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The need for collaborative and transparent sharing of COVID-19 clinical trial and large-scale observational study data to accelerate scientific discovery and inform clinical practice is critical. Responsible data-sharing requires addressing challenges associated with data privacy and confidentiality, data linkage, data quality, variable harmonization, data formats, and comprehensive metadata documentation to produce a high-quality, contextually rich, findable, accessible, interoperable, and reusable (FAIR) dataset. This communication explores the experiences and lessons learned from sharing National Heart Lung and Blood Institute (NHLBI) COVID-19 clinical trial (including adaptive platform trials) and cohort study datasets through the NHLBI BioData Catalyst® (BDC) ecosystem, focusing on the challenges and successes of harmonizing these datasets for broader research use. Our findings highlight the importance of establishing standardized data formats, adopting common data elements and creating and maintaining robust data governance structures that address common challenges (i.e., data privacy and data-sharing limitations resulting from informed consent). These efforts resulted in a set of comprehensive and interoperable datasets from 5 clinical trials and 13 cohort studies that will enable downstream reuse in analyses and collaborations. The principles and strategies outlined, derived through experience with consortia data, can lay the groundwork for advancing collaborative and efficient data sharing.
Acute clinical deterioration in hospital inpatients can be caused by a range of factors including dementia, delirium, substance withdrawal and psychiatric disturbance, creating challenges in diagnosis, often requiring a management plan with input from multiple disciplines. Staff forums and broader literature have confirmed that healthcare staff working in non-mental health settings, may not be as skilled in recognising and managing early signs of emerging and/or escalating clinical agitation. The BoC RRT is a consultation service within the Division of Medicine and CL Psychiatry. Staffed by Medical Registrars and Mental Health Nurses, the collaboration provides a unique healthcare response to acute general wards. The BoC RRT has been implemented to address the rising number of incidences whereby staff and patient safety are compromised. Using evidence-based skills the team aimed to: respond to episodes of clinical agitation that require an internal security response, assist ward referrals by exploring biopsychosocial contributants to behaviour, develop individual patient support plans and review and reduce restrictive intervention practices.
Objectives
To determine if the rapid response model has influenced:
- The impact on staff/patient safety
- Frequency of emergency responses for aggression
- Frequency of restrictive intervention use
Methods
This project was approved as a quality assurance project (QA2022018). The patients within scope of the BoC RRT include inpatients in medical and surgical wards. It excludes patients in Emergency Departments, mental health units, outpatient clinics, and visitors. The evaluation of the pilot has used a PDSA (Plan, Do, Study, Act) cycle when implementing new improvements. A mixed methods approach explored the impact of the BoC RRT. Staff consultation will identify challenges in responding to scenarios whereby there is risk of harm to staff and patients. Staff feedback and the emergency response data was monitored.
Results
In 2021, there was approx. 720 code greys per month, requiring a security response. Since the implementation of BoC RRT, these numbers have reduced to 527. Reviewing restrictive intrvention practices has identified areas for policy review and need for education. Staff consultation found that nurses were confident caring for those patients exhibiting clinical agitation associated with delirium and dementia. However, caring for people with mental health or substance use disorders were more challenging.
Conclusions
These interim results indicate that BoC RRT has been generally well received by clinical staff. The decline in code grey responses indicates that it is likely having a positive impact in early identification and management of clinical agitation for hospital inpatients. There is support for this response model to continue beyond the pilot phase and further area for research.
Abnormal reward functioning is central to anhedonia and amotivation symptoms of schizophrenia (SCZ). Reward processing encompasses a series of psychological components. This systematic review and meta-analysis examined the brain dysfunction related to reward processing of individuals with SCZ spectrum disorders and risks, covering multiple reward components.
Methods
After a systematic literature search, 37 neuroimaging studies were identified and divided into four groups based on their target psychology components (i.e. reward anticipation, reward consumption, reward learning, effort computation). Whole-brain Seed-based d Mapping (SDM) meta-analyses were conducted for all included studies and each component.
Results
The meta-analysis for all reward-related studies revealed reduced functional activation across the SCZ spectrum in the striatum, orbital frontal cortex, cingulate cortex, and cerebellar areas. Meanwhile, distinct abnormal patterns were found for reward anticipation (decreased activation of the cingulate cortex and striatum), reward consumption (decreased activation of cerebellum IV/V areas, insula and inferior frontal gyri), and reward learning processing (decreased activation of the striatum, thalamus, cerebellar Crus I, cingulate cortex, orbitofrontal cortex, and parietal and occipital areas). Lastly, our qualitative review suggested that decreased activation of the ventral striatum and anterior cingulate cortex was also involved in effort computation.
Conclusions
These results provide deep insights on the component-based neuro-psychopathological mechanisms for anhedonia and amotivation symptoms of the SCZ spectrum.
Customer churn, which insurance companies use to describe the non-renewal of existing customers, is a widespread and expensive problem in general insurance, particularly because contracts are usually short-term and are renewed periodically. Traditionally, customer churn analyses have employed models which utilise only a binary outcome (churn or not churn) in one period. However, real business relationships are multi-period, and policyholders may reside and transition between a wider range of states beyond that of the simply churn/not churn throughout this relationship. To better encapsulate the richness of policyholder behaviours through time, we propose multi-state customer churn analysis, which aims to model behaviour over a larger number of states (defined by different combinations of insurance coverage taken) and across multiple periods (thereby making use of readily available longitudinal data). Using multinomial logistic regression (MLR) with a second-order Markov assumption, we demonstrate how multi-state customer churn analysis offers deeper insights into how a policyholder’s transition history is associated with their decision making, whether that be to retain the current set of policies, churn, or add/drop a coverage. Applying this model to commercial insurance data from the Wisconsin Local Government Property Insurance Fund, we illustrate how transition probabilities between states are affected by differing sets of explanatory variables and that a multi-state analysis can potentially offer stronger predictive performance and more accurate calculations of customer lifetime value (say), compared to the traditional customer churn analysis techniques.
In March 2018, the US Food and Drug Administration (FDA), US Centers for Disease Control and Prevention, California Department of Public Health, Los Angeles County Department of Public Health and Pennsylvania Department of Health initiated an investigation of an outbreak of Burkholderia cepacia complex (Bcc) infections. Sixty infections were identified in California, New Jersey, Pennsylvania, Maine, Nevada and Ohio. The infections were linked to a no-rinse cleansing foam product (NRCFP), produced by Manufacturer A, used for skin care of patients in healthcare settings. FDA inspected Manufacturer A's production facility (manufacturing site of over-the-counter drugs and cosmetics), reviewed production records and collected product and environmental samples for analysis. FDA's inspection found poor manufacturing practices. Analysis by pulsed-field gel electrophoresis confirmed a match between NRCFP samples and clinical isolates. Manufacturer A conducted extensive recalls, FDA issued a warning letter citing the manufacturer's inadequate manufacturing practices, and federal, state and local partners issued public communications to advise patients, pharmacies, other healthcare providers and healthcare facilities to stop using the recalled NRCFP. This investigation highlighted the importance of following appropriate manufacturing practices to minimize microbial contamination of cosmetic products, especially if intended for use in healthcare settings.
Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.
Methods
Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.
Results
We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.
Conclusions
Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.
Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.
To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.
Design:
Prospective observational study.
Setting:
Neonatal intensive care unit (NICU).
Methods:
We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.
Results:
A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.
Conclusions:
In comparison to fast outbreaks, outbreaks that are “slow and sustained” may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.
To characterize and compare severe acute respiratory coronavirus virus 2 (SARS-CoV-2)–specific immune responses in plasma and gingival crevicular fluid (GCF) from nursing home residents during and after natural infection.
Design:
Prospective cohort.
Setting:
Nursing home.
Participants:
SARS-CoV-2–infected nursing home residents.
Methods:
A convenience sample of 14 SARS-CoV-2–infected nursing home residents, enrolled 4–13 days after real-time reverse transcription polymerase chain reaction diagnosis, were followed for 42 days. After diagnosis, plasma SARS-CoV-2–specific pan-Immunoglobulin (Ig), IgG, IgA, IgM, and neutralizing antibodies were measured at 5 time points, and GCF SARS-CoV-2–specific IgG and IgA were measured at 4 time points.
Results:
All participants demonstrated immune responses to SARS-CoV-2 infection. Among 12 phlebotomized participants, plasma was positive for pan-Ig and IgG in all 12 participants. Neutralizing antibodies were positive in 11 participants; IgM was positive in 10 participants, and IgA was positive in 9 participants. Among 14 participants with GCF specimens, GCF was positive for IgG in 13 participants and for IgA in 12 participants. Immunoglobulin responses in plasma and GCF had similar kinetics; median times to peak antibody response were similar across specimen types (4 weeks for IgG; 3 weeks for IgA). Participants with pan-Ig, IgG, and IgA detected in plasma and GCF IgG remained positive throughout this evaluation, 46–55 days after diagnosis. All participants were viral-culture negative by the first detection of antibodies.
Conclusions:
Nursing home residents had detectable SARS-CoV-2 antibodies in plasma and GCF after infection. Kinetics of antibodies detected in GCF mirrored those from plasma. Noninvasive GCF may be useful for detecting and monitoring immunologic responses in populations unable or unwilling to be phlebotomized.
Anticipatory pleasure deficits are closely correlated with negative symptoms in schizophrenia, and may be found in both clinical and subclinical populations along the psychosis continuum. Prospection, which is an important component of anticipatory pleasure, is impaired in individuals with social anhedonia (SocAnh). In this study, we examined the neural correlates of envisioning positive future events in individuals with SocAnh.
Methods
Forty-nine individuals with SocAnh and 33 matched controls were recruited to undergo functional MRI scanning, during which they were instructed to simulate positive or neutral future episodes according to cue words. Two stages of prospection were distinguished: construction and elaboration.
Results
Reduced activation at the caudate and the precuneus when prospecting positive (v. neutral) future events was observed in individuals with SocAnh. Furthermore, compared with controls, increased functional connectivity between the caudate and the inferior occipital gyrus during positive (v. neutral) prospection was found in individuals with SocAnh. Both groups exhibited a similar pattern of brain activation for the construction v. elaboration contrast, regardless of the emotional context.
Conclusions
Our results provide further evidence on the neural mechanism of anticipatory pleasure deficits in subclinical individuals with SocAnh and suggest that altered cortico-striatal circuit may play a role in anticipatory pleasure deficits in these individuals.
Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of ‘brain disconnection’ and ‘brain connectivity compensation’ to ‘brain connectivity decompensation’.
Methods
In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated.
Results
We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network.
Conclusions
These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.
Background: Atrial fibrillation (AF) is a risk for stroke. The Canadian Cardiovascular Society advises patients who are CHADS65 positive should be started on oral anticoagulation (OAC). Our local emergency department (ED) review showed that only 16% of CHADS65 positive patients were started on OAC and that 2% of our patients were diagnosed with stroke within 90 days. We implemented a new pathway for initiation of OAC in the ED (the SAFE pathway). Aim Statement: We report the effectiveness and safety of the SAFE pathway for initiation of OAC in patients treated for AF in the ED. Measures & Design: A multidisciplinary group of physicians and pharmacist developed the SAFE pathway for patients who are discharged home from the ED with a diagnosis of AF. Step 1: contraindications to OAC, Step 2: CHADS65 score, Step 3: OAC dosing if indicated. The pathway triggers referral to AF clinic, family physician letter and follow up call from the ED pharmacist. Patients are followed for 90 days by a structured medical record review and a structured telephone interview. We record persistence with OAC, stroke, TIA, systemic arterial embolism and major bleeding (ISTH criteria). Patient outcomes are fed back to the treating ED physician. Evaluation/ Results: The SAFE pathway was introduced in two EDs in June 2018. In total, 177 patients have had the pathway applied. The median age was 70 (interquartile range (IQR) 61-78), 48% male, median CHADS2 score 2 (IQR 0-2). 19/177 patients (11%) had a contraindication to initiating OAC. 122 patients (69%) had no contraindication to OAC and were CHADS65 positive. Of these 122 patients, 109 were given a prescription for OAC (96 the correct dose, 9 too high a dose and 4 too low a dose). 6 patients declined OAC and the physician did not want to start OAC for 7 patients. 73/122 were contacted by phone at 90 days, 15 could not be reached and 34 have not completed 90 days of follow up since their ED visit. Of the 73 who were reached by phone after 90 days, 65 were still taking an anticoagulant. To date, 1 patient who declined OAC (CHADS2 score of 2) had a stroke within 90 days and one patient prescribed OAC had a gastrointestinal bleed. Discussion/Impact: The SAFE pathway appears safe and effective although we continue to evaluate and improve the process.
To assess the impact of a newly developed Central-Line Insertion Site Assessment (CLISA) score on the incidence of local inflammation or infection for CLABSI prevention.
Design:
A pre- and postintervention, quasi-experimental quality improvement study.
Setting and participants:
Adult inpatients with central venous catheters (CVCs) hospitalized in an intensive care unit or oncology ward at a large academic medical center.
Methods:
We evaluated CLISA score impact on insertion site inflammation and infection (CLISA score of 2 or 3) incidence in the baseline period (June 2014–January 2015) and the intervention period (April 2015–October 2017) using interrupted times series and generalized linear mixed-effects multivariable analyses. These were run separately for days-to-line removal from identification of a CLISA score of 2 or 3. CLISA score interrater reliability and photo quiz results were evaluated.
Results:
Among 6,957 CVCs assessed 40,846 times, percentage of lines with CLISA score of 2 or 3 in the baseline and intervention periods decreased by 78.2% (from 22.0% to 4.7%), with a significant immediate decrease in the time-series analysis (P < .001). According to the multivariable regression, the intervention was associated with lower percentage of lines with a CLISA score of 2 or 3, after adjusting for age, gender, CVC body location, and hospital unit (odds ratio, 0.15; 95% confidence interval, 0.06–0.34; P < .001). According to the multivariate regression, days to removal of lines with CLISA score of 2 or 3 was 3.19 days faster after the intervention (P < .001). Also, line dwell time decreased 37.1% from a mean of 14 days (standard deviation [SD], 10.6) to 8.8 days (SD, 9.0) (P < .001). Device utilization ratios decreased 9% from 0.64 (SD, 0.08) to 0.58 (SD, 0.06) (P = .039).
Conclusions:
The CLISA score creates a common language for assessing line infection risk and successfully promotes high compliance with best practices in timely line removal.
Copy number variations (CNVs), as an important source of genetic variation, can affect a wide range of phenotypes by diverse mechanisms. The somatostatin receptor 2 (SSTR2) gene plays important roles in cell proliferation and apoptosis. Recently, this gene was mapped to a CNV region, which encompasses quantitative trait loci of cattle economic traits including body weight, marbling score, etc. Therefore, SSTR2 CNV may exhibit phenotypic effects on cattle growth traits. In the current study, distribution of SSTR2 gene CNVs was investigated in six Chinese cattle breeds (XN, QC, NY, JA, LX and PN), and the results showed higher CNV polymorphisms in XN, QC and NY cattle. Next, association analysis between growth traits and SSTR2 CNV was performed for XN, QC and NY cattle. In NY, individuals with fewer copies showed better performance than those with more copies. Further, the effects of SSTR2 CNV on the SSTR2 mRNA level were also investigated, but revealed no significant correlation in either muscle or adipose tissue of adult NY cattle. The results suggested the potential for use of SSTR2 CNV as a marker for the molecular breeding of NY cattle.
Anisocotyly, the unequal development of cotyledons post germination, is a unique trait observed only in Old World Gesneriaceae (Lamiales). New World Gesneriaceae have isocotylous seedlings. In both Old and New World Gesneriaceae, cotyledons initially grow equally for a short period just after germination. In the New World species, both cotyledons cease their growth at the same time early on, whereas in Old World species one cotyledon continues to expand to become a macrocotyledon while the other withers away. In this study, cotyledon growth was observed in two European Old World Gesneriaceae: Haberlea rhodopensis and Ramonda myconi. The results were compared with those for the typical anisocotylous species Streptocarpus rexii and the typical isocotylous species Corytoplectus speciosus. We found that the cotyledon growth patterns in Haberlea rhodopensis and Ramonda myconi were intermediate between the typical anisocotylous or isocotylous species. Haberlea rhodopensis and Ramonda myconi showed irregular growth patterns, with some plants being slightly anisocotylous but most being isocotylous. The developmental basis for the residual anisocotyly, the extended basal meristem activity in the macrocotyledon, appeared to be identical in the European species to that in the typical Old World Streptocarpus rexii but weakly expressed, rare and terminated early. In conclusion, European Gesneriaceae retain a reduced anisocotylous growth that may be linked to their early plumule development.
The oriental armyworm, Mythimna separata is an important crop pest in eastern Asia. Nocturnal insects, including nocturnal moths, have phototactic behavior to an artificial light source. Phototactic behavior in insects is species-specific in response to different wavelengths of light sources. Our previous study showed that green (520 nm) light emitting diode (LED) light resulted in a significantly higher phototactic behavior in M. separata moths compared to the other wavelength LED lights. The goal of the present study is to investigate the influence of green light illumination on biological characteristics of different developmental stages in M. separata. Our results revealed that when different developmental stages of M. separata were exposed to the green light illumination in a dark period, several biological characteristics in all developmental stages except for egg stage were positively changed, but those of F1 generation M. separata which are next generation of the adults exposed to the green light did not significantly change compared with the control level. These findings suggest that green light illumination at night (or dark period) has a positive effect on the development and longevity of M. separata.
Salvia daiguii Y.K.Wei & Y.B.Huang, a new species from China, is described. Salvia daiguii belongs to Salvia subg. Glutinaria (Raf.) G.X.Hu, C.L.Xiang & B.T.Drew, sect. Sobiso (Raf.) G.X.Hu, A.Takano & B.T.Drew, and is distinguished from morphologically similar species by differences in its habit, leaves, inflorescences and flowers. It has a narrow distribution in a karst region of Yongding District, Hunan Province, central China. A key to the Chinese species of section Sobiso is also presented.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.