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.
Bipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk.
Neuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12–30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions.
Compared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independent of time, the HR group had greater cortical thickness in the left caudal anterior cingulate cortex, larger volume in the right medial orbitofrontal cortex and greater area of right accumbens, compared to controls. This pattern was evident even in those without the new onset of psychopathology during the inter-scan interval.
This study suggests that differences previously observed in BD are developing prior to the onset of the disorder. The pattern of pathological acceleration of cortical thinning is likely consistent with a disturbance of molecular mechanisms responsible for normal cortical thinning. We also demonstrate that neuroanatomical differences in HR individuals may be progressive in some regions and stable in others.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
The extent of intertidal flats in the Yellow Sea region has declined significantly in the past few decades, resulting in severe population declines in several waterbird species. The Yellow Sea region holds the primary stopover sites for many shorebirds during their migration to and from northern breeding grounds. However, the functional roles of these sites in shorebirds’ stopover ecology remain poorly understood. Through field surveys between July and November 2015, we investigated the stopover and moult schedules of migratory shorebirds along the southern Jiangsu coast, eastern China during their southbound migration, with a focus on the ‘Critically Endangered’ Spoon-billed Sandpiper Calidris pygmaea and ‘Endangered’ Nordmann’s Greenshank Tringa guttifer. Long-term count data indicate that both species regularly occur in globally important number in southern Jiangsu coast, constituting 16.67–49.34% and 64.0–80.67% of their global population estimates respectively, and it is highly likely that most adults undergo their primary moult during this southbound migration stopover. Our results show that Spoon-billed Sandpiper and Nordmann’s Greenshank staged for an extended period of time (66 and 84 days, respectively) to complete their primary moult. On average, Spoon-billed Sandpipers and Nordmann’s Greenshanks started moulting primary feathers on 8 August ± 4.52 and 27 July ± 1.56 days respectively, and their moult durations were 72.58 ± 9.08 and 65.09 ± 2.40 days. In addition, some individuals of several other shorebird species including the ‘Endangered’ Great Knot Calidris tenuirostris, ‘Near Threatened’ Bar-tailed Godwit Limosa lapponica, ‘Near Threatened’ Eurasian Curlew Numenius arquata and Greater Sand Plover Charadrius leschenaultii also underwent primary moult. Our work highlights the importance of the southern Jiangsu region as the primary moulting ground for these species, reinforcing that conservation of shorebird habitat including both intertidal flats and supratidal roosting sites in this region is critical to safeguard the future of some highly threatened shorebird species.
Innovation Concept: Research training programs for students, especially in emergency medicine (EM), may be difficult to initiate due to lack of protected time, resources, and mentors (Chang Y, Ramnanan CJ. Academic Medicine 2015). We developed a ten-week summer program for medical students aimed at cultivating research skills through mentorship, clinical enrichment, and immersion in EM research culture through shadowing and project support. Methods: Five second year Ontario medical students were recruited to participate in the Summer Training and Research in Emergency Medicine (STAR-EM) program at University Health Network, Toronto, from June - Aug, 2019. Program design followed review of existing summer research programs and literature regarding challenges to EM research (McRae, Perry, Brehaut et al. CJEM 2018). The program had broad emergency physician (EP) engagement, with five EP research project mentors, and over ten EPs delivering academic sessions. Curriculum development was collaborative and iterative. All projects were approved by the hospital Research Ethics Board (REB). Curriculum, Tool or Material: Each weekly academic morning comprised small group teaching (topics including research methodology, manuscript preparation, health equity, quality improvement, and wellness), followed by EP-led group progress review of each student's project. Each student spent one half day per week in the emergency department (ED), shadowing an EP and identifying patients for recruitment for ongoing mentor-initiated ED research projects. Remaining time was spent on independent student project work. Presentation to faculty and program evaluation occurred in week 10. Scholarly output included one abstract submitted for publication per student. Program evaluation by students reflected a uniform impression that course material and mentorship were each excellent (100%, n = 5). Interest in pursuing academic EM as a career was identified by all students. Faculty researchers rated the program as very effective (80%, n = 4) or somewhat effective (20%, n = 1) in terms of enhancing productivity and scholarly output. Conclusion: The STAR-EM program provides a transferable model for other academic departments seeking to foster the development of future clinician investigators and enhance ED research culture. Program challenges included delays in REB approval for student projects and engaging recalcitrant staff to participate in research.
For high switching speed HV Schottky diodes, with very high work function metal and extremely lightly doped epi, the built-in potential may be too high for thermionic emission to occur, when the applied external voltage is quite low (near VF = 0.07V). If the epi is lightly doped p type, the built-in potential (VBuilt-in: potential difference between the metal and silicon Fermi levels) is 1.0V (measured with CV). If the external bias is 0.1V, near the measured VF, it is not enough to overcome the built-in potential for thermionic emission as illustrated. It is likely that in addition to thermionic emission, tunnelling and diffusion currents also contribute to the total HV Schottky diode forward current. TCAD simulation of HV Schottky diodes with N+ guard bands suggests the potential barrier and electric fields at the Schottky junction are relatively high for thermionic emission to occur, when external bias V ≈ VF. In this paper we report HV Schottky diodes fabricated with various metals, metal alloys and epitaxial films. Metal work functions and epi doping profiles are extracted with high frequency Capacitance-Voltage (CV) technique. 150V of breakdown voltage and very low forward voltage (VF = 0.07V) are demonstrated. The measured data indicate very high work function metal or metal alloy is needed to achieve high switching speed and low forward voltage.
Nudging in microbiology is an antimicrobial stewardship strategy to influence decision making through the strategic reporting of microbiology results while preserving prescriber autonomy. The purpose of this scoping review was to identify the evidence that demonstrates the effectiveness of nudging strategies in susceptibility result reporting to improve antimicrobial use.
A search for studies in Ovid MEDLINE, Embase, PsycINFO, and All EBM Reviews was conducted. All simulated and vignette studies were excluded. Two independent reviewers were used throughout screening and data extraction.
Of a total of 1,346 citations screened, 15 relevant studies were identified. Study types included pre- and postintervention (n = 10), retrospective cohort (n = 4), and a randomized controlled trial (n = 1). Most studies were performed in acute-care settings (n = 13), and the remainder were in primary care (n = 2). Most studies used a strategy to alter the default antibiotic choices on the antibiotic report. All studies reported at least 1 outcome of antimicrobial use: utilization (n = 9), appropriateness (n = 7), de-escalation (n = 2), and cost (n = 1). Moreover, 12 studies reported an overall benefit in antimicrobial use outcomes associated with nudging, and 4 studies evaluated the association of nudging strategy with subsequent antimicrobial resistance, with 2 studies noting overall improvement.
The number of heterogeneous studies evaluating the impact of applying nudging strategies to susceptibility result reports is small; however, most strategies do show promise in altering prescriber’s antibiotic selection. Selective and cascade reporting of targeted agents in a hospital setting represent the majority of current research. Gaps and opportunities for future research identified from our scoping review include performing prospective randomized controlled trials and evaluating other approaches aside from selective reporting.
Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children’s behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children’s behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children’s behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children’s internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children’s behavioural psychopathology.
Section 1 of the FM14 focus on bridging the astronomy research and outreach communities - recent highlights, emerging collaborations, best practices and support structures. This paper also contains supplementary materials that point to contributed talks and poster presentations that can be found online.
Antibiotic use varies widely between hospitals, but the influence of antimicrobial stewardship programs (ASPs) on this variability is not known. We aimed to determine the key structural and strategic aspects of ASPs associated with differences in risk-adjusted antibiotic utilization across facilities.
Observational study of acute-care hospitals in Ontario, Canada
A survey was sent to hospitals asking about both structural (8 elements) and strategic (32 elements) components of their ASP. Antibiotic use from hospital purchasing data was acquired for January 1 to December 31, 2014. Crude and adjusted defined daily doses per 1,000 patient days, accounting for hospital and aggregate patient characteristics, were calculated across facilities. Rate ratios (RR) of defined daily doses per 1,000 patient days were compared for hospitals with and without each antimicrobial stewardship element of interest.
Of 127 eligible hospitals, 73 (57%) participated in the study. There was a 7-fold range in antibiotic use across these facilities (min, 253 defined daily doses per 1,000 patient days; max, 1,872 defined daily doses per 1,000 patient days). The presence of designated funding or resources for the ASP (RRadjusted, 0·87; 95% CI, 0·75–0·99), prospective audit and feedback (RRadjusted, 0·80; 95% CI, 0·67–0·96), and intravenous-to-oral conversion policies (RRadjusted, 0·79; 95% CI, 0·64–0·99) were associated with lower risk-adjusted antibiotic use.
Wide variability in antibiotic use across hospitals may be partially explained by both structural and strategic ASP elements. The presence of funding and resources, prospective audit and feedback, and intravenous-to-oral conversion should be considered priority elements of a robust ASP.
Background: Inadequate postoperative pain control is common and is associated with negative clinical outcomes. The objective is to identify preoperative predictors of poor postoperative pain control in the adult population undergoing inpatient surgery. Methods: Meta-analysis was performed according to MOOSE guidelines. Studies were included if they evaluated postoperative pain using a validated instrument in adults undergoing inpatient surgery and reported a measure of association between poor postoperative pain control and at least one preoperative predictor. Measures of association were pooled using random effects models. Results: A total of 33 studies representing 59,259 patients were included. Significant preoperative predictors of poor postoperative pain included sleeping difficulties (OR 2.32 [95% CI 1.46-3.69]), history of depressive symptoms (OR 1.71 [95% CI 1.32-2.22]), use of preoperative analgesia (OR 1.54 [95% CI 1.18-2.03]), smoking (OR 1.33 [95% CI 1.09-1.61]), -female sex (OR 1.29 [95% CI 1.17-1.43]), presence of preoperative pain (OR 1.21 [95% CI 1.10-1.32]], history of anxiety symptoms (OR 1.22 [95% CI 1.09-1.36)], younger age (OR 1.18 [95% CI 1.05-1.32)], and higher BMI (OR 1.02 [95% CI 1.01-1.03]). Conclusions: Nine significant predictors of poor postoperative pain control were identified and these should be recognized as important factors when developing pre- and peri-operative strategies to improve pain outcomes.
Background: Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease. In June 2017, Health Canada approved Nusinersen, currently the only available drug for SMA. Since 2016, patients in Ontario have been treated clinically with Nusinersen through different access programs. Methods: Retrospective case series of patients with SMA treated clinically with Nusinersen in Ontario, describing clinical characteristics and logistics of intrathecal Nusinersen administration. Results: Twenty patients have been treated across four centres. To date, we have reviewed 8 cases at one centre (seven SMA Type I, one SMA Type II). Age at first dose ranged from 3-156 months and disease duration 9-166 months. Patients had received 4-7 doses at last evaluation. Three patients with scoliosis (2 with spinal rods) required fluoroscopy-guided radiologist administration, and 4 required general anesthesia. No complications/adverse events were reported. At last follow up, 5/8 families reported improved daily activities. Of 5 patients with baseline and follow up motor function testing, 3 demonstrated improved scores. One patient died due to respiratory decline at age 9 months, despite improved motor outcome scores. Conclusions: We describe the first Canadian post-marketing experience with Nusinersen. Timely dissemination of this information is needed to guide clinicians, hospital administrators, and policy-makers.
Outpatient parenteral antimicrobial therapy (OPAT) programmes facilitate hospital discharge, but patients remain at risk of complications and consequent healthcare utilisation (HCU). Here we elucidated the incidence of and risk factors associated with HCU in OPAT patients. This was a retrospective, single-centre, case–control study of adult patients discharged on OPAT. Cases (n = 63) and controls (n = 126) were patients that did or did not utilise the healthcare system within 60 days. Characteristics associated with HCU in bivariate analysis (P ≤ 0.2) were included in a multivariable logistic regression model. Variables were retained in the final model if they were independently (P < 0.05) associated with 60-day HCU. Among all study patients, the mean age was 55 ± 16, 65% were men, and wound infection (22%) and cellulitis (14%) were common diagnoses. The cumulative incidence of 60-day unplanned HCU was 27% with a disproportionately higher incidence in the first 30 days (21%). A statin at discharge (adjusted odds ratios (aOR) 0.23, 95% confidence intervals (CIs) 0.09–0.57), number of prior admissions in past 12 months (aOR 1.48, 95% CIs 1.05–2.10), and a sepsis diagnosis (aOR 4.62, 95% CIs 1.23–17.3) were independently associated with HCU. HCU was most commonly due to non-infection related complications (44%) and worsening primary infection (31%). There are multiple risk factors for HCU in OPAT patients, and formal OPAT clinics may help to risk stratify and target the highest risk groups.
Nasal obstruction is a common ENT complaint; however, decisions on its management are challenging, with high rates of dissatisfaction following surgery. This study investigated the practice of UK clinicians in the evaluation of nasal patency.
Seventy-eight UK-based rhinologists were surveyed at the 2015 British Academic Conference in Otolaryngology.
Clinical history and examination are almost universally used to evaluate nasal blockage. The most commonly used test was the nasal misting pattern (73 per cent), followed by peak nasal inspiratory flow (19 per cent). The Sino-Nasal Outcome Test 22 or 23 was utilised by 29 per cent of respondents. Sixty-three per cent of respondents reported that a lack of equipment was the principle reason for not using objective measures, followed by time constraints and a lack of correlation with symptom scores.
British clinicians rely on clinical skills to evaluate nasal blockage. There is a desire for a simple, non-invasive device that objectively measures airflow for nasal breathing during physiological resting and correlates with subjective symptom scores.