We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure coreplatform@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Experiential learning, such as simulation-based training, is widely used in health education. Dramatic self-expression adds another layer through enacted perspective taking, and embodied self-exploration of interaction with others, to foster situated learning. We describe the evaluation of an innovative drama-based experiential learning project involving collaboration between multidisciplinary mental healthcare staff and people with lived experience of mental illness. The programme was facilitated at East London NHS Foundation Trust by a theatre company experienced in delivering workshops with service users. A weekly group programme took place online over 8 weeks during the COVID-19 pandemic and included activities of improvisation, embodied enactments and debriefing. The programme led to co-production of a drama piece that was filmed and distributed online. It was hypothesised that the experiential learning might result in individual benefits for all participants, such as improved well-being and increased mutual understanding of each other's experience of mental health care. The project aimed to improve relationships between healthcare disciplines, and between staff and service users. Additionally, aims were to empower service users, and support staff to practice core interpersonal skills. Objectives of the evaluation were to study the impact of the experiential learning, understand participants’ experience, and explore challenges and benefits.
Methods
A mixed methods approach was taken to evaluate the programme. Following completion of the project, participants were invited to complete a questionnaire utilising a Likert scale rating of overall satisfaction with the project, perceived benefit and impact on specific domains such as working with others. One-to-one semi-structured interviews were conducted according to a topic-guide, and qualitative data were analysed using open & axial coding for thematic analysis.
Results
11 participants, including Psychiatrists, Occupational Therapists and current service users, completed the experiential learning and filming. Questionnaire data suggested participants were highly satisfied with the learning and felt it would be valuable to others. Themes include the positive experience of creativity, dismantling of hierarchy, improved empathy, confidence and connection. Potential challenges were digital inequality and lack of dedicated time for professional development.
Conclusion
A drama-based experiential learning group programme for healthcare staff and service users is a highly beneficial learning experience. Participants describe changes on a personal level as well as improved understanding of others’ perspectives. This form of experiential learning features collaborative working that aligns with principles of co-production and supports the development of interpersonal skills; the findings suggest that drama-based experiential learning is a useful method in health education to complement knowledge acquisition.
Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.
OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.
In a 1916 paper, Ramanujan studied the additive convolution
$S_{a, b}(n)$
of sum-of-divisors functions
$\sigma_a(n)$
and
$\sigma_b(n)$
, and proved an asymptotic formula for it when a and b are positive odd integers. He also conjectured that his asymptotic formula should hold for all positive real a and b. Ramanujan’s conjecture was subsequently proved by Ingham, and then by Halberstam with a power saving error term.
In this paper, we give a new proof of Ramanujan’s conjecture that obtains lower order terms in the asymptotics for most ranges of the parameters. We also describe a connection to a counting problem in geometric topology that was studied in the second author’s thesis and which served as our initial motivation in studying this sum.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
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.
The most immediate response of the research community to COVID-19 has been a focus on understanding the effects, treatment and prevention of infection. Of equal and ongoing importance is elucidating the impact of mitigation measures, such as lockdown, on the well-being of societies. Research about mental health and lockdown in the UK has predominately involved large surveys that are likely to encounter self-selection bias. Further, self-reporting does not constitute a clinical judgement.
Aims
To (a) compare the age, gender and ethnicity of patients experiencing mental health emergencies prior compared with during lockdown, (b) determine whether the nature of mental health emergencies has changed during compared with before lockdown, (c) explore the utility of emergency medical service data for identifying vulnerability to mental health emergencies in real time during a pandemic.
Method
A total of 32 401 clinical records of ambulance paramedics attending mental health emergencies in the East Midlands of the UK between 23 March and 31 July 2020 and the same period in 2019 were analysed using binary logistic regression.
Results
People of younger age, male gender and South Asian and Black ethnicity are particularly vulnerable to acute mental health conditions during lockdown. Patients with acute cases of anxiety have increased during lockdown whereas suicide and intentional drug overdose have decreased.
Conclusions
Self-reported data may underrepresent the true impact of lockdown on male mental health and ethnic minority groups. Emergency medical data can be used to identify vulnerable communities in the context of the extraordinary circumstances surrounding the current pandemic, as well as under more ordinary circumstances.
Wavelength-dispersive X-ray (WDX) spectroscopy was used to measure silicon atom concentrations in the range 35–100 ppm [corresponding to (3–9) × 1018 cm−3] in doped AlxGa1–xN films using an electron probe microanalyser also equipped with a cathodoluminescence (CL) spectrometer. Doping with Si is the usual way to produce the n-type conducting layers that are critical in GaN- and AlxGa1–xN-based devices such as LEDs and laser diodes. Previously, we have shown excellent agreement for Mg dopant concentrations in p-GaN measured by WDX with values from the more widely used technique of secondary ion mass spectrometry (SIMS). However, a discrepancy between these methods has been reported when quantifying the n-type dopant, silicon. We identify the cause of discrepancy as inherent sample contamination and propose a way to correct this using a calibration relation. This new approach, using a method combining data derived from SIMS measurements on both GaN and AlxGa1–xN samples, provides the means to measure the Si content in these samples with account taken of variations in the ZAF corrections. This method presents a cost-effective and time-saving way to measure the Si doping and can also benefit from simultaneously measuring other signals, such as CL and electron channeling contrast imaging.
A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).
Methods
The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.
Results
When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).
Conclusions
We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.
Background: In January 2019, our large academic medical center implemented hard stops for ordering Clostridiodes difficile nucleic acid amplification testing (NAAT), and required a discussion with an infectious diseases physician if the order was placed in a clinical scenario not consistent with the 2017 IDSA/SHEA C. difficile infection (CDI) testing guidelines. Recently, some groups have expressed concerns that requiring the discontinuation of laxatives may delay the diagnosis of CDI and result in serious adverse outcomes. Methods:C. difficile testing stewardship interventions were performed at 2 hospitals within the same university health system to reduce inappropriate testing. In January 2019, a best practice advisory (BPA) was implemented to alert providers ordering C. difficile NAAT if patients had received laxatives within 24 hours, requiring a discussion with the ID physician to override the hard stop. We reviewed clinical outcomes of patients who had a BPA alert due to laxative use within the past 24 hours April 23 to October 23, 2019. Results: During the study period, there were 235 patients with a BPA because of laxative use within the past 24 hours. Moreover, 55 (23.4%) continued to experience diarrhea after the discontinuation of laxatives and were retested for CDI within 7 days. Only 8 tests returned positive, suggesting that, at most, 3.4% of cases had delayed diagnoses because of the hard stop. This finding is supported by the increase in the percentage of tests positive from 11.6% observed overall to 14.6% (8 of 55) after this intervention. There were no severe CDI cases (ICU admission, colectomy, or death) among patients who had delayed testing due to laxative use. Conclusions: In the setting of laxative use, C. difficile testing stewardship interventions with C. difficile NAAT using a hard-stop BPA are effective in reducing unnecessary testing and safe if they are used in combination with a real-time expert input of the risk of clinical disease.
We reviewed stroke care delivery during the COVID-19 pandemic at our stroke center and provincial telestroke system. We counted referrals to our prevention clinic, code strokes, thrombolysis, endovascular thrombectomies, and activations of a provincial telestroke system from February to April of 2017–2020. In April 2020, there was 28% reduction in prevention clinic referrals, 32% reduction in code strokes, and 26% reduction in telestroke activations compared to prior years. Thrombolysis and endovascular thrombectomy rates remained constant. Fewer patients received stroke services across the spectrum from prevention, acute care to telestroke care in Ontario, Canada, during the COVID-19 pandemic.
Since the International Agency on Cancer Research’s monograph found glyphosate to be a likely carcinogen, the regulatory focus on the chemical has centred on this determinative criterion for regulatory action. Yet, other pertinent factors, such as the effects of glyphosate on fresh and ground water and ensuing effects on biodiversity, have received less attention as legitimate rationales for regulating the chemical. This underrepresentation prevents a wider policy discussion on the environmental and human health effects of the chemical and fails to disrupt assumptions of path-dependently continuing on agriculture’s chemical treadmill. To avoid ad hoc post hoc chemical regulation, we assess four areas of chemical regulatory oversight in Europe with regard to glyphosate affecting water: (1) the undue emphasis on in laboratorio versus in situ testing; (2) assessing single chemicals (isolated glyphosate) versus admixtures (glyphosate plus surfactants and adjuvants) that are used in practice; (3) the tendency to downplay harms to non-human life; and (4) the lack of policy coherence in the existing regulatory framework. Focusing on European Union regulation of pesticide and water policy affecting aquatic environments, we conclude that issues of measurement and priority have become highly politicised in both science and policy, requiring preventative, precautionary frameworks utilising plural forms of measurement.
The output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors.
Methods
To test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients.
Results
Compared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (<1.5 h) as quantified by a larger scaling exponent (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week.
Conclusions
Our results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Methods:
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Results:
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
Conclusion:
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
In the final pages of David Leeming’s magisterial biography James Baldwin, the author recounts an intimate confession that Baldwin made to him in their final conversation, which took place on November 24, 1987, just seven days before Baldwin’s death: “That night Jimmy and I talked about theater. If he could have started all over again, he might have concentrated on being a playwright and maybe an actor; he liked the immediacy of the stage, working with live people and having the audience right there.” What might happen to our understanding of Baldwin’s life and legacy if we linger with this minor detail? I suggest that the implications of this short, often overlooked passage when situated in the context of the other biographical details of the last year of Baldwin’s life – namely the fact that he was at work on what was to be the loosely autobiographical play The Welcome Table – are significant. Baldwin’s deathbed longing to start life “all over again” with a focus on playwriting and performance might come to some as a stunning admission. But for those attuned to the minor frequencies of the author’s life, Baldwin’s confession simply gives voice to a desire (specifically the desire/impulse toward theater and theatricality) that seems to have been with him – even if never fully realized – all throughout his life. Baldwin’s journey as a playwright was a lifelong expedition that began in his earliest moments as a fledgling writer. As early as 1941 – a full decade before the publication of his novelistic debut Go Tell It on the Mountain (1953) – Baldwin had already penned a drama entitled These Two, a short play about two young black men, one of whom commits suicide and one of whom is killed by the police. His career as a published playwright also included his 1958 stage version of Giovanni’s Room, which ran at The Actors Studio in Greenwich Village under the direction of Turkish director Elia Kazan (where he met actor Engin Cezzar, who would later become the driving force behind Baldwin’s decade in Istanbul, Turkey); his 1964 Blues for Mister Charlie (which he famously dedicated to the memories of Medgar Evers and Emmett Till); and 1954’s The Amen Corner (which he had workshopped for well over a decade – including an early run at Howard University in 1955 – before eventually making its doomed arrival on the Broadway stage, where it closed after only eighty-four performances).