We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The United States Government (USG) public-private partnership “Accelerating COVID-19 Treatment Interventions and Vaccines” (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during “peacetime,” as well.
Auditory verbal hallucinations (AVHs) in schizophrenia have been suggested to arise from failure of corollary discharge mechanisms to correctly predict and suppress self-initiated inner speech. However, it is unclear whether such dysfunction is related to motor preparation of inner speech during which sensorimotor predictions are formed. The contingent negative variation (CNV) is a slow-going negative event-related potential that occurs prior to executing an action. A recent meta-analysis has revealed a large effect for CNV blunting in schizophrenia. Given that inner speech, similar to overt speech, has been shown to be preceded by a CNV, the present study tested the notion that AVHs are associated with inner speech-specific motor preparation deficits.
Objectives
The present study aimed to provide a useful framework for directly testing the long-held idea that AVHs may be related to inner speech-specific CNV blunting in patients with schizophrenia. This may hold promise for a reliable biomarker of AVHs.
Methods
Hallucinating (n=52) and non-hallucinating (n=45) patients with schizophrenia, along with matched healthy controls (n=42), participated in a novel electroencephalographic (EEG) paradigm. In the Active condition, they were asked to imagine a single phoneme at a cue moment while, precisely at the same time, being presented with an auditory probe. In the Passive condition, they were asked to passively listen to the auditory probes. The amplitude of the CNV preceding the production of inner speech was examined.
Results
Healthy controls showed a larger CNV amplitude (p = .002, d = .50) in the Active compared to the Passive condition, replicating previous results of a CNV preceding inner speech. However, both patient groups did not show a difference between the two conditions (p > .05). Importantly, a repeated measure ANOVA revealed a significant interaction effect (p = .007, ηp2 = .05). Follow-up contrasts showed that healthy controls exhibited a larger CNV amplitude in the Active condition than both the hallucinating (p = .013, d = .52) and non-hallucinating patients (p < .001, d = .88). No difference was found between the two patient groups (p = .320, d = .20).
Conclusions
The results indicated that motor preparation of inner speech in schizophrenia was disrupted. While the production of inner speech resulted in a larger CNV than passive listening in healthy controls, which was indicative of the involvement of motor planning, patients exhibited markedly blunted motor preparatory activity to inner speech. This may reflect dysfunction in the formation of corollary discharges. Interestingly, the deficits did not differ between hallucinating and non-hallucinating patients. Future work is needed to elucidate the specificity of inner speech-specific motor preparation deficits with AVHs. Overall, this study provides evidence in support of atypical inner speech monitoring in schizophrenia.
OBJECTIVES/GOALS: To tackle population-level health disparities, quality dashboards can leverage individual socioeconomic status (SES) measures, which are not always readily accessible. This study aimed to assess the feasibility of a population health management strategy for colorectal cancer (CRC) screening rates using the HOUSES index and heatmap analysis. METHODS/STUDY POPULATION: We applied the 2019 Minnesota Community Measurement data for optimal CRC screening to eligible Mayo Clinic Midwest panel patients. SES was defined by HOUSES index, a validated SES measure based on publicly available property data for the U.S. population. We first assessed the association of suboptimal CRC screening rate with HOUSES index adjusting for age, sex, race/ethnicity, comorbidity, and Zip-code level deprivation by using a mixed effects logistic regression model. We then assessed changes in ranking for performance of individual clinics (i.e., % of patients with optimal CRC screening rate) before and after adjusting for HOUSES index. Geographical hotspots of high proportions of low SES AND high proportions of suboptimal CRC screening were superimposed to identify target population for outreach. RESULTS/ANTICIPATED RESULTS: A total of 58,382 adults from 41 clinics were eligible for CRC screening assessment in 2019 (53% Female). Patients with lower SES defined by HOUSES quartile 1-3 have significantly lower CRC screening compared to those with highest SES (HOUSES quartile 4) (adj. OR [95% CI]: 0.52 [0.50-0.56] for Q1, 0.66 [0.62-0.70] for Q2, and 0.81 [0.76-0.85]) for Q3). Ranking of 26 out of 41 (63%) clinics went down after adjusting for HOUSES index suggesting disproportionately higher proportion of underserved patients with suboptimal CRC screening. We were able to successfully identify hotspots of suboptimal CRC (area with greater than 130% of expected value) and overlay with higher proportion of underserved population (HOUSES Q1), which can be used for data-driven targeted interventions such as mobile health clinics. DISCUSSION/SIGNIFICANCE: HOUSES index and associated heatmap analysis can contribute to advancing health equity. This approach can aid health care organizations in meeting the newly established standards by The Joint Commission, which have elevated health equity to a national safety priority.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Studies examining the role of geographic factors in coronavirus disease-2019 (COVID-19) epidemiology among rural populations are lacking.
Methods:
Our study is a population-based longitudinal study based on rural residents in four southeast Minnesota counties from March through October 2020. We used a kernel density estimation approach to identify hotspots for COVID-19 cases. Temporal trends of cases and testing were examined by generating a series of hotspot maps during the study period. Household/individual-level socioeconomic status (SES) was measured using the HOUSES index and examined for association between identified hotspots and SES.
Results:
During the study period, 24,243 of 90,975 residents (26.6%) were tested for COVID-19 at least once; 1498 (6.2%) of these tested positive. Compared to other rural residents, hotspot residents were overall younger (median age: 40.5 vs 43.2), more likely to be minorities (10.7% vs 9.7%), and of higher SES (lowest HOUSES [SES] quadrant: 14.6% vs 18.7%). Hotspots accounted for 30.1% of cases (14.5% of population) for rural cities and 60.8% of cases (27.1% of population) for townships. Lower SES and minority households were primarily affected early in the pandemic and higher SES and non-minority households affected later.
Conclusion:
In rural areas of these four counties in Minnesota, geographic factors (hotspots) play a significant role in the overall burden of COVID-19 with associated racial/ethnic and SES disparities, of which pattern differed by the timing of the pandemic (earlier in pandemic vs later). The study results could more precisely guide community outreach efforts (e.g., public health education, testing/tracing, and vaccine roll out) to those residing in hotspots.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
Although several initiatives have produced core competency domains for training the translational science workforce, training resources to help clinical research professionals advance these skills reside primarily within local departments or institutions. The Development, Implementation, and AssessMent of Novel Training in Domain (DIAMOND) project was designed to make this training more readily and publicly available. DIAMOND includes a digital portal to catalog publicly available educational resources and an ePortfolio to document professional development. DIAMOND is a nationally crowdsourced, federated, online catalog providing a platform for practitioners to find and share training and assessment materials. Contributors can share their own educational materials using a simple intake form that creates an electronic record; the portal enables users to browse or search this catalog of digital records and access the resources. Since September 2018, the portal has been visited more than 5,700 times and received over 280 contributions from professionals. The portal facilitates opportunities to connect and collaborate regarding future applications of these resources. Consequently, growing the collection and increasing numbers of both contributors and users remains a priority. Results from a small subset of users indicated over half accomplished their purpose for visiting the site, while qualitative results showed that users identified several benefits and helpful features of the ePortfolio.
Depression is a common mental disorder that substantially impairs a client's functioning. the aim of this study is to examine the predictive factors of quality of life (QOL) for depression from longitudinal perspectives. 237 outpatients with depression were recruited in the study. They were from a psychiatric outpatient clinic in northern Taiwan. All subjects were tested on the baseline and followed up twice during 3-year period. the average age of subjects was 47.1 years. Most subjects were female, married and lived with their spouses.Seventy subjects participated in both follow ups (T2 and T3). there were no significant differences on the demographic characteristics at T1 between the respondents (N = 70) and non-respondents (N = 167) except for gender. the subjects were tested on the WHOQOL-BREF-Taiwan version, occupational self assessment, mastery, social support and Center of Epidemiology Study-Depression Scale (CESD). the data were analyzed by mixed effect model using SAS computer program.The severity of depression could predict overall QOL, overall health and 13 items of QOL. the type of antidepressants had significant impact on the subjects’ QOL in 10 items. the occupational competence and sense of mastery predicted 13 items (50%) and 14 items (53.8%), respectively.In order to advance the treatment outcomes, the professionals should pay more attention on the enhancement of the sense of competence and mastery. We suggested that treatments should target at improving adaptive skills, lifestyle, and occupational competence.
Prior studies indicate greater disease burden for obesity among rural compared with urban residents but no differences for mood disorder based on geographic location. Recent attention has focused on the need to examine regional rural–urban disparities in disease burden. We focused on mood disorders and obesity prevalence within three southeastern Minnesota counties served by the Mayo Clinic Center for Translational Science Award, in Rochester, Minnesota, as these were top priorities identified in community health needs assessments.
Methods:
Cross-sectional study to assess the association of rural–urban locality on 5-year (2009–2014) prevalence of mood disorder and obesity obtained using the Rochester Epidemiological Project medical records linkage system, among subjects residing in three mixed rural–urban counties on April 1, 2014. Multivariable analyses adjusted for demographics, socioeconomic status using an individual housing-based measure, and counties.
Results:
The study cohort (percent rural location) included 91,202 (15%) for Olmsted, 10,197 (51%) in Dodge, and 10,184 (57%) in Wabasha counties. On multivariate analysis, 5-year prevalence of mood disorders and obesity was significantly greater for urban compared with rural residents, after adjusting for confounders; odds ratios (95% confidence intervals): 1.21 (1.17–1.26), P < 0.001, and 1.05 (1.01–1.10), P = 0.016, respectively. Observed effects were not modified in additional models adjusted for health care utilization (HCU; ≥1 general medical examination visit and flu vaccination).
Conclusions:
Rural–urban health disparities for burden of mood disorders and obesity are independent of socioeconomic status and HCU in a Midwestern community. It is important to assess potential regional heterogeneity of rural–urban disparities on health outcomes.
In this book, a new approach is pioneered in providing a unified theory in continuum mechanics. General Continuum Mechanics is intended for the beginner, but it develops advanced material covering interdisciplinary subjects. With applications of convective, Lagrangian, and Eulerian coordinates and the first and second laws of thermodynamics, the first-year graduate student will learn solid mechanics and fluid mechanics as an integrated subject. Electromagnetic continuum and relativistic continuum are included. The conservational properties of mass, momentum, and energy on earth and in the universe constitute the ingredients of this book. They are the monumental contributions of Newton, Maxwell, and Einstein, a panorama of beauty of universal laws that evolved over the last four centuries. No boundaries are needed to separate them, but rather we integrate them in harmony and place them in perspective. This is the book for interdisciplinary studies to carry out the modern scientific projects in which engineering, physics, and applied mathematics must be combined.
Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions.
Methods
A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49−51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.
Results
At baseline, the prevalence of VMS (40%, range 13–62%) and depressed mood (26%, 8–41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27–1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47–2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90–1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38–2.34).
Conclusions
Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.
Plant defence systems can be induced by biotic and abiotic stress. Experiments were undertaken to explore the feasibility of different fungal proteins for the reduction of vegetable diseases. Total proteins purified from three soil-borne and five foliar fungal pathogens had no fungistatic effects nor did they trigger hypersensitive reactions on test plants. The abilities to promote plant growth and to reduce disease severity varied among test proteins and plants. Depending on test proteins, experiments have demonstrated that exogenous application of fungal proteins could reduce Alternaria brassicicola-induced black spot severity on cabbage, Colletotrichum spp.-induced anthracnose on Chinese cabbage and cucumber, Rhizoctonia solani-induced damping-off on sweet pepper and Chinese cabbage, and powdery mildew on cucumber seedlings. An Alternariaprotein effector 1 (Ape1)-coding gene was cloned from two Alternaria spp. and expressed in Escherichia coli. The expressed Ape1 reduced anthracnose incidence on cucumber leaves, indicating that Ape1 was the primary activator in the crude protein extracts responsible for disease reduction. Application of Alternaria proteins onto Chinese cabbage seedlings caused an increase of phenylalanine ammonia lyase and peroxidase activities in treated seedlings, which may have played a role in host defence.
The bentgrasses comprise an adaptable group of grasses that include introduced species, cultivated turfgrasses, and native plants in North America. Their distribution in cultural landscapes has not been documented, and this gap in knowledge has limited the development of predictive ecological risk assessments for creeping bentgrass engineered for herbicide resistance. In this study, bentgrass distribution and abundance were surveyed in 289 plots in an 8.5 km2 site surrounding a golf course in the northeastern United States. Four introduced species and two native bentgrasses were identified in seminatural and managed plant communities. Across the study site, 77% of the plots containing creeping bentgrass also had invasive plants. Bentgrasses co-occurred with critical habitat for threatened or endangered animals. Multivariate logistic regression analysis showed that bentgrasses were positively correlated with herbaceous plant cover and mowing, but negatively correlated with tree canopy cover, shrub cover, poorly drained soils, and leaf litter. The most influential ecological factors were tree canopy cover and soil moisture. Geospatial information about these two ecological factors was combined with mathematical models to generate two habitat suitability maps. The favorable environments map (FEM) showed that highly suitable bentgrass habitat covered 36% of the study site and included common features such as home lawns and railroad right-of-ways. Our results suggest that release of herbicide-resistant creeping bentgrass in this cultural landscape could potentially result in pollen-mediated gene flow, interspecific hybridization, environmental hazards, and herbicide selection pressure in some areas. Habitat suitability maps could be critical tools for predictive ecological risk assessments, monitoring projects, and management of herbicide-resistant bentgrasses.
Improving neurocognitive outcomes following treatment for brain metastases have become increasingly important. We propose that a brief telephone-based neurocognitive assessment may improve follow-up cognitive assessments in this palliative population. Aim: To prospectively assess the feasibility and reliability of a telephone based brief neurocognitive assessment compared to the same tests delivered face-to-face. Methods: Brain metastases patients to be treated with whole brain radiotherapy (WBRT) were assessed using a brief validated neurocognitive battery at baseline, at 1 month and 3 months following WBRT (in person and over the phone). The primary outcome was feasibility and inter-procedural (in person versus telephone) reliability. The secondary objective was to evaluate the change in neurocognitive function before and after WBRT. Results: Out of 39 patients enrolled, 82% of patients completed the baseline in-person and telephone neurocognitive assessments. However, at 1 month, only 41% of enrolled patients completed the in-person and telephone cognitive assessments and at 3 months, only 10% of patients completed them. Results pertaining to reliability and change in neurocognitive function will be updated. Conclusion: The pre-defined definition of feasibility (at least 80% completion for face to face and telephone neurocognitive assessments) was met at baseline. However, a large proportion of participants did not complete either telephone or in person neurocognitive follow-up at 1 month and at 3 months post-WBRT. Attrition remained a challenge for neurocognitive testing in this population even when a telephone-based brief assessment was used.
Language use is often disrupted in patients with schizophrenia; novel computational approaches may provide new insights.
Aims
To test word use patterns as markers of the perceptual, cognitive and social experiences characteristic of schizophrenia.
Method
Word counting software was applied to first-person accounts of schizophrenia and mood disorder.
Results
More third-person plural pronouns (‘they’) and fewer first-person singular pronouns (‘I’) were used in schizophrenia than mood disorder accounts. Schizophrenia accounts included fewer words related to the body and ingestion, and more related to religion. Perceptual and causal language were negatively correlated in schizophrenia accounts but positively correlated in mood disorder accounts.
Conclusions
Differences in pronouns suggest decreased self-focus or perhaps even an understanding of self as other in schizophrenia. Differences in how perceptual and causal words are correlated suggest that long-held delusions represent a decreased coupling of explanations with sensory experience over time.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
Enterotoxigenic Escherichia coli (ETEC) is now recognized as a common cause of foodborne outbreaks. This study aimed to describe the first ETEC O169 outbreak identified in Korea. In this outbreak, we identified 1642 cases from seven schools. Retrospective cohort studies were performed in two schools; and case-control studies were conducted in five schools. In two schools, radish kimchi was associated with illness; and in five other schools, radish or cabbage kimchi was found to have a higher risk among food items. Adjusted relative risk of kimchi was 5·87–7·21 in schools that underwent cohort studies; and adjusted odds ratio was 4·52–12·37 in schools that underwent case-control studies. ETEC O169 was isolated from 230 affected students, and was indistinguishable from the isolates detected from the kimchi product distributed by company X, a food company that produced and distributed kimchi to all seven schools. In this outbreak, we found that the risk of a kimchi-borne outbreak of ETEC O169 infection is present in Korea. We recommend continued monitoring regarding food safety in Korea, and strengthening surveillance regarding ETEC O169 infection through implementation of active laboratory surveillance to confirm its infection.
The Night Sky Monitoring Network is a project that aims to study the extent, distribution, and properties of the light pollution condition in the populous metropolis of Hong Kong. Continuous measurements of the Night Sky Brightness (NSB) at strategically chosen locations that cover a wide range of population density and land usage were made, with over 2.5 million NSB readings collected in 18 months up to June 2012. Results from the project are presented, with focus on the contrast between the urban and rural night sky profiles, and light pollution contributions from artificial lightings. This project is supported by the Environment and Conservation Fund of the Hong Kong SAR government (ECF 10/2009, ECF 1/2007).