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Using [18F]altanserin, a serotonin 2A receptor (5-HT2AR) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HT2AR binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HT2AR agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HT2AR and neuroticism are both modulated by HPA axis function.
Aims
In this study, we examined whether the association between 5-HT2AR binding and the inward facets of neuroticism can be replicated in an independent healthy cohort using the new 5-HT2AR agonist tracer [11C]Cimbi-36, and if their association is moderated by cortisol awakening response (CAR), an index of HPA axis function. If so, this could advance mechanistic insights into interventions that target the 5-HT2AR and reduce neuroticism.
Method
Eighty healthy volunteers underwent [11C]Cimbi-36 PET scans and completed the NEO personality inventory (NEO-PI-R) for the assessment of neuroticism. Salivary samples were available for determination of CAR in 70 of the participants. Using linear latent variable models, we evaluated the association between 5-HT2AR binding and inward facets of neuroticism, namely depression, anxiety, self-consciousness and vulnerability to stress, and whether CAR moderated this association.
Results
The study confirms the positive association between 5-HT2AR binding and the inward facets of neuroticism (β = 0.01, 95% CI = [0.0005: 0.02], P = 0.04), and this association is independent of CAR (P = 0.33).
Conclusions
The findings prompt consideration of whether novel interventions such as psilocybin that actively targets 5-HT2AR and causes changes in personality could be particularly beneficial if implemented as a targeted approach based on neuroticism profiles.
There is a significant contribution of genetic factors to the etiology of bipolar disorder (BD). Unaffected first-degree relatives of patients (UR) with BD are at increased risk of developing mental disorders and may manifest cognitive impairments and alterations in brain functional and connective dynamics, akin to their affected relatives.
Methods
In this prospective longitudinal study, resting-state functional connectivity was used to explore stable and progressive markers of vulnerability i.e. abnormalities shared between UR and BD compared to healthy controls (HC) and resilience i.e. features unique to UR compared to HC and BD in full or partial remission (UR n = 72, mean age = 28.0 ± 7.2 years; HC n = 64, mean age = 30.0 ± 9.7 years; BD patients n = 91, mean age = 30.6 ± 7.7 years). Out of these, 34 UR, 48 BD, and 38 HC were investigated again following a mean time of 1.3 ± 0.4 years.
Results
At baseline, the UR showed lower connectivity values within the default mode network (DMN), frontoparietal network, and the salience network (SN) compared to HC. This connectivity pattern in UR remained stable over the follow-up period and was not present in BD, suggesting a resilience trait. The UR further demonstrated less negative connectivity between the DMN and SN compared to HC, abnormality that remained stable over time and was also present in BD, suggesting a vulnerability marker.
Conclusion
Our findings indicate the coexistence of both vulnerability-related abnormalities in resting-state connectivity, as well as adaptive changes possibly promoting resilience to psychopathology in individual at familial risk.
Persistent cognitive deficits are prevalent in patients with bipolar disorder (BD) and unipolar disorder (UD), but treatments effectively targeting cognition in these mood disorders are lacking. This is partly due to poor insight into the neuronal underpinnings of cognitive deficits.
Methods
The aim of this functional magnetic resonance imaging (fMRI) study was to investigate the neuronal underpinnings of working memory (WM)-related deficits in somatically healthy, remitted patients with BD or UD (n = 66) with cognitive and functional impairments compared to 38 healthy controls (HC). The participants underwent neuropsychological testing and fMRI, while performing a visuospatial and a verbal N-back WM paradigm.
Results
Relative to HC, patients exhibited hypo-activity across dorsolateral prefrontal cortex as well as frontal and parietal nodes of the cognitive control network (CCN) and hyper-activity in left orbitofrontal cortex within the default mode network (DMN) during both visuospatial and verbal WM performance. Verbal WM-related response in the left posterior superior frontal gyrus (SFG) within CCN was lower in patients and correlated positively with out-of-scanner executive function performance across all participants.
Conclusions
Our findings suggest that cognitive impairments across BD and UD are associated with insufficient recruitment of task-relevant regions in the CCN and down-regulation of task-irrelevant orbitofrontal activity within the DMN during task performance. Specifically, a lower recruitment of the left posterior SFG within CCN during verbal WM was associated with lower cognitive performance.
To describe outcomes of acute coronavirus disease 2019 in paediatric and young adult patients with underlying cardiac disease and evaluate the association between cardiac risk factors and hospitalisation.
Study design
We conducted a retrospective single-institution review of patients with known cardiac disease and positive severe acute respiratory syndrome coronavirus 2 RT-PCR from 1 March, 2020 to 30 November, 2020. Extracardiac comorbidities and cardiac risk factors were compared between those admitted for coronavirus disease 2019 illness and the rest of the cohort using univariate analysis.
Results
Forty-two patients with a mean age of 7.7 ± 6.7 years were identified. Six were 18 years of age or more with the oldest being 22 years of age. Seventy-six percent were Hispanic. The most common cardiac diagnoses were repaired cyanotic (n = 7, 16.6%) and palliated single ventricle (n = 7, 16.6%) congenital heart disease. Fourteen patients (33.3%) had underlying syndromes or chromosomal anomalies, nine (21%) had chronic pulmonary disease and eight (19%) were immunosuppressed. Nineteen patients (47.6%) reported no symptoms. Sixteen (38.1%) reported only mild symptoms. Six patients (14.3%) were admitted to the hospital for acute coronavirus disease 2019 illness. Noncardiac comorbidities were associated with an increased risk of hospitalisation (p = 0.02), particularly chronic pulmonary disease (p = 0.01) and baseline supplemental oxygen requirement (p = 0.007). None of the single ventricle patients who tested positive required admission.
Conclusions
Hospitalisations for coronavirus disease 2019 were rare among children and young adults with underlying cardiac disease. Extracardiac comorbidities like pulmonary disease were associated with increased risk of hospitalisation while cardiac risk factors were not.
Opioid use disorder is a major public health crisis, and evidence suggests ways of better serving patients who live with opioid use disorder in the emergency department (ED). A multi-disciplinary team developed a quality improvement project to implement this evidence.
Methods
The intervention was developed by an expert working group consisting of specialists and stakeholders. The group set goals of increasing prescribing of buprenorphine/naloxone and providing next day walk-in referrals to opioid use disorder treatment clinics. From May to September 2018, three Alberta ED sites and three opioid use disorder treatment clinics worked together to trial the intervention. We used administrative data to track the number of ED visits where patients were given buprenorphine/naloxone. Monthly ED prescribing rates before and after the intervention were considered and compared with eight nonintervention sites. We considered whether patients continued to fill opioid agonist treatment prescriptions at 30, 60, and 90 days after their index ED visit to measure continuity in treatment.
Results
The intervention sites increased their prescribing of buprenorphine/naloxone during the intervention period and prescribed more buprenorphine/naloxone than the controls. Thirty-five of 47 patients (74.4%) discharged from the ED with buprenorphine/naloxone continued to fill opioid agonist treatment prescriptions 30 days and 60 days after their index ED visit. Thirty-four patients (72.3%) filled prescriptions at 90 days.
Conclusions
Emergency clinicians can effectively initiate patients on buprenorphine/naloxone when supports for this standardized evidence-based care are in place within their practice setting and timely follow-up in community is available.
Subjective cognitive difficulties are common in mental illness and have a negative impact on role functioning. Little is understood about subjective cognition and the longitudinal relationship with depression and anxiety symptoms in young people.
Aims
To examine the relationship between changes in levels of depression and anxiety and changes in subjective cognitive functioning over 3 months in help-seeking youth.
Method
This was a cohort study of 656 youth aged 12–25 years attending Australian headspace primary mental health services. Subjective changes in cognitive functioning (rated as better, same, worse) reported after 3 months of treatment was assessed using the Neuropsychological Symptom Self-Report. Multivariate multinomial logistic regression analysis was conducted to evaluate the impact of baseline levels of and changes in depression (nine-item Patient Health Questionnaire; PHQ9) and anxiety symptoms (seven-item Generalised Anxiety Disorder scale; GAD7) on changes in subjective cognitive function at follow-up while controlling for covariates.
Results
With a one-point reduction in PHQ9 at follow-up, there was an estimated 11–18% increase in ratings of better subjective cognitive functioning at follow-up, relative to stable cognitive functioning. A one-point increase in PHQ9 from baseline to follow-up was associated with 7–14% increase in ratings of worse subjective cognitive functioning over 3 months, relative to stable cognitive functioning. A similar attenuated pattern of findings was observed for the GAD7.
Conclusions
A clear association exists between subjective cognitive functioning outcomes and changes in self-reported severity of affective symptoms in young people over the first 3 months of treatment. Understanding the timing and mechanisms of these associations is needed to tailor treatment.
First-order modeling suggests that a low-water phase in late-glacial Lake Agassiz can be explained through changes in the balance between evaporation, precipitation, and runoff, rather than drainage. The low-water Moorhead Phase is often attributed to drainage through outlets opened by isostatic depression and retreat of the Laurentide ice margin. However, new data indicate that the proposed outlets were ice-covered during the Moorhead Phase. Instead, the lake water levels dropped to the Moorhead Phase before the start of the Younger Dryas chronozone and remained there until 11.3 ka. Thus, drainage seems to be an implausible explanation for Younger Dryas-aged low water levels in Lake Agassiz. An alternative explanation is that evaporation equaled or exceeded water inputs from the adjacent ice margin and the deglaciated parts of the drainage basin. To evaluate whether this hypothesis is plausible, we constructed a simple model that considers the paleo-basin geometry, hydrology, and meltwater production from the adjacent ice margin. Modest hydrologic changes (within the range of present-day variability), coupled with low meltwater production, produce a closed basin. Shifts in the location of the polar jet, driven by increased Arctic albedo, may explain our inferred hydrologic changes.
Polarization is a topic of intense interest among social scientists, but there is significant disagreement regarding the character of the phenomenon and little understanding of underlying mechanics. A first problem, we argue, is that polarization appears in the literature as not one concept but many. In the first part of the article, we distinguish nine phenomena that may be considered polarization, with suggestions of appropriate measures for each. In the second part of the article, we apply this analysis to evaluate the types of polarization generated by the three major families of computational models proposing specific mechanisms of opinion polarization.
This study analyzes the important role state political culture played in the race for the 2016 Republican presidential nomination. Donald Trump appealed to demographically distinct types of voters in the 2016 Republican presidential primaries and caucuses that varied considerably from previous Republican presidential nominees. Relative to the demographics of the primary electorates, however, this study finds that state political culture played an outsized role in determining Donald Trump’s relative level of support in a particular state. When state demographics are utilized in ordinary least squares regression models as independent variables with state partisanship and Daniel Elazar’s state political culture typology, political culture proves to be a significant determinant of the level of support given to Trump in a state. States that are characterized by a more moralistic political culture are considerably more likely to have given Trump a lower share of the vote while voters in states that are characterized by a more traditionalistic or individualistic culture were more likely to support Trump.
Understanding the dynamics of information is crucial to many areas of research, both inside and outside of philosophy. Using computer simulations of three kinds of information, germs, genes, and memes, we show that the mechanism of information transfer often swamps network structure in terms of its effects on both the dynamics and the fitness of the information. This insight has both obvious and subtle implications for a number of questions in philosophy, including questions about the nature of information, whether there is genetic information, and how to arrange scientific communities.
A scientific community can be modeled as a collection of epistemic agents attempting to answer questions, in part by communicating about their hypotheses and results. We can treat the pathways of scientific communication as a network. When we do, it becomes clear that the interaction between the structure of the network and the nature of the question under investigation affects epistemic desiderata, including accuracy and speed to community consensus. Here we build on previous work, both our own and others’, in order to get a firmer grasp on precisely which features of scientific communities interact with which features of scientific questions in order to influence epistemic outcomes.
Here we introduce a measure on the landscape meant to capture some aspects of the difficulty of answering an empirical question. We then investigate both how different communication networks affect whether the community finds the best answer and the time it takes for the community to reach consensus on an answer. We measure these two epistemic desiderata on a continuum of networks sampled from the Watts–Strogatz spectrum. It turns out that finding the best answer and reaching consensus exhibit radically different patterns. The time it takes for a community to reach a consensus in these models roughly tracks mean path length in the network. Whether a scientific community finds the best answer, on the other hand, tracks neither mean path length nor clustering coefficient.
The catalytic influence of Ni, Zr2Ni5, and LaNi5 on the dehydrogenation properties of milled MgH2 was investigated. MgH2 milled in the presence of Ni (5 wt%) and Zr2Ni5 (5 wt%) catalysts for 2 h showed apparent activation energies, EA, of 81 and 79 kJ/mol, respectively, corresponding to ∼50% decrease in EA and a moderate decrease (∼100 °C) in the decomposition temperature (Tdec). A further 27 °C decrease in Tdec was observed after milling with 10 wt%Ni. Based on the EA values, the catalytic activity decreased in the following order: Ni ≈ Zr2Ni5 > LaNi5. X-ray photoelectron spectroscopy analysis of the milled and dehydrogenated states of the hydrides modified with Ni catalyst revealed that the observed reduction in EA may be due to the ability of Ni catalyst to decrease the amount of oxygen atoms in defective positions that are capable of blocking catalytically active sites thereby enhancing the dehydrogenation kinetics. In particular, our results reveal a strong correlation between the type of oxygen species adsorbed on Ni-modified MgH2 and the EA of the dehydrogenation reaction.
Retropubic Burch colposuspension has been considered by many to be the “gold standard” procedure for the treatment of female stress urinary incontinence for almost 40 years. Vancaillie and Schuessler introduced the laparoscopic approach to retropubic colposuspension in 1991. Numerous reports followed in subsequent years describing laparoscopic colposuspensions and their efficacy. Analysis of the outcomes of these various laparoscopic “Burch” colposuspensions is difficult because many of the techniques are not true Burch procedures but rather other modified retropubic colposuspensions. In this section, we describe the laparoscopic Burch colposuspension, including patient selection, preoperative evaluation, operative technique, possible complications, and efficacy. We review the efficacy of the laparoscopic Burch colposuspension studies that use the Burch—Tanagho procedure and compare these techniques to other popular anti-incontinence procedures. The many modified laparoscopic retropubic procedures are not addressed.
BURCH COLPOSUSPENSION: THE EVOLUTION OF A PROCEDURE
In 1961, Burch published the description of a new female anti-incontinence procedure, based on a technique started in 1958. The technique involved entering the space of Retzius via a paramedian incision. After clearing the periurethral tissue of its overlying fat and areolar tissue, three 2-0 chromic sutures were placed at the mid-urethra and the bladder neck and then fixed to Cooper's ligament. Burch reported a subjective cure rate of 92% in 143 patients with 10 to 60 months of followup.
In 2002, the Chicago Department of Public Health (CDPH; Chicago, Illinois) convened the Chicago-Area Neonatal MRSA Working Group (CANMWG) to discuss and compare approaches aimed at control of methicillin-resistant Staphylococcus aureus (MRSA) in neonatal intensive care units (NICUs). To better understand these issues on a regional level, the CDPH and the Evanston Department of Health and Human Services (EDHHS; Evanston, Illinois) began an investigation.
Design.
Survey to collect demographic, clinical, microbiologic, and epidemiologic data on individual cases and clusters of MRSA infection; an additional survey collected data on infection control practices.
Setting.
Level III NICUs at Chicago-area hospitals.
Participants.
Neonates and healthcare workers associated with the level III NICUs.
Methods.
From June 2001 through September 2002, the participating hospitals reported all clusters of MRSA infection in their respective level III NICUs to the CDPH and the EDHHS.
Results.
Thirteen clusters of MRSA infection were detected in level III NICUs, and 149 MRSA-positive infants were reported. Infection control surveys showed that hospitals took different approaches for controlling MRSA colonization and infection in NICUs.
Conclusion.
The CANMWG developed recommendations for the prevention and control of MRSA colonization and infection in the NICU and agreed that recommendations should expand to include future data generated by further studies. Continuing partnerships between hospital infection control personnel and public health professionals will be crucial in honing appropriate guidelines for effective approaches to the management and control of MRSA colonization and infection in NICUs.
This study investigated the microstructural characteristics of directionally solidified freeze-dried silica sols. Porous structures were formed by depositing silica sol on silicon (100) single crystals. The deposited sols were unidirectionaly solidified by placing the silicon substrate on a copper block immersed in liquid nitrogen and then subsequently freeze-dried. Freeze drying removal of ice crystals created three-dimensional pore channels ranging from 3 to10 micrometers in diameter aggregated in grain like colonies 50–100 micrometers in diameter. Pore size, spacing, colony size and microstructure were determined using optical microscopy (OM) and scanning electron microscopy (SEM) while the structure of the amorphous SiO2 was characterized by X-ray diffraction (XRD). The microstructure results are compared and contrasted with silica aerogel obtained through conventional processing using supercritical CO2.