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Early detection and intervention strategies in patients at clinical high-risk (CHR) for syndromal psychosis have the potential to contain the morbidity of schizophrenia and similar conditions. However, research criteria that have relied on severity and number of positive symptoms are limited in their specificity and risk high false-positive rates. Our objective was to examine the degree to which measures of recency of onset or intensification of positive symptoms [a.k.a., new or worsening (NOW) symptoms] contribute to predictive capacity.
We recruited 109 help-seeking individuals whose symptoms met criteria for the Progression Subtype of the Attenuated Positive Symptom Psychosis-Risk Syndrome defined by the Structured Interview for Psychosis-Risk Syndromes and followed every three months for two years or onset of syndromal psychosis.
Forty-one (40.6%) of 101 participants meeting CHR criteria developed a syndromal psychotic disorder [mostly (80.5%) schizophrenia] with half converting within 142 days (interquartile range: 69–410 days). Patients with more NOW symptoms were more likely to convert (converters: 3.63 ± 0.89; non-converters: 2.90 ± 1.27; p = 0.001). Patients with stable attenuated positive symptoms were less likely to convert than those with NOW symptoms. New, but not worsening, symptoms, in isolation, also predicted conversion.
Results suggest that the severity and number of attenuated positive symptoms are less predictive of conversion to syndromal psychosis than the timing of their emergence and intensification. These findings also suggest that the earliest phase of psychotic illness involves a rapid, dynamic process, beginning before the syndromal first episode, with potentially substantial implications for CHR research and understanding the neurobiology of psychosis.
Southern crabgrass [Digitaria ciliaris (Retz.) Koeler] is an annual grass weed that commonly infests turfgrass, roadsides, wastelands, and cropping systems throughout the southeastern United States. Two biotypes of D. ciliaris (R1 and R2) with known resistance to cyclohexanediones (DIMs) and aryloxyphenoxypropionates (FOPs) previously collected from sod production fields in Georgia were compared with a separate susceptible biotype (S) collected from Alabama for the responses to pinoxaden and to explore the possible mechanisms of resistance. Increasing rates of pinoxaden (0.1 to 23.5 kg ha−1) were evaluated for control of R1, R2, and S. The resistant biotypes, R1 and R2, were resistant to pinoxaden relative to S. The S biotype was completely controlled at rates of 11.8 and 23.5 kg ha−1, resulting in no aboveground biomass at 14 d after treatment. Pinoxaden rates at which tiller length and aboveground biomass would be reduced 50% (I50) and 90% (I90) for R1, R2, and S ranged from 7.2 to 13.2 kg ha−1, 6.9 to 8.6 kg ha−1, and 0.7 to 2.1 kg ha−1, respectively, for tiller length, and 7.7 to 10.2 kg ha−1, 7.2 to 7.9 kg ha−1, and 1.6 to 2.3 kg ha−1, respectively, for aboveground biomass. Prior selection pressure from DIM and FOP herbicides could result in the evolution of D. ciliaris cross-resistance to pinoxaden herbicides. Amplification of the carboxyl-transferase domain of the plastidic ACCase by standard PCR identified a point mutation resulting in an Ile-1781-Leu amino acid substitution only for the resistant biotype, R1. Further cloning of PCR product surrounding the 1781 region yielded two distinct ACCase gene sequences, Ile-1781 and Leu-1781. The amino acid substitution, Ile-1781-Leu in both resistant biotypes (R1 and R2), however, was revealed by next-generation sequencing of RNA using Illumina platform. A point mutation in the Ile-1781 codon leading to herbicide insensitivity in the ACCase enzyme has been previously reported in other grass species. Our research confirms that the Ile-1781-Leu substitution is present in pinoxaden-resistant D. ciliaris.
After a population of laser-driven hot electrons traverses a limited thickness solid target, these electrons will encounter the rear surface, creating TV/m fields that heavily influence the subsequent hot-electron propagation. Electrons that fail to overcome the electrostatic potential reflux back into the target. Those electrons that do overcome the field will escape the target. Here, using the particle-in-cell (PIC) code EPOCH and particle tracking of a large population of macro-particles, we investigate the refluxing and escaping electron populations, as well as the magnitude, spatial and temporal evolution of the rear surface electrostatic fields. The temperature of both the escaping and refluxing electrons is reduced by 30%–50% when compared to the initial hot-electron temperature as a function of intensity between
. Using particle tracking we conclude that the highest energy internal hot electrons are guaranteed to escape up to a threshold energy, below which only a small fraction are able to escape the target. We also examine the temporal characteristic of energy changes of the refluxing and escaping electrons and show that the majority of the energy change is as a result of the temporally evolving electric field that forms on the rear surface.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
In 2013, the national surveillance case definition for West Nile virus (WNV) disease was revised to remove fever as a criterion for neuroinvasive disease and require at most subjective fever for non-neuroinvasive disease. The aims of this project were to determine how often afebrile WNV disease occurs and assess differences among patients with and without fever. We included cases with laboratory evidence of WNV disease reported from four states in 2014. We compared demographics, clinical symptoms and laboratory evidence for patients with and without fever and stratified the analysis by neuroinvasive and non-neuroinvasive presentations. Among 956 included patients, 39 (4%) had no fever; this proportion was similar among patients with and without neuroinvasive disease symptoms. For neuroinvasive and non-neuroinvasive patients, there were no differences in age, sex, or laboratory evidence between febrile and afebrile patients, but hospitalisations were more common among patients with fever (P < 0.01). The only significant difference in symptoms was for ataxia, which was more common in neuroinvasive patients without fever (P = 0.04). Only 5% of non-neuroinvasive patients did not meet the WNV case definition due to lack of fever. The evidence presented here supports the changes made to the national case definition in 2013.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
Targeted screening for carbapenem-resistant organisms (CROs), including carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing organisms (CPOs), remains limited; recent data suggest that existing policies miss many carriers.
Our objective was to measure the prevalence of CRO and CPO perirectal colonization at hospital unit admission and to use machine learning methods to predict probability of CRO and/or CPO carriage.
We performed an observational cohort study of all patients admitted to the medical intensive care unit (MICU) or solid organ transplant (SOT) unit at The Johns Hopkins Hospital between July 1, 2016 and July 1, 2017. Admission perirectal swabs were screened for CROs and CPOs. More than 125 variables capturing preadmission clinical and demographic characteristics were collected from the electronic medical record (EMR) system. We developed models to predict colonization probabilities using decision tree learning.
Evaluating 2,878 admission swabs from 2,165 patients, we found that 7.5% and 1.3% of swabs were CRO and CPO positive, respectively. Organism and carbapenemase diversity among CPO isolates was high. Despite including many characteristics commonly associated with CRO/CPO carriage or infection, overall, decision tree models poorly predicted CRO and CPO colonization (C statistics, 0.57 and 0.58, respectively). In subgroup analyses, however, models did accurately identify patients with recent CRO-positive cultures who use proton-pump inhibitors as having a high likelihood of CRO colonization.
In this inpatient population, CRO carriage was infrequent but was higher than previously published estimates. Despite including many variables associated with CRO/CPO carriage, models poorly predicted colonization status, likely due to significant host and organism heterogeneity.
Childhood adversity is associated with poor mental and physical health outcomes across the life span. Alterations in the hypothalamic–pituitary–adrenal axis are considered a key mechanism underlying these associations, although findings have been mixed. These inconsistencies suggest that other aspects of stress processing may underlie variations in this these associations, and that differences in adversity type, sex, and age may be relevant. The current study investigated the relationship between childhood adversity, stress perception, and morning cortisol, and examined whether differences in adversity type (generalized vs. threat and deprivation), sex, and age had distinct effects on these associations. Salivary cortisol samples, daily hassle stress ratings, and retrospective measures of childhood adversity were collected from a large sample of youth at risk for serious mental illness including psychoses (n = 605, mean age = 19.3). Results indicated that childhood adversity was associated with increased stress perception, which subsequently predicted higher morning cortisol levels; however, these associations were specific to threat exposures in females. These findings highlight the role of stress perception in stress vulnerability following childhood adversity and highlight potential sex differences in the impact of threat exposures.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
The authors developed a practical and clinically useful model to predict the risk of psychosis that utilizes clinical characteristics empirically demonstrated to be strong predictors of conversion to psychosis in clinical high-risk (CHR) individuals. The model is based upon the Structured Interview for Psychosis Risk Syndromes (SIPS) and accompanying clinical interview, and yields scores indicating one's risk of conversion.
Baseline data, including demographic and clinical characteristics measured by the SIPS, were obtained on 199 CHR individuals seeking evaluation in the early detection and intervention for mental disorders program at the New York State Psychiatric Institute at Columbia University Medical Center. Each patient was followed for up to 2 years or until they developed a syndromal DSM-4 disorder. A LASSO logistic fitting procedure was used to construct a model for conversion specifically to a psychotic disorder.
At 2 years, 64 patients (32.2%) converted to a psychotic disorder. The top five variables with relatively large standardized effect sizes included SIPS subscales of visual perceptual abnormalities, dysphoric mood, unusual thought content, disorganized communication, and violent ideation. The concordance index (c-index) was 0.73, indicating a moderately strong ability to discriminate between converters and non-converters.
The prediction model performed well in classifying converters and non-converters and revealed SIPS measures that are relatively strong predictors of conversion, comparable with the risk calculator published by NAPLS (c-index = 0.71), but requiring only a structured clinical interview. Future work will seek to externally validate the model and enhance its performance with the incorporation of relevant biomarkers.
Three-dimensional (3D) printing technology is a promising method for bone tissue engineering applications. For enhanced bone regeneration, it is important to have printable ink materials with appealing properties such as construct interconnectivity, mechanical strength, controlled degradation rates, and the presence of bioactive materials. In this respect, we develop a composite ink composed of polycaprolactone (PCL), poly(D,L-lactide-co-glycolide) (PLGA), and hydroxyapatite particles (HAps) and 3D print it into porous constructs. In vitro study revealed that composite constructs had higher mechanical properties, surface roughness, quicker degradation profile, and cellular behaviors compared to PCL counterparts. Furthermore, in vivo results showed that 3D-printed composite constructs had a positive influence on bone regeneration due to the presence of newly formed mineralized bone tissue and blood vessel formation. Therefore, 3D printable ink made of PCL/PLGA/HAp can be a highly useful material for 3D printing of bone tissue constructs.
The Latino population in the United States is rapidly growing and faces profound health disparities; however, engagement of Latinos in biomedical research remains low. Our community-based participatory research partnership has recruited 2083 Spanish-speaking Latinos into 21 studies over 15 years. We sought to identify and describe the strategies we have used to successfully recruit and retain Spanish-speaking Latinos in research.
We abstracted and analyzed data from archived study notes, progress reports, team meeting minutes, and in-depth interviews conducted annually from community-based participatory research partnership members. We used a nominal group process to refine and prioritize strategies.
Overall, 13 recruitment strategies and 12 retention strategies emerged. These strategies relied on the creativity and perseverance of the study team and partners.
It is essential that we develop and disseminate effective recruitment and retention strategies that engage Latinos in biomedical research to reduce health disparities and promote health equity.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Introduction: TREKK is a national knowledge mobilization network of clinicians, researchers and parents aimed at improving emergency care for children by increasing collaborations between general and pediatric emergency departments (ED). This study aimed to determine patterns of knowledge sharing within the network and identify connections, barriers and opportunities to obtaining pediatric information and training. Methods: Social network analysis (SNA) uses network theory to understand patterns of interaction. Two SNAs were conducted in 2014 and 2015 using an online network survey distributed to 37 general EDs. Data was analyzed using UCI Net and Netdraw to identify connections, knowledge sharing and knowledge brokers within the network. Building on these results, we then conducted 22 semi-structured follow-up interviews (2016) with healthcare professionals (HCPs) at General EDs across Canada, purposefully sampled to include individuals from connected and disconnected sites, as identified in the SNA. Interviews were analyzed by 2 reviewers using content and thematic analysis. Results: SNA data was analyzed for 135 participants across the network. Results from 2014 showed that the network was divided along provincial lines, with most individuals connecting with colleagues within their own institution. Results from 2015 showed more inter-site interconnectivity and a reduction in isolated sites over time from 17 to 3. Interview participants included physicians (59%) and nurses (41%) from 18 general EDs in urban (68%) and rural/remote (32%) Canada. HCPs sought information both formally and informally, by using guidelines, talking to colleagues, and attending pediatric related training sessions. Network structure and processes were felt to increase connections, support practice change, and promote standards of care. Participants identified personal, organizational and system-level barriers to information and skill acquisition, including resources and personal costs, geography, dissemination, and time. Providing easy access to information at the point of care was promoted through enhancing content visibility and by embedding resources into local systems. There remains a need to share successful methods of local dissemination and implementation across the network, and to leverage local professional champions such as clinical nurse liaisons. Conclusion: This study highlights the power of a network to increase connections between HCPs working in general and pediatric EDs. Findings reinforce the critical role of ongoing network evaluation to improve the design and delivery of knowledge mobilization initiatives.
Introduction: Emergency Department Overcrowding (EDOC) is a multifactorial issue that leads to Access Block for patients needing emergency care. Identified as a national problem, patients presenting to a Canadian Emergency Department (ED) at a time of overcrowding have higher rates of admission to hospital and increased seven-day mortality. Using the well accepted input-throughput-output model to study EDOC, current research has focused on throughput as a measure of patient flow, reported as ED length of stay (LOS). In fact, ED LOS and ED beds occupied by inpatients are two “extremely important indicators of EDOC identified by a 2005 survey of Canadian ED directors. One proposed solution to improve ED throughput is to utilize a physician at triage (PAT) to rapidly assess newly arriving patients. In 2017, a pilot PAT program was trialed at Kelowna General Hospital (KGH), a tertiary care hospital, as part of a PDSA cycle. The aim was to mitigate EDOC by improving ED throughput by the end of 2018, to meet the national targets for ED LOS suggested in the 2013 CAEP position statement. Methods: During the fiscal periods 1-6 (April 1 to September 7, 2017) a PAT shift occurred daily from 1000-2200, over four long weekends. ED LOS, time to inpatient bed, time to physician initial assessment (PIA), number of British Columbia Ambulance Service (BCAS) offload delays, and number of patients who left without being seen (LWBS) were extracted from an administrative database. Results were retrospectively analyzed and compared to data from 1000-2200 of non-PAT trial days during the trial periods. Results: Median ED LOS decreased from 3.8 to 3.4 hours for high-acuity patients (CTAS 1-3), from 2.1 to 1.8 hours for low-acuity patients (CTAS 4-5), and from 9.3 to 8.0 hours for all admitted patients. During PAT trial weekends, there was a decrease in the average time to PIA by 65% (from 73 to 26 minutes for CTAS 2-5), average number of daily BCAS offload delays by 39% (from 2.3 to 1.4 delays per day), and number of patients who LWBS from 2.4% to 1.7%. Conclusion: The implementation of PAT was associated with improvements in all five measures of ED throughput, providing a potential solution for EDOC at KGH. ED LOS was reduced compared to non-PAT control days, successfully meeting the suggested national targets. PAT could improve efficiency, resulting in the ability to see more patients in the ED, and increase the quality and safety of ED practice. Next, we hope to prospectively evaluate PAT, continuing to analyze these process measures, perform a cost-benefit analysis, and formally assess ED staff and patient perceptions of the program.
Antimicrobial resistance is a limiting factor for the success of the treatment of infectious diseases and is associated with increased morbidity and cost. The present study aims to evaluate prescribing patterns of antimicrobials and quantify progress in relation to targets for quality improvement in the prescription of antimicrobials in Northern Ireland's secondary care sector using three repetitive point prevalence surveys (PPS) over a 6-year period: the European Surveillance of Antimicrobial Consumption (ESAC-PPS) in 2009 and 2011 and the Global-PPS on Antimicrobial Consumption and Resistance in 2015. Out of 3605 patients surveyed over the three time points, 1239 (34.4%) were treated with an antibiotic, the most frequently prescribed antibiotic groups were a combination of penicillins, including β-lactamase inhibitors. Compliance with hospital antibiotic policies in 2009, 2011 and 2015 were 54.5%, 71.5% and 79.9%, respectively. Likewise, an indication for treatment was recorded in patient notes 88.5%, 87.7% and 90.6% in 2009, 2011 and 2015, respectively, and surgical prophylactic antibiotic prescriptions for >24 h was 3.9%, 3.2% and 0.7% in 2009, 2011 and 2015, respectively. Treatment based on biomarker data was used in 61.5% of cases. In conclusion, a general trend in the improvement of key antimicrobial-related quality indicators was noted. The PPS tool provided a convenient, inexpensive surveillance system of antimicrobial consumption and should be considered an essential component to establish and maintain informed antibiotic stewardship in hospitals.