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.
Background: Despite a higher prevalence of traumatic spinal cord injury (TSCI) amongst Canadian Indigenous peoples, there is a paucity of studies focused on Indigenous TSCI. We present the first Canada-wide study comparing TSCI amongst Canadian Indigenous and non-Indigenous peoples. Methods: This study is a retrospective analysis of prospectively-collected TSCI data from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) from 2004-2019. We divided participants into Indigenous and non-Indigenous cohorts and compared them with respect to demographics, injury mechanism, level, severity, and outcomes. Results: Compared with non-Indigenous patients, Indigenous patients were younger, more female, less likely to have higher education, and less likely to be employed. The mechanism of injury was more likely due to assault or transportation-related trauma in the Indigenous group. The length of stay for Indigenous patients was longer. Indigenous patients were more likely to be discharged to a rural setting, less likely to be discharged home, and more likely to be unemployed following injury. Conclusions: Our results suggest that more resources need to be dedicated for transitioning Indigenous patients sustaining a TSCI to community living and for supporting these patients in their home communities. A focus on resources and infrastructure for Indigenous patients by engagement with Indigenous communities is needed.
Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\alpha$. We find an approximately linear dependence of $L_\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\langle L_\alpha \rangle = ( ( 1154 \pm 121) - ( 0.81 \pm 0.14) \, ( \nu /{\rm MHz}) ) \,{\rm m}$ for frequencies ν ∈ [145 − 350] MHz.
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.
This chapter begins by surveying the current literature on constitutional design constitutions for divided societies and constitutional approaches to power sharing. It pays particular attention to the view that constitutions are best understood not as contracts, but rather as coordination devices. An implication of this view for constitutional design is that, in deeply divided societies, successful coordination (and thus successful constitution-writing) may be easier to achieve if the constitution deliberately leaves certain divisive constitutional questions unresolved, with the understanding that those questions will be resolved incrementally over time. Against this theoretical background, the chapter uses the history and constitutional history of Afghanistan to illuminate the challenges of developing a constitution that can coordinate politics in a deeply divided society, and it evaluates the pros and cons of different approaches to constitutional design in such contexts.
We present the most sensitive and detailed view of the neutral hydrogen (
${\rm H\small I}$
) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal
${\rm H\small I}$
in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K (
$1.6\,\mathrm{mJy\ beam}^{-1}$
)
$\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$
spectral channel with an angular resolution of
$30^{\prime\prime}$
(
${\sim}10\,\mathrm{pc}$
). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire
${\sim}25\,\mathrm{deg}^2$
field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes
${\rm H\small I}$
test observations.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.
Methods
Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.
Results
The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.
Conclusions
The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
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.
Immune system abnormalities exist across a range of psychiatric disorders. Autoimmunity, characterized by the production of antibodies against the body’s own antigens, is a feature of immune system dysfunction and could play a role in mental disorder pathophysiology. Better understanding of the associations of auto-immunoglobulin G (IgG) repertoires with clinical features of mental illness could yield novel models of psychosis pathophysiology and markers for biological patient stratification.
Objectives
To undertake global screening for auto-IgG expression in a large cohort of people with psychotic disorders; to determine whether associations exist between autoantibody expression and clinical features.
Methods
Cross-sectional quantification of auto-IgGs in blood plasma of 461 people with established psychotic disorder diagnoses. For global screening, pooled samples of phenotypically representative patient groups were exposed to planar protein microarrays containing 42,000 human antigens. For targeted profiling, expression levels of 380 autoantibodies were quantified by suspension bead array (SBA) in each patient’s plasma.
Results
We identified highly individual autoantibody profiles with no evidence for co-expression patterns. We found 6 autoantibodies robustly associated with specific psychopathology: anti-AP3B2, detected in 5% of the cohort of whom 100% had persecutory delusions; anti-TDO2 (5% of the cohort, 100% hallucinations); anti-CRYGN (4%, 86% initial insomnia); anti-APMAP (3%, 86% poor appetite); anti-OLFM1 (2.5%, 100% above median cognitive function); and anti-WHAMMP3 (2%, 90% anhedonia and dysphoria). Examination of the auto-IgG binding site on the TDO2 protein revealed a putative pathophysiological mechanism involving the kynurenine pathway.
Conclusions
We identified 6 frequently occurring autoantibodies that were associated with specific clinical features in people with psychotic disorders.
Quasi-periodic plasmoid formation at the tip of magnetic streamer structures is observed to occur in experiments on the Big Red Ball as well as in simulations of these experiments performed with the extended magnetohydrodynamics code, NIMROD. This plasmoid formation is found to occur on a characteristic time scale dependent on pressure gradients and magnetic curvature in both experiment and simulation. Single mode, or laminar, plasmoids exist when the pressure gradient is modest, but give way to turbulent plasmoid ejection when the system drive is higher, which produces plasmoids of many sizes. However, a critical pressure gradient is also observed, below which plasmoids are never formed. A simple heuristic model of this plasmoid formation process is presented and suggested to be a consequence of a dynamic loss of equilibrium in the high-$\beta$ region of the helmet streamer. This model is capable of explaining the periodicity of plasmoids observed in the experiment and simulations, and produces plasmoid periods of 90 minutes when applied to two-dimensional models of solar streamers with a height of $3R_\odot$. This is consistent with the location and frequency at which periodic plasma blobs have been observed to form by Large Angle and Spectrometric Coronograph and Sun Earth Connection Coronal and Heliospheric Investigation instruments.
Magnetic reconnection is explored on the Terrestrial Reconnection Experiment (TREX) for asymmetric inflow conditions and in a configuration where the absolute rate of reconnection is set by an external drive. Magnetic pileup enhances the upstream magnetic field of the high-density inflow, leading to an increased upstream Alfvén speed and helping to lower the normalized reconnection rate to values expected from theoretical consideration. In addition, a shock interface between the far upstream supersonic plasma inflow and the region of magnetic flux pileup is observed, important to the overall force balance of the system, thereby demonstrating the role of shock formation for configurations including a supersonically driven inflow. Despite the specialized geometry where a strong reconnection drive is applied from only one side of the reconnection layer, previous numerical and theoretical results remain robust and are shown to accurately predict the normalized rate of reconnection for the range of system sizes considered. This experimental rate of reconnection is dependent on system size, reaching values as high as 0.8 at the smallest normalized system size applied.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
Sleep and circadian timing shifts later during adolescence, conflicting with early school start times, and resulting in circadian misalignment. Although circadian misalignment has been linked to depression, substance use, and altered reward function, a paucity of experimental studies precludes the determination of causality. Here we tested, for the first time, whether experimentally-imposed circadian misalignment alters the neural response to monetary reward and/or response inhibition.
Methods
Healthy adolescents (n = 25, ages 13–17) completed two in-lab sleep schedules in counterbalanced order: An ‘aligned’ condition based on typical summer sleep-wake times (0000–0930) and a ‘misaligned’ condition mimicking earlier school year sleep-wake times (2000–0530). Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward (morning only) and response inhibition (morning and afternoon) tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively.
Results
Bilateral ventral striatal (VS) activation during reward outcome was lower during the Misaligned condition after accounting for the prior night's total sleep time. Bilateral VS activation during reward anticipation was lower during the Misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the Misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan.
Conclusions
Our findings provide novel experimental evidence that circadian misalignment analogous to that resulting from school schedules may have measurable impacts on healthy adolescents' reward processing and inhibition of prepotent responses.
When presenting with a first episode of psychosis (FEP), migrants can have different demographic and clinical characteristics to the native-born population and this was examined in an Irish Early Intervention for Psychosis service.
Methods:
All cases of treated FEP from three local mental health services within a defined catchment area were included. Psychotic disorder diagnoses were determined using the SCID and symptom and functioning domains were measured using validated and reliable measures.
Results:
From a cohort of 612 people, 21.1% were first-generation migrants and there was no difference in the demographic characteristics, diagnoses, symptoms or functioning between migrants and those born in the Republic of Ireland, except that migrants from Africa presented with less insight. Of those admitted, 48.6% of admissions for migrants were involuntary compared to 37.7% for the native-born population (p = 0.09).
Conclusions:
First-generation migrants now make up a significant proportion of people presenting with a FEP to an Irish EI for psychosis service. Broadly the demographic and clinical characteristics of migrants and those born in the Republic of Ireland are similar, except for less insight in migrants from Africa and a trend for a higher proportion of involuntary admissions in the total migrant group.
Quantum decision theory corrects categorical and propositional logic pathologies common to classic statistical goal-oriented reasoning, such as rational neuroeconomics-based optimal foraging. Within this ecosalient framework, motivation, perception, learning, deliberation, brain computation, and conjunctive risk-order errors may be understood for subjective utility judgments underlying either rational or irrational canonical decisions-actions used to choose, procure, and consume rewarding nutrition with variable fitness.