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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.
Methods:
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.
Results:
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.
Conclusions:
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.
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.
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.
Filamentary structures can form within the beam of protons accelerated during the interaction of an intense laser pulse with an ultrathin foil target. Such behaviour is shown to be dependent upon the formation time of quasi-static magnetic field structures throughout the target volume and the extent of the rear surface proton expansion over the same period. This is observed via both numerical and experimental investigations. By controlling the intensity profile of the laser drive, via the use of two temporally separated pulses, both the initial rear surface proton expansion and magnetic field formation time can be varied, resulting in modification to the degree of filamentary structure present within the laser-driven proton beam.
A new sample support film for small spot XRF analysis has been developed that improves detection limits by a factor of 10 over traditional polymer supports. The surface characteristics of this new film are excellent for retaining drops of sample solution in one place and allowing the solution to dry into a single spot A dimpling technique was developed to further aid in concentrating the evaporated samples to the prescribed spot size and position. The film showed good resistance to chemical attacfc from the solution, even some strong acids and bases. The detection limits achieved using micro sample XRF with the ultra thin sample support were sufficient to be a comparable alternative to ICP-MS and GFAAS for elemental analysis.
To test the feasibility of using telehealth to support antimicrobial stewardship at Veterans Affairs medical centers (VAMCs) that have limited access to infectious disease-trained specialists.
Design
A prospective quasi-experimental pilot study.
Setting
Two rural VAMCs with acute-care and long-term care units.
Intervention
At each intervention site, medical providers, pharmacists, infection preventionists, staff nurses, and off-site infectious disease physicians formed a videoconference antimicrobial stewardship team (VAST) that met weekly to discuss cases and antimicrobial stewardship-related education.
Methods
Descriptive measures included fidelity of implementation, number of cases discussed, infectious syndromes, types of recommendations, and acceptance rate of recommendations made by the VAST. Qualitative results stemmed from semi-structured interviews with VAST participants at the intervention sites.
Results
Each site adapted the VAST to suit their local needs. On average, sites A and B discussed 3.5 and 3.1 cases per session, respectively. At site A, 98 of 140 cases (70%) were from the acute-care units; at site B, 59 of 119 cases (50%) were from the acute-care units. The most common clinical syndrome discussed was pneumonia or respiratory syndrome (41% and 35% for sites A and B, respectively). Providers implemented most VAST recommendations, with an acceptance rate of 73% (186 of 256 recommendations) and 65% (99 of 153 recommendations) at sites A and B, respectively. Qualitative results based on 24 interviews revealed that participants valued the multidisciplinary aspects of the VAST sessions and felt that it improved their antimicrobial stewardship efforts and patient care.
Conclusions
This pilot study has successfully demonstrated the feasibility of using telehealth to support antimicrobial stewardship at rural VAMCs with limited access to local infectious disease expertise.
OBJECTIVES/SPECIFIC AIMS: Background: Delirium is a well described form of acute brain organ dysfunction characterized by decreased or increased movement, changes in attention and concentration as well as perceptual disturbances (i.e., hallucinations) and delusions. Catatonia, a neuropsychiatric syndrome traditionally described in patients with severe psychiatric illness, can present as phenotypically similar to delirium and is characterized by increased, decreased and/or abnormal movements, staring, rigidity, and mutism. Delirium and catatonia can co-occur in the setting of medical illness, but no studies have explored this relationship by age. Our objective was to assess whether advancing age and the presence of catatonia are associated with delirium. METHODS/STUDY POPULATION: Methods: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Measures of association (OR) were assessed with a simple logistic regression model with catatonia as the independent variable and delirium as the dependent variable. Effect measure modification by age was assessed using a Likelihood ratio test. RESULTS/ANTICIPATED RESULTS: Results: We enrolled 136 medical and surgical critically ill patients with 452 matched (concomitant) delirium and catatonia assessments. Median age was 59 years (IQR: 52–68). In our cohort of 136 patients, 58 patients (43%) had delirium only, 4 (3%) had catatonia only, 42 (31%) had both delirium and catatonia, and 32 (24%) had neither. Age was significantly associated with prevalent delirium (i.e., increasing age associated with decreased risk for delirium) (p=0.04) after adjusting for catatonia severity. Catatonia was significantly associated with prevalent delirium (p<0.0001) after adjusting for age. Peak delirium risk was for patients aged 55 years with 3 or more catatonic signs, who had 53.4 times the odds of delirium (95% CI: 16.06, 176.75) than those with no catatonic signs. Patients 70 years and older with 3 or more catatonia features had half this risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Catatonia is significantly associated with prevalent delirium even after controlling for age. These data support an inverted U-shape risk of delirium after adjusting for catatonia. This relationship and its clinical ramifications need to be examined in a larger sample, including patients with dementia. Additionally, we need to assess which acute brain syndrome (delirium or catatonia) develops first.
Children reared in impoverished environments are at risk for enduring psychological and physical health problems. Mechanisms by which poverty affects development, however, remain unclear. To explore one potential mechanism of poverty's impact on social–emotional and cognitive development, an experimental examination of a rodent model of scarcity-adversity was conducted and compared to results from a longitudinal study of human infants and families followed from birth (N = 1,292) who faced high levels of poverty-related scarcity-adversity. Cross-species results supported the hypothesis that altered caregiving is one pathway by which poverty adversely impacts development. Rodent mothers assigned to the scarcity-adversity condition exhibited decreased sensitive parenting and increased negative parenting relative to mothers assigned to the control condition. Furthermore, scarcity-adversity reared pups exhibited decreased developmental competence as indicated by disrupted nipple attachment, distress vocalization when in physical contact with an anesthetized mother, and reduced preference for maternal odor with corresponding changes in brain activation. Human results indicated that scarcity-adversity was inversely correlated with sensitive parenting and positively correlated with negative parenting, and that parenting fully mediated the association of poverty-related risk with infant indicators of developmental competence. Findings are discussed from the perspective of the usefulness of bidirectional–translational research to inform interventions for at-risk families.
Crib–biting is a stereotypic behaviour performed by approximately 5% of captive domestic horses. Dietary factors have been strongly associated with the development of oral stereotypies and risk factors for crib–biting, identified in recent epidemiological studies, include feeding high concentrate and/or low forage diets (Waters et al., 2002). Experimental work has shown that such diets are likely to result in increased gastric acidity (Murray and Eichorn, 1996; Nadeau et al., 2000). We therefore propose that young horses initiate crib–biting in an attempt to produce alkaline saliva to buffer their stomachs when alternative opportunities for mastication are limited. The aim of this study was to determine whether there was an association between crib–biting behaviour and stomach condition in foals.
Foals that had recently started to perform crib–biting were recruited into the study and compared with non–stereotypic foals. The stomachs of 15 crib-biting foals and 9 normal foals were examined using a video endoscope.
A significant number of X-ray binaries are now known to exhibit long-term periodicities on timescales of ~10 - 100 days. Several physical mechanisms have been proposed that give rise to such periodicities, one of which is radiation-driven warping and precession of the accretion disk. Recent theoretical work predicts the stability to disk warping as a, function of the mass ratio, binary radius, viscosity and accretion efficiency. We investigate the stability of the superorbital periodicities in the neutron star X-ray binaries Cyg X-2, LMC X-4, SMC X-l and Her X-l, and thereby confront stability predictions with observation. We find that the period and nature of the superorbital variations in these sources is consistent with the predictions of warping theory.
Recent analysis pointed towards visual imaging analysis (VIA), which yields pig body size measures and shape indices from two-dimensional visual images of living pigs, as a potential technique for estimating fat and lean content in pig carcasses (Doeschl et al., 2004). The present analysis further explored the potential of using VIA body size and shape indices as indicators of the proportion of lean and fat in various carcass joints, either alone or in combination with ultrasonic backfat depth of the live animal. Due to increasing interest in the shape of retail cuts in the meat industry, the association between VIA size measures and the dimensions of the longissimus dorsi and gluteobiceps muscles is also assessed.
The Molonglo Observatory Synthesis Telescope (MOST) is an 18000 m2 radio telescope located 40 km from Canberra, Australia. Its operating band (820–851 MHz) is partly allocated to telecommunications, making radio astronomy challenging. We describe how the deployment of new digital receivers, Field Programmable Gate Array-based filterbanks, and server-class computers equipped with 43 Graphics Processing Units, has transformed the telescope into a versatile new instrument (UTMOST) for studying the radio sky on millisecond timescales. UTMOST has 10 times the bandwidth and double the field of view compared to the MOST, and voltage record and playback capability has facilitated rapid implementaton of many new observing modes, most of which operate commensally. UTMOST can simultaneously excise interference, make maps, coherently dedisperse pulsars, and perform real-time searches of coherent fan-beams for dispersed single pulses. UTMOST operates as a robotic facility, deciding how to efficiently target pulsars and how long to stay on source via real-time pulsar folding, while searching for single pulse events. Regular timing of over 300 pulsars has yielded seven pulsar glitches and three Fast Radio Bursts during commissioning. UTMOST demonstrates that if sufficient signal processing is applied to voltage streams, innovative science remains possible even in hostile radio frequency environments.
The class of radio transients called Fast Radio Bursts (FRBs) encompasses enigmatic single pulses, each unique in its own way, hindering a consensus for their origin. The key to demystifying FRBs lies in discovering many of them in order to identity commonalities – and in real time, in order to find potential counterparts at other wavelengths. The recently upgraded UTMOST in Australia, is undergoing a backend transformation to rise as a fast transient detection machine. The first interferometric detections of FRBs with UTMOST, place their origin beyond the near-field region of the telescope thus ruling out local sources of interference as a possible origin. We have localised these bursts to much better than the ones discovered at the Parkes radio telescope and have plans to upgrade UTMOST to be capable of much better localisation still.
Objectives: Studies suggest that impairments in some of the same domains of cognition occur in different neuropsychiatric conditions, including those known to share genetic liability. Yet, direct, multi-disorder cognitive comparisons are limited, and it remains unclear whether overlapping deficits are due to comorbidity. We aimed to extend the literature by examining cognition across different neuropsychiatric conditions and addressing comorbidity. Methods: Subjects were 486 youth consecutively referred for neuropsychiatric evaluation and enrolled in the Longitudinal Study of Genetic Influences on Cognition. First, we assessed general ability, reaction time variability (RTV), and aspects of executive functions (EFs) in youth with non-comorbid forms of attention-deficit/hyperactivity disorder (ADHD), mood disorders and autism spectrum disorder (ASD), as well as in youth with psychosis. Second, we determined the impact of comorbid ADHD on cognition in youth with ASD and mood disorders. Results: For EFs (working memory, inhibition, and shifting/ flexibility), we observed weaknesses in all diagnostic groups when participants’ own ability was the referent. Decrements were subtle in relation to published normative data. For RTV, weaknesses emerged in youth with ADHD and mood disorders, but trend-level results could not rule out decrements in other conditions. Comorbidity with ADHD did not impact the pattern of weaknesses for youth with ASD or mood disorders but increased the magnitude of the decrement in those with mood disorders. Conclusions: Youth with ADHD, mood disorders, ASD, and psychosis show EF weaknesses that are not due to comorbidity. Whether such cognitive difficulties reflect genetic liability shared among these conditions requires further study. (JINS, 2018, 24, 91–103)
A prompt radio burst has been observed from the supernova 1987a in the Large Magellanic Cloud. Observations were made at 0.843, 1.415, 2.29, and 8.41 GHz. At frequencies around 1 GHz, the peak flux density reached about 150 mJy and occurred within four days of the supernova. This event may be a weak precursor to a major radio outburst of the type previously observed in other extragalactic supernovae. Radio monitoring of the supernova is continuing at each of the above frequencies, and coordination is underway of a southern hemisphere VLBI array to map the radio outburst region as it expands. Differential astrometry carried out on prime-focus plates taken with the Anglo-Australian telescope indicates that the component, star 1, of Sanduleak's star SK-69202 is within 0.05 ± 0.13 arcsec of the supernova.
Specimens of polycrystalline ice were experimentally deformed in plane strain at a temperature of –1°C, under a constant load and with shortening strains varying from 2 to 27%. The random c-axis orientation of the initial ice aggregates changes continuously with increasing strain towards a steady-state, small-circle containing two maxima lying about the shortening direction. The ice microstructure is sequentially transformed from undeformed grains to smaller, irregular, deformed grains containing recrystallized grains. Grain growth then occurs forming a coarse interlocking-grain aggregate. These microstructural changes are attributed to solid-state processes occurring during deformation. The previously deformed specimens were then annealed without a load at –1°C. Annealing resulted in a substantial grain-size coarsening. However, no c-axis preferred-orientation difference developed between annealed and unannealed samples.
Accurate models of X-ray absorption and re-emission in partly stripped ions are necessary to calculate the structure of stars, the performance of hohlraums for inertial confinement fusion and many other systems in high-energy-density plasma physics. Despite theoretical progress, a persistent discrepancy exists with recent experiments at the Sandia Z facility studying iron in conditions characteristic of the solar radiative–convective transition region. The increased iron opacity measured at Z could help resolve a longstanding issue with the standard solar model, but requires a radical departure for opacity theory. To replicate the Z measurements, an opacity experiment has been designed for the National Facility (NIF). The design uses established techniques scaled to NIF. A laser-heated hohlraum will produce X-ray-heated uniform iron plasmas in local thermodynamic equilibrium (LTE) at temperatures
${\geqslant}150$
eV and electron densities
${\geqslant}7\times 10^{21}~\text{cm}^{-3}$
. The iron will be probed using continuum X-rays emitted in a
${\sim}200$
ps,
${\sim}200~\unicode[STIX]{x03BC}\text{m}$
diameter source from a 2 mm diameter polystyrene (CH) capsule implosion. In this design,
$2/3$
of the NIF beams deliver 500 kJ to the
${\sim}6$
mm diameter hohlraum, and the remaining
$1/3$
directly drive the CH capsule with 200 kJ. Calculations indicate this capsule backlighter should outshine the iron sample, delivering a point-projection transmission opacity measurement to a time-integrated X-ray spectrometer viewing down the hohlraum axis. Preliminary experiments to develop the backlighter and hohlraum are underway, informing simulated measurements to guide the final design.