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To characterize the spectrum of BRCA1 and BRCA2 pathogenic germline variants in women from south-west Poland and west Ukraine affected with breast or ovarian cancer. Testing in women at high risk of breast and ovarian cancer in these regions is currently mainly limited to founder mutations.
Unrelated women affected with breast and/or ovarian cancer from Poland (n = 337) and Ukraine (n = 123) were screened by targeted sequencing. Excluded from targeted sequencing were 34 Polish women who had previously been identified as carrying a founder mutation in BRCA1. No prior testing had been conducted among the Ukrainian women. Thus, this study screened BRCA1 and BRCA2 in the germline DNA of 426 women in total.
We identified 31 and 18 women as carriers of pathogenic/likely pathogenic (P/LP) genetic variants in BRCA1 and BRCA2, respectively. We observed five BRCA1 and eight BRCA2 P/LP variants (13/337, 3.9%) in the Polish women. Combined with the 34/337 (10.1%) founder variants identified prior to this study, the overall P/LP variant frequency in the Polish women was thus 14% (47/337). Among the Ukrainian women, 16/123 (13%) women were identified as carrying a founder mutation and 20/123 (16.3%) were found to carry non-founder P/LP variants (10 in BRCA1 and 10 in BRCA2).
These results indicate that genetic testing in women at high risk of breast and ovarian cancer in Poland and Ukraine should not be limited to founder mutations. Extended testing will enhance risk stratification and management for these women and their families.
In this paper, we review empirical studies of multidisciplinary collaboration in design and innovation activities. From 200 papers, we selected 17 for a meta-synthesis review. When revisited and compared, they present common themes and dichotomy in findings. This literature review discusses such diversity, offering a methodological critique of unclear areas. Four emerged themes were identified: (1) Knowledge diversity, (2) Trust, (3) Barrier and (4) Jargon and communication, providing perspectives for further research on how online collaboration will influence multidisciplinary team processes.
Introduction: Wide variability exists in emergency department (ED) syncope management. The Canadian Syncope Risk Score (CSRS) was derived and validated to predict the probability of 30-day serious outcomes after ED disposition. The objective was to identify barriers and facilitators among physicians for CSRS use to stratify risk and guide disposition decisions Methods: We conducted semi-structured interviews with physicians involved in ED syncope care at 8 Canadian sites. We used purposive sampling, contacting ED physicians, cardiologists, internists, and hospitalists until theme saturation was reached. Interview questions were designed to understand whether the CSRS recommendations are consistent with current practice, barriers and facilitators for application into practice, and intention for future CSRS use. Interviews were conducted via telephone or videoconference. Two independent raters coded interviews using an inductive approach to identify themes, with discrepancies resolved through consensus. Our methods were consistent with the Knowledge to Action Framework, which highlights the need to assess barriers and facilitators for knowledge use and for adapting new interventions into local contexts. Results: We interviewed 14 ED physicians, 7 cardiologists, and 10 hospitalists/internists across 8 sites. All physicians reported the use of electrocardiograms for patients with syncope, a key component in the CSRS criteria. Almost all physicians reported that the low risk recommendation (discharge without specific follow-up) was consistent with current practice, while less consistency was seen for moderate (15 days outpatient monitoring) and high risk recommendations (outpatient monitoring and/or admission). Key barriers to following the CSRS included a lack of access to outpatient monitoring and uncertainty over timely follow-up care. Other barriers included patient/family concerns, social factors, and necessary bloodwork. Facilitators included assisting with patient education, reassurance of their clinical gestalt, and optimal patient factors (e.g. reliability to return, support at home, few comorbidities). Conclusion: Physicians are receptive to using the CSRS tool for risk stratification and decision support. Implementation should address identified barriers, and adaptation to local settings may involve modifying the recommended clinical actions based on local resources and feasibility.
Introduction: Emergency department (ED) syncope management is extremely variable. We developed practice recommendations based on the validated Canadian Syncope Risk Score (CSRS) and outpatient cardiac monitoring strategy with physician input. Methods: We used a 2-step approach. Step-1: We pooled data from the derivation and validation prospective cohort studies (with adequate sample size) conducted at 11 Canadian sites (Sep 2010 to Apr 2018). Adults with syncope were enrolled excluding those with serious outcome identified during index ED evaluation. 30-day adjudicated serious outcomes were arrhythmic (arrhythmias, unknown cause of death) and non-arrhythmic (MI, structural heart disease, pulmonary embolism, hemorrhage)]. We compared the serious outcome proportion among risk categories using Cochran-Armitage test. Step-2: We conducted semi-structured interviews using observed risk to develop and refine the recommendations. We used purposive sampling of physicians involved in syncope care at 8 sites from Jun-Dec 2019 until theme saturation was reached. Two independent raters coded interviews using an inductive approach to identify themes; discrepancies were resolved by consensus. Results: Of the 8176 patients (mean age 54, 55% female), 293 (3.6%; 95%CI 3.2-4.0%) experienced 30-day serious outcomes; 0.4% deaths, 2.5% arrhythmic, 1.1% non-arrhythmic outcomes. The serious outcome proportion significantly increased from low to high-risk categories (p < 0.001; overall 0.6% to 27.7%; arrhythmic 0.2% to 17.3%; non-arrhythmic 0.4% to 5.9% respectively). C-statistic was 0.88 (95%CI0.86–0.90). Non-arrhythmia risk per day for the first 2 days was 0.5% for medium-risk, 2% for high-risk and very low thereafter. We recruited 31 physicians (14 ED, 7 cardiologists, 10 hospitalists/internists). 80% of physicians agreed that low risk patients can be discharged without specific follow-up with inconsistencies around length of ED observation. For cardiac monitoring of medium and high-risk, 64% indicated that they don't have access; 56% currently admit high-risk patients and an additional 20% agreed to this recommendation. A deeper exploration led to following refinement: discharge without specific follow-up for low-risk, a shared decision approach for medium-risk and short course of hospitalization for high-risk patients. Conclusion: The recommendations were developed (with online calculator) based on in-depth feedback from key stakeholders to improve uptake during implementation.
Using baseline and outcome data collected in the Calgary Region Children and Adolescent Mental Health Program (CAMHP) over the last six years, a profile was developed for those who are at risk for poor treatment outcomes.
Based on the data collected in CAMHP, 6229 completed measurable treatment plans (MTP) were analyzed for consistency (by year) and theoretical meaningfulness (by clinical level). A table was developed to describe by quartiles those who improved and those who got worse in terms of problem severity and function. A multi-variable linear regression model was developed for function with linked data that predicted the profile of those at risk for poor treatment outcomes.
MTP scores reflecting problem severity and function were consistent over time. Further, MTP scores were theoretically meaningful (e.g., inpatients were more severe on admission than those receiving community or day hospital-based treatment). In total, 659 MTPs indicated no improvement for a negative state and an additional 830 changed negatively in problem severity and Children's Global Assessment Scale (C-GAS) scores. The multivariable model based on admission data provided a risk profile for this group that accounted for 52% of the variance for discharge function.
The baseline and outcome data gathered from the Regional Access and Intake System (RAIS) serving CAMHP may be used effectively to predict clinical outcomes in ways that can draw attention to those at risk for poor outcomes.
The aim of this study was to assess alcoholic inpatients' smoking and coffee intake variation following withdrawal. Only moderate smokers (less than 30 cigarettes/day) showed a significant increase of cigarette consumption after alcohol withdrawal. However, their urinary cotinine level did not vary, suggesting a behavioral, and not biological, compensation through smoking following alcohol withdrawal. Heavy smokers (30 cigarettes/day or more) showed no significant clinical or biological variation of smoking behavior. Coffee consumption increased after alcohol withdrawal in all patients, irrespective of smoking habits.
Preliminary evidence has suggested that high-fat diets (HFD) enriched with SFA, but not MUFA, promote hyperinsulinaemia and pancreatic hypertrophy with insulin resistance. The objective of this study was to determine whether the substitution of dietary MUFA within a HFD could attenuate the progression of pancreatic islet dysfunction seen with prolonged SFA-HFD. For 32 weeks, C57BL/6J mice were fed either: (1) low-fat diet, (2) SFA-HFD or (3) SFA-HFD for 16 weeks, then switched to MUFA-HFD for 16 weeks (SFA-to-MUFA-HFD). Fasting insulin was assessed throughout the study; islets were isolated following the intervention. Substituting SFA with MUFA-HFD prevented the progression of hyperinsulinaemia observed in SFA-HFD mice (P < 0·001). Glucose-stimulated insulin secretion from isolated islets was reduced by SFA-HFD, yet not fully affected by SFA-to-MUFA-HFD. Markers of β-cell identity (Ins2, Nkx6.1, Ngn3, Rfx6, Pdx1 and Pax6) were reduced, and islet inflammation was increased (IL-1β, 3·0-fold, P = 0·007; CD68, 2·9-fold, P = 0·001; Il-6, 1·1-fold, P = 0·437) in SFA-HFD – effects not seen with SFA-to-MUFA-HFD. Switching to MUFA-HFD can partly attenuate the progression of SFA-HFD-induced hyperinsulinaemia, pancreatic inflammation and impairments in β-cell function. While further work is required from a mechanistic perspective, dietary fat may mediate its effect in an IL-1β–AMP-activated protein kinase α1-dependent fashion. Future work should assess the potential translation of the modulation of metabolic inflammation in man.
Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1–79 years in 2012–2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%–6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%–6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%–8.0%). More males were seropositive (6.9%; 95% CI 5.2%–8.6%) than females (4.2%; 95% CI 2.9%–5.5%) with peak seroprevalence at 50–59 years (9.2%; 95% CI 5.2%–13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.
There is a need for accurate and efficient assessment tools that cover a range of mental health and psychosocial problems. Existing, lengthy self-report assessments may reduce accuracy due to respondent fatigue. Using data from a sample of adults enrolled in a psychotherapy randomized trial in Thailand and a cross-sectional sample of adolescents in Zambia, we leveraged Item Response Theory (IRT) methods to create brief, psychometrically sound, mental health measures.
We used graded-response models to refine scales by identifying and removing poor performing items that were not well correlated with the underlying trait, and by identifying well-performing items at varying levels of a latent trait to assist in screening or monitoring purposes.
In Thailand, the original 17-item depression scale was shortened to seven items and the 30-item Posttraumatic Stress Scale (PTS) was shortened to 10. In Zambia, the Child Posttraumatic Stress Scale (CPSS) was shortened from 17 items to six. Shortened scales in both settings retained the strength of their psychometric properties. When examining longitudinal intervention effects in Thailand, effect sizes were comparable in magnitude for the shortened and standard versions.
Using Item Response Theory (IRT) we created shortened valid measures that can be used to help guide clinical decisions and function as longitudinal research tools. The results of this analysis demonstrate the reliability and validity of shortened scales in each of the two settings and an approach that can be generalized more broadly to help improve screening, monitoring, and evaluation of mental health and psychosocial programs globally.
The neuro-endoscopy is a surgical technique that allows the neurosurgeon to maintain a visual contact while operating inside the brain of a patient. A special instrument called the neuro-endoscope is inserted in the brain until the neurosurgeon reaches his/her target. Its manipulation requires a high level of training for neurosurgeons. To enforce both quality and safety of neuro-endoscopy, we propose a robotic manipulator based on a Spherical Decoupled Mechanism. This mechanical architecture has been modified from a 5-Bar Spherical Linkages and adapted to this medical application. It is able to generate a Remote Center of Motion of 2 Degrees of Freedom. It merges the advantages of parallel mechanisms with the kinematic and control simplicity of decoupled mechanisms, while having a very simple architecture. Motion capture experiments using a brain simulation model have been performed with a team of neurosurgeons to obtain the kinematic data of the neuro-endoscope during brain exploration. Based on the identified workspace, the mechanism has been optimized using kinematic performance and architectural compactness as criteria. An optimum mechanism has been selected, showing better kinematic performances than the original 5-bar spherical linkage mechanism.
Increasing weed control costs and limited herbicide options threaten vegetable crop profitability. Traditional interrow mechanical cultivation is very effective at removing weeds between crop rows. However, weed control within the crop rows is necessary to establish the crop and prevent yield loss. Currently, many vegetable crops require hand weeding to remove weeds within the row that remain after traditional cultivation and herbicide use. Intelligent cultivators have come into commercial use to remove intrarow weeds and reduce cost of hand weeding. Intelligent cultivators currently on the market such as the Robovator, use pattern recognition to detect the crop row. These cultivators do not differentiate crops and weeds and do not work well among high weed populations. One approach to differentiate weeds is to place a machine-detectable mark or signal on the crop (i.e., the crop has the mark and the weed does not), thereby facilitating weed/crop differentiation. Lettuce and tomato plants were marked with labels and topical markers, then cultivated with an intelligent cultivator programmed to identify the markers. Results from field trials in marked tomato and lettuce found that the intelligent cultivator removed 90% more weeds from tomato and 66% more weeds from lettuce than standard cultivators without reducing yields. Accurate crop and weed differentiation described here resulted in a 45% to 48% reduction in hand-weeding time per hectare.
In engineering applications, it is pretty often to have domain heat source involved inside. This article proposes an approach using the boundary element method to study thermal stresses in 3D anisotropic solids when internal domain heat source is involved. As has been well noticed, thermal effect will give rise to a volume integral, where its direct evaluation will need domain discretization. This shall definitely destroy the most distinctive notion of the boundary element method that only boundary discretization is required. The present work presents an analytical transformation of the volume integral in the boundary integral equation due to the presence of internal volume heat source. For simplicity, distribution of the heat source is modeled by a quadratic function. When needed, the formulations can be further extended to treat higher-ordered volume heat sources. Indeed, the present work has completely restored the boundary discretization feature of the boundary element method for treating 3D anisotropic thermoelasticity involving volume heat source.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Background: Déjà vu is a common manifestation of temporal lobe seizures. It can be reproduced by electrical stimulation of the hippocampus, amygdala and temporal neocortex with stereotactically implanted electrodes. We report here déjà vu triggered by the stimulation of the insula. Methods: Two patients suffering from intractable temporal lobe epilepsy exhibiting auras of déjà vu underwent invasive EEG studies. One patient had a prior temporal lobectomy with reoccurrence of similar symptoms after surgery. We performed functional connectivity analyses using phase locking value (PLV) to estimate changes in connectivity between different brain regions in the standard EEG frequency bands during stimulation. Results: Stimulation of the insular cortex induced reproducible déjà vu symptoms in both patients. In one patient, PLV analysis showed increased synchronization in the alpha band between insular and temporal regions after an evoked déjà vu compared to a control stimulation. Conclusions: Our results suggest that the insula may in rare occasions generate déjà vu. This implies that insular epileptogenicity cannot be ruled out in patients exhibiting such an aura nor in patients with persisting déjà vu despite an initial amygdalo-hippocampectomy.