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We implemented universal SARS-CoV-2 testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic SARS-CoV-2 infection was <0.5%, and suggests that early local public health interventions were successful. While our protocol was resource-intensive, it prevented exposures to healthcare team members.
Taxonomic identification of archaeofauna relies on techniques and anatomical traits that should be valid, reliable, and usable, but which are rarely tested. Identification protocols (techniques and anatomical traits), particularly those used to distinguish taxa of similar size and morphology, should be rigorously tested to ensure a solid interpretive foundation. Blind testing of a protocol for identifying stylohyoid bones of North American artiodactyls was performed by three analysts who independently employed the protocol to identify 77 anatomically complete specimens of known taxonomic identity, representing 54 individuals and 11 species. Identifications were identical in 89% of cases and in conflict in 3% of cases. The remainder involved differences in resolution; two analysts identified specimens to species, whereas the third identified specimens to more general taxonomic groups. Inter-analyst variability in identification was a result of differences in protocol application. Identifications were consistent with known taxon in 92%–96% of cases. Results indicate that the protocol is valid, reliable, and usable, and it can be applied to archaeological specimens with confidence. Testing of other identification criteria employed by zooarchaeologists is encouraged.
Vitamin E is known to scavenge lipid peroxy radicals and has a purported role in preventing seed deterioration during storage. In our previous studies using 20 rice varieties from different variety groups, the specific ratio of vitamin E homologues rather than total vitamin E content was associated with seed longevity. To validate this result, we extended the experiment to a rice panel composed of 185 Aus (semi-wild rice) varieties. Seed longevity values were determined through storage experiments at 45°C and 10.9% seed moisture content (MC). Eight types of vitamin E homologues (α-, β-, γ- and δ-tocopherol/tocotrienol) were quantified by ultra-performance liquid chromatography. The theoretical initial viability in NED, Ki, was positively correlated with γ- and δ-tocopherols and negatively correlated with α-tocotrienol. The time for viability to fall to 50% during storage at elevated temperature and relative humidity, p50, was positively correlated with δ-tocopherol. The harvest MC was negatively correlated with all seed longevity traits. Taking this factor into account in a genome-wide association (GWA) analysis, we were able to correct false positives. A consistent major peak on chromosome 4 associated with −σ−1 was detected with a mixed linear analysis. Based on rice genome annotation and gene network ontology databases, we suggest that RNA modification, oxidation–reduction, protein–protein interactions and abscisic acid signal transduction play roles in seed longevity extension of Aus rice. Although major GWA regions were not overlapped across traits, three genetic markers, on chromosomes 1, 3 and 4, were associated with both δ-tocopherol and Ki and two markers on chromosome 1 and 8 were associated with both δ-tocopherol and p50.
Little is known about the determinants of community integration (i.e. recovery) for individuals with a history of homelessness, yet such information is essential to develop targeted interventions.
We recruited homeless Veterans with a history of psychotic disorders and evaluated four domains of correlates of community integration: perception, non-social cognition, social cognition, and motivation. Baseline assessments occurred after participants were engaged in supported housing services but before they received housing, and again after 12 months. Ninety-five homeless Veterans with a history of psychosis were assessed at baseline and 53 returned after 12 months. We examined both cross-sectional and longitudinal relationships with 12-month community integration.
The strongest longitudinal association was between a baseline motivational measure and social integration at 12 months. We also observed cross-sectional associations at baseline between motivational measures and community integration, including social, work, and independent living. Cross-lagged panel analyses did not suggest causal associations for the motivational measures. Correlations with perception and non-social cognition were weak. One social cognition measure showed a significant longitudinal correlation with independent living at 12 months that was significant for cross-lagged analysis, consistent with a causal relationship and potential treatment target.
The relatively selective associations for motivational measures differ from what is typically seen in psychosis, in which all domains are associated with community integration. These findings are presented along with a partner paper (Study 2) to compare findings from this study to an independent sample without a history of psychotic disorders to evaluate the consistency in findings regarding community integration across projects.
Porous metals represent a class of materials where the interplay of ligament length, width, node structure, and local geometry/curvature offers a rich parameter space for the study of critical length scales on mechanical behavior. Colloidal crystal templating of three-dimensionally ordered macroporous (3DOM, i.e., inverse opal) tungsten provides a unique structure to investigate the mechanical behavior at small length scales across the brittle–ductile transition. Micropillar compression tests show failure at 50 MPa contact pressure at 30 °C, implying a ligament yield strength of approximately 6.1 GPa for a structure with 5% relative density. In situ SEM frustum indentation tests with in-plane strain maps perpendicular to loading indicate local compressive strains of approximately 2% at failure at 30 °C. Increased sustained contact pressure is observed at 225 °C, although large (20%) nonlocal strains appear at 125 °C. The elevated-temperature mechanical performance is limited by cracks that initiate on planes of greatest shear under the indenter.
Waters, Ruiz, and Roisman (2017) recently published evidence based on the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) that sensitive caregiving during childhood is associated with higher levels of secure base script knowledge during the Adult Attachment Interview (AAIsbs). At present, however, little is known about the role of variation in atypical caregiving, including abuse and/or neglect, in explaining individual differences in AAIsbs. This study revisited data from the MLSRA (N = 157) to examine the association between experiencing abuse and/or neglect in the first 17.5 years of life and secure base script knowledge measured at ages 19 and 26 years. Several aspects of abuse and/or neglect experiences were assessed, including perpetrator identity, timing, and type. Regressions revealed that childhood abuse and/or neglect was robustly associated with lower AAIsbs scores in young adulthood, above and beyond previously documented associations with maternal sensitivity and demographic covariates. Follow-up analyses provided evidence that the predictive significance of abuse for secure base script knowledge was specific to perpetration by parental figures, rather than non-caregivers. Exploratory analyses indicated that abuse and/or neglect: (a) in middle childhood and adolescence (but not infancy and early childhood) and (b) physical abuse (but not sexual abuse or neglect) were uniquely associated with lower AAIsbs scores.
OBJECTIVES/GOALS: To characterize the oncogenic potential of HNSCC cell lines harboring 17 non-canonical PIK3CA mutations. METHODS/STUDY POPULATION: Non-canonical PIK3CA mutant constructs generated via site-directed mutagenesis are subcloned into doxycycline-inducible vector pLVX-Puro. Serum-dependent HNSCC cell line (PCI-52-SD1) is then stably transfected with vectors and undergo doxycycline-induction. Cell survival is determined by depriving cells of fetal bovine serum for 72 hours and quantifying remaining cells with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Cell proliferation and migration is evaluated with colony formation assays and transwell assays respectively. RESULTS/ANTICIPATED RESULTS: To date, the survival behavior of eight non-canonical mutants was assessed. Three mutants – Q75E, V71I, and E970K – exhibited 18.7-26.7% greater survival rate relative to cells transfected with wild-type. Five mutants – R519G, Y606C, W328S, C905S, and M1040I – demonstrated survival rates that differed only by −4.3% to +6.6% relative to wild-type. We hypothesize the three activating mutants that exhibited increased survival will also demonstrate increased cell proliferation and migratory behavior whereas the three neutral mutants will not differ from control. DISCUSSION/SIGNIFICANCE OF IMPACT: Ongoing HNSCC PI3K inhibitor trials could be more effective if all PIK3CA hyperactivation mutations are known. Identifying non-canonical mutation effects could result in greater efficacy if drugs are restricted only to those with activating mutations. CONFLICT OF INTEREST DESCRIPTION: JRG and DEJ are co-inventors of cyclic STAT3 decoy and have financial interests in STAT3 Therapeutics, Inc. STAT3 Therapeutics, Inc. holds an interest in a cyclic STAT3 decoy oligonucleotide. The remaining authors declare no conflicts.
The present study tests the Shallow Structure Hypothesis (SSH), which claims that compared to L1 processing, L2 language processing generally underuses grammatical information, prioritizing nongrammatical information. Specifically, this cross-modal priming study tests SSH at the level of morphology, investigating whether late advanced L2 learners construct hierarchically structured representations for trimorphemic derived words during real-time processing as native speakers do. Our results support SSH. In lexical decision on English trimorphemic words (e.g., unkindness or [[un-[kind]]-ness]), L1 recognition of the targets was facilitated by their bimorphemic morphological-structural constituent primes (e.g., unkind), but not by their bimorphemic nonconstituent primes (e.g., kindness), which were only semantically and formally related to the target. In contrast, L2 recognition was equally facilitated by both constituent and nonconstituent primes. These results suggest that unlike L1 processing, L2 processing of multimorphemic words is not mainly guided by detailed morphological structure, overrelying on nonstructural information.
OBJECTIVES/GOALS: Utilize polymer-based fiber scaffolds and machine learning methods applied to patient biomarker data to enhance and personalize T cell expansion and production for T cell therapy in chronic lymphocytic leukemia. METHODS/STUDY POPULATION: Scaffolds are 1) generated from a co-polymer blend of PDMS and PCL with controlled fiber diameters and pore size, 2) coated with activating antibodies to CD3 and CD28, and 3) used to stimulate T cells from both healthy donors and CLL patients. CLL patients have pre-annotated mutation burdens and clinical biomarkers. T cell populations will be analyzed for exhaustion markers and phenotypes before, during, and after expansion. Cell functionality will be measured by cytokine secretion, cell cycle analysis, and fold expansion, with respect to platform parameters, and analyzed with inputs of disease markers and exhaustion profile of isolated T cells using regression and random forest classifiers. RESULTS/ANTICIPATED RESULTS: We previously showed that engineering the mechanical rigidity of activating substrates can enhance and rescue T cell expansion from exhausted populations. Now we aim to study a broader range of compositions and geometry of scaffolds with respect to capacity to expand CLL T cells. Preliminary data with fiber diameters ranging from 300 nm to 6 um confirm the effect of geometry in modulating expansion. A biorepository of T cells from 80 CLL patients have been isolated concurrently. Anticipated results include correlating exhaustion profile of T cells with clinical biomarkers and identifying markers associated with expansion on panel of platform parameters. DISCUSSION/SIGNIFICANCE OF IMPACT: T cell therapy has shown particular promise in treating blood cancers, yet significant percentage of T cells isolated from patients undergoing treatments are unresponsive to activation. A powerful tool is to predict if and how patient T cells can be robustly expanded on a personalized approach.
In an initial study (Study 1), we found that motivation predicted community integration (i.e. functional recovery) 12 months after receiving housing in formerly homeless Veterans with a psychotic disorder. The current study examined whether the same pattern would be found in a broader, more clinically diverse, homeless Veteran sample without psychosis.
We examined four categories of variables as potential predictors of community integration in non-psychotic Veterans: perception, non-social cognition, social cognition, and motivation at baseline (after participants were engaged in a permanent supported housing program but before receiving housing) and a 12-month follow-up. A total of 82 Veterans had a baseline assessment and 41 returned for testing after 12 months.
The strongest longitudinal association was between an interview-based measure of motivation (the motivation and pleasure subscale from the Clinical Assessment Interview for Negative Symptoms) at baseline and measures of social integration at 12 months. In addition, cross-lagged panel analyses were consistent with a causal influence of general psychiatric symptoms at baseline driving social integration at 12 months, and reduced expressiveness at baseline driving independent living at 12 months, but there were no significant causal associations with measures of motivation.
The findings from this study complement and reinforce those in Veterans with psychosis. Across these two studies, our findings suggest that motivational factors are associated at baseline and at 12 months and are particularly important for understanding and improving community integration in recently-housed Veterans across psychiatric diagnoses.
In 2014, a Nutrition Report Card (NRC) was developed as a sustainable, low-cost framework to assess the healthfulness of children’s food environments and highlight action to support healthy eating. We summarise our experiences in producing, disseminating, evaluating and refining an annual NRC in a Canadian province from 2015 to 2019.
To produce the NRC, children’s food environment indicator data are collected, analyzed and compiled for consensus grading by an Expert Working Group of researchers and practitioners. Knowledge translation activities are tailored annually to the needs of target audiences: researchers, practitioners, policymakers and the public. Evaluation of reach is conducted through diverse strategies, including tracking media coverage and website traffic. Assessment of impact on diets and health outcomes is planned.
The grading process has facilitated refining the NRC to enhance its relevance and utility as a tool for its target audiences. Its public release consistently captures media interest and policymakers’ attention. The importance of partnerships in revealing data sources and in strategising to enhance policy approaches to improve food environments is apparent. The NRC has benchmarked progress and stimulated dialogue regarding healthy food environments for children.
The NRC may help to foster a supportive climate for improving the quality of children’s food environments. As an engaging and accessible document, the NRC represents a key mechanism for collating data related to children’s food environments and ensuring it reaches the audiences best positioned to use it. Efforts are underway to expand the NRC across Canada.
Introduction: In a busy emergency department (ED), effective communication is integral to the provision of safe medical care. Physicians working in the ED interact with multiple team members including patients, allied healthcare professionals and other physicians, who all need to understand their verbal and written instructions. Our study's objective was to identify and describe communication problems occurring in the ED setting, and how these problems contributed to patient safety events and increased medico-legal risk for physicians. Methods: The Canadian Medical Protective Association (CMPA) is a not-for-profit, medico-legal organization which represented over 97,000 physicians at the time of this study. We conducted a retrospective descriptive analysis where we extracted five years (2013-2017) of CMPA data describing closed medico-legal cases occurring in the ED involving physicians (any specialty) who experienced complaints due to communication issues. We then applied an internal contributing factor framework to identify data themes. Data were summarized using descriptive statistics. Results: We identified 517 eligible cases involving 521 patients (some cases involved >1 patient). We found that 99.8% (520/521) of patients experienced some form of healthcare-related harm in the ED. Specifically, there was poor communication between: the physician and patient or patient's family (202/517, 39.1%); two or more physicians (79/517, 15.3%), and physicians and other healthcare providers (55/517, 10.6%). Inadequate documentation was observed in more than half of the cases (324/517, 62.7%) and poor team communication affected physicians’ decision making process (326/517, 63%) in areas such as deficient assessments, inadequate investigations, failure or delay to attend to the patient, and disposition decisions. Conclusion: Team communication issues are prevalent among physician medico-legal cases occurring in the ED. Efforts to strengthen communication skills may enhance patient safety and reduce medico-legal risk.
Introduction: Crowding is associated with poor patient outcomes in emergency departments (ED). Measures of crowding are often complex and resource-intensive to score and use in real-time. We evaluated single easily obtained variables to establish the presence of crowding compared to more complex crowding scores. Methods: Serial observations of patient flow were recorded in a tertiary Canadian ED. Single variables were evaluated including total number of patients in the ED (census), in beds, in the waiting room, in the treatment area waiting to be assessed, and total inpatient admissions. These were compared with Crowding scores (NEDOCS, EDWIN, ICMED, three regional hospital modifications of NEDOCS) as predictors of crowding. Predictive validity was compared to the reference standard of physician perception of crowding, using receiver operator curve analysis. Results: 144 of 169 potential events were recorded over 2 weeks. Crowding was present in 63.9% of the events. ED census (total number of patients in the ED) was strongly correlated with crowding (AUC = 0.82 with 95% CI = 0.76 - 0.89) and its performance was similar to that of NEDOCS (AUC = 0.80 with 95% CI = 0.76 - 0.90) and a more complex local modification of NEDOCS, the S-SAT (AUC = 0.83, 95% CI = 0.74 - 0.89). Conclusion: The single indicator, ED census was as predictive for the presence of crowding as more complex crowding scores. A two-stage approach to crowding intervention is proposed that first identifies crowding with a real-time ED census statistic followed by investigation of precipitating and modifiable factors. Real time signalling may permit more standardized and effective approaches to manage ED flow.
Introduction: The elderly (65 yo and more) increase in Canada is well documented along with a disproportionate use of Emergency Departments after a minor injury. These patients requires specific care given a 16% risk of functional decline following a visit to ED. To prevent functional decline, a multidimensional assessment of the elderly is recommended in the emergency department. Objective: To determine if ED grip strength can predict functional decline at 3 or 6 months post-injury. Methods: A multicentre prospective study in 5 ED across Canada was realized between 2013 and 16. Patients 65 years old and over, autonomous in daily living activities and consulting the emergency department for minor trauma were recruited 7 days a week. Clinical-demographic data, functional status, fear of falling, number of falls in the last month, grip strength measurement were collected in the ED. Functional decline (loss of at least points to functional status) was calculated at 3 and 6 months. Descriptive statistics and linear regression model with repeated measurements were used to determine if the grip strength was predictive of functional decline at 3 or 6 months. Results: 387 patient were recruited. Mean age was 74 ± 7 years old, 52% were male. XXX experienced a fall in the last month. The initial maximum grip strength was (24 ± 10 intervention vs. 28 ± 13 control; p ≤ 0.05). grip strength is associated with pre-injury functional status (p < 0.0001) and fear of falling (p = 0.0001) but does not predict 3 or 6 month functional decline. Conclusion: Given the strong association with fear of falling and functional status at initial ED evaluation, we recommend that grip strength measurement could be included in a multidisciplinary geriatric emergency department assessment as needed.
Cardiac surgery induces profound sympathetic nervous system and inflammatory responses. This so-called ‘stress response’ to surgery causes a multitude of adverse haemodynamic, metabolic, haematological, endocrine and immunological effects. In the setting of cardiac surgery, the attenuation of pain and sympathetic autonomic activity has many theoretical attractions. The introduction of high-dose opioid techniques into cardiac anaesthesia was based, in part, on the belief that they would inhibit the stress response. Failure to block the stress response completely, combined with equivocal evidence of clinical benefit and the need for prolonged postoperative mechanical ventilation, made the technique unpopular. The demonstration that thoracic sympathetic blockade improves the blood flow in severely diseased coronary arteries, the emergence of less invasive cardiac surgical techniques and economic pressures have prompted renewed interest in regional anaesthetic techniques.
The endothelial glycocalyx layer (EGL) is a brush-like layer that lines the internal surfaces of blood vessels. It is thought to serve a number of physiological functions, including as a mechanotransducer of fluid loadings to the vessel wall. However, the fragility of the EGL makes it difficult to examine experimentally, and so there is much value in theoretical models that can help to explain the dynamical behaviour of the EGL. Most previous models have employed mixture theory to mechanically describe the layer, which treats the EGL as a isotropic linearly poroelastic layer. However, there is increasing experimental evidence to suggest that the EGL has a well-defined organisational structure that might not necessarily be well captured by such mixture theory descriptions. We therefore employ homogenisation theory to incorporate into the models some of the possible EGL microstructure suggested by the current biological literature. We explore how mechanotransduction varies under the different possible EGL microstructures, which potentially has important consequences to our understanding of how structural changes to the EGL might affect a vessel’s ability to respond to hemodynamical cues. We also find that, whereas mechanotransduction through the solid components of the EGL is dominated by the fluid tractions applied at the lumen–EGL interface, the component carried through its fluid phase is most sensitive to pressure gradients within the bulk EGL. This is relevant, since it is known that the underlying endothelial cells respond differently to these two different forms of mechanical loading.
Physiological regulation may interact with early experiences such as maltreatment to increase risk for behavior problems. In the current study, we investigate the role of parasympathetic nervous system regulation (respiratory sinus arrhythmia [RSA] at rest and in response to a frustration task) as a moderator of the association between early risk for maltreatment (i.e., involvement with Child Protective Services; CPS) and externalizing behavior problems in middle childhood. CPS involvement was associated with elevated externalizing problems, but only among children with average to high RSA at rest and average to high RSA withdrawal in response to frustration. Effects appeared to be specific to CPS involvement as the association between cumulative risk (i.e., nonmaltreatment experiences of early adversity) and externalizing problems was not significantly moderated by RSA activity. These findings are consistent with the theoretical idea that the consequences of early maltreatment for later externalizing behavior problems depend on children's biological regulation abilities.
Bupropion is a catecholamine reuptake inhibitor and also a potent noncompetitive ion channel site antagonist at the nicotinic acetylcholine receptor. Bupropion is indicated for use in combination with behavioral modification programs for smoking cessation. There have been a few studies about the effect of bupropion on smoking cessation in schizophrenia. Therefore, we aimed investigated the change of the symptomatology after smoking cessation with bupropion in the patients with schizophrenia.
There were fifty-six patients with smoking in the psychiatric ward of Hapcheon Korea Hospital. among them, thirty-nine inpatients meeting the DSM-IV criteria for schizophrenia were recruited. for 4 weeks, treatment team persuaded the patients to enter the program of smoking cessation. with the exception, if the patients did not agree the program, the patients were able to be transferred to another ward that smoking was permitted. All patients agreed to the program. Postive and Negative Symptom Scale (PANSS), Temperament and Character Inventory(TCI), State-Trait Anxiety Inventory(STAI), Fagerstrom Test for Nicotine Dependence(FTND) were evaluated at the beginning of the study and 12 weeks of Bupropion treatment.
At 12 weeks after successful smoking cessation with bupropion, FTND scores were significantly decreased after smoking cessation. the scores of STAI and PANSS were not significantly changed. the subcale of TCI, Novelty Seeking showed decreasing tendency after smoking cessation, although there was no statistical significance(p=0.054).
These results suggest that bupropion is an effective antidepressant on smoking cessation and does not aggravate the psychotic symptoms in schizophrenia. Further investigation with larger number of subjects is needed.