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Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions (ADRs). Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2 + antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of ADRs: QT interval prolongation, hyperprolactinaemia, and increased body weight [body mass index (BMI) ⩾ 25].
Methods
We extracted anonymised EHR data. Patients aged 16 + receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively.
Results
We identified 35 409 observations of antipsychotic prescribing among 13 391 patients. Compared with antipsychotic monotherapy, APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% CI 1.87–3.24) and of registering a BMI > 25 (adjusted odds ratio 1.75; 95% CI 1.33–2.31) in the period following the APP prescribing.
Conclusions
Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.
The new mineral flaggite (IMA2021-044), Pb4Cu2+4Te6+2(SO4)2O11(OH)2(H2O), occurs at the Grand Central mine in the Tombstone district, Cochise County, Arizona, USA, in cavities in quartz matrix in association with alunite, backite, cerussite, jarosite and rodalquilarite. Flaggite crystals are lime-green to yellow-green tablets, up to 0.5 mm across. The mineral has a very pale green streak and adamantine lustre. It is brittle with irregular fracture and a Mohs hardness of ~3. It has one excellent cleavage on {010}. The calculated density is 6.137 g cm–3. Optically, the mineral is biaxial (+) with α = 1.95(1), β = 1.96(1), γ = 2.00(1) (white light); 2V = 54(2)°; pleochroism: X green, Y light yellow green, Z nearly colourless; X > Y > Z. The Raman spectrum exhibits bands consistent with TeO6 and SO4. Electron microprobe analysis provided the empirical formula Pb3.88Cu2+3.89Te6+2.08(SO4)2O11(OH)2(H2O) (–0.03 H). Flaggite is triclinic, P1, a = 9.5610(2), b = 9.9755(2), c = 10.4449(3) Å, α = 74.884(1), β = 89.994(1), γ = 78.219(1)°, V = 939.97(4) Å3 and Z = 2. The structure of flaggite (R1 = 0.0342 for 5936 I > 2σI) contains hexagonal-close-packed, stair-step-like layers comprising TeO6 octahedra and Jahn-Teller distorted CuO6 octahedra. The layers in the structure of flaggite are very similar to those in bairdite, timroseite and paratimroseite.
To investigate the downstream rim seal gas ingestion characteristics of a 1.5-stage turbine, the URANS equations were solved numerically using the SST turbulence model. The effects of different purge flow rates and the second vane on the ingestion characteristics of the aft cavity and the nonuniform fluctuations of the main gas path pressure are analysed. The results showed that the aft cavity is affected by the combined effects of the blade and the second vane, and the potential field at the leading edge of the second vane greatly influence the airflow variation in the aft cavity, which enhances the ingress of the mainstream into the wheel-space. The front purge flow weakens the egress between the suction side of the blade and the suction side of the second vane. The potential field at the leading edge of the second vane suppresses the nonuniform distribution of airflow in the aft cavity caused by the rotational effect of the blade.
Informal carers play an essential role in the care of individuals with Parkinson’s disease (PD). This role, however, is often fraught with difficulties, including emotional, physical, and financial. Coping styles and relationship quality have been hypothesized to influence the impact of stressors. The aim of this study is to examine the relationship between carers’ coping style, relationship quality, and carer burden.
Design:
Cross-sectional.
Participants:
Thirty-nine PD patient carer dyads were included in the study.
Measurements:
Participants completed self-rated questionnaires including the Dyadic Adjustment Scale, Zarit Burden Interview, and Brief Coping Orientation to Problems Experienced Inventory.
Results:
Correlational analyses found significant and positive correlation between carer burden and all three coping styles (problem-focused, emotion-focused, and dysfunctional). There was also a moderate association between carers’ perceived relationship quality and satisfaction and carer burden. Regression analyses found that carer’s gender, severity of PD, relationship quality, emotion-focused, and dysfunctional coping styles did not predict carer burden. Conversely, problem-focused coping style predicted carer burden.
Conclusion:
The results highlight that there is no perfect way to react and care for a loved one and serves as important information for practitioners who design and implement interventions.
Enhanced fluctuations, steep gradients, and intensified heat transfer are characteristics of wall-bounded turbulence at transcritical conditions. Although such conditions are prevalent in numerous technical applications, the structure of the thermal boundary layer under realistic density gradients and heating conditions remains poorly understood. Specifically, statistical descriptions of the temperature field in such flows are provided inconsistently using existing models. To address this issue, direct numerical simulations are performed by considering fully developed transcritical turbulent channel flow at pressure and temperature conditions that cause density changes of a factor of up to $O(20)$ between the hot and cold walls. As a consequence of the proximity of the Widom line to the hot wall, significant asymmetries are observed when comparing regions near the cold wall and near the hot wall. Previous transformations that attempt to collapse the near-wall mean temperature profiles among different cases to a single curve are examined. By addressing model deficiencies of these transformations, a formulation for an improved mean temperature transformation is proposed, with appropriate considerations for real fluid effects that involve strong variations in thermodynamic quantities. Our proposed transformation is shown to perform well in collapsing the slope of the logarithmic region to a single universal value with reduced uncertainty. Coupled with a predictive framework to estimate the non-universal shift parameter of the logarithmic region using a priori information, our transformation provides an analytic profile to model the near-wall mean temperature. These results thus provide a framework to guide the development of models for wall-bounded transcritical turbulence.
Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:
– high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;
– putative fossils on Mars will likely be ambiguous biomarkers for life;
– microbial contamination resulting from human habitation is unavoidable; and
– based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.
Some of the outstanding questions are:
– which interpretation of the hemispheric dichotomy of the planet is correct;
– to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;
– in what abundance are carbonates formed by atmospheric processes;
– what properties of martian meteorites could be used to constrain their source locations;
– the origin(s) of organic macromolecules;
– was/is Mars inhabited;
– how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;
– how can we ensure that humans and microbes form a stable and benign biosphere; and
– should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?
Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.
The pandemic caused by severe acute respiratory coronavirus virus 2 (SARS-CoV-2) has dramatically increased cheshospitalizations, and it is often difficult to determine whether there is a bacterial or fungal coinfection at time of presentation. In this study, we sought to determine the rates of coinfection and utilization of antibiotics in SARS-CoV-2 disease.
Methods:
Retrospective chart review of patients hospitalized with COVID-19 pneumonia from April 13, 2020, to July 14, 2020.
Results:
In total, 277 patients were hospitalized for COVID-19 pneumonia during this period. Patients that received antibiotics within 48 hours of presentation were more likely to be febrile (59.3% vs 41.2%; P = .01) and to have leukocytosis (23.9% vs 5.9%; P < .01) and were less likely to have a procalcitonin level <0.25 ng/mL (58.8% vs 74.5%; P = .04). In total, 45 patients had positive blood cultures collected during hospitalization, 16 of which were clinically significant. Of the clinically significant blood cultures, 5 were collected <48 hours of admission. Moreover, 18 sputum cultures were clinically significant, 2 of which were collected within 48 hours of admission.
Conclusion:
Bacterial and fungal coinfections in COVID-19 appear to be rare on presentation; thus, this factor may be a good target for enhanced antibiotic stewardship.
Frequent freezing injury greatly influences winter wheat production; thus, effective prevention and a command of agricultural production are vital. The freezing injury monitoring method integrated with ‘3S’ (geographic information systems (GIS), global positioning system (GPS) and remote sensing (RS)) technology has an unparalleled advantage. Using HuanJing (HJ)-1A/1B satellite images of a winter wheat field in Shanxi Province, China plus a field survey, crop types and winter wheat planting area were identified through repeated visual interpretations of image information and spatial analyses conducted in GIS. Six vegetation indices were extracted from processed HJ-1A/1B satellite images to determine whether the winter wheat suffered from freezing injury and its degree of severity and recovery, using change vector analysis (CVA), the freeze injury representative vegetation index and the combination of the two methods, respectively. Accuracy of the freezing damage classification results was verified by determining the impact of freezing damage on yield and quantitative analysis. The CVA and the change of normalized difference vegetation index (ΔNDVI) monitoring results were different so a comprehensive analysis of the combination of CVA and ΔNDVI was performed. The area with serious freezing injury covered 0.9% of the total study area, followed by the area of no freezing injury (3.5%), moderate freezing injury (10.2%) and light freezing injury (85.4%). Of the moderate and serious freezing injury areas, 0.2% did not recover; 1.2% of the no freezing injury and light freezing injury areas showed optimal recovery, 15.6% of the light freezing injury and moderate freezing injury areas showed poor recovery, and the remaining areas exhibited general recovery.
Background: Embolization represents a minimally invasive treatment modality for arteriovenous malformations (AVMs), tumors, aneurysms, and vessel sacrifice, but can be limited by currently available embolization agents. Discovery of new and improved agents could lead to better treatment outcomes. The goal of this project was to develop and test a novel embolization agent using hydrogels, a class of materials which may be bioengineered to suit a variety of indications. Methods: We devised a method of liquid hydrogel embolization with photo-modulated crosslinking for intravascular solidification, using a custom microcatheter set-up. We tested this in swine blood vessels (n=3), the swine renal arterial trees as a vascular tumor model (n=5), and the swine arterial-arterial networks of the rete mirabile as an AVM model (n=3). Hydrogel embolization was assessed for treatment efficacy and safety. Follow-up angiography was performed at 2-4 week intervals. Results: Hydrogel embolization was technically successful in all animals, with full occlusion of the vascular target immediately following embolization and at follow-up. There were no instances of clinical or angiographic complications. Conclusions: We demonstrated a novel method of dynamic photomodulation and delivery of bioengineered hydrogels to address current limitations of endovascular embolization therapies. This promising technology will be investigated further with longer-term comparative animal trials.
Background: The mechanism of aneurysmal healing after flow-diversion treatment of cerebral aneurysms remains unknown. The purpose of this research to is to utilize a novel technology called endovascular optical coherence tomography (OCT) to characterise and improve our understanding of aneurysmal healing after flow-diversion using a rabbit aneurysm model. Methods: Saccular aneurysms were created in 10 New Zealand white rabbits. The aneurysms were treated with a flow-diverting stent 28 days after creation. OCT and histopathologic examinations included: luminal thrombosis, endothelial loss, inflammation, fibrin, smooth muscle cell loss, disruption of the internal and external elastic lamina, and tunica adventitia changes Results: OCT revealed endothelialization across the stent, appearing to originate from the parent vessel, along with small amounts of thrombus on the stent-struts. Minimal thrombus was visualized within the aneurysm sac. Histologic examination revealed that OCT can accurately define endothelialization across the sent, and define patent segments across the neck. Conclusions: Aneurysmal healing appears to originate at the parent vessel/stent interface, and use the stent as a scaffold to grow across the neck of the aneurysm. Minimal thrombus was visualized within the aneurysm sac, with ongoing flow observed in the setting of incomplete neck endothelialization. This technology has great potential for assessing aneurysmal healing in real-time.
This study investigated the audiometric and sound localisation results in patients with conductive hearing loss after bilateral Bonebridge implantation.
Method
Eight patients with congenital microtia and atresia supplied with bilateral Bonebridge devices were enrolled in this study. Hearing tests and sound localisation were tested under unaided, unilateral and bilateral aided conditions.
Results
Mean functional gain was higher with a bilateral fitting than with a unilateral fitting, especially at 1.0–4.0 kHz (p < 0.05, both). The improvement in speech reception threshold in noise with a bilateral fitting was a 2.3 dB higher signal-to-noise ratio compared with unilateral fitting (p < 0.05). Bilateral fitting had better sound localisation than unilateral fitting (p <0.001). Four participants who attended follow up showed improved sound localisation ability after one year.
Conclusion
Patients demonstrated better hearing threshold, speech reception thresholds in noise and directional hearing with bilateral Bonebridge devices than with a unilateral Bonebridge device. Sound localisation ability with bilateral Bonebridge devices can be improved through long-term training.
Prior investigation of adult patients with obsessive compulsive disorder (OCD) has found greater functional connectivity within orbitofrontal–striatal–thalamic (OST) circuitry, as well as altered connectivity within and between large-scale brain networks such as the cingulo-opercular network (CON) and default mode network (DMN), relative to controls. However, as adult OCD patients often have high rates of co-morbid anxiety and long durations of illness, little is known about the functional connectivity of these networks in relation to OCD specifically, or in young patients near illness onset.
Methods
In this study, unmedicated female patients with OCD (ages 8–21 years, n = 23) were compared to age-matched female patients with anxiety disorders (n = 26), and healthy female youth (n = 44). Resting-state functional connectivity was used to determine the strength of functional connectivity within and between OST, CON, and DMN.
Results
Functional connectivity within the CON was significantly greater in the OCD group as compared to the anxiety and healthy control groups. Additionally, the OCD group displayed greater functional connectivity between OST and CON compared to the other two groups, which did not differ significantly from each other.
Conclusions
Our findings indicate that previously noted network connectivity differences in pediatric patients with OCD were likely not attributable to co-morbid anxiety disorders. Moreover, these results suggest that specific patterns of hyperconnectivity within CON and between CON and OST circuitry may characterize OCD relative to non-OCD anxiety disorders in youth. This study improves understanding of network dysfunction underlying pediatric OCD as compared to pediatric anxiety.
Metformin is widely used in pregnancy, despite lack of long-term safety for children. We hypothesised that metformin exposure in utero is associated with increased cardiovascular risk. We tested this hypothesis in a follow-up study of children born to obese mothers who had participated in a randomised controlled trial of metformin versus placebo in pregnancy (EMPOWaR). We measured body composition, peripheral blood pressure (BP), arterial pulse wave velocity and central haemodynamics (central BP and augmentation index) using an oscillometric device in 40 children of mean (SD) age 5.78 (0.93) years, exposed to metformin (n = 19) or placebo (n = 21) in utero. There were no differences in any of the anthropometric or vascular measures between metformin and placebo-exposed groups in univariate analyses, or after adjustment for potential confounders including the child’s behaviour, diet and activity levels. Post-hoc sample size calculation indicated we would have detected large clinically significant differences between the groups but would need an unfeasible large number to detect possible subtle differences in key cardiovascular risk parameters in children at this age of follow-up. Our findings suggest no evidence of increased cardiovascular risk in children born to obese mothers who took metformin in pregnancy and increase available knowledge of the long-term safety of metformin on childhood outcomes.
Cube arrays are one of the most extensively studied types of surface roughness, and there has been much research on cubical roughness with low-to-moderate surface coverage densities. In order to help populate the literature of flow over cube arrays with high surface coverage densities, we conduct direct numerical simulations (DNSs) of flow over aligned cube arrays with coverage densities $\lambda =0.25$ (for validation and comparison purposes), $0.5$, $0.6$, $0.7$, $0.8$ and $0.9$. The roughness are in the d-type roughness regime. Essential flow quantities, including the mean velocity profiles, Reynolds stresses, dispersive stresses and roughness properties, are reported. Special attention is given to secondary turbulent motions in the roughness sublayer. The spanwise-alternating pattern of the thin slots between two neighbouring cubes gives rise to spanwise-alternating regions of low- and high-momentum pathways above the cube crests. We show that the strength and spanwise location of these low- and high-momentum pathways depend on the surface coverage density, and that the high-momentum pathways are not necessarily located directly above the roughness elements. In order to determine the physical processes responsible for the generation and the destruction of these secondary turbulent motions, we analyse the dispersive kinetic energy (DKE) budget. The data shows that the secondary motions get their energy from the DKE-specific production term and the wake production term, and lose energy to the DKE-specific dissipation term.
Global health disasters are on the rise and can occur at any time with little advance warning, necessitating preparation. The authors created a comprehensive evidence-based Emergency Preparedness Training Program focused on long-term retention and sustained learner engagement.
Method:
A prospective observational study was conducted of a simulation-based mass casualty event training program designed using an outcomes-based logic model. A total of 25 frontline healthcare workers from multiple hospital sites in the New York metropolitan area participated in an 8-hour immersive workshop. Data was collected from assessments, and surveys provided to participants 3 weeks prior to the workshop, immediately following the workshop, and 3 months after completion of the workshop.
Results:
The mean percentage of total knowledge scores improved across pre-workshop, post-workshop and retention (3 months post-workshop) assessments (53.2% vs. 64.8% vs. 67.6%, P < 0.05). Average comfort scores in the core MCI competencies increased across pre-workshop, post-workshop and retention self-assessments (P < 0.01). Of the participants assessed at 3 months retention (n = 14, 56%), 50.0% (n = 7) assisted in updating their hospital’s emergency operations plan and 50.0% (n = 7) pursued further self-directed learning in disaster preparedness medicine.
Conclusions:
The use of the logic model provided a transparent framework for the design, implementation, and evaluation of a competency-based EPT program at a single academic center.
Separating and reattaching turbulent flows induced by a forward-facing step subjected to an incoming fully developed turbulent channel flow are studied using direct numerical simulation. The step height is one quarter of the channel height, and the Reynolds number based on friction velocity and half-channel height at the inlet is 180. The three-dimensional spatio-temporal characteristics of separation bubbles upstream and downstream of the step are analysed with particular attention to the effects of impinging hairpin structures and the topology of principal stretching. Immediately upstream of the step, the fluctuating vorticity parallel to the mean streamlines is significant. On the frontal surface of the step, strong spanwise skin friction appears in the form of alternating positive and negative values in vertical strips. Over the step, the principal stretching switches orientation along a curve emanating from the leading edge, which is termed the principal stretching line (PSL). The reverse flows upstream and downstream of the step possess dominant and harmonic frequencies that mirror those of the incoming flow. As a hairpin structure leans over the step, the associated vorticity is deformed by the principal stretching. Specifically, PSL marks the lower bound of the deformed hairpin legs, and an opposite-signed pair of counter-rotating quasi-streamwise vortices are induced near the top surface of the step. Consequently, the separation bubbles upstream of and over the step are enlarged and suppressed, respectively. For a sufficiently strong hairpin structure interacting with the step, an open-type separation occurs upstream of the step, while dual separation bubbles appear over the step.
Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumefactive lesion with unclear pathogenesis. It is diagnosed by pathological findings of the typical histological features that include granular amorphous cores with palisading spindle to epithelioid cells, variable fibrous stroma, foreign-body reaction with giant cells, and calcification/ossification occasionally with psammoma bodies. However, its histopathology may be variable and currently immunohistochemistry plays a limited role in its diagnosis and understanding the pathogenesis. In this study, we examined 6 cases of CAPNONs including 3 intracranial and 3 spinal epidural lesions (age range: 59–69 years; 3 males and 3 females). Immunohistochemistry revealed that all CAPNON cores contain abundant positive deposits of neurofilament protein (NFP), which was supported by electron microscopy finding of filaments (8–13 nm in diameter). In comparison, no NFP positivity was found in 5 psammomatous/metaplastic meningiomas or 7 intervertebral tissue lesions with calcification/ossification. In addition, CAPNON cellular areas showed variable numbers of CD8+ cytotoxic T-cells with less CD4+ T-cells and a decreased ratio of CD4/CD8+ cells, versus the intervertebral tissue lesions without CD8+ or CD4+ cells. Our findings suggest that NFP may be a principal constituent of CAPNONs, and thus involved in the pathogenesis of CAPNON. Given the decreased CD4/CD8 ratio, the pathogenic process of CAPNON is possibly immune- mediated.
LEARNING OBJECTIVES
The presentation will enable the learner to:
1. Discuss histopathological features of calcifying pseudoneoplasm of the neuraxis (CAPNON) with variation of non-core components.
2. Explore diagnostic and pathogenic roles of immunohistochemical markers including neurofilament protein and CD4/CD8 in CAPNON.