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We present the case of 53-year-old woman with a late diagnosis of an right pulmonary artery-left atrium fistula who underwent transcatheter device closure using multi-modality imaging for pre-procedural planning and procedural guidance.
Persistent brain fog is common in adults with Post-Acute Sequelae of SARS-CoV-2 infection (PASC), in whom it causes distress and in many cases interferes with performance of instrumental activities of daily living (IADL) and return-to-work. There are no interventions with rigorous evidence of efficacy for this new, often disabling condition. The purpose of this pilot is to evaluate the efficacy, on a preliminary basis, of a new intervention for this condition termed Constraint-Induced Cognitive therapy (CICT). CICT combines features of two established therapeutic approaches: cognitive speed of processing training (SOPT) developed by the laboratory of K. Ball and the Transfer Package and task-oriented training components of Constraint-Induced Movement therapy developed by the laboratory of E. Taub and G. Uswatte.
Participants and Methods:
Participants were > 3 months after recovery from acute COVID symptoms and had substantial brain fog and impairment in IADL. Participants were randomized to CICT immediately or after a 3-month delay. CICT involved 36 hours of outpatient therapy distributed over 4-6 weeks. Sessions had three components: (a) videogamelike training designed to improve how quickly participants process sensory input (SOPT), (b) training on IADLs following shaping principles, and (c) a set of behavioral techniques designed to transfer gains from the treatment setting to daily life, i.e., the Transfer Package. The Transfer Package included (a) negotiating a behavioral contract with participants and one or more family members about the responsibilities of the participants, family members, and treatment team; (b) assigning homework during and after the treatment period; (c) monitoring participants’ out-of-session behavior; (d) supporting problem-solving by participants and family members about barriers to performance of IADL; and (e) making follow-up phone calls. IADL performance, brain fog severity, and cognitive impairment were assessed using validated, trans-diagnostic measures before and after treatment and three months afterwards in the immediate-CICT group and on parallel occasions in the delayed-CICT group (aka waitlist controls).
Results:
To date, five were enrolled in the immediate-CICT group; four were enrolled in the wait-list group. All had mild cognitive impairment, except for one with moderate impairment in the immediate-CICT group. Immediate-CICT participants, on average, had large reductions in brain fog severity on the Mental Clutter Scale (MCS, range = 0 to 10 points, mean change = -3.7, SD = 2.0); wait-list participants had small increases (mean change = 1.0, SD = 1.4). Notably, all five in the immediate-CICT group had clinically meaningful improvements (i.e., changes > 2 points) in performance of IADL outside the treatment setting as measured by the Canadian Occupational Performance Measure (COPM) Performance scale; only one did in the wait-list group. The advantage for the immediate-CICT group was very large on both the MCS and COPM (d’s = 1.7, p’s < .05). In follow-up, immediate-CICT group gains were retained or built-upon.
Conclusions:
These preliminary findings warrant confirmation by a large-scale randomized controlled trial. To date, CICT shows high promise as an efficacious therapy for brain fog due to PASC. CICT participants had large, meaningful improvements in IADL performance outside the treatment setting, in addition to large reductions in brain fog severity.
Depressive symptomatology has long been shown to be associated with the onset of dementia, though the exact form and directionality of this association remains unclear. While much research has gone into confirming this link, there has been little investigation into the effects of depression on dementia progression after diagnosis. The aim of this study is to investigate the relationship between depressive symptomatology and cognitive and behavioural decline over the following year.
Participants and Methods:
In a Rural and Remote Memory Clinic, 375 patients consecutively diagnosed with mild cognitive impairment (MCI), Alzheimer’s Disease (AD), or non-AD dementia completed the Center for Epidemiological Studies Depression Scale (CES-D) at first visit and one-year follow-up to assess depressive symptomatology. The same cohort were evaluated for cognitive and behavioural decline through the completion of five clinical tests performed at the first visit and at one-year follow-up. Cognitive decline was assessed using the Mini Mental Status Exam (MMSE) and the Clinical Dementia Rating Scale (CDR). Neuropsychiatric symptoms were assessed using two subsets of data from the Neuropsychiatric Inventory (NPI severity and distress), both of which are completed by the patients’ caregivers. Functional decline was assessed using the Functional Activities Questionnaire (FAQ). In both cognitive and functional decline, data were analyzed with linear regression analysis in the population subgroups of All Type Dementia (ATD, which includes MCI for this study) (N=375), Alzheimer’s type dementia (N=187), and Mild Cognitive Impairment (N=74).
Results:
In this study, we observed no correlation between CES-D scores at baseline and cognitive or functional decline over one year. However, we observed a significant positive correlation between changes in CES-D scores and NPI-severity scores over one year in patients with ATD (likely the most reliable observation from this study due to larger statistical power) and in the MCI subgroup, but not in the AD subgroup. This relationship may be attributable to a relationship between depression and neuropsychiatric symptoms in general, or to the fact that a person with dementia who exhibits more depressive symptomatology appears more impaired and causes greater distress in their caregivers, despite stability in the objective measures of their cognitive and functional status. This finding may indicate that intervention for depression is needed to alleviated caregiver burden when managing dementia patients.
Conclusions:
Increasingly severe depressive symptomatology may exacerbate neuropsychiatric symptomatology but did not correlate with cognitive and functional decline in patients with dementia. More studies are needed to help delineate the relationship between depression and dementia progression.
One difficulty with sketching pedagogy is the tendency to assess growth according to outcomes, as opposed to processes. We assessed eye gaze patterns between advanced and intermediate design sketchers and anticipated correlations between eye-gaze practices and sketching proficiency. Participants sketched two different objects using analogue materials, a potted plant from memory, and a MacBook from observation.
The study utilised Tobii 3 adjustable eye-tracking glasses and Tobii Pro data processing software. Twenty-five design sketching students and six design sketching instructors participated in the study.
Metrics measured include the quantity of reference line gazes, eye movement during line creation (targeting vs tracking), eye fixation duration, work checks per minute and subject gazes per minute.
The results show a difference in gaze patterns between intermediate and advanced sketchers, both in terms of practice and consistency. Eye-tracking sketching behaviours has revealed a new understanding of how teaching gaze habits could lead to improved methods of design sketching instruction.
Traumatic brain injury (TBI) was first proposed as a potential risk factor for developing a glioma in the 1800s, and conditions for establishing a causal relationship between brain injury and gliomas have since been proposed. Given the medical and legal ramifications, the current literature was reviewed to better understand this possible association. Articles that examined the relationship between TBI and glioma formation in adults and were published in English between 1978 and 2022 were reviewed. There were 19 case reports of 25 patients and 16 observational studies. The case reports describe glioma formation at the precise site of prior brain injury in continuity with traumatic scar; the observational studies report conflicting findings, but they largely demonstrate no association. Most of the observational studies are limited by their retrospective nature, but we identified one prospective cohort study which found a positive association. Altogether, we suggest that glioma formation after TBI is a rare occurrence that warrants further study.
Using physiological markers to detect patients at risk of deterioration is common. Deaths at music festivals in Australia prompted scrutiny of tools to identify critically unwell patients for transport to hospital. This study evaluated initial physiological parameters to identify patients selected for transport to hospital from a music festival.
Methods:
A retrospective audit of 2045 presentations at music festivals in Victoria, Australia, was performed. Presentation heart rate, systolic blood pressure, respiratory rate, oxygen saturation, temperature, and Glasgow Coma Scale were assessed using area under the receiver operating characteristic curve (AUROC) analysis, with a prespecified threshold of 0.7.
Results:
The only measured variable to exceed the prespecified cutpoint was initial systolic blood pressure, with an AUROC of 0.72 and optimal cutpoint of 122 mmHg. Using commonly accepted cutpoints for variables did not improve detection performance to acceptable levels, nor did using combination systems of cutpoints.
Conclusions:
Initial physiological variables are poor predictors of the decision to transport to hospital from music festivals. Systolic blood pressure was significant, but only at a clinically insignificant value. Decisions on which patients to transport from an event site should incorporate more information than initial physiology. Senior clinicians should lead decision-making about hospital transport from music festivals.
Many countries have constitutional rules, granted to prime ministers, presidents or cabinets, that govern early parliamentary dissolution. Although there are sharply divergent theoretical expectations about the consequences of such powers for both democratic representation and accountability, there have been no empirical examinations of these arguments. Using data from the European Social Survey (2002–16) in 26 European countries, we test whether such provisions for early election calling affect citizens' satisfaction with democracy, and if so, which rules and how. While it appears that no form of constitutional rules for early election is directly related to citizen satisfaction with democracy, when early elections are called by prime ministers or presidents, democratic satisfaction drops significantly, and this effect is more pronounced the later in the term the early election is called. These findings have important implications for academic and policy debates about the desirability of constitutional change designed to limit early election calling for opportunistic purposes.
In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.1
A series of eleven patients prescribed intramuscular clozapine at five UK sites is presented. Using routinely collected clinical data, we describe the use, efficacy and safety of this treatment modality.
Results
We administered 188 doses of intramuscular clozapine to eight patients. The remaining three patients accepted oral medication. With the exception of minor injection site pain and nodules, side-effects were as expected with oral clozapine, and there were no serious untoward events. Nine patients were successfully established on oral clozapine with significant improvement in their clinical presentations.
Clinical implications
Although a novel formulation in the UK, we have shown that intramuscular clozapine can be used safely and effectively when the oral route is initially refused.
Objectives: Essential tremor (ET) confers an increased risk for developing both amnestic and non-amnestic mild cognitive impairment (MCI). Yet, the optimal measures for detecting mild cognitive changes in individuals with this movement disorder have not been established. We sought to identify the cognitive domains and specific motor-free neuropsychological tests that are most sensitive to mild deficits in cognition as defined by a Clinical Dementia Rating (CDR) of 0.5, which is generally associated with a clinical diagnosis of MCI. Methods: A total of 196 ET subjects enrolled in a prospective, longitudinal, clinical-pathological study underwent an extensive motor-free neuropsychological test battery and were assigned a CDR score. Logistic regression analyses were performed to identify the neuropsychological tests which best identified individuals with CDR of 0.5 (mild deficits in cognition) versus 0 (normal cognition). Results: In regression models, we identified five tests in the domains of Memory and Executive Function which best discriminated subjects with CDR of 0.5 versus 0 (86.9% model classification accuracy). These tests were the California Verbal Learning Test II Total Recall, Logical Memory II, Verbal-Paired Associates I, Category Switching Fluency, and Color-Word Inhibition. Conclusions: Mild cognitive difficulty among ET subjects is best predicted by combined performance on five measures of memory and executive function. These results inform the nature of cognitive dysfunction in ET and the creation of a brief cognitive battery to assess patients with ET for cognitively driven dysfunction in life that could indicate the presence of MCI. (JINS, 2018, 24, 1084–1098)
In recent years, those involved in regulating, forming or advising faith communities have had much to contend with: the expansion of the vicarious liability doctrine, the status of ministers of religion and the decision in Shergill v Khaira, not to mention the General Data Protection Regulation. These issues share a common denominator: they require faith communities to give close consideration to the values which they seek to articulate and foster in the expression of their own autonomy and right of self-determination. That is, they serve as a prompt to reconnect with the intellectus and vinculo iuris of their own ecclesial norms. This article is intended to encourage such an exercise and to contribute to a discussion of the potential points of collaboration between the civil law and faith communities in securing dispute resolution by which ecclesial values may be accommodated.
Total-dissolvable iron has been measured in sections of three ice cores from Law Dome, East Antarctica, and the results used to calculate atmospheric iron deposition over this region during the late Holocene and to provide a preliminary estimate of aerosol iron deposition during the Last Glaciol Maximum I LGM). Ice-core sections dating from 56-2730 BP (late Holocene) and ~18000 BP (LGM) were decontaminated using trace-metal clean techniques, and total-dissolvable iron was determined in the acidified meltwatcrs by flow-injection analysis. Our results suggest that the atmospheric iron flux onto the Law Dome region has varied significantly over time-scales ranging from seasonal to Glaciol-interglaciol. The iron concentrations in ice-core sections from the past century suggest (1) a 2 4-fold variation in the atmospheric iron flux over a single annual cycle, with the highest flux occurring during the spring and summer, and (2) a nearly 7-fold variation in the annual maximum atmospheric iron flux over a 14 year period. The average estimated atmospheric iron flux calculated from our late-Holocene samples is 0.056-0.14 mg m a−1, which agrees well with Holocene flux estimates derived from aluminium measurements in inland Antarctic ice cores and a recent order-of-magnitude estimate of present-day atmospheric iron deposition over the Southern Ocean. The iron concentration of an ice-corc section dating from the LGM was more than 50 times higher than in the late-Holocene ice samples. Using a snow-accumulation rate estimate of 130 kg m −2 a−1 for this period, we calculate 0.87 mgm −2 a−1 as a preliminary estimate of atmospheric iron deposition during the LGM, which is 6-16 times greater than our average late-Holocene iron flux. Our data are consistent with the suggestion that there was a significantly greater flux of atmospheric iron onto the Southern Ocean during the LGM than during then Holocene.
Individuals with essential tremor (ET) exhibit a range of cognitive deficits generally conceptualized as “dysexecutive” or “fronto-subcortical,” and thought to reflect disrupted cortico-cerebellar networks. In light of emerging evidence that ET increases risk for Alzheimer’s disease (AD), it is critical to more closely examine the nature of specific cognitive deficits in ET, with particular attention to amnestic deficits that may signal early AD.
Methods
We performed a cross-sectional analysis of baseline data from 128 ET cases (age 80.4±9.5 years) enrolled in a longitudinal, clinical-pathological study. Cases underwent a comprehensive battery of motor-free neuropsychological tests and a functional assessment to inform clinical diagnoses of normal cognition (ET-NC), mild cognitive impairment (MCI) (ET-MCI), or dementia (ET-D). ET-MCI was subdivided into subtypes including: amnestic single-domain (a-MCI), amnestic multi-domain (a-MCI+), non-amnestic single-domain (na-MCI), or non-amnestic multi-domain (na-MCI+).
Results
Ninety-one (71.1%) cases were ET-NC, 24 (18.8%) were ET-MCI, and 13 (10.2%) were ET-D. Within MCI, the a-MCI+ subtype was the most common (13/24; 54.2%) followed by a-MCI (4/24; 16.7%), na-MCI+ (4/24; 16.7%), and na-MCI (3/24; 12.5%). Cases with amnestic MCI demonstrated lower recognition memory Z-scores (−2.4±1.7) than non-amnestic groups (−0.9±1.2) (p=.042).
Conclusions
Amnestic MCI, defined by impaired memory recall but associated with lower memory storage scores, was the most frequent MCI subtype in our study. Such impairment has not been explicitly discussed in the context of ET and may be an early hallmark of AD. Results have implications for the prognosis of specific cognitive deficits in ET. (JINS, 2017, 23, 390–399)
The isotopic composition of Pb and the concentrations of Pb, Ba and Bi wert- measured in selected ice-core samples from Law Dome, East Antarctica, to a depth of 1196 m. The range of concentrat ions found in decontaminated ice was 0.03-1.5 pgg−1 for Pb, 0.9-6.1 pgg−1 for Ba and 0.4 17 fgg −1 for Bi, excluding the deepest sample which contained ~1 pjpm of rock dust. The abundances of all four stable lead isotopes were measured and gave 206Pb/207Pb ratios up to ~1.23. Avalue of 208Pb/207Pb= 2.78 was measured in the deepest sample and is consistent with reported Pb isotope ratios of Antarctic gran-ulites. Although the element concentrations in some samples were lower than have been reported elsewhere, geochemkal and isotopic evidence indicated that a number of samples were contaminated with Pb not present in the original ice. However, it appears that the technical skills now available are approaching the level where careful sample selection, decontamination and analysis can yield accurate results for the concentration and isotopic composition of Pb in Earth's purest naturally occurring ice.
Apart from their effector functions in allergic disorders, tissue-resident mast cells (MC) are gaining recognition as initiators of inflammatory events through their distinctive ability to secrete many bioactive molecules harbored in cytoplasmic granules. Activation triggers mediator release through a regulated exocytosis named degranulation. MC activation is still substantiated by measuring systemic levels of MC-restricted mediators. However, identifying the anatomical location of MC activation is valuable for disease diagnosis. We designed a computer-assisted morphometric method based on image analysis of methylene blue (MB)-stained normal mouse skin tissue sections that quantitates actual in situ MC activation status. We reasoned MC cytoplasm could be viewed as an object featuring unique relative mass values based on activation status. Integrated optical density and area (A) ratios were significantly different between intact and degranulated MC (p<0.001). The examination of fractal characteristics is of translational diagnostic/prognostic value in cancer and readily applied to quantify cytoskeleton morphology and vasculature. Fractal dimension (D), a measure of their comparative space filling capacity and structural density, also differed significantly between intact and degranulated MC (p<0.001). Morphometric analysis provides a reliable and reproducible method for in situ quantification of MC activation status.