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The persistence of stigma of mental illness and seeking therapy perpetuates suffering and keeps people from getting the help they need and deserve. This volume, analysing the most up-to-date research on this process and ways to intervene, is designed to give those who are working to overcome stigma a strong, research-based foundation for their work. Chapters address stigma reduction efforts at the individual, community, and national levels, and discuss what works and what doesn't. Others explore how holding different stigmatized identities compounds the burden of stigma and suggest ways to attend to these differences. Throughout, there is a focus on the current state of the research knowledge in the field, its applications, and recommendations for future research. The Handbook provides a compelling case for the benefits reaped from current research and intervention, and shows why continued work is needed.
Localized contamination from research-related activities and its effects on macrofauna communities in the marine environment were investigated at Palmer Station, a medium-sized Antarctic research station. Relatively low concentrations of polycyclic aromatic hydrocarbons (PAHs; 32–302 ng g-1) and total petroleum hydrocarbons (TPHs; 0.9–8.9 μg g-1) were detected in sediments adjacent to the sewage outfall and pier, where most human activities were expected to have occurred, and at even lower concentrations at two seemingly reference areas (PAHs 6–30 ng g-1, TPHs 0.03–5.1 μg g-1). Elevated concentrations of PAHs in one sample taken in one reference area (816 ng g-1) and polychlorinated biphenyls (353 ng g-1) and dichloro-diphenyl-trichloroethane (3.2 and 25.3 ng g-1) in two samples taken adjacent to the sewage outfall indicate spatial heterogeneity of localized sediment contamination. Limpet (Nacella concinna) tissues collected adjacent to Palmer Station had high concentrations of PAHs, copper, lead, zinc and several other metals relative to outlying islands. Sediment and limpet tissue contaminant concentrations have decreased since the early 1990s following the Bahía Paraíso spill. Natural sediment characteristics affected macrofaunal community composition more than contamination adjacent to Palmer Station, presumably because of the low overall contamination levels.
Sudden onset severe headache is usually caused by a primary headache disorder but may be secondary to a more serious problem, such as subarachnoid hemorrhage (SAH). Very few patients who present to hospital with headache have suffered a SAH, but early identification is important to improve patient outcomes. A systematic review was undertaken to assess the clinical effectiveness of different care pathways for the management of headache, suspicious for SAH, in the Emergency Department. Capturing the perspective of patients was an important part of the research.
The project team included a patient collaborator with experience of presenting to the Emergency Department with sudden onset severe headache. Three additional patients were recruited to our advisory group. The patient's perspective was collected at various points through the project including at team meetings, during protocol development and when interpreting the results of the systematic review and drawing conclusions.
Patients were reassured by the very high diagnostic accuracy of computed tomography (CT) for detecting SAH. Patients and clinicians emphasized the importance of shared decision making about whether to undergo additional tests to rule out SAH, after a negative CT result. When lumbar puncture was necessary, patients expressed a preference to have it on an ambulatory basis; further research on the safety and acceptability of ambulatory lumbar puncture was recommended.
Patient input at the protocol development stage helped researchers understand the patient experience and highlighted important outcomes for assessment. Patient involvement added context to the review findings and highlighted the preferences of patients regarding the management of headache.
Sudden onset severe headache is usually caused by a primary headache disorder but occasionally is secondary to a more serious problem, such as subarachnoid hemorrhage (SAH). Guidelines recommend non-contrast brain computed tomography (CT) followed by lumbar puncture (LP) to exclude SAH. However, guidelines pre-date the introduction of more sensitive modern CT scanners. A systematic review was undertaken to assess the clinical effectiveness of different care pathways for the management of headache in the Emergency Department.
Eighteen databases (including MEDLINE and Embase) were searched to February 2020. Studies were quality assessed using criteria relevant to the study design; most studies were assessed using the QUADAS-2 tool for diagnostic accuracy studies. Where sufficient information was reported, diagnostic accuracy data were extracted into 2 × 2 tables to calculate sensitivity, specificity, false-positive and false-negative rates. Where possible, hierarchical bivariate meta-analysis was used to synthesize results, otherwise studies were synthesized narratively.
Fifty-one studies were included in the review. Eight studies assessing the accuracy of the Ottawa SAH clinical decision rule were pooled; sensitivity was 99.5 percent, specificity was 23.7 percent. The high false positive rate suggests that 76.3 percent SAH-negative patients would undergo further investigation unnecessarily. Four studies assessing the accuracy of CT within six hours of headache onset were pooled; sensitivity was 98.7 percent, specificity was 100 percent. CT sensitivity beyond six hours was considerably lower (≤90%; 2 studies). Three studies assessing LP following negative CT were pooled; sensitivity was 100 percent, specificity was 95.2 percent. LP-related adverse events were reported in 5.3–9.5 percent of patients.
The evidence suggests that the Ottawa SAH Rule is not sufficiently accurate for ruling out SAH and does little to aid clinical decision making. Modern CT within six hours of headache onset (with images assessed by a neuroradiologist) is highly accurate, but sensitivity reduces considerably over time. The CT-LP pathway is highly sensitive for detecting SAH, although LP resulted in some false-positives and adverse events.
Web-based interventions are increasingly used for the prevention, treatment and aftercare of mental disorders. A crucial factor to the efficacy of such online programmes is adherence to the intervention content and procedure. It has been frequently suggested that adherence in web-based interventions is low and little is known about which factors influence adherence. To increase intervention uptake and completion, studies increasingly include interventions with some form of guidance. Guided interventions have been shown to have higher efficacy, however, evidence for the impact on adherence is limited and mixed. This meta-analysis explored the impact of human guidance on intervention completion in web-based mental health interventions. A total of 22 studies were included with interventions primarily targeting symptoms of depression and anxiety disorders. Results showed that guidance significantly increases the average amount of intervention completion [g = 0.29, 95% confidence interval (CI) 0.18–0.40] and the proportion of intervention completers [log odds ratio (OR) = 0.50, 95% CI 0.34–0.66] with small effects. On average, full completion rates were 12% higher in guided intervention groups. This meta-analysis demonstrated that guidance in web-based mental health interventions does increase adherence, but more research is required to better understand the specific mechanisms between guidance, adherence and outcomes.
Background: Tubular retractors are FDA approved and in the Neurosurgical marketplace, but adaptation has been hampered by lack of evidence showing superiority over traditional retractors when performing subcortical surgery. This study examines brain injury associated with traditional brain retractors versus tubular retractors. Methods: Nine porcine models underwent a simulated neurosurgical operation. Retractors were inserted for four hours after which the porcine model was euthanized. The en-bloc extracted porcine brain was fixed in 10% formalin, paraffin embedded, sectioned at 4 um and stained with hematoxylin and eosin (H&E) using standard laboratory protocols. Computer algorithms were generated to calculate areas of cerebral edema and hemorrhage adjacent to retractor surfaces. Results: Using a two-tailed t-test with a significance level of 0.05, traditional brain retractors were associated with statistically significant greater areas of cerebral edema when compared to tubular retractors (17.36 um2 vs. 12.42 um2; p = 0.0038). There was no statistically significant difference in mean areas of hemorrhage between traditional brain retractors and tubular retractors (3.43 um2 vs 3.60 um2; p = 0.8297). Conclusions: Tubular retractors are associated with significantly less edema in surrounding brain than traditional retractors. On histopathological merits, this study supports the application of tubular retractors over traditional retractors.
Background: Autoimmune encephalitis (AE) is a recently described entity that presents with seizures, neuropsychiatric manifestations, and movement disorders. This observational chart review of AE aims to assess the burden of AE and related disorders at two Vancouver academic medical centers. Methods: All patients with Mitogen Laboratory AE antibody testing in 2018 were identified. Electronic hospital records were used to determine patient characteristics. Results: 1266 unique tests were ordered on 315 inpatients and outpatients. Of 37/315 (11.7%) seropositive patients, 26/37 (70.2%) patients had clinical data. Seropositive results included autoantibodies to NMDA (n=3), LG1 (n=2), CASPR2 (n=1) and paraneoplastic autoantibodies included GAD65 (n=2), PNMA2 (n=5), recoverin (n=3). There were four AE cases in 14 seronegative patients based on discharge diagnosis. 15/30 of patients had seizures and three developed status epilepticus. 15 had neuropsychiatric manifestations. 14 had a movement disorder. For inpatients, average length of stay was 24.3 days and there were 5 intensive care unit (ICU) admissions. Immunotherapies used included corticosteroids, PLEX, rituximab, IVIg, and cyclophosphamide. Conclusions: In two hospitals serving approximately two million people in 2018, there were 30 cases of AE in 2018. AE presents with a broad range of neurologic symptoms and seronegative testing does not preclude AE.
In the early twentieth century, Thomas Ashby published extensively on the Roman roads of Italy. The BSR Director was determined to create a lasting record of the ancient Roman road network before it was lost forever. Yet Ashby's research vision was grand and it was too ambitious a task for one man to accomplish on his own. This paper investigates the crucial role of BSR scholars in Ashby's research. It discusses his relationship with the community of residents and scholars at the BSR in the pre- and post-World War I years, especially those with whom he collaborated in order to survey, map and record the Roman roads and their surrounding countryside. Focus is given to Ashby's research on roads like the Via Flaminia and Via Appia as this work highlights his methodology, the collegial environment at the BSR during his directorship, and his successful collaboration with award-holders. To date, the role of these BSR scholars has largely been underrated. Yet there were BSR award-holders — historians, archaeologists and architects — who helped to keep Ashby's research vision alive. Without them, he could not have produced such a comprehensive and impressive body of work on Italy's Roman roads.
Meta-analyses show an association between perfectionism and depression and anxiety (negative affect), and that therapy for perfectionism impacts positively on negative affect. No systematic reviews have focused on qualitative studies of perfectionism.
Our aim was to perform a systematic, meta-synthesis of qualitative literature to (i) help inform our understanding of how perfectionism is associated with negative affect, so that we can (ii) inform future development of treatment for perfectionism in young people and to make it more effective.
Included in the meta-synthesis were 37 qualitative studies.
Six themes related to perfectionism were found: (1) the association with negative affect, (2) self-worth dependent on achievement, (3) cognitive and behavioural maintaining factors, (4) the expectations of others, (5) effective elements of interventions, and (6) barriers to treatment.
The qualitative literature supports the notion of perfectionism as an important construct to consider in reducing negative affect. While cognitive behavioural therapy for perfectionism holds promise as a treatment to target negative affect, there was a paucity of qualitative research, particularly related to young people. A greater understanding of the views of young people are required to help tailor more effective interventions for perfectionism that can impact negative affect in this group.
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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
Studies examining the impact of adolescent and young adult cannabis use on structural outcomes have been heterogeneous. One already-identified moderator is sex, while a novel potential moderator is extent of aerobic fitness. Here, we sought to investigate the associations of cannabis use, sex, and aerobic fitness levels on brain volume. Second, we explored brain–behavior relationships to interpret these findings.
Seventy-four adolescents and young adults (36 cannabis users and 38 controls) underwent 3 weeks of monitored cannabis abstinence, aerobic fitness testing, structural neuroimaging, and neuropsychological testing. Linear regressions examined cannabis use and its interaction with sex and aerobic fitness on whole-brain cortical volume and subcortical regions of interests.
No main-effect differences between cannabis users and nonusers were observed; however, cannabis-by-sex interactions identified differences in frontal, temporal, and paracentral volumes. Female cannabis users generally exhibited greater volume while male users exhibited less volume compared to same-sex controls. Positive associations between aerobic fitness and frontal, parietal, cerebellum, and caudate volumes were observed. Cannabis-by-fitness interaction was linked with left superior temporal volume. Preliminary brain–behavior correlations revealed that abnormal volumes were not advantageous in either male or female cannabis users.
Aerobic fitness was linked with greater brain volume and sex moderated the effect of cannabis use on volume; preliminary brain–behavior correlations revealed that differences in cannabis users were not linked with advantageous cognitive performance. Implications of sex-specific subtleties and mechanisms of aerobic fitness require large-scale investigation. Furthermore, present findings and prior literature on aerobic exercise warrant examinations of aerobic fitness interventions that aimed at improving neurocognitive health in substance-using youth.
Verbal memory deficits are linked to cannabis use. However, self-reported episodic use does not allow for assessment of variance from other factors (e.g., cannabis potency, route of consumption) that are important for assessing brain-behavior relationships. Further, co-occurring nicotine use may moderate the influence of cannabis on cognition. Here we utilized objective urinary measurements to assess the relationship between metabolites of cannabis, 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THCCOOH), and nicotine (cotinine) on verbal memory in young adults.
Adolescents and young adults (n = 103) aged 16–22 completed urinary drug testing and verbal memory assessment (RAVLT). Linear regressions examined the influence of THCCOOH and cotinine quantitative concentrations, and their interaction, on RAVLT scores, controlling for demographics and alcohol. Cannabis intake frequency was also investigated. Secondary analyses examined whether past month or recency of use related to performance, while controlling for THCCOOH and cotinine concentrations.
THCCOOH concentration related to both poorer total learning and long delay recall. Cotinine concentration related to poorer short delay recall. Higher frequency cannabis use status was associated with poorer initial learning and poorer short delay. When comparing to self-report, THCCOOH and cotinine concentrations were negatively related to learning and memory performance, while self-report was not.
Results confirm the negative relationship between verbal memory and cannabis use, extending findings with objective urinary THCCOOH, and cotinine concentration measurements. No moderating relationship with nicotine was found, though cotinine concentration independently associated with negative short delay performance. Findings support the use of both urinary and self-report metrics as complementary methods in substance use research.
We examined parent- and adolescent-reported executive functioning (EF) behaviors following pediatric traumatic brain injury (TBI) in the context of Online Family Problem-Solving Therapy (OFPST) and moderators of change in EF behaviors.
In total, 274 families were randomized to OFPST or an internet resource comparison group. Parents and adolescents completed the Behavior Rating Inventory of Executive Function at four time points. Mixed models were used to examine EF behaviors, assessing the effects of visit, treatment group, rater, TBI severity, age, socioeconomic status, and family functioning.
Parents rated their adolescents’ EF as poorer (F(3,1156) = 220.15, p < .001; M = 58.11, SE = 0.73) than adolescents rated themselves (M = 51.81, SE = 0.73). Across raters, EF behaviors were poorer for adolescents whose parents had less education (F(3,1156) = 8.60, p = .003; M = 56.76, SE = 0.98) than for those with more education (M = 53.16, SE = 0.88). Age at baseline interacted with visit (F(3,1156) = 5.05, p = .002), such that families of older adolescents reported improvement in EF behaviors over time. Family functioning also interacted with visit (F(3, 1156) = 2.61, p = .049), indicating more improvement in EF behaviors over time in higher functioning families. There were no effects of treatment or TBI severity.
We identified a discrepancy between parent- and adolescent-reported EF, suggesting reduced awareness of deficits in adolescents with TBI. We also found that poorer family functioning and younger age were associated with poorer recovery after TBI, whereas adolescents of parents with less education were reported as having greater EF deficits across time points.
In the library of Winchester College is a multi-lingual psalter formerly owned by the diplomat and scholar, Richard Pace (c.1483–1536). Pace left extensive notes in this volume, the product of his study of the Hebrew Scriptures in comparison with the Vulgate and Greek Septuagint. They demonstrate his engagement with a variety of Jewish, patristic and humanist learning. A broader set of theological and devotional themes also emerge. For Pace, the Psalms were primarily a prophetic text, foretelling the coming of Christ and the Gospels, but they likewise reflected an interest in devotion, rhetoric and prayer typical of humanists of the period.
We show that the dynamical degree of an (i.i.d) random sequence of dominant, rational self-maps on projective space is almost surely constant. We then apply this result to height growth and height counting problems in random orbits.
Passive wearable exoskeletons are desirable as they can provide assistance during user movements while still maintaining a simple and low-profile design. These can be useful in industrial tasks where an ergonomic device could aid in load lifting without inconveniencing them and reducing fatigue and stress in the lower limbs. The SpringExo is a coil-spring design that aids in knee extension. In this paper, we describe the muscle activation of the knee flexors and extensors from seven healthy participants during repeated squats. The outcome measures are the timings of the key events during squat, flexion angle, muscle activation of rectus femoris and bicep femoris, and foot pressure characteristics of the participants. These outcome measures assess the possible effects of the device during lifting operations where reduced effort in the muscles is desired during ascent phase of the squat, without changing the knee and foot kinematics. The results show that the SpringExo significantly decreased rectus femoris activation during ascent (−2%) without significantly affecting either the bicep femoris or rectus femoris muscle activations in descent. This implies that the user could perform a descent without added effort and ascent with reduced effort. The exoskeleton showed other effects on the biomechanics of the user, increasing average squat time (+0.02 s) and maximum squat time (+0.1 s), and decreasing average knee flexion angle (−4°). The exoskeleton has no effect on foot loading or placement, that is, the user did not have to revise their stance while using the device.
Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized.
Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status.
Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern.
Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.