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.
An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
Building on prior work using Tom Dishion's Family Check-Up, the current article examined intervention effects on dysregulated irritability in early childhood. Dysregulated irritability, defined as reactive and intense response to frustration, and prolonged angry mood, is an ideal marker of neurodevelopmental vulnerability to later psychopathology because it is a transdiagnostic indicator of decrements in self-regulation that are measurable in the first years of life that have lifelong implications for health and disease. This study is perhaps the first randomized trial to examine the direct effects of an evidence- and family-based intervention, the Family Check-Up (FCU), on irritability in early childhood and the effects of reductions in irritability on later risk of child internalizing and externalizing symptomatology. Data from the geographically and sociodemographically diverse multisite Early Steps randomized prevention trial were used. Path modeling revealed intervention effects on irritability at age 4, which predicted lower externalizing and internalizing symptoms at age 10.5. Results indicate that family-based programs initiated in early childhood can reduce early childhood irritability and later risk for psychopathology. This holds promise for earlier identification and prevention approaches that target transdiagnostic pathways. Implications for future basic and prevention research are discussed.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
As in vivo cellular imaging becomes the necessary norm for understanding cancer and other diseases, new non-toxic nanoprobes are going to be required to replace the high quality cadmium based nanoprobes in use today. We are developing less toxic probes based on two types of luminescent ceramic nanoparticles: naturally occurring fluorescent (NOF) mimics and Ln-based ceramic oxide materials. The NOF minerals of interest and that have demonstrated initial luminosity of sufficient brightness for use in cellular studies that include sphalerite, scheelite, manganoan and perovskite nanoparticles. For Ln-based materials we have shown that Ln-doped zincite will also luminesce enough to allow for quantification in cellular activity. Once formed, these probes are functionalized such that they can be delivered to desired cellular targets. Probe derivatization has focused on surface capping with functionalized poly(ethyleneglycol) molecules/lipids to yield water soluble NCs and polyarginine-based transporters for transmembrane delivery. The probes are being evaluated for their luminescent properties, as well as their non-toxicity and ability to report on cell-signaling events with various cell lines using multi-spectral, confocal microscopy, and other techniques. Preliminary interdisciplinary studies have validated the basic approaches for the synthesis of NOF nanoprobes and the bio-delivery and imaging of nanoparticles. Work to optimize the design, delivery, and imaging of these new nanoprobes is expected to achieve the NIH directed goal of increasing in the sensitivity and specificity of molecular probes for imaging. Details of the synthesis, functionalization and biological imaging using these probes will be presented. This work partially supported by the United States Department of Energy under contract number DE-AC04-94AL85000. Sandia is a multi-program laboratory operated by Sandia Corporation, a Lockheed-Martin Company, for the United States Department of Energy and by the National Institutes of health through the NIH Roadmap for Medical Research, Grant #1 R21 EB005365-01. Information on this RFA (Innovation in Molecular Imaging Probes) can be found at http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-021.html.
Much of what is known about the Indigenous city of Cahokia, located in and influential on the North American midcontinent during the eleventh through fourteenth centuries AD, derives from decades of salvage, research, and CRM excavations in the surrounding American Bottom region. We use this robust dataset to explore patterns of building conflagration that suggest these practices of burning were part of pre-Mississippian traditions that were bundled into new Cahokian landscapes during the early consolidation of the city. These bundled practices entangled sources of power that were at once political and religious, thus transforming the practices and meanings associated with terminating building use via fire.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Introduction: Simulation is becoming widely adopted across medical disciplines and by different medical professionals. For medical students, emergency medicine simulation has been shown to increase knowledge, confidence and satisfaction. At the University of Ottawa Skills and Simulation Centre, third-year medical students participate in simulated scenarios common to Emergency Medicine (EM) as part of their mandatory EM clerkship rotation. This study aims to evaluate simulation as part of the EM clerkship rotation by assessing changes in student confidence following a simulation session. Methods: In groups of seven, third year medical students at the University of Ottawa completed simulation sessions of the following: Status Asthmaticus, Status Epilepticus, Urosepsis and Breaking Bad News. Student confidence with each topic was assessed before and after simulation with a written survey. Confidence scores pre- and post-simulation were compared with the Wilcoxon signed rank test. Results: Forty-eight third years medical students in their core EM clerkship rotation, between September 2017 and August 2018 participated in this study. Medical student confidence with diagnosis of status asthmaticus (N = 44, p = 0.0449) and status epilepticus (N = 45, p = 0.0011) increased significantly following simulation, whereas confidence with diagnosis of urosepsis was unchanged (N = 45, p = 0.0871). Treatment confidence increased significantly for status asthmaticus (N = 47, p = 0.0009), status epilepticus (N = 48, p = 0.0005) and urosepsis (N = 48, p < 0.0001). Confidence for breaking bad news was not significantly changed after simulation (N = 47, p = 0.0689). Conclusion: Simulation training in our EM clerkship rotation significantly increased the confidence of medical students for certain common EM presentations, but not for all. Further work will aim to understand why some simulation scenarios did not improve confidence, and look to improve existing scenarios.
Introduction: Acute aortic syndrome (AAS) is a time sensitive aortic catastrophe that is often misdiagnosed. There are currently no Canadian guidelines to aid in diagnosis. Our goal was to adapt the existing American Heart Association (AHA) and European Society of Cardiology (ESC) diagnostic algorithms for AAS into a Canadian evidence based best practices algorithm targeted for emergency medicine physicians. Methods: We chose to adapt existing high-quality clinical practice guidelines (CPG) previously developed by the AHA/ESC using the GRADE ADOLOPMENT approach. We created a National Advisory Committee consisting of 21 members from across Canada including academic, community and remote/rural emergency physicians/nurses, cardiothoracic and cardiovascular surgeons, cardiac anesthesiologists, critical care physicians, cardiologist, radiologists and patient representatives. The Advisory Committee communicated through multiple teleconference meetings, emails and a one-day in person meeting. The panel prioritized questions and outcomes, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations. The algorithm was prepared and revised through feedback and discussions and through an iterative process until consensus was achieved. Results: The diagnostic algorithm is comprised of an updated pre test probability assessment tool with further testing recommendations based on risk level. The updated tool incorporates likelihood of an alternative diagnosis and point of care ultrasound. The final best practice diagnostic algorithm defined risk levels as Low (0.5% no further testing), Moderate (0.6-5% further testing required) and High ( >5% computed tomography, magnetic resonance imaging, trans esophageal echocardiography). During the consensus and feedback processes, we addressed a number of issues and concerns. D-dimer can be used to reduce probability of AAS in an intermediate risk group, but should not be used in a low or high-risk group. Ultrasound was incorporated as a bedside clinical examination option in pre test probability assessment for aortic insufficiency, abdominal/thoracic aortic aneurysms. Conclusion: We have created the first Canadian best practice diagnostic algorithm for AAS. We hope this diagnostic algorithm will standardize and improve diagnosis of AAS in all emergency departments across Canada.
Geophysical survey and excavations from 2010–2016 at Lawrenz Gun Club (11CS4), a late pre-Columbian village located in the central Illinois River valley in Illinois, identified 10 mounds, a central plaza, and dozens of structures enclosed within a stout 10 hectare bastioned palisade. Nineteen radiocarbon (14C) measurements were taken from single entities of wood charcoal, short-lived plants, and animal bones. A site chronology has been constructed using a Bayesian approach that considers the stratigraphic contexts and feature formation processes. The village was host to hundreds of years of continuous human activity during the Mississippi Period. Mississippian activity at the site is estimated to have begun in cal AD 990–1165 (95% probability), ended in cal AD 1295–1450 (95% probability), and lasted 150–420 yr (95% probability) in the primary Bayesian model with similar results obtained in two alternative models. The palisade is estimated to have been constructed in cal AD 1150–1230 (95% probability) and was continuously repaired and rebuilt for 15–125 yr (95% probability), probably for 40–85 yr (68% probability). Comparison to other studies demonstrates that the bastioned palisade at Lawrenz was one of the earliest constructed in the midcontinental United States.
Declining mortality following invasive pneumococcal disease (IPD) has been observed concurrent with a reduced incidence due to effective pneumococcal conjugate vaccines. However, with IPD now increasing due to serotype replacement, we undertook a statistical analysis to estimate the trend in all-cause 30-day case fatality rate (CFR) in the North East of England (NEE) following IPD. Clinical, microbiological and demographic data were obtained for all laboratory-confirmed IPD cases (April 2006–March 2016) and the adjusted association between CFR and epidemiological year estimated using logistic regression. Of the 2510 episodes of IPD included in the analysis, 486 died within 30 days of IPD (CFR 19%). Increasing age, male sex, a diagnosis of septicaemia, being in ⩾1 clinical risk groups, alcohol abuse and individual serotypes were independently associated with increased CFR. A significant decline in CFR over time was observed following adjustment for these significant predictors (adjusted odds ratio 0.93, 95% confidence interval 0.89–0.98; P = 0.003). A small but significant decline in 30-day all-cause CFR following IPD has been observed in the NEE. Nonetheless, certain population groups remain at increased risk of dying following IPD. Despite the introduction of effective vaccines, further strategies to reduce the ongoing burden of mortality from IPD are needed.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
Most people can readily identify a forest, or a grassland, or a wetland - these are the simple labels we give different plant communities. The aim of this book is to move beyond these simple descriptions to investigate the 'hidden' structure of vegetation, asking questions such as how do species in a community persist over time? What prevents the strongest species from taking over? And, are there rules that confer stability and produce repeatable patterns? Answers to these questions are fundamental to community ecology, and for the successful management of the world's varied ecosystems, many of which are currently under threat. In addition to reviewing and synthesising our current knowledge of species interactions and community assembly, this book also seeks to offer a different viewpoint - to challenge the reader, and to stimulate ecologists to think differently about plant communities and the processes that shape them.