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Longitudinal studies of first episode of psychosis (FEP) patients are critical to understanding the dynamic clinical factors influencing functional outcomes; negative symptoms and verbal memory (VM) deficits are two such factors that remain a therapeutic challenge. This study uses white-gray matter contrast at the inner edge of the cortex, in addition to cortical thickness, to probe changes in microstructure and their relation with negative symptoms and possible intersections with verbal memory.
T1-weighted images and clinical data were collected longitudinally for patients (N = 88) over a two-year period. Cognitive data were also collected at baseline. Relationships between baseline VM (immediate/delayed recall) and rate of change in two negative symptom dimensions, amotivation and expressivity, were assessed at the behavioral level, as well as at the level of brain structure.
VM, particularly immediate recall, was significantly and positively associated with a steeper rate of expressivity symptom decline (r = 0.32, q = 0.012). Significant interaction effects between baseline delayed recall and change in expressivity were uncovered in somatomotor regions bilaterally for both white-gray matter contrast and cortical thickness. Furthermore, interaction effects between immediate recall and change in expressivity on cortical thickness rates were uncovered across higher-order regions of the language processing network.
This study shows common neural correlates of language-related brain areas underlying expressivity and VM in FEP, suggesting deficits in these domains may be more linked to speech production rather than general cognitive capacity. Together, white-gray matter contrast and cortical thickness may optimally inform clinical investigations aiming to capture peri-cortical microstructural changes.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Introduction: Although use of point of care ultrasound (PoCUS) protocols for patients with undifferentiated hypotension in the Emergency Department (ED) is widespread, our previously reported SHoC-ED study showed no clear survival or length of stay benefit for patients assessed with PoCUS. In this analysis, we examine if the use of PoCUS changed fluid administration and rates of other emergency interventions between patients with different shock types. The primary comparison was between cardiogenic and non-cardiogenic shock types. Methods: A post-hoc analysis was completed on the database from an RCT of 273 patients who presented to the ED with undifferentiated hypotension (SBP <100 or shock index > 1) and who had been randomized to receive standard care with or without PoCUS in 6 centres in Canada and South Africa. PoCUS-trained physicians performed scans after initial assessment. Shock categories and diagnoses recorded at 60 minutes after ED presentation, were used to allocate patients into subcategories of shock for analysis of treatment. We analyzed actual care delivered including initial IV fluid bolus volumes (mL), rates of inotrope use and major procedures. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: Although there were expected differences in the mean fluid bolus volume between patients with non-cardiogenic and cardiogenic shock, there was no difference in fluid bolus volume between the control and PoCUS groups (non-cardiogenic control 1878 mL (95% CI 1550 – 2206 mL) vs. non-cardiogenic PoCUS 1687 mL (1458 – 1916 mL); and cardiogenic control 768 mL (194 – 1341 mL) vs. cardiogenic PoCUS 981 mL (341 – 1620 mL). Likewise there were no differences in rates of inotrope administration, or major procedures for any of the subcategories of shock between the control group and PoCUS group patients. The most common subcategory of shock was distributive. Conclusion: Despite differences in care delivered by subcategory of shock, we did not find any significant difference in actual care delivered between patients who were examined using PoCUS and those who were not. This may help to explain the previously reported lack of outcome difference between groups.
Introduction: Point of care ultrasound has been reported to improve diagnosis in non-traumatic hypotensive ED patients. We compared diagnostic performance of physicians with and without PoCUS in undifferentiated hypotensive patients as part of an international prospective randomized controlled study. The primary outcome was diagnostic performance of PoCUS for cardiogenic vs. non-cardiogenic shock. Methods: SHoC-ED recruited hypotensive patients (SBP < 100 mmHg or shock index > 1) in 6 centres in Canada and South Africa. We describe previously unreported secondary outcomes relating to diagnostic accuracy. Patients were randomized to standard clinical assessment (No PoCUS) or PoCUS groups. PoCUS-trained physicians performed scans after initial assessment. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses including shock category were recorded at 0 and 60 minutes. Final diagnosis was determined by independent blinded chart review. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: 273 patients were enrolled with follow-up for primary outcome completed for 270. Baseline demographics and perceived category of shock were similar between groups. 11% of patients were determined to have cardiogenic shock. PoCUS had a sensitivity of 80.0% (95% CI 54.8 to 93.0%), specificity 95.5% (90.0 to 98.1%), LR+ve 17.9 (7.34 to 43.8), LR-ve 0.21 (0.08 to 0.58), Diagnostic OR 85.6 (18.2 to 403.6) and accuracy 93.7% (88.0 to 97.2%) for cardiogenic shock. Standard assessment without PoCUS had a sensitivity of 91.7% (64.6 to 98.5%), specificity 93.8% (87.8 to 97.0%), LR+ve 14.8 (7.1 to 30.9), LR- of 0.09 (0.01 to 0.58), Diagnostic OR 166.6 (18.7 to 1481) and accuracy of 93.6% (87.8 to 97.2%). There was no significant difference in sensitivity (-11.7% (-37.8 to 18.3%)) or specificity (1.73% (-4.67 to 8.29%)). Diagnostic performance was also similar between other shock subcategories. Conclusion: As reported in other studies, PoCUS based assessment performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test. However performance was similar to standard (non-PoCUS) assessment, which was excellent in this study.
There is a growing interest in the use of alternative fuels in gas turbine engines to reduce emissions. Testing of alternative fuels is expensive when done on a large-scale gas turbine engine. In this study, a re-commissioned small gas turbine auxiliary power unit (APU) has been used to test various blends of Jet A-1, synthetic paraffinic kerosene (SPK) and diesel with as well as eight other novel fuels. A detailed analysis of performance, gaseous emissions and particulate emissions has been presented in this study. It is observed that aromatic content in general as well as the particular chemical composition of the aromatic compound plays a vital role in particulate emissions generation. SPK fuel shows substantially lower particulate emissions with respect to Jet A. However, not all the species of aromatics negatively impact particulate emissions. Gaseous emissions measured are comparable for all the fuels tested in this study.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
Environmental risk factors for dementia are poorly understood. Aluminium and fluorine in drinking water have been linked with dementia but uncertainties remain about this relationship.
In the largest longitudinal study in this context, we set out to explore the individual effect of aluminium and fluoride in drinking water on dementia risk and, as fluorine can increase absorption of aluminium, we also examine any synergistic influence on dementia.
We used Cox models to investigate the association between mean aluminium and fluoride levels in drinking water at their residential location (collected 2005–2012 by the Drinking Water Quality Regulator for Scotland) with dementia in members of the Scottish Mental Survey 1932 cohort who were alive in 2005.
A total of 1972 out of 6990 individuals developed dementia by the linkage date in 2012. Dementia risk was raised with increasing mean aluminium levels in women (hazard ratio per s.d. increase 1.09, 95% CI 1.03–1.15, P < 0.001) and men (1.12, 95% CI 1.03–1.21, P = 0.004). A dose-response pattern of association was observed between mean fluoride levels and dementia in women (1.34, 95% CI 1.28–1.41, P < 0.001) and men (1.30, 95% CI 1.22–1.39, P < 0.001), with dementia risk more than doubled in the highest quartile compared with the lowest. There was no statistical interaction between aluminium and fluoride levels in relation with dementia.
Higher levels of aluminium and fluoride were related to dementia risk in a population of men and women who consumed relatively low drinking-water levels of both.
The days of Debye-Scherrer film as a recording medium for X-ray powder patterns are all but gone with the development of precise, high sensitivity diffractometer systems. However, film does present some advantages over diffractometry (digital positioning and recording) for certain applications, A scanning densitometer system is described which totally automates the analysis of Debye-Scherrer film. It is much more precise and more capable than the simple line readers available in the past and can reduce the analysis time of complicated patterns from hours to minutes.
OBJECTIVES/SPECIFIC AIMS: The objective of this project is to determine whether HRV, collected peri-operatively, is predictive of cognitive decline among older adults who undergo elective surgery/anesthesia. METHODS/STUDY POPULATION: This project is a part of the ongoing INTUIT/PRIME study, which is collecting pre- and post-operative cognitive testing, fMRI imaging, CSF samples, and EEG recordings from 200 older adults (age ≥ 60) undergoing elective non-cardiac/non-neurologic surgery scheduled to last > 2 hours at Duke University Medical Center and Duke Regional Hospital. This project utilizes data from the first 60 INTUIT participants who contributed continuous heart rate data before and during surgery. Participants undergo cognitive testing prior to surgery (baseline) and at 6 weeks after surgery. Our primary dependent variable is the change in the composite score from baseline to 6-weeks. Delirium is assessed in the hospital with the twice daily 3D-CAM tool, so we will report the proportion of individuals with 6-week cognitive decline who exhibited delirium in the days following surgery. Participants’ echocardiogram (ECG) recordings are extracted pre- and intraoperatively from B650/B850 patient monitors with VSCapture software. HRV is defined as the variability between successive R-spikes or inter-beat-intervals on ECG. RESULTS/ANTICIPATED RESULTS: We anticipate that lower intraoperative HRV is associated with worse cognitive decline at 6 weeks after surgery. As secondary objectives, we will determine whether pre-operative HRV or change in HRV (from pre-operative to intra-operative measures) are predictive of cognitive decline after surgery. We expect that in-hospital delirium will be detected in a higher proportion of those with 6-week cognitive decline, compared to those with stable or improved cognition at 6 weeks. DISCUSSION/SIGNIFICANCE OF IMPACT: HRV may address the present need for pre- and intra-operative cognitive risk stratification in the elderly. Physiological indices like HRV have the potential to dramatically change our understanding of CI in older adults undergoing surgery, as they offer an accessible, cost-effective, and non-invasive means whereby clinicians, particularly those unfamiliar with the nuances of geriatric and CI/dementia-related care, can monitor patients and refer those at high-risk of CI after surgery for early intervention.
Healthcare organizations are required to provide workers with respiratory protection (RP) to mitigate hazardous airborne inhalation exposures. This study sought to better identify gaps that exist between RP guidance and clinical practice to understand issues that would benefit from additional research or clarification.
Current work in multicultural competency has emphasized factors such as race and ethnicity, age, disability status, socioeconomic status, sexual orientation and gender. For those clinicians who work with military and veteran populations, grounding in military cultural competence is also critical as a prerequisite for providing quality care. We believe that engaging these populations from a specifically cognitive behavioural orientation allows bridging of cultural gaps and that there is a natural alignment between cognitive behavioural therapy (CBT) and many aspects of warrior culture. This paper outlines several factors related to the values of military culture and strategies of the CBT therapist to better understand and use these values effectively in clinical practice, including lessons learned from an intensive outpatient program providing speciality care to veterans and military service members.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
Middle-third helical rim defects may arise from trauma or oncological resection, and pose a challenging reconstructive problem. Reconstructing defects larger than 2 cm using traditional methods commits patients to the inconvenience of staged procedures.
This paper describes a single-stage helical rim reconstruction technique using a post-auricular bipedicled flap and ipsilateral conchal cartilage graft for delayed middle-third helical rim reconstruction.
Two examples of this technique used in post-trauma and oncological reconstruction cases are presented, with pre- and post-operative photographs provided for demonstration.
Contralateral graft harvest and staged operations for helical rim reconstruction are associated with donor site morbidity and the inconvenience of multiple operations to achieve the desired reconstructive outcome. Our single-stage helical rim reconstruction technique was well tolerated by patients, and showed satisfactory aesthetic results in terms of size and symmetry.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.