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Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Evidence from high-income countries suggests that childhood trauma is associated with schizophrenia. Studies of childhood trauma and schizophrenia in low and middle income (LMIC) countries are limited. This study examined the prevalence of childhood traumatic experiences among cases and controls and the relationship between specific and cumulative childhood traumatic experiences and schizophrenia in a sample in South Africa.
Data were from the Genomics of Schizophrenia in the South African Xhosa people study. Cases with schizophrenia and matched controls were recruited from provincial hospitals and clinics in the Western and Eastern Cape regions in South Africa. Childhood traumatic experiences were measured using the Childhood Trauma Questionnaire (CTQ). Adjusted logistic regression models estimated associations between individual and cumulative childhood traumatic experiences and schizophrenia.
Traumatic experiences were more prevalent among cases than controls. The odds of schizophrenia were 2.44 times higher among those who experienced any trauma than those who reported no traumatic experiences (95% CI 1.77–3.37). The odds of schizophrenia were elevated among those who experienced physical/emotional abuse (OR 1.59, CI 1.28–1.97), neglect (OR 1.39, CI 1.16–1.68), and sexual abuse (OR 1.22, CI 1.03–1.45) compared to those who did not. Cumulative physical/emotional abuse and neglect experiences increased the odds of schizophrenia as a dose–response relationship.
Childhood trauma is common in this population. Among many other benefits, interventions to prevent childhood trauma may contribute to a decreasing occurrence of schizophrenia.
Jurassic siliceous hot-spring (sinter) deposits from Argentine Patagonia were evaluated to determine the distribution and preservation quality of their entombed microbial fabrics. Detailed study showed that the Claudia palaeo-geothermal field hosts the best-preserved sinter apron in the Deseado Massif geological province, where we also found hot-spring silica–biotic interactions extending into hydrothermally influenced fluvial and lacustrine settings. Carbonaceous material was identified by petrography and Raman spectroscopy mapping; it is inter-laminated with silica across proximal vent to distal marsh facies. The ubiquitous presence of microbial biosignatures has application to studies of hydrothermal settings of early life on Earth and potentially Mars.
In a 2017 article, Holen and colleagues reported evidence for a 130 000-year-old
archaeological site in California. Acceptance of the site would overturn current
understanding of global human migrations. The authors here consider Holen
et al.’s conclusions through critical evaluation of
their replicative experiments. Drawing on best practice in experimental
archaeology, and paying particular attention to the authors’ chain of
inference, Magnani et al. suggest that to argue convincingly
for an early human presence at the Cerutti Mastodon site, Holen et
al. must improve their analogical foundations, test alternative
hypotheses, increase experimental control and quantify their results.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Oats can be processed in a variety of ways ranging from minimally processed such as steel-cut oats (SCO), to mildly processed such as large-flake oats (old fashioned oats, OFO), moderately processed such as instant oats (IO) or highly processed in ready-to-eat oat cereals such as Honey Nut Cheerios (HNC). Although processing is believed to increase glycaemic and insulinaemic responses, the effect of oat processing in these respects is unclear. Thus, we compared the glycaemic and insulinaemic responses elicited by 628 kJ portions of SCO, OFO, IO and HNC and a portion of Cream of Rice cereal (CR) containing the same amount of available-carbohydrate (23 g) as the oatmeals. Healthy males (n 18) and females (n 12) completed this randomised, cross-over trial. Blood was taken fasting and at intervals for 3 h following test-meal consumption. Glucose and insulin peak-rises and incremental AUC (iAUC) were subjected to repeated-measures ANOVA using Tukey’s test (two-sided P<0·05) to compare individual means. Glucose peak-rise (primary endpoint, mean (sem) mmol/l) after OFO, 2·19 (sem 0·11), was significantly less than after CR, 2·61 (sem 0·13); and glucose peak-rise after SCO, 1·93 (sem 0·13), was significantly less than after CR, HNC, 2·49 (sem 0·13) and IO 2·47 (sem 0·13). Glucose iAUC was significantly lower after SCO than CR and HNC. Insulin peak rise was similar among the test meals, but insulin iAUC was significantly less after SCO than IO. Thus, the results show that oat processing affects glycaemic and insulinaemic responses with lower responses associated with less processing.
Introduction: Patients with advanced or end-stage illness frequently present to emergency departments (EDs), many of whom are in need of palliative care (PC). Emergency physicians have struggled in providing high quality care to these patients and there is a need to identify cost-effective PC interventions delivered in the ED to improve patient outcomes. The objective of this systematic review was to examine the effectiveness of ED-based PC interventions. Methods: A comprehensive search of nine electronic databases and grey literature sources was conducted to identify any comparative studies assessing the effectiveness of ED-based PC interventions to improve health outcomes of patients with advanced or end-stage illness. Two independent reviewers completed study selection, quality assessment, and data extraction. Differences were mediated via third-party adjudication. Relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random effects model and heterogeneity (I2) was reported. Results: From 5882 potentially eligible citations, 12 studies were included. Two studies are currently on-going clinical trials, and as such, 10 studies were included in this analysis. The studies consisted of before-after studies (n = 5), RCTs (n = 4), and an observational cohort (n = 1). Interventions assessed among the included studies consisted primarily of ED-directed PC consultations (n = 6), while other studies assessed screening of patients with advanced or end-stage illness and PC needs (n = 2), education on PC for ED-staff (n = 1), and an ED-based critical care unit (n = 1). Infrequent reporting of important outcomes (e.g., Mortality, ED relapse) limited the ability of this review to conduct meaningful meta-analysis. There was no difference in patient mortality between two studies assessing ED-directed PC consultations (RR = 0.89; 95% CI: 0.71, 1.13; I2 = 0%). One before-after study (RR = 0.73; 95% CI: 0.47, 1.13) and two RCTs (RR = 2.19; 95% CI: 0.40, 11.92; I2 = 96%) did not identify significant differences in PC consultations intervention (implementation of ED-directed PC consultations) and control (usual care) patients. Conclusion: This review found limited evidence to support the recommendation of any particular ED-based intervention for patients presenting to the ED with advanced or end-stage illness. High quality studies and standardized outcome reporting are needed to better understand the impact of PC interventions in the ED setting.
Introduction: With an increasing proportion of patients in need of end-of-life (EOL) care presenting to the emergency department (ED), many of these patients may benefit from early palliative care (PC) referral. In fact, early PC referral is one of the Choosing Wisely ED recommendations in the USA. As such, there is a potential benefit to identifying patients with advanced or end-stage illness with PC needs. The objective of this systematic review is to identify and synthesize the available evidence regarding the existence and psychometric properties of screening tools to identify patients with advanced or end-stage illness and PC needs presenting to EDs. Methods: A comprehensive search of eight electronic databases and the grey literature was conducted. Studies assessing the ability of a screening instrument to identify ED patients with advanced or end-stage illness in need of PC were eligible for inclusion. Two independent reviewers completed study selection, quality assessment, and data extraction. Disagreements were resolved through third-party adjudication. Due to the significant heterogeneity, as well as inconsistent outcome reporting, a descriptive summary of the results was completed. Results: Once duplicates were removed, the title and abstracts of 3516 studies were screened, of which, 15 studies were included. Overall, 10 unique screening instruments were assessed across the studies. The most commonly assessed screening tool was the use of the modified surprise question (SQ), in which physicians were asked if they would be surprised if the patient died within a specified period of time. Only four of the included studies assessed the diagnostic or psychometric properties of the screening tools. One study reported that the modified SQ predicted PC consultation with 35% sensitivity, 89% specificity, and a negative predictive value of 97%. The proportion of patients identified with PC needs ranged from 12% to 73%, with studies utilizing the SQ reporting a range of 12% to 33%. Conclusion: A variety of screening tools are available to identify ED patients with advanced or end-stage illness who would benefit from a referral for PC. While the modified SQ was the most common instrument assessed and appears to be simple to implement, it is unclear if the diagnostic and psychometric properties of this tool are sufficiently robust to warrant widespread implementation.
Introduction: Atrial fibrillation (AF) is the most common arrhythmia treated in the emergency department (ED) and is associated with an increased risk of ischemic stroke. Studies have shown that only oral anticoagulant (OAC) therapy reduces risk of AF related stroke. Our objective was to measure the prescribing practices for OACs for new onset AF at a tertiary ED and two surrounding community EDs, and identify rates of adverse effects within 90 days. The findings of this study will provide quality assurance information for the management of patients with new onset AF. This information has the potential to promote adherence to prescribing guidelines for AF in the ED and the reduction of common adverse events such as ischemic stroke. Methods: We conducted a retrospective chart review of 385 patients with new onset AF who presented to the ED between November 2014 to Mach 2018. We defined new onset as symptoms <48 hours and had AF confirmed with electrocardiogram. We recorded the selected therapy choice of cardioversion and/or rate control, gender, age, and assessed CHADS-65 score. We recorded who was prescribed OAC and those who were referred to cardiology, family medicine, or did not have a documented follow up plan. Patients with a previous history of AF or current anticoagulant therapy were excluded. We recorded if any patients returned to the ED within 90 days with ischemic stroke, AF recurrence, myocardial infarction, other embolic disease or death. Results: 86 of 294 (29.5%) of patients who qualified under CHADS-65 received OACs appropriately. 64 of 66 (97.0%) of patients who did not qualify under CHADS-65 did not receive OACs appropriately. 5 patients overall returned within 90 days with ischemic stroke, 4 of those were not prescribed OACs, however this was not statistically significant (P = 0.999). Conclusion: This data suggests that physicians in the study are under-prescribing OACs relative to published guidelines. A larger study is necessary to elucidate the effect of ED OAC prescribing patterns on long-term patient outcome.
Every four years leading researchers gather to survey the latest developments in all aspects of group theory. Initially held in St Andrews, these meetings have become the premier forum for group theory across the whole of the UK. Since 1981, the proceedings of 'Groups St Andrews' have provided a regular snapshot of the state-of-the-art in group theory and helped to shape the direction of research in the field. This volume contains papers from the 2017 meeting held in Birmingham. It includes expository articles from the invited speakers, and further surveys contributed by the participants. Topics include: generation of finite simple groups, block theory, fusion systems, algebraic groups, one-relator groups, geometric group theory, and Beauville groups.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
Approximately 70% of the 30 000 known bee (Hymenoptera) species and most flower-visiting, solitary wasps (Hymenoptera) nest in the ground. However, nesting behaviours of most ground-nesting bees and wasps are poorly understood. Habitat loss, including nesting habitat, threatens populations of ground-nesting bees and wasps. Most ground-nesting bee and wasp studies implement trapping methods that capture foraging individuals, but provide little insight into the nesting preferences of these taxa. Some researchers have suggested that emergence traps may provide a suitable means by which to determine ground-nesting bee and wasp abundance. We sought to evaluate nest-site selection of ground-nesting bees and wasps using emergence traps in two study systems: (1) planted wildflower enhancement plots and fallow control plots in agricultural land; and (2) upland pine and hammock habitat in forests. Over the course of three years (2015–2017), we collected 306 ground-nesting bees and wasps across all study sites from emergence traps. In one study, we compared captures per trap between coloured pan traps and emergence traps and found that coloured pan traps captured far more ground-nesting bees and wasps than did emergence traps. Based on our emergence trap data, our results also suggest ground-nesting bees and wasps are more apt to nest within wildflower enhancement plots than in fallow control plots, and in upland pine habitats than in hammock forests. In conclusion, emergence traps have potential to be a unique tool to gain understanding of ground-nesting bee and wasp habitat requirements.