To send 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 sending content to .
To send content items to your Kindle, first ensure email@example.com
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 sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent 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.
U.S. government leaders have long considered Latin America their proverbial backyard and have recurrently intervened in the region. In earlier periods of U.S. imperialism, U.S. government leaders justified such intervention with reference to allegedly scientific racial hierarchies, which placed White, Anglo-Saxon Protestants (WASPs) at the top of this artificial hierarchy. In more recent episodes of U.S. imperialism leading into the twenty-first century, however, U.S. leaders have publicly used the language of democracy and human rights to justify intervention. In the instance of contemporary Venezuela, while U.S leaders indeed use the language of human rights and democracy, they also draw on racist tropes of Latin Americans to justify their intervention. Through interviews with U.S. foreign policymakers and analysis of U.S. government documents, I find that U.S. leaders depict former Venezuelan President Hugo Chávez as an irrational, uncivilized, and beastly leader, who manipulates ideas of racial inequality to maintain power. In addition, U.S. leaders understand him as manipulating an uncritical mass of Venezuelans who cannot think for themselves. U.S. leaders believe it thus their duty to intervene in order to promote democracy and show Venezuelans their true political-economic interests. I connect these dynamics with a history of U.S. intervention into the region and a history of racist and imperial thinking that continues to shape the logic of U.S. foreign policymaking into the present.
Background: Children with pathogenic variations in SCN8A can present with early infantile epileptic encephalopathy-13, benign familial infantile seizures-5 or intellectual disability alone without epilepsy. In this case series, we discuss six children with variants in SCN8A managed at BC Children’s Hospital. Methods: We describe clinical and genetic results on six individuals with SCN8A variants identified via clinical or research next-generation sequencing. Functional consequences of two SCN8A variants were assessed using electrophysiological analyses in transfected cells. Results: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Phenotypes and genotypes in our cohort are described in the table below. Functional analysis supported gain-of-function in P2 and loss-of-function in P4. Conclusions: Our cohort expands the clinical and genotypic spectrum of SCN8A-related disorders. We establish functional evidence for two missense variants in SCN8A, including LoF variant in a patient with intellectual disability, and autism spectrum disorder without seizures.
Table for P.120
Current antiseizure medication
Infantile spasms, LGS, hyperkinetic movements
3y - EEG abnormality only
Sodium valproate (discontinued)
No clinical seizure
c.971G>A (p.Cys324Tyr)/LoF, VUS in KCNQ3
Abbreviations: *Father with similar history, y Years, m Months, GDD Global developmental delay, LGS Lennox-Gastaut syndrome, VUS Variant of unknown significance, LoF Loss-of-function, GoF Gain-of-function, EEG Electroencephalogram, F - Female, M - Male, CBD - Cannabidiol
Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults.
Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention.
The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (β = 0.29, p = 0.036, r = 0.27), right supplementary motor area (β = 0.30, p = 0.031, r = 0.29), and both right (β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups.
At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
In 2005 Elizabeth Parker and fellow researchers described the first case of Hyperthymestic Syndrome, a woman going by initials AJ. Thereafter, a handful more of such cases have emerged. Older descriptions of extraordinary memory in medical literature mainly considered semantic and working memories. Jorge Luis Borges in his 1930s short story ‘Funes, his Memory’ writes about his, presumably fictitious, encounter with a man named Ireno Funes who possessed an extraordinary memory and a knack for keeping track of briefest of passing moment. Among many qualities that Funes and AJ share are their extraordinary memories, obsession for keeping track of time, and their problems with abstraction. After describing his extraordinary memory, Borges says of Funes, ‘I suspect nevertheless, that he was not very good at thinking. To think is to ignore (or forget) differences, to generalize, to abstract.’ Similarly, AJ has been described to have impaired abstraction, hypothesis formation and conceptual shifting. Moreover, both Funes and AJ see their capability as a burden rather than a gift. “My memory, sir, is like a garbage heap.” Says Funes.
A brief exploration of Jorge Luis Borges’ works in the context of autobiographical memory.
The comparisons between Borges’ description of his character’s autobiographical memory and findings of modern research techniques will be done qualitatively.
Effort is made to undersatnd Borges philosophy in context of mordern memory research.
An in depth look into Borges’ philosohies linking perception of time, coding of memory, abstration and language can inform further line of research regarding autobiographical memory.
As Ireland confronts the many challenges of broadening the introduction of early intervention services (EIS) for first episode psychosis (FEP) as national policy, this article describes Carepath for Overcoming Psychosis Early (COPE), the EIS of Cavan–Monaghan Mental Health Service, and presents prospective research findings during its first 5 years of operation.
COPE was launched as a rural EIS with an embedded research protocol in early 2012, following an education programme for general practitioners (GPs). Here, operational activities are documented and research findings presented through to late 2016.
During this period, 115 instances of FEP were incepted into COPE, 70.4% via their GP and 29.6% via the Emergency Department. The annual rate of inception was 24.8/100,000 of population aged > 15 years and was 2.1-fold more common among men than women. Mean duration of untreated psychosis was 5.7 months and median time from first psychotic presentation to initiation of antipsychotic treatment was zero days. Assessments of psychopathology, neuropsychology, neurology, premorbid functioning, quality of life, insight, and functionality compared across 10 DSM-IV psychotic diagnoses made at six months following presentation indicated minimal differences between them, other than more prominent negative symptoms in schizophrenia and more prominent mania in bipolar disorder.
COPE illustrates the actuality of introducing and the challenges of operating a rural EIS for FEP. Prospective follow-up studies of the 5-year COPE cohort should inform on the effectiveness of this EIS model in relation to long-term outcome in psychotic illness across what appear to be arbitrary diagnostic boundaries at FEP.
There is growing evidence for human use of geophytes long before the advent of agriculture. Rich in carbohydrates, geophytes were important in many coastal areas where protein-rich marine foods are abundant. On California's Channel Islands, scholars have long questioned how maritime peoples sustained themselves for millennia with limited plant resources. Recent research demonstrates that geophytes were heavily used on the islands for 10,000 years, and here we describe geophyte and other archaeobotanical remains from an approximately 11,500-year-old site on Santa Rosa Island. Currently the earliest evidence for geophyte consumption in North America, our data extend geophyte use on the Channel Islands by roughly 1,500 years and document a diverse and balanced economy for early Paleocoastal peoples. Experimental return rates for a key island geophyte support archaeological evidence that the corms of blue dicks (Dipterostemon capitatus) were a high-ranked staple resource throughout the Holocene.
Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.
Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.
Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.
Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.
This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI).
Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted.
Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065–.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052–.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029).
Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.
Antibiotic-resistant Gram-negative bacteraemias (GNB) are increasing in incidence. We aimed to investigate the impact of empirical antibiotic therapy on clinical outcomes by carrying out an observational 6-year cohort study of patients at a teaching hospital with community-onset Escherichia coli bacteraemia (ECB), Klebsiella pneumoniae bacteraemia (KPB) and Pseudomonas aeruginosa bacteraemia (PsAB). Antibiotic therapy was considered concordant if the organism was sensitive in vitro and discordant if resistant. We estimated the association between concordant vs. discordant empirical antibiotic therapy on odds of in-hospital death and ICU admission for KPB and ECB. Of 1380 patients, 1103 (79.9%) had ECB, 189 (13.7%) KPB and 88 (6.4%) PsAB. Discordant therapy was not associated with increased odds of either outcome. For ECB, severe illness and non-urinary source were associated with increased odds of both outcomes (OR of in-hospital death for non-urinary source 3.21, 95% CI 1.73–5.97). For KPB, discordant therapy was associated with in-hospital death on univariable but not multivariable analysis. Illness severity was associated with increased odds of both outcomes. These findings suggest broadening of therapy for low-risk patients with community-onset GNB is not warranted. Future research should focus on the relationship between patient outcomes, clinical factors, infection focus and causative organism and resistance profile.
In clinical and translational research, data science is often and fortuitously integrated with data collection. This contrasts to the typical position of data scientists in other settings, where they are isolated from data collectors. Because of this, effective use of data science techniques to resolve translational questions requires innovation in the organization and management of these data.
We propose an operational framework that respects this important difference in how research teams are organized. To maximize the accuracy and speed of the clinical and translational data science enterprise under this framework, we define a set of eight best practices for data management.
In our own work at the University of Rochester, we have strived to utilize these practices in a customized version of the open source LabKey platform for integrated data management and collaboration. We have applied this platform to cohorts that longitudinally track multidomain data from over 3000 subjects.
We argue that this has made analytical datasets more readily available and lowered the bar to interdisciplinary collaboration, enabling a team-based data science that is unique to the clinical and translational setting.
Estimation of RMR using prediction equations is the basis for calculating energy requirements. In the present study, RMR was predicted by Harris–Benedict, Schofield, Henry, Mifflin–St Jeor and Owen equations and measured by indirect calorimetry in 125 healthy adult women of varying BMI (17–44 kg/m2). Agreement between methods was assessed by Bland–Altman analyses and each equation was assessed for accuracy by calculating the percentage of individuals predicted within ± 10 % of measured RMR. Slopes and intercepts of bias as a function of average RMR (mean of predicted and measured RMR) were calculated by regression analyses. Predictors of equation bias were investigated using univariate and multivariate linear regression. At group level, bias (the difference between predicted and measured RMR) was not different from zero only for Mifflin–St Jeor (0 (sd 153) kcal/d (0 (sd 640) kJ/d)) and Henry (8 (sd 163) kcal/d (33 (sd 682) kJ/d)) equations. Mifflin–St Jeor and Henry equations were most accurate at the individual level and predicted RMR within 10 % of measured RMR in 71 and 66 % of participants, respectively. For all equations, limits of agreement were wide, slopes of bias were negative, and intercepts of bias were positive and significantly (P < 0⋅05) different from zero. Increasing age, height and BMI were associated with underestimation of RMR, but collectively these variables explained only 15 % of the variance in estimation bias. Overall accuracy of equations for prediction of RMR is low at the individual level, particularly in women with low and high RMR. The Mifflin–St Jeor equation was the most accurate for this dataset, but prediction errors were still observed in about one-third of participants.
Background – Ecstasy is a recreational drug with an anecdotal reputation for safety. However, reports of adverse effects and fatalities have increased in the medical and popular press.
Method – Literature search and review.
Results – Acute Ecstasy toxicity does not appear to be due to overdose and cannot be solely attributed to the nature of the usual ambient environment. Adverse effects include hyperthermia, seizures, cardiac arrhythmias, hepatotoxicity, hyponatraemia and many psychiatric disorders. Ecstasy causes serotonergic neurotoxicity in the brains of animals at doses close to those used by humans, but its long-term effect on the human brain is unknown.
Conclusion – Ecstasy toxicity should be considered in the differential diagnosis of a variety of medical and psychiatric conditions. Given its popularity, both the acute and the potential long-term effects are a cause for concern.
The advent of genome wide association studies have resulted in the identification of a number of novel genetic loci for schizophrenia and related disorders. Understanding the functional impact of these variants on brain structure and function is crucial to understand their role in disease pathology. We presents data based on our genetic and neuropsychological assessment of almost 700 patients and healthy participants for a number of these variants and replication of our findings in independent samples of almost 1500 cases and controls. Specifically, we will use this data to suggest that the risk associated with some genetics variants (e.g. NOS1) is being mediated by an influence on variation in intelligence and other cognitive phenotypes, while other risk variants (e.g. ZNF804A) delineate illness subtypes in which cognitive deficits are a less prominent feature.
Brain-derived neurotrophic factor (BDNF) gene variants may potentially influence behaviour. In order to test this hypothesis, we investigated the relationship between BDNF Val66Met polymorphism and aggressive behaviour in a population of schizophrenic patients. Our results showed that increased number of BDNF Met alleles was associated with increased aggressive behaviour.