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We sought to develop a teaching pilot to help year 2 medical students meet the following learning outcomes: Develop a better understanding of patient and carer experiences of mental illness; Recognise and challenge unhelpful attitudes towards people with mental illness; Promote a broader understanding of cultural issues surrounding mental illness, including stigma and discrimination.
337 medical students were invited to attend a lecture by author LQ, a documentary photographer who presented a narrative of his brother Justin's lived experience of schizophrenia (louisquail.com/big-brother-introduction). 197 students attended the session, which was recorded and made available online. Students were invited to enter a competition to win a signed copy of LQ's book, ‘Big Brother’ and asked to submit either a 500-word written reflective piece, or a creative work accompanied by a 200-word statement. 13 submissions were received, including paintings, drawings, collage, photography, and poetry, all of which were blind rated by authors SR and GB, based on originality and quality of reflection. Of the six shortlisted, three winning entries were chosen by author LQ.
All reflections moved away from a technical understanding of schizophrenia, towards person-centred interpretations, with dominant themes of ‘stigma’, ‘disempowerment’, ‘understanding people as individuals’, ‘subjective experience of mental illness’, ‘inclusion’ and ‘healing power of nature’.
The three prize winners (authors GY, AK and KT) used different mediums: GY painted an osprey over a chaotic collage of disordered and stigmatizing words (the osprey representing empowerment and the “reservoir for wellbeing in nature”); AK's sonnet began as an ode to the chaos of Justin's experience, but the concluding lines reframed this struggle, conveying feelings of hope and beauty; and KT's self-portrait, produced with a slow shutter-speed photograph, powerfully conveyed a sense of disorientation and disturbance. She reflected on how the stigma of mental illness affects self-perception. The talk was well-attended, and reflections were of high quality. A limitation of this pilot was that only a small proportion of students completed the reflective assignment.
Innovative teaching strategies are needed to address negative attitudes towards mental illness and psychiatry, which are prevalent amongst the medical profession. This pilot provides a model for combining carer-led, reflective, and creative elements in undergraduate psychiatry teaching, with the aim of challenging stigma. This model will be evaluated in a further study involving fifth year medical students, which will use a validated scale to measure change in students’ attitudes towards mental illness and psychiatry.
Mild cognitive impairment (MCI) types may have distinct neuropathological substrates with hippocampal atrophy particularly common in amnestic MCI (aMCI). However, depending on the MCI classification criteria applied to the sample (e.g., number of abnormal test scores considered or thresholds for impairment), volumetric findings between MCI types may change. Additionally, despite increased clinical use, no prior research has examined volumetric differences in MCI types using the automated volumetric software, Neuroreader™.
The present study separately applied the Petersen/Winblad and Jak/Bondi MCI criteria to a clinical sample of older adults (N = 82) who underwent neuropsychological testing and brain MRI. Volumetric data were analyzed using Neuroreader™ and hippocampal volumes were compared between aMCI and non-amnestic MCI (naMCI).
T-tests revealed that regardless of MCI classification criteria, hippocampal volume z-scores were significantly lower in aMCI compared to naMCI (p’s < .05), and hippocampal volume z-scores significantly differed from 0 (Neuroreader™ normative mean) in the aMCI group only (p’s < .05). Additionally, significant, positive correlations were found between measures of delayed recall and hippocampal z-scores in aMCI using either MCI classification criteria (p’s < .05).
We provide evidence of correlated neuroanatomical changes associated with memory performance for two commonly used neuropsychological MCI classification criteria. Future research should investigate the clinical utility of hippocampal volumes analyzed via Neuroreader™ in MCI.
To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies.
Setting and population:
Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States.
Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014–May 2016) and after the intervention (June 2016–December 2018). These data were compared using interrupted time series analysis.
In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality.
Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.
While genome-wide association analysis and related multi-omic strategies have in recent years dominated the field of complex disorders including mental health and addictions, in pharmacogenomics, drug metabolizing enzymes show Mendelian patterns of inheritance with correspondingly large effect sizes. Consistent with this, genes encoding these enzymes make up the majority of the genes for which the strength of the association with clinical effect of psychiatric medications is sufficient to recommend clinical utility (Bousman et al., 2018). Moreover, such enzymes are expressed in the brain (Aitchison et al., 2010; Kalow & Tyndale, 1992). We herein provide a comprehensive review of the relevance of drug metabolizing enzyme and transporter genes to mental health and addictions.
The extent of intertidal flats in the Yellow Sea region has declined significantly in the past few decades, resulting in severe population declines in several waterbird species. The Yellow Sea region holds the primary stopover sites for many shorebirds during their migration to and from northern breeding grounds. However, the functional roles of these sites in shorebirds’ stopover ecology remain poorly understood. Through field surveys between July and November 2015, we investigated the stopover and moult schedules of migratory shorebirds along the southern Jiangsu coast, eastern China during their southbound migration, with a focus on the ‘Critically Endangered’ Spoon-billed Sandpiper Calidris pygmaea and ‘Endangered’ Nordmann’s Greenshank Tringa guttifer. Long-term count data indicate that both species regularly occur in globally important number in southern Jiangsu coast, constituting 16.67–49.34% and 64.0–80.67% of their global population estimates respectively, and it is highly likely that most adults undergo their primary moult during this southbound migration stopover. Our results show that Spoon-billed Sandpiper and Nordmann’s Greenshank staged for an extended period of time (66 and 84 days, respectively) to complete their primary moult. On average, Spoon-billed Sandpipers and Nordmann’s Greenshanks started moulting primary feathers on 8 August ± 4.52 and 27 July ± 1.56 days respectively, and their moult durations were 72.58 ± 9.08 and 65.09 ± 2.40 days. In addition, some individuals of several other shorebird species including the ‘Endangered’ Great Knot Calidris tenuirostris, ‘Near Threatened’ Bar-tailed Godwit Limosa lapponica, ‘Near Threatened’ Eurasian Curlew Numenius arquata and Greater Sand Plover Charadrius leschenaultii also underwent primary moult. Our work highlights the importance of the southern Jiangsu region as the primary moulting ground for these species, reinforcing that conservation of shorebird habitat including both intertidal flats and supratidal roosting sites in this region is critical to safeguard the future of some highly threatened shorebird species.
Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction.
Methods and Results:
Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with ≥2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with ≥1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had ≥2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 ± 4.6 years, with an average first ejection fraction of 63.1 ± 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 ± 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate.
In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function.
Oxidative stress is implicated in the aetiology of schizophrenia, and the antioxidant defence system (AODS) may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain and its correlates with clinical and demographic variables in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r = −0.46, p = 0.015), and a trend-level positive relationship between GSH and duration of illness (r = 0.34, p = 0.076).
Our findings are consistent with a possible compensatory upregulation of the AODS with longer duration of illness and suggest that the AODS may play a role in schizophrenia.
Background: CNS innate immune cells, microglia and macrophages (MMs), are the largest component of the inflammatory infiltrate in glioblastoma (GBM). They initially participate in tumor surveillance, but are subverted by GBM. Immunotherapies have proven incredibly successful in cancers such as melanoma, but not against GBM in part because GBM-associated MMs are not well understood. We hypothesized the content and inflammatory phenotype of MMs in GBM is variable between patients. We suspect MMs in IDH-wildtype and –mutant GBMs display divergent inflammatory phenotypes that helps explain the latter's better prognosis. Understanding GBM-associated MM heterogeneity will allow for better immunotherapy development and selection. Methods: MMs were isolated from untreated human IDH-wildtype and -mutant GBMs using flow cytometry and cultured for collection of conditioned media and analysis of secretory products. Automated segmentation with a high-content analysis system was used to quantitate MM content and inflammatory phenotype in frozen sections. New bioinformatics techniques allowed the comparison of MM profiles in publicly available single-cell RNA-sequencing databases with IDH-wildtype and -mutant GBMs. Results: Surprisingly marked variation in MM content exists between GBMs ranging from ~0-70%. A mixture of pro- and anti-inflammatory MMs are found in each GBM. Interestingly, IDH-mutant GBM-associated MMs were more activated than MMs in IDH-wildtype GBMs. Conclusions: Taken together, the highly variable MM content and phenotype of GBMs suggests the success of immunotherapies hinges on taking a precision medicine approach. MM-rich GBMs would benefit more from therapies that target them. MM activation in IDH-mutant GBMs may contribute to better patient prognoses.
Non-compliance with food record submission can induce bias in nutritional epidemiological analysis and make it difficult to draw inference from study findings. We examined the impact of demographic, lifestyle and psychosocial factors on such non-compliance during the first 3 years of participation in a multidisciplinary prospective paediatric study.
The Environmental Determinants of Diabetes in the Young (TEDDY) study collects a 3 d food record quarterly during the first year of life and semi-annually thereafter. High compliance with food record completion was defined as the participating families submitting one or more days of food record at every scheduled clinic visit.
Three centres in the USA (Colorado, Georgia/Florida and Washington) and three in Europe (Finland, Germany and Sweden).
Families who finished the first 3 years of TEDDY participation (n 8096).
High compliance was associated with having a single child, older maternal age, higher maternal education and father responding to study questionnaires. Families showing poor compliance were more likely to be living far from the study centres, from ethnic minority groups, living in a crowded household and not attending clinic visits regularly. Postpartum depression, maternal smoking behaviour and mother working outside the home were also independently associated with poor compliance.
These findings identified specific groups for targeted strategies to encourage completion of food records, thereby reducing potential bias in multidisciplinary collaborative research.
Despite accumulating evidence of structural deficits in individuals with
psychopathy, especially in frontal regions, our understanding of
systems-level disturbances in cortical networks remains limited. We applied
novel graph theory-based methods to assess information flow and connectivity
based on cortical thickness measures in 55 individuals with psychopathy and
47 normal controls. Compared with controls, the psychopathy group showed
significantly altered interregional connectivity patterns. Furthermore,
bilateral superior frontal cortices in the frontal network were identified
as information flow control hubs in the psychopathy group in contrast to
bilateral inferior frontal and medial orbitofrontal cortices as network hubs
of the controls. Frontal information flow and connectivity may have a
significant role in the neuropathology of psychopathy.
We examined white matter volumes in four prefrontal subregions using
structural magnetic resonance imaging in 10 pathological liars, 14
antisocial controls, and 20 normal controls. Liars showed a relatively
widespread increase in white matter (23-36%) in orbitofrontal, middle and
inferior, but not superior, frontal gyri compared with antisocial and normal
controls. This white matter increase may predispose some individuals to
Recent efforts to improve the performance of mid-infrared antimonide-based semiconductor lasers have focused on enhancing the absorption of the pump beam to maximize power conversion efficiencies and minimize threshold intensities. One successful approach has been the optical pumping injection cavity (OPIC) laser, in which a type-II W active region is enclosed between distributed Bragg reflector (DBR) mirrors in order to achieve multiple passes of the pump beam and thereby to enhance absorption.
Previously, fixed wavelength sources have been used for optical pumping of OPIC laser structures, with limited tuning available by adjusting the incident angle. By tuning the pump wavelength using an optical parametric oscillator, we demonstrate minimum threshold intensities and maximum slope efficiencies at the resonance of the DBR cavity surrounding the active region, further demonstrating the potential of OPIC lasers. A 3.2 μm OPIC laser operated at 350 K in pulsed mode (at the highest operating temperature of the dewar), with a characteristic temperature of 50 K. The power conversion efficiency for a single facet at 300 K was the highest ever observed in the mid-IR, at approximately 4%.
Results are presented for two OPIC samples (emitting at ∼3.2 μm and 4.3 μm at high temperature), one of which was designed with a broadened cavity resonance, suitable for pumping with a multi-mode source. Threshold intensities and slope efficiencies measured as a function of pump wavelength demonstrate the strong resonance effect, and that the “broadened OPIC” does in fact manifest a much wider resonance than the non-broadened resonance cavity design.
This book is concerned with the modern theory of Fourier series. Treating developments since Zygmund's classic study, the authors begin with a thorough discussion of the classical one-dimensional theory from a modern perspective. The text then takes up the developments of the 1970s, beginning with Fefferman's famous disc counterexample. The culminating chapter presents Cordoba's geometric theory of Kayeka maximal functions and multipliers. Research workers in the fields of Fourier analysis and harmonic analysis will find this a valuable account of these developments. Second year graduate students, who are familiar with Lebesgue theory and are acquainted with distributions, will be able to use this as a textbook which will bring them up to the exciting open questions in the field.
The purpose of this book is to give a self-contained exposition of the geometric theory of Bochner-Riesz means. The subject deals with the most basic topic in Fourier analysis, the question of when a Fourier series converges to its original function. Substantial progress was made in the mid 1970's, but the techniques are still avaliable only in the technical literature. Our intent is to present an account accessible to graduate students. We have slighted certain important topics in order to maintain a consistent presentation. We have assumed that the reader is familiar with real analysis at a graduate level, and with basic facts about distributions and the Fourier transform. A basic reference is the text by Stein and Weiss, Introduction to Fourier Analysis on Euclidean Spaces , and the texts of Rudin,  and .
In writing this book, we benefitted with extensive conversations over many years with our colleagues. We wish to thank Professors E. Fabes, R. Fefferman, and E. M. Stein for their help with the material in Chapters 1, 2 and 3. The contents of Chapters 4 and 5 were influenced by conversations with Professor A. W. Knapp. For the general philosophy of Chapters 7 and 8 we are indebted to Professors A. Cordoba and C. Fefferman. The first draft of this book was written while the first author was supported by NSF grants MCS 8202165 and 8001799.