed by using parental reports the Development and Well-Being Assessment (DAWBA). We applied Generalized Estimating Equation (GEE) modelling to examine associations across the four time points.
Maternal postnatal depressive symptoms were associated with more a two-fold increased risk of ODD overall. Third trimester depressive symptoms (measured at 32 weeks of gestation) increased risk of ODD by 72%. Offspring of mothers who had depressive symptoms both during pregnancy and in the first year of postpartum period have a four-fold increased risk of ODD over time (adjusted OR = 3.59 (1.98-6.52).
Offspring of mothers with perinatal depressive symptoms are at an increased risk of developing behavioural disorders.
This chapter presents an overview of the nature, assessment, and treatment of obsessive-compulsive and related disorders (OCRD), including obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), hoarding disorder (HD), hair-pulling disorder (HPD), and skin-picking disorder (SPD). Specifically, we review the DSM-V diagnostic criteria, epidemiology and impact, clinical features and course, and etiological insights for each of these disorders in turn. Next, we discuss key points to consider when making a differential diagnosis with disorders outside the OCRD category. From there, we turn to a discussion of the assessment and treatment of these disorders using pharmacological, cognitive-behavioral, and neuromodulation interventions. Future directions in the research on OCRDs then follows.
Research was conducted to evaluate acetyl-Coenzyme A carboxylase (ACCase) enzyme activity using a functional malachite green colorimetric assay previously identified as resistant to sethoxydim, and select aryloxyphenoxypropionate (FOPs) herbicides, fenoxaprop, and fluazifop. Two resistant southern crabgrass [Digitaria ciliaris (Retz.) Koeler] biotypes, R1 and R2, containing an Ile-1781-Leu amino acid substitution and previously identified as resistant to sethoxydim, pinoxaden, and fluazifop but not clethodim was utilized as the resistant chloroplastic ACCase source compared to known susceptible (S) ACCase. Dose-response studies with sethoxydim, clethodim, fluazifop-p-butyl, and pinoxaden (0.6 to 40 µM) were conducted to compare the ACCase enzyme-herbicides interaction of R1, R2, and S using the malachite green functional assay. Assay results indicated that R biotypes required more ACCase-targeting herbicides to inhibit ACCase activity compared to S. IC50 values of all four herbicides for R biotypes were consistently an order of magnitude greater than S. No sequencing differences in the carboxyltransferase domain was observed for R1 and R2, however, R2 IC50 values were greater across all herbicides. These results indicate the malachite green functional assay is effective in evaluating ACCase enzyme activity of R and S biotypes in the presence of ACCase-targeting herbicides, which can be used as a replacement for the 14C-based radiometric functional assay.
This study aimed to describe meat consumption rationalisation and relationships with meat consumption patterns and food choice motivations in New Zealand adolescents.
This was a cross-sectional study of adolescents from high schools across New Zealand. Demographics, dietary habits, and motivations and attitudes towards food were assessed by online questionnaire and anthropometric measurements taken by researchers. The 4Ns questionnaire assessed meat consumption rationalisation with four subscales: ‘Nice’, ‘Normal’, ‘Necessary’ and ‘Natural’.
Nineteen secondary schools from eight regions in New Zealand, with some purposive sampling of adolescent vegetarians in Otago, New Zealand.
Questionnaires were completed by 385 non-vegetarian and vegetarian (self-identified) adolescents.
A majority of non-vegetarian adolescents agreed that consuming meat was ‘nice’ (65 %), but fewer agreed that meat consumption was ‘necessary’ (51 %). Males agreed more strongly than females with all 4N subscales. High meat consumers were more likely to agree than to disagree that meat consumption was nice, normal, necessary and natural, and vegetarians tended to disagree with all rationalisations. Adolescent non-vegetarians whose food choice was motivated more by convenience, sensory appeal, price and familiarity tended to agree more with all 4N subscales, whereas adolescents motivated by animal welfare and environmental concerns were less likely to agree.
To promote a reduction in meat consumption in adolescents, approaches will need to overcome beliefs that meat consumption is nice, normal, necessary and natural.
Recent work has revived interest in the scattering matrix formulation of electron scattering in transmission electron microscopy as a stepping stone toward atomic-resolution structure determination in the presence of multiple scattering. We discuss ways of visualizing the scattering matrix that make its properties clear. Through a simulation-based case study incorporating shot noise, we shown how regularizing on this continuity enables the scattering matrix to be reconstructed from 4D scanning transmission electron microscopy (STEM) measurements from a single defocus value. Intriguingly, for crystalline samples, this process also yields the sample thickness to nanometer accuracy with no a priori knowledge about the sample structure. The reconstruction quality is gauged by using the reconstructed scattering matrix to simulate STEM images at defocus values different from that of the data from which it was reconstructed.
In the UK, acute mental healthcare is provided by in-patient wards and crisis resolution teams. Readmission to acute care following discharge is common. Acute day units (ADUs) are also provided in some areas.
To assess predictors of readmission to acute mental healthcare following discharge in England, including availability of ADUs.
We enrolled a national cohort of adults discharged from acute mental healthcare in the English National Health Service (NHS) between 2013 and 2015, determined the risk of readmission to either in-patient or crisis teams, and used multivariable, multilevel logistic models to evaluate predictors of readmission.
Of a total of 231 998 eligible individuals discharged from acute mental healthcare, 49 547 (21.4%) were readmitted within 6 months, with a median time to readmission of 34 days (interquartile range 10–88 days). Most variation in readmission (98%) was attributable to individual patient-level rather than provider (trust)-level effects (2.0%). Risk of readmission was not associated with local availability of ADUs (adjusted odds ratio 0.96, 95% CI 0.80–1.15). Statistically significant elevated risks were identified for participants who were female, older, single, from Black or mixed ethnic groups, or from more deprived areas. Clinical predictors included shorter index admission, psychosis and being an in-patient at baseline.
Relapse and readmission to acute mental healthcare are common following discharge and occur early. Readmission was not influenced significantly by trust-level variables including availability of ADUs. More support for relapse prevention and symptom management may be required following discharge from acute mental healthcare.
Scimitar syndrome is a rare CHD composed of partial anomalous pulmonary venous connection from the right lung, via a scimitar vein, to the inferior vena cava rather than the left atrium. Genetic conditions associated with scimitar syndrome have not been well investigated at present.
Our study included patients with scimitar syndrome diagnosed at Texas Children’s Hospital from January 1987 to July 2020. Medical records were evaluated to determine if genetic testing was performed, including chromosomal microarray analysis or whole-exome sequencing. Copy number variants identified as pathogenic/likely pathogenic and variants of unknown significance were collected. Analyses of cardiac and extracardiac findings were performed via chart review.
Ninety-eight patients were identified with scimitar syndrome, 89 of which met inclusion criteria. A chromosome analysis or chromosomal microarray analysis was performed in 18 patients (20%). Whole-exome sequencing was performed in six patients following negative chromosomal microarray analysis testing. A molecular genetic diagnosis was made in 7 of 18 cases (39% of those tested). Ninety-six per cent of the cohort had some type of extracardiac finding, with 43% having asthma and 20% having a gastrointestinal pathology. Of the seven patients with positive genetic testing, all had extracardiac anomalies with all but one having gastrointestinal findings and 30% having congenital diaphragmatic hernia.
Genetic testing revealed an underlying diagnosis in roughly 40% of those tested. Given the relatively high prevalence of pathogenic variants, we recommend chromosomal microarray analysis and whole-exome sequencing for patients with scimitar syndrome and extracardiac defects.
Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’s anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.
263 individuals were categorized into four groups: HIV− non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal–Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.
HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV− non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05).
Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.
A goosegrass [Eleusine indica (L.) Gaertn.] population uncontrolled by paraquat (R) in a vegetable production field in St. Clair County, AL, was collected in summer 2019. Research was conducted to assess the level of resistance of the suspected resistant population compared with three populations with no suspected paraquat resistance (S1, S2, and S3). Visual injury at all rating dates and biomass reduction at 28 d after treatment (DAT) of S populations occurred exponentially to increasing paraquat rates. S biotypes were injured more than R at 3 DAT, with biomass recovery at 28 DAT only occurring at rates <0.28 kg ha−1. Plant death or biomass reduction did not occur for any rate at any date for R. Paraquat rates that induced 50% or 90% injury or reduced biomass 50% or 90% compared with the non-treated (I50 or I90, respectively) ranged from 10 to 124 times higher I50 for R compared with S and 54 to 116 times higher I90 for R compared with S biotypes. These data confirm a paraquat-resistant E. indica biotype in Alabama, providing additional germplasm for study of resistance to photosystem I electron-diverting (PSI-ED) resistance mechanisms.
This study investigated death anxiety in patients with primary brain tumor (PBT). We examined the psychometric properties of two validated death anxiety measures and determined the prevalence and possible determinants of death anxiety in this often-overlooked population.
Two cross-sectional studies in neuro-oncology were conducted. In Study 1, 81 patients with PBT completed psychological questionnaires, including the Templer Death Anxiety Scale (DAS). In Study 2, 109 patients with PBT completed similar questionnaires, including the Death and Dying Distress Scale (DADDS). Medical and disease-specific variables were collected across participants in both studies. Psychometric properties, including construct validity, internal consistency, and concurrent validity, were investigated. Levels of distress were analyzed using frequencies, and determinants of death anxiety were identified using logistic regression.
The DADDS was more psychometrically sound than the DAS in patients with PBT. Overall, 66% of PBT patients endorsed at least one symptom of distress about death and dying, with 48% experiencing moderate-severe death anxiety. Generalized anxiety symptoms and the fear of recurrence significantly predicted death anxiety.
Significance of results
The DADDS is a more appropriate instrument than the DAS to assess death anxiety in neuro-oncology. The proportion of patients with PBT who experience death anxiety appears to be higher than in other advanced cancer populations. Death anxiety is a highly distressing symptom, especially when coupled with generalized anxiety and fears of disease progression, which appears to be the case in patients with PBT. Our findings call for routine monitoring and the treatment of death anxiety in neuro-oncology.