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ABSTRACT IMPACT: Identifying factors associated with opioid overdoses will enable better resource allocation in communities most impacted by the overdose epidemic. OBJECTIVES/GOALS: Opioid overdoses often occur in hotspots identified by geographic and temporal trends. This study uses principles of community engaged research to identify neighborhood and community-level factors associated with opioid overdose within overdose hotspots which can be targets for novel intervention design. METHODS/STUDY POPULATION: We conducted an environmental scan in three overdose hotspots’‘ two in an urban center and one in a small city’‘ identified by the Rhode Island Department of Health as having the highest opioid overdose burden in Rhode Island. We engaged hotspot community stakeholders to identify neighborhood factors to map within each hotspot. Locations of addiction treatment, public transportation, harm reduction programs, public facilities (i.e., libraries, parks), first responders, and social services agencies were converted to latitude and longitude and mapped in ArcGIS. Using Esri Service Areas, we will evaluate the service areas of stationary services. We will overlay overdose events and use logistic regression identify neighborhood factors associated with overdose by comparing hotspot and non-hotspot neighborhoods. RESULTS/ANTICIPATED RESULTS: We anticipate that there will be differing neighborhood characteristics associated with overdose events in the densely populated urban area and those in the smaller city. The urban area hotspots will have overlapping social services, addiction treatment, and transportation service areas, while the small city will have fewer community resources without overlapping service areas and reduced public transportation access. We anticipate that overdoses will occur during times of the day when services are not available. Overall, overdose hotspots will be associated with increased census block level unemployment, homelessness, vacant housing, and low food security. DISCUSSION/SIGNIFICANCE OF FINDINGS: Identifying factors associated with opioid overdoses will enable better resource allocation in communities most impacted by the overdose epidemic. Study results will be used for novel intervention design to prevent opioid overdose deaths in communities with high burden of opioid overdose.
New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother–child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14–0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01–0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this “triple exposure” hypothesis.
Infection prevention and control (IPC) workflows are often retrospective and manual. New tools, however, have entered the field to facilitate rapid prospective monitoring of infections in hospitals. Although artificial intelligence (AI)–enabled platforms facilitate timely, on-demand integration of clinical data feeds with pathogen whole-genome sequencing (WGS), a standardized workflow to fully harness the power of such tools is lacking. We report a novel, evidence-based workflow that promotes quicker infection surveillance via AI-assisted clinical and WGS data analysis. The algorithm suggests clusters based on a combination of similar minimum inhibitory concentration (MIC) data, timing of sample collection, and shared location stays between patients. It helps to proactively guide IPC professionals during investigation of infectious outbreaks and surveillance of multidrug-resistant organisms and healthcare-acquired infections. Methods: Our team established a 1-year workgroup comprised of IPC practitioners, clinical experts, and scientists in the field. We held weekly roundtables to study lessons learned in an ongoing surveillance effort at a tertiary care hospital—utilizing Philips IntelliSpace Epidemiology (ISEpi), an AI-powered system—to understand how such a tool can enhance practice. Based on real-time case discussions and evidence from the literature, a workflow guidance tool and checklist were codified. Results: In our workflow, data-informed clusters posed by ISEpi underwent triage and expert follow-up analysis to assess: (1) likelihood of transmission(s); (2) potential vector(s) identity; (3) need to request WGS; and (4) intervention(s) to be pursued, if warranted. In a representative sample (spanning October 17, 2019, to November 7, 2019) of 67 total isolates suggested for inclusion in 19 unique cluster investigations, we determined that 9 investigations merited follow-up. Collectively, these 9 investigations involved 21 patients and required 115 minutes to review in ISEpi and an additional 70 minutes of review outside of ISEpi. After review, 6 investigations were deemed unlikely to represent a transmission; the other 3 had potential to represent transmission for which interventions would be performed. Conclusions: This study offers an important framework for adaptation of existing infection control workflow strategies to leverage the utility of rapidly integrated clinical and WGS data. This workflow can also facilitate time-sensitive decisions regarding sequencing of specific pathogens given the preponderance of available clinical data supporting investigations. In this regard, our work sets a new standard of practice: precision infection prevention (PIP). Ongoing effort is aimed at development of AI-powered capabilities for enterprise-level quality and safety improvement initiatives.
Funding: Philips Healthcare provided support for this study.
Disclosures: Alan Doty and Juan Jose Carmona report salary from Philips Healthcare.
Massive, early-type stars have been detected as radio sources for many decades. Their thermal winds radiate free–free continuum and in binary systems hosting a colliding-wind region, non-thermal emission has also been detected. To date, the most abundant data have been collected from frequencies higher than 1 GHz. We present here the results obtained from observations at 325 and 610 MHz, carried out with the Giant Metrewave Radio Telescope, of all known Wolf-Rayet and O-type stars encompassed in area of
15 sq degrees centred on the Cygnus region. We report on the detection of 11 massive stars, including both Wolf-Rayet and O-type systems. The measured flux densities at decimeter wavelengths allowed us to study the radio spectrum of the binary systems and to propose a consistent interpretation in terms of physical processes affecting the wide-band radio emission from these objects. WR 140 was detected at 610 MHz, but not at 325 MHz, very likely because of the strong impact of free–free absorption (FFA). We also report—for the first time—on the detection of a colliding-wind binary system down to 150 MHz, pertaining to the system of WR 146, making use of complementary information extracted from the Tata Institute of Fundamental Research GMRT Sky Survey. Its spectral energy distribution clearly shows the turnover at a frequency of about 600 MHz, that we interpret to be due to FFA. Finally, we report on the identification of two additional particle-accelerating colliding-wind binaries, namely Cyg OB2 12 and ALS 15108 AB.
Neurocognitive abnormalities are prevalent in both first episode schizophrenia patients and in ultra high risk (UHR) patients.
To compare verbal fluency performance at baseline in UHR in patients that did and did not make the transition to psychosis.
Baseline verbal fluency performance in UHR-patients (n = 47) was compared to match first episode patients (n = 69) and normal controls (n = 42).
Verbal fluency (semantic category) scores in UHR-patients did not differ significantly from the score in first episode schizophrenia patients. Both the UHR group (p < 0.003) and the patient group (p < 0.0001) performed significantly worse than controls. Compared to the non-transition group, the transition group performed worse on verbal fluency, semantic category (p < 0.006) at baseline.
Verbal fluency (semantic category) is disturbed in UHR-patients that make the transition to psychosis and could contribute to an improved prediction of transition to psychosis in UHR-patients.
Regional cerebral blood flow (rCBF) values were measured by single photon emission computed tomography (SPECT) in different regions of the brain in 27 patients with DAT. Significant correlations were found between rCBF in left parieto-temporooccipital regions and psychometric test scores. Patients with hemisphere asymmetry in SPECT performed worse on psychometric tests. SPECT did not permit prediction of or differentiation between depressive and psychotic symptoms.
Schizophrenia is a devastating mental disorder with diverse dimensions of symptoms like delusions, hallucinations, affective symptoms and alterations in cognition. Declarative memory deficits are among the most important factors leading to poor functional outcomes in this disorder. Recently it was supposed, that sleep disturbances in patients with schizophrenia might contribute to these memory impairments (Manoach et al. 2009, Ferrarelli et al. 2010, Lu and Göder 2012). In young healthy subjects it was shown that declarative memory consolidation was enhanced by inducing slow oscillation-like potential fields during sleep (Marshall et al. 2006). In the present study transcranial direct current stimulation (tDCS) was applied to 14 patients with schizophrenia on stable medication with a mean age of 33 years. The main effects of tDCS in comparison to sham stimulation were: An enhancement in declarative memory retention and an increase in mood after sleep. In conclusion, so-tDCS offers an interesting approach for studying the relationship of sleep and memory in psychiatric disorders and could possibly improve disturbed memory processing in patients with schizophrenia.
Research is one of the most attractive fields for young doctors training in psychiatry. The acquisition of research skills by all trainees has been recommended by recent consensus documents on standards of psychiatric training in Europe. However, not always trainees have adequate access to all the phases of a research project during their residencies. Joining professional associations provides opportunities for participating in research activities and establishing networks with other colleagues. In this respect, the European Federation of Psychiatric Trainees (EFPT) in 2008 started a research group with the aim of facilitating trainee-led collaborative studies. Over the years several international research projects on training-related areas have been conducted and published in international peer-reviewed journals. EFPT members can participate to all the phases of the projects as national coordinators and share with other colleagues their research competencies. Furthermore, many EFPT research projects have had the possibility to rely on supervision by internationally renowned experts.
Currently, the topics of the main ongoing studies are: 1) Early career psychiatrists views on psychiatric training (in collaboration with European Psychiatric Association - Early Career Psychiatric Committee); 2) Relationship between trainees and pharmaceutical industries; 3) Child and Adolescent psychiatric training; 4) Trainees’ views on the future of psychiatry and psychiatric training; 5) Trainees’ access to information and use of information technologies during training. In this presentation, issues in research training will be discussed, the EFPT cooperative trainee-led research network will be described and an overview of the results of the ongoing studies will be provided.
Thromboxane (TX) A2 and the activation of its receptor have been shown to modulate vasoconstriction, platelet aggregation, but also dopaminergic and serotonergic signaling.
As dopaminergic and serotonergic systems play a crucial role in the pathophysiology of schizophrenia and as these systems are main targets of antipsychotics, we hypothesized that antipsychotics might also influence TXA2 production.
We measured levels of TXB2, the metabolite of the very unstable molecule TXA2, in the stimulated blood of 10 healthy female subjects in a whole blood assay using the toxic shock syndrome toxin-1 (TSST-1) and the monoclonal antibody against the surface antigen CD3 combined with the protein CD40 (OKT3/CD40) as stimulants. Blood was either supplemented with antipsychotics (chlorpromazine, clozapine, and its metabolite N-desmethylclozapine with four different concentrations each) or not.
Under TSST-1 as well as OKT3/CD40 stimulation, mean TXB2 concentrations were significantly (p < 0.05) decreased by clozapine over all of the applied concentrations. N-desmethylclozapine led to a decrease in TXB2 levels under TSST-1 stimulation only. Chlorpromazine did not show any significant influence on TXB2 production.
Clozapine might, complementary to serotonin and dopamine receptor binding, act on the dopaminergic and serotonergic system via a modulation of TXA2 production. Additionally, side effects of clozapine such as orthostatic hypotension may be a result of the reported TXA2 changes.
Evidence has suggested that immune imbalance is involved with bipolar disorder (BD); however, its precise mechanism is poorly understood.
This study investigated whether biochemical changes in the serum from BD patients could modulate the phenotype of macrophages.
Eighteen subjects with BD and healthy individuals (n = 5) were included in this study. The human monocyte cell line U-937 was activated with PMA (phorbol 12-myristate 13-acetate) and polarization was induced with RPMI-1640 media supplemented with 10% serum from each patient for 24 h. Gene expression of selected M1 and M2 markers was assessed by qPCR.
Macrophages exposed to serum of manic and depressive BD patients displayed an increase of IL-1β (6.40 ± 3.47 and 9.04 ± 5.84 versus 0.23 ± 0.11; P < 0.05) and TNF-α (2.23 ± 0.91 and 2.03 ± 0.45 versus 0.62 ± 0.24; P = 0.002 and P = 0.004, respectively) compared to remitted group. In parallel, U-937 macrophages treated with serum of patients in acute episode displayed a down-regulation of CXCL9 (0.29 ± 0.20 versus 1.86 ± 1.61; P = 0.006) and CXCL10 expression (0.36 ± 0.15 and 0.86 ± 0.24 versus 1.83 ± 0.88; P < 0.000 and P = 0.04) compared to remitters.
Our results are consistent with previous studies showing that changes in peripheral blood markers could modulate M1/M2 polarization in BD. The evidence of macrophages as source of inflammatory cytokines might be helpful to unravel how the mononuclear phagocyte system can be involved in the etiology of BD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Both blood- and milk-based biomarkers have been analysed for decades in research settings, although often only in one herd, and without focus on the variation in the biomarkers that are specifically related to herd or diet. Biomarkers can be used to detect physiological imbalance and disease risk and may have a role in precision livestock farming (PLF). For use in PLF, it is important to quantify normal variation in specific biomarkers and the source of this variation. The objective of this study was to estimate the between- and within-herd variation in a number of blood metabolites (β-hydroxybutyrate (BHB), non-esterified fatty acids, glucose and serum IGF-1), milk metabolites (free glucose, glucose-6-phosphate, urea, isocitrate, BHB and uric acid), milk enzymes (lactate dehydrogenase and N-acetyl-β-D-glucosaminidase (NAGase)) and composite indicators for metabolic imbalances (Physiological Imbalance-index and energy balance), to help facilitate their adoption within PLF. Blood and milk were sampled from 234 Holstein dairy cows from 6 experimental herds, each in a different European country, and offered a total of 10 different diets. Blood was sampled on 2 occasions at approximately 14 days-in-milk (DIM) and 35 DIM. Milk samples were collected twice weekly (in total 2750 samples) from DIM 1 to 50. Multilevel random regression models were used to estimate the variance components and to calculate the intraclass correlations (ICCs). The ICCs for the milk metabolites, when adjusted for parity and DIM at sampling, demonstrated that between 12% (glucose-6-phosphate) and 46% (urea) of the variation in the metabolites’ levels could be associated with the herd-diet combination. Intraclass Correlations related to the herd-diet combination were generally higher for blood metabolites, from 17% (cholesterol) to approximately 46% (BHB and urea). The high ICCs for urea suggest that this biomarker can be used for monitoring on herd level. The low variance within cow for NAGase indicates that few samples would be needed to describe the status and potentially a general reference value could be used. The low ICC for most of the biomarkers and larger within cow variation emphasises that multiple samples would be needed - most likely on the individual cows - for making the biomarkers useful for monitoring. The majority of biomarkers were influenced by parity and DIM which indicate that these should be accounted for if the biomarker should be used for monitoring.
Aircraft handling qualities may be influenced by wing-tip flow separations and horizontal tail (HT) reduced efficiency caused by loss of local dynamic pressure or local tailplane flow separations in high angle-of-attack manoeuvres. From the flight tester’s perspective, provided that the test aircraft presents sufficient longitudinal control authority to overcome an uncommanded nose-up motion, this characteristic should not be a safety factor. Monitoring and measuring the local airflow in the aircraft’s HT provides information for safe flight-test envelope expansion and data for early aerodynamic knowledge and model validation. This work presents the development, installation and pre-flight calibration using computational fluid dynamics (CFD), flight-test calibration, results and benefits of differential pressure based local angle-of-attack and total pressure measurements through 20 static pressure ports and a Kiel pitot. These sensors were installed in a single-aisle, four-abreast, full fly-by-wire medium-range jet airliner with twin turbofan engines and conventional HT (low vertical position).
We studied trends in the incidence of health care-associated infections (HAIs) in LTCFs between 2009 and 2015 and determined the effect of participation in our network. Elder-care physicians reported weekly the number of cases of influenza-like illness, gastroenteritis, (probable) pneumonia, urinary tract infections (UTIs) and all-cause mortality. Trends in the incidence of infection and mortality in relation to LTCF characteristics were calculated using multilevel univariate and multivariate logistic regression. Thirty LTCF participated for 3 years or more, 16 for 2 years and the remaining 12 LTCF for 1 year. During the study period, the median number of beds decreased from 158 to 139, whereas the percentage of residents with private bedrooms increased from 14% to 87%. UTIs were the most frequently reported infections, followed by (probable) pneumonia and gastroenteritis. Adjusted for calendar year and season, we observed a statistically significant decrease in the incidence of influenza-like illness (odds ratio (OR) = 0.8, P < 0.01) and (probable) pneumonia (OR = 0.8, P < 0.01) for each extra year an LTCF participated. Although there are other likely contributors, such as more private rooms and enhanced infection control measures, the decreasing trend of HAI in LTCFs participating in surveillance implies that surveillance is a valuable addition to current strategies to optimise infection control.
Investigations into the existence of life in other parts of the cosmos find strong parallels with studies of the origin and evolution of life on our own planet. In this way, astrobiology and paleobiology are married by their common interest in disentangling the interconnections between life and the surrounding environment. In this way, a cross-point of both sciences is paleometry, which involves a myriad of imaging and geochemical techniques, usually non-destructive, applied to the investigation of the fossil record. In the last decades, paleometry has benefited from an unprecedented technological improvement, thus solving old questions and raising new ones. This advance has been paralleled by conceptual approaches and discoveries fuelled by technological evolution in astrobiological research. In this context, we present some new data and review recent advances on the employment of paleometry to investigations on paleobiology and astrobiology in Brazil in areas such biosignatures in Ediacaran microbial mats, biogenicity tests on enigmatic Ediacaran structures, research on Ediacaran metazoan biomineralization, fossil preservation in Cretaceous insects and fish, and finally the experimental study on the decay of fish to test the effect of distinct types of sediment on soft-tissue preservation, as well as the effects of early diagenesis on fish bone preservation.
Elizabeth Stuart (1635–1650), the second daughter of Charles I and Henrietta Maria, influenced both Royalists and Parliamentarians as a symbol of prosperity, piety, and scholarly excellence despite effectively being Parliament’s hostage during the first half of the English Civil War. She was a persistent force for causes she believed in, influencing politics with both her private writing and public countenance. This influence was even remarked on by political foes including Thomas Fairfax and Oliver Cromwell. Tragically, Elizabeth did not survive her imprisonment, dying days before Parliament ordered her release, and she was mourned by her family, her public, and the rest of Europe's monarchies as a great loss. The modern historical narrative, however, has largely forgotten her, and recognising her influence enhances our understanding of the English Civil War.
Keywords: female influence; royal images; historical revisionism; English Civil War; Royalists and Parliamentarians
For two centuries, the chancel of St. Thomas's Church in Newport, on the Isle of Wight, held the obscured remains of Princess Elizabeth Stuart (1635–1650), marked only by the letters ‘E.S.’ carved into the wall nearby. In 1856, during the church's renovations, Queen Victoria ordered that a monument be erected as ‘a token of respect for her virtues, and of sympathy for her misfortunes’. Around the same time as Victoria's public honouring of the Stuart princess, Elizabeth was (re)introduced to popular culture: Mary Anne Everett Green published the multi-volumed Lives of the Princesses of England: From the Norman Conquest in 1855, which was followed in 1888 by Agnes Strickland's Lives of the Tudor and Stuart Princesses. Both texts included biographical chapters on Elizabeth that detailed her life as a child in the royal court, as well as her actions and involvement during the English Civil War. However, Elizabeth is still a figure on the edge of Stuart scholarship, and is routinely absent from accounts of the period. She is absent from the recent Biographical Encyclopedia of Early Modern Englishwomen, and her entry in the Oxford Dictionary of National Biography is no more detailed than the Wikipedia article about her life. The most recent work to include an account of her life is Linda Porter's Royal Renegades.
This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.
Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.
The IPS–WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS–WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS–WFM intervention (45 v. 26 weeks, p < 0.004).
The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.
Evolutionary theory makes further predictions about conflict. It predicts sex differences in the proclivity to attack and defend. It further suggests complementary biases in what we expect of the sexes. Finally, it suggests that the forms of human facial expressions of anger and happiness may have coevolved with the regularity of conflict as a means of signaling, bluffing, and defusing attack.
Dr. Irving I. Gottesman was very creative in applying twin research designs to test hypotheses and predictions about human behavior. Two designs stand out among others: twins reared apart from birth and the twin-family study. I (NS) was inspired to incorporate both of these approaches into my own research programs at California State University, Fullerton. Gottesman's involvement and contributions to reared-apart twin research are described, followed by selected findings from the Minnesota Study of Twins Reared Apart (MISTRA), the Fullerton Study of Chinese Twins Reared Apart (CTA), a case report on separated monozygotic (MZ) female twins from South Korea, and doubly exchanged MZ male twin pairs from Colombia, South America. Recent findings from an ongoing twin-family study of social closeness, and future directions, are also presented.