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The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored.
Aims
To explore the clustering pattern of chronic PCNPS in a cohort of patients having their first COVID infection during the ‘Omicron wave’ and discover phenotypes of patients based on their symptoms’ patterns using a pre-registered protocol.
Method
We assessed 1205 eligible subjects in Hong Kong using app-based questionnaires and cognitive tasks.
Results
Partial network analysis of chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint–fatigue and anxiety–depression) and a minor headache–dizziness cluster, like our pre-Omicron cohort. Participants with high numbers of symptoms could be further grouped into two distinct phenotypes: a cognitive complaint–fatigue predominant phenotype and another with symptoms across multiple clusters. Multiple logistic regression showed that both phenotypes were predicted by the level of pre-infection deprivation (adjusted P-values of 0.025 and 0.0054, respectively). The severity of acute COVID (adjusted P = 0.023) and the number of pre-existing medical conditions predicted only the cognitive complaint–fatigue predominant phenotype (adjusted P = 0.003), and past suicidal ideas predicted only the symptoms across multiple clusters phenotype (adjusted P < 0.001). Pre-infection vaccination status did not predict either phenotype.
Conclusions
Our findings suggest that we should pursue a phenotype-driven approach with holistic biopsychosocial perspectives in disentangling the heterogeneity under the umbrella of chronic PCNPS. Management of patients complaining of chronic PCNPS should be stratified according to their phenotypes. Clinicians should recognise that depression and anxiety cannot explain all chronic post-COVID cognitive symptoms.
Background: Our prior six-year review (n=2165) revealed 24% of patients undergoing posterior decompression surgeries (laminectomy or discectomy) sought emergency department (ED) care within three months post-surgery. We established an integrated Spine Assessment Clinic (SAC) to enhance patient outcomes and minimize unnecessary ED visits through pre-operative education, targeted QI interventions, and early post-operative follow-up. Methods: We reviewed 13 months of posterior decompression data (n=205) following SAC implementation. These patients received individualized, comprehensive pre-operative education and follow-up phone calls within 7 days post-surgery. ED visits within 90 days post-surgery were tracked using provincial databases and compared to our pre-SAC implementation data. Results: Out of 205 patients, 24 (11.6%) accounted for 34 ED visits within 90 days post-op, showing a significant reduction in ED visits from 24% to 11.6%, and decreased overall ED utilization from 42.1% to 16.6% (when accounting for multiple visits by the same patient). Early interventions including wound monitoring, outpatient bloodwork, and prescription adjustments for pain management, helped mitigate ED visits. Patient satisfaction surveys (n=62) indicated 92% were “highly satisfied” and 100% would recommend the SAC. Conclusions: The SAC reduced ED visits after posterior decompression surgery by over 50%, with pre-operative education, focused QI initiatives, and its individualized, proactive approach.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Palmer amaranth with resistance to dicamba, glufosinate, and protoporphyrinogen oxidase inhibitors has been documented in several southern states. With extensive use of these and other herbicides in South Carolina, a survey was initiated in fall 2020 and repeated in fall 2021 and 2022 to determine the relative response of Palmer amaranth accessions to selected preemergence and postemergence herbicides. A greenhouse screening experiment was conducted in which accessions were treated with three preemergence (atrazine, S-metolachlor, and isoxaflutole) and six postemergence (glyphosate, thifensulfuron-methyl, fomesafen, glufosinate, dicamba, and 2,4-D) herbicides at the 1× and 2× use rates. Herbicides were applied shortly after planting (preemergence) or at the 2- to 4-leaf growth stage (postemergence). Percent survival was evaluated 5 to 14 d after application depending on herbicide activity. Sensitivity to atrazine preemergence was lower for 49 and 33 accessions out of 115 to atrazine applied preemergence at the 1× and 2× rate, respectively. Most of the accessions (90%) were controlled by isoxaflutole applied preemergence at the 1× rate. Response to S-metolachlor applied preemergence indicated that 34% of the Palmer amaranth accessions survived the 1× rate (>60% survival). Eleven accessions exhibited reduced sensitivity to fomesafen applied postemergence; however, these percentages were not different from the 0% survivor group. Glyphosate applied postemergence at the 1× rate did not control most accessions (79%). Palmer amaranth response to thifensulfuron-methyl applied postemergence varied across the accessions, with only 36% and 28% controlled at the 1× rate and 2× rate, respectively. All accessions were controlled by 2,4-D, dicamba, or glufosinate when they were applied postemergence. Palmer amaranth accessions from this survey exhibited reduced susceptibility to several herbicides commonly used in agronomic crops in South Carolina. Therefore, growers should use multiple management tactics to minimize the evolution of herbicide resistance in Palmer amaranth in South Carolina.
School connectedness, a construct indexing supportive school relationships, has been posited to promote resilience to environmental adversity. Consistent with prominent calls in the field, we examined the protective nature of school connectedness against two dimensions of early adversity that index multiple levels of environmental exposure (violence exposure, social deprivation) when predicting both positive and negative outcomes in longitudinal data from 3,246 youth in the Fragile Families and Child Wellbeing Study (48% female, 49% African American). Child and adolescent school connectedness were promotive, even when accounting for the detrimental effects of early adversity. Additionally, childhood school connectedness had a protective but reactive association with social deprivation, but not violence exposure, when predicting externalizing symptoms and positive function. Specifically, school connectedness was protective against the negative effects of social deprivation, but the effect diminished as social deprivation became more extreme. These results suggest that social relationships at school may compensate for low levels of social support in the home and neighborhood. Our results highlight the important role that the school environment can play for youth who have been exposed to adversity in other areas of their lives and suggest specific groups that may especially benefit from interventions that boost school connectedness.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Childhood adversity is thought to undermine youth socioemotional development via altered neural function within regions that support emotion processing. These effects are hypothesized to be developmentally specific, with adversity in early childhood sculpting subcortical structures (e.g., amygdala) and adversity during adolescence impacting later-developing structures (e.g., prefrontal cortex; PFC). However, little work has tested these theories directly in humans. Using prospectively collected longitudinal data from the Fragile Families and Child Wellbeing Study (FFCWS) (N = 4,144) and neuroimaging data from a subsample of families recruited in adolescence (N = 162), the current study investigated the trajectory of harsh parenting across childhood (i.e., ages 3 to 9) and how initial levels versus changes in harsh parenting across childhood were associated with corticolimbic activation and connectivity during socioemotional processing. Harsh parenting in early childhood (indexed by the intercept term from a linear growth curve model) was associated with less amygdala, but not PFC, reactivity to angry facial expressions. In contrast, change in harsh parenting across childhood (indexed by the slope term) was associated with less PFC, but not amygdala, activation to angry faces. Increases in, but not initial levels of, harsh parenting were also associated with stronger positive amygdala–PFC connectivity during angry face processing.
Optical tracking systems typically trade off between astrometric precision and field of view. In this work, we showcase a networked approach to optical tracking using very wide field-of-view imagers that have relatively low astrometric precision on the scheduled OSIRIS-REx slingshot manoeuvre around Earth on 22 Sep 2017. As part of a trajectory designed to get OSIRIS-REx to NEO 101955 Bennu, this flyby event was viewed from 13 remote sensors spread across Australia and New Zealand to promote triangulatable observations. Each observatory in this portable network was constructed to be as lightweight and portable as possible, with hardware based off the successful design of the Desert Fireball Network. Over a 4-h collection window, we gathered 15 439 images of the night sky in the predicted direction of the OSIRIS-REx spacecraft. Using a specially developed streak detection and orbit determination data pipeline, we detected 2 090 line-of-sight observations. Our fitted orbit was determined to be within about 10 km of orbital telemetry along the observed 109 262 km length of OSIRIS-REx trajectory, and thus demonstrating the impressive capability of a networked approach to Space Surveillance and Tracking.
Toxoplasma gondii (T. gondii) is an important human disease-causing parasite. In the USA, T. gondii infects >10% of the population, accrues economic losses of US$3.6 billion/year, and ranks as the second leading culprit of foodborne illness-related fatalities. We assessed toxoplasmosis risk among the Old Order Amish, a mostly homogenous population with a high prevalence of T. gondii seropositivity, using a questionnaire focusing on food consumption/preparation behaviours and environmental risk factors. Analyses were conducted using multiple logistic regression. Consuming raw meat, rare meat, or unpasteurised cow or goat milk products was associated with increased odds of seropositivity (unadjusted Odds Ratios: 2.192, 1.613, and 1.718 , respectively). In separate models by sex, consuming raw meat, or consuming unpasteurised cow or goat milk products, was associated with increased odds of seropositivity among women; washing hands after touching meat with decreased odds of seropositivity among women (adjusted OR (AOR): 0.462); and cleaning cat litterbox with increased odds of seropositivity among men (AOR: 5.241). This is the first study to assess associations between behavioural and environmental risk factors and T. gondii seropositivity in a US population with high seroprevalence for T. gondii. Our study emphasises the importance of proper food safety behaviours to avoid the risk of infection.
Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1–15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1–15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.
Antibiotics are overly prescribed in nursing homes. Recent antibiotic stewardship efforts attempt to reduce inappropriate use. Our objective was to describe antibiotic use from 2012 to 2016 among nursing-home residents with various health conditions.
Design:
Retrospective, repeated cross-sectional analysis.
Setting and participants:
All long-term residents in a random 10% sample of national nursing homes: 2,092,809 assessments from 319,615 nursing-home residents in 1,562 nursing homes.
Measurements:
We calculated a 1-day antibiotic prevalence using all annual and quarterly clinical assessments in the Minimum Data Set (MDS) from April 2012 through December 2016. We calculated prevalence of antibiotic use overall and within conditions of interest: Alzheimer’s disease and related dementias (ADRD), advanced cognitive impairment (ACI), and infections likely to be treated with antibiotics. We applied logistic regressions with nursing-home cluster, robust standard errors to assess changes in conditions and antibiotic use 2012–2016.
Results:
Overall, antibiotic use did not change (2012 vs 2016, adjusted odds ratio [AOR], 1.00; 95% CI, 0.97–1.03). Antibiotic use was higher in 2016 versus 2012 among assessments with any infection (AOR, 1.10; 95% CI, 1.04–1.16), urinary tract infection (AOR, 1.18; 95% CI, 1.12–1.25), and no infection (AOR, 1.13; 95% CI, 1.09–1.17). Results were similar by cognitive status.
Conclusions:
The increased proportion of assessments recording antibiotics but no infection may not be clinically appropriate. Higher antibiotic use among infected residents with advanced cognitive impairment is also concerning. Further efforts to understand mechanisms driving these trends and to promote antibiotic stewardship in nursing homes are warranted.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
The mineralogy of the clay fractions of two soil profiles representing the end-members of a catena developed on a glacial till derived from basic lavas has been determined. Particular attention has been given to the assessment of the nature of the amorphous inorganic material in the clay fraction of these soils. Chemical dissolution techniques were used and their effects on the clay fraction were followed by X-ray diffraction, differential thermal, infrared absorption, electron-optical and surface area measurements. The principal conclusion is that the soil clays are a continuum from completely disordered, through poorly ordered to well crystallized material.
The removal of the alkali-soluble fraction from soil clays has been found to influence markedly the efficiency with which iron oxides can be removed from such clays. In clays pretreated with 5% Na2CO3, up to 40% more iron oxide was extracted by dithionite (Na2S2O4) than from soil clays treated with this reagent alone. Chemical analysis, electron microscopy, X-ray and differential thermal examination, and specific surface area and cation-exchange capacity measurements indicated an improved dispersion brought about by the removal of aluminosilicate binding material by Na2CO3. The electron-optical studies also showed that the dithionite-soluble iron was principally in the form of small granules. These were amorphous to X-rays and electrons and chemical analysis of the dithionite-soluble fraction suggested that they were ferruginous complexes containing considerable quantities of silica and alumina.
The Dalradian meta-limestones of the Banffshire coast have been investigated as part of a study of the mineralogy of Scottish sedimentary and metamorphic rocks, the main purpose of which is to assess the extent to which soil minerals are inherited from such parent rocks. Saponite was found to be a common constituent of the non-carbonate fraction. Thin sections of the limestones were examined microscopically and the textural relationships between the saponite and the other minerals, particularly those of undoubted metamorphic origin, suggest that the saponite was formed during the metamorphism. Recent reports of the hydrothermal synthesis of saponite at elevated temperatures and pressures support this hypothesis.
In this paper we undertake a quantitative analysis of the dynamic process by which ice underneath a dry porous debris layer melts. We show that the incorporation of debris-layer airflow into a theoretical model of glacial melting can capture the empirically observed features of the so-called Østrem curve (a plot of the melt rate as a function of debris depth). Specifically, we show that the turning point in the Østrem curve can be caused by two distinct mechanisms: the increase in the proportion of ice that is debris-covered and/or a reduction in the evaporative heat flux as the debris layer thickens. This second effect causes an increased melt rate because the reduction in (latent) energy used for evaporation increases the amount of energy available for melting. Our model provides an explicit prediction for the melt rate and the temperature distribution within the debris layer, and provides insight into the relative importance of the two effects responsible for the maximum in the Østrem curve. We use the data of Nicholson and Benn (2006) to show that our model is consistent with existing empirical measurements.
Functional neurological disorders (FNDs), also known as conversion disorder, are unexplained neurological symptoms unrelated to a neurological cause. The disorder is common, yet poorly understood. The symptoms are experienced as involuntary but have similarities to voluntary processes. Here we studied intention awareness in FND.
Method
A total of 26 FND patients and 25 healthy volunteers participated in this functional magnetic resonance study using Libet's clock.
Results
FND is characterized by delayed awareness of the intention to move relative to the movement itself. The reporting of intention was more precise, suggesting that these findings are reliable and unrelated to non-specific attentional deficits. That these findings were more prominent with aberrant positive functional movement symptoms rather than negative symptoms may be relevant to impairments in timing for an inhibitory veto process. Attention towards intention relative to movement was associated with lower right inferior parietal cortex activity in FND, a region early in the processing of intention. During rest, aberrant functional connectivity was observed with the right inferior parietal cortex and other motor intention regions.
Conclusions
The results converge with observations of low inferior parietal activity comparing involuntary with voluntary movement in FND, emphasizing core deficiencies in intention. Heightened precision of this impaired intention is consistent with Bayesian theories of impaired top-down priors that might influence the sense of involuntariness. A primary impairment in voluntary motor intention at an early processing stage might explain clinical observations of slowed effortful voluntary movement, heightened self-directed attention and underlie functional movements. These findings further suggest novel therapeutic targets.
A relatively lightweight and simple airborne system for surface elevation profiling of glaciers in narrow mountain valleys has been developed and tested. The aircraft position is determined by kinematic global positioning system (GPS) methods. The distance to the glacier surface is determined with a laser ranger. The accuracy is about 0.3 m, sufficient to permit future changes to be observed over short time intervals. Long-term changes can be estimated by comparison of profiles with existing maps. Elevation profiles obtained in 1993–94 from three glaciers in central and south-central Alaska are compared with maps made about 1950. The resulting area-averaged, seasonally corrected thickness changes during the interval are: Gulkana Glacier (central Alaska Range)–11 m, Worthington Glacier (central Chugach Mountains) +7 m, and Bear Lake Glacier (Kenai Mountains) −12 m. All three glaciers retreated during the interval of comparison. The estimated uncertainty in the average thickness change is ±5 m. which is mainly due to errors in the existing maps. Constraints on the accuracy of the maps are obtained by profiling in proglacial areas.
A transverse profile of velocity was measured across Ice Stream B, West Antarctica, in order to determine the role of the margins in the force balance of an active ice stream. The profile extended from near the ice-stream center line, through a marginal shear zone and on to the slow-moving ice sheet. The velocity profile exhibits a high degree of shear deformation within a marginal zone, where intense, chaotic crevassing occurs. Detailed analysis of the profile, using analytical and numerical models of ice flow, leads to the following conclusions regarding the roles of the bed and the margins in ice-stream dynamics:
(i) The overall resistive drag on the ice stream is partitioned nearly equally between the margins and the bed and, thus, both are important in the force balance of the ice stream.
(ii) The ice within the chaotic zone must be about 10 times softer than the ice in the central part of the ice stream.
(iii) The average basal shear stress is 0.06 × 105 Pa. This implies that the entire bed cannot be blanketed by the weak, deformable till observed by Engelhardt and others (1990) near the center of the ice stream — there must be regions of increased basal drag.
(iv) High strain rates and shear stresses in the marginal zones indicate that strain heating in the margins may be significant.
While the exact quantitative values leading to these conclusions are somewhat model and location-dependent, the overall conclusions are robust. As such, they are likely to have importance for ice-stream dynamics in general.