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This is a copy of the slides presented at the meeting but not formally written up for the volume.
At heterojunctions between different oxide perovskite phases both lattice and electronic structure is modified by the junction. One interesting question that several groups have studied is just how far into the neighboring materials these perturbations extend. We have studied this for insulating phases as well as conducting phases. For insulating phases it appears that the lattice distortions are healed in a layer about one unit cell thick. By stacking different materials each of which is only a single unit cell thick we have obtained materials that exhibit new properties determined by the stacking architecture. For example, superlattices that lack inversion symmetry have a built-in polarization that is controlled by the direction of the strain asymmetry. For conducting phases, the electronic structure also seems to be modified mainly in a layer only a few unit cells thick. We have studied this in superlattices of SrTiO3 and LaMnO3 in which we vary the thickness of the layers. We use optical conductivity to probe the electronic structure in the near infrared to near ultraviolet spectral region. The conductivity is close to the average of the two constituents, but differs in certain spectral regions, especially for the films with the thinnest supercells.This work was supported by the Department of Energy Basic Energy Sciences program at the Fredrick Seitz Materials Research Laboratory at the University of Illinois, Urbana, IL.
Recognising the significant extent of poor-quality care and human rights issues in mental health, the World Health Organization launched the QualityRights initiative in 2013 as a practical tool for implementing human rights standards including the United Nations Convention on Rights of Persons with Disabilities (CRPD) at the ground level.
To describe the first large-scale implementation and evaluation of QualityRights as a scalable human rights-based approach in public mental health services in Gujarat, India.
This is a pragmatic trial involving implementation of QualityRights at six public mental health services chosen by the Government of Gujarat. For comparison, we identified three other public mental health services in Gujarat that did not receive the QualityRights intervention.
Over a 12-month period, the quality of services provided by those services receiving the QualityRights intervention improved significantly. Staff in these services showed substantially improved attitudes towards service users (effect sizes 0.50–0.17), and service users reported feeling significantly more empowered (effect size 0.07) and satisfied with the services offered (effect size 0.09). Caregivers at the intervention services also reported a moderately reduced burden of care (effect size 0.15).
To date, some countries are hesitant to reforming mental health services in line with the CRPD, which is partially attributable to a lack of knowledge and understanding about how this can be achieved. This evaluation shows that QualityRights can be effectively implemented even in resource-constrained settings and has a significant impact on the quality of mental health services.
Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron (SMN1) gene. In the phase 1 trial (NCT02122952), SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of 15 symptomatic SMA1 patients (3 at a lower dose [cohort 1] and 12 at the proposed therapeutic dose [cohort 2]). This report describes long-term follow-up study design and data from the phase 1 study. Methods: Patients in the phase 1 study could rollover into a long-term follow-up study (NCT03421977). The primary objective is to collect long-term safety data (serious adverse events, hospitalizations, and adverse events of special interest). Annual follow-up will occur for 15 years. Additionally, patient record transfers from local clinician(s) will be requested. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include physical examination to assess developmental milestones. Results: As of September 27, 2018, the oldest patients are 59.2 (cohort 1) and 52.1 (cohort 2) months old and free of permanent ventilation. Preliminary data, including survival and developmental milestones, will be presented. Conclusions: Patients treated with a one-time dose of AVXS-101 continue to gain strength, develop, and achieve new milestones, demonstrating a long-term, durable response.
Introduction: Accurate forecasting of emergency department (ED) patient visits can inform better resource matching. Calendar variables such as day of week and time of day are routinely used as predictors of ED volume. Further improvement in forecasting will likely come from dynamic variables. The effect of snowfall on ED volumes in colder climates remains poorly understood. We sought to determine whether accounting for snowfall improves ED patient volume forecasting. Our secondary objective was to characterize the magnitude of effect of snowfall on ED volume. Methods: This was a retrospective observational study using historical patient volume data and local snowfall records from April 1st, 2011 to March 31st, 2018 (2,542 days) at a single urban ED. We fit a series of four generalized linear models: a baseline model which included calendar variables and three different snowfall models which contained the variables in the baseline model plus an indicator variable for modelling snowfall. Each snowfall model had a different daily threshold for its indicator variable: any snowfall ( >0cm), moderate snowfall ( > = 1 cm), or high snowfall ( > = 5 cm). We modeled daily ED volume as the dependent variable using a Poisson distribution. To evaluate model fit, we examined the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) in each of the four models. In both cases, a lower number indicates better model fit. Incident rate ratios were calculated to determine the effect of snowfall. We used the delta method to calculate confidence intervals. Results: A total of 2542 days were used to develop the model. All three snowfall models demonstrated improved model fit compared to the baseline model with lower AIC and BIC values. The best fitting model included a binary variable for moderate snowfall ( > = 1cm/day). This model showed a statistically significant decrease in ED volume of 2.65% (95% CI: 1.23% -4.00%) on snowfall days, representing 5.4 (95% CI: 2.5 -8.2) patients per day at our hospital with an average daily volume of 205 patients. Conclusion: The addition of a snowfall variable results in improved forecasting model performance in ED volume forecasting with optimal threshold set at 1 cm of snow in our setting. Snowfall is associated with a modest, but statistically significant reduction in ED volume.
Introduction: Intranasal dexmedetomidine (IND) is an emerging agent for procedural distress in children. However, studies to date have been limited by small samples and imprecise estimates of effect size. We sought to summarize the evidence on the effectiveness of IND for procedures associated with distress in children. Methods: We performed electronic searches of MEDLINE (1946-2018), EMBASE (1980-2018), Google Scholar (2018), CINAHL (1981-2018), Cochrane Central Register of Controlled Trials (2018), 6 clinical trials registries and conference proceedings (2010-2018). Title searches, data abstraction, and risk of bias assessments were performed in duplicate. We included all published and unpublished, randomized and quasi-randomized trials of IND for procedures in children younger than 19 years of age without language restriction. The methodological quality of studies was evaluated using the Cochrane Collaboration's Risk of Bias tool. The primary outcome was the proportion of participants that were deemed to be adequately sedated for the procedure. Results: Of 661 studies, 18 met inclusion criteria. Trials involved 2128 participants, age 1 month - 14 years (836, 39.3% females), who received IND 1 - 4 mcg/kg either by drops (n = 12), atomizer (n = 4), or both (n = 2). 12 trials were eligible for meta-analysis. 13 trials used validated instruments to assess sedation. All studies except one were associated with low or moderate risk of bias. For painful procedures (IV insertion; laceration repair; dental extraction), the pooled OR (95% CI) for adequate sedation and need for additional analgesia was non-significant [1.19 (0.53, 2.65)] and [2.16 (0.62, 7.49)], respectively (n = 5). For non-painful procedures (diagnostic imaging), the corresponding pooled OR (95% CI) favored IND [3.04 (1.58, 5.82)] and [4.44 (2.11, 9.35)], respectively (n = 7). Time to onset and duration of sedation ranged from 13-31 minutes and 41-91.5 minutes, respectively. For adverse effects, the pooled OR (95% CI) was not significantly different between IND and comparators [0.58 (0.22, 1.55] and there were no serious adverse events. Conclusion: IND at doses 1 to 4 mcg/kg are safe and adequately sedate children undergoing non-painful procedures, although the ease of administration must be weighed against the risk of prolonged sedation. Additional trials with larger sample sizes and greater methodologic rigor are needed for painful emergency department procedures such as laceration repair and IV insertion.
A method was described for determining the thickness of epitaxical thin films common to electronic materials. The equations were developed based on the kinematical theory of X-ray diffraction and effects of both primary and secondary extinctions were considered. As an example of the applications of this method, thickness measurement of AlGaAs thin films on GaAs was demonstrated. These films were grown by molecular beam epitaxy. The integrated reflected intensities from the film and the substrate were obtained by the X-ray double crystal diffractometer. An excellent agreement was obtained between the results from X-ray measurements and RHEED oscillation data.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
Introduction: Emergency department (ED) physicians strive to provide analgesia, amnesia and sedation for patients when performing painful procedures through the use of procedural sedation (PS). Examination of the literature suggests that the application of PS appears to be variable with institutional influences and clinician disagreement on pharmacology, airway management, and monitoring. The primary goal of this research project was to describe the variability of practice with respect to pharmacologic choices and clinical applications of PS among Canadian ED physicians. Methods: An electronic survey was distributed through the Canadian Association of Emergency Physicians (CAEP). Practicing physician members of CAEP were invited to complete the survey. The 20 question survey encompassed various aspects of PS including physician choices regarding PS indications and pharmacology. The primary outcome was the quantification of practice variability among ED physicians with respect to the above listed aspects of PS. The data was presented with simple descriptive statistics. Results: To date, 278 ED physicians responded to our survey (response rate 20.3%). Respondents were primarily academic hospital (53.2%) or community hospital based (38.2%). With emergency medicine training as: CCFP-EM (55.2%), FRCPC (30.1%), and CCFP (9.0%). There was relative agreement on the following interventions requiring PS: 98.4% applied PS for electrical cardioversion and 98.1% for brief (<10 mins) orthopedic manipulations. However, only 36.3% utilized PS for burn debridement in the ED. PS was utilized less frequently (78.1%) for prolonged (>10mins) orthopedic manipulations than brief manipulations. For all procedures aggregated, in hemodynamically stable patients with an American Society of Anesthesiology (ASA) score of 1, ED physicians utilized propofol 76.3% of the time. Additional agents were utilized at the following rates: fentanyl-propofol (7.6%), ketamine (7.6%), and fentanyl (4%). This inclination towards propofol alone appears to be consistent across modality of ER training, type of ER setting (rural vs academic), and volume of PS performed. Conclusion: This study demonstrates that Canadian ED physicians have a clear preference for propofol as a first line pharmacologic agent when administering PS in hemodynamically stable, ASA1 patients. Conversely, there appears to be more variation amongst ED physicians with respect to second line pharmaceutical choices for PS.
Introduction: Emergency department (ED) physicians strive to provide analgesia, amnesia and sedation for patients undergoing painful procedures through the use of procedural sedation (PS). While, PS is generally safe and effective in the ED, there is institutional variability and clinician disagreement with respect to the bedside equipment required for airway management and the monitoring of adverse events. The primary goal of this research project was to describe the variability of the bedside setup utilized by Canadian ED physicians preforming PS in conjunction with self-reported adverse events. Methods: An electronic survey was distributed through the Canadian Association of Emergency Physicians (CAEP). Practicing physician members of CAEP were invited to complete the survey. The 20 question survey encompassed various aspects of PS including physician choices regarding bedside setup of airway equipment, and prevalence of self-reported adverse events. The primary outcome was the quantification of variability among ED physicians with respect to the above listed aspects of PS. Data was presented with simple descriptive statistics. Results: 278 ED physicians responded to our survey (response rate 20.9%). Respondents were primarily academic (53.2%) or community hospital based (38.2%). With emergency medicine training as: CCFP-EM (55.2%), FRCPC (30.1%), and CCFP (9.0%). The ED area in which PS was carried out varied; bedside (30.5%), procedure room (37.1%), resuscitation area (31.2%). The basic equipment set utilized appears to be a bag valve mask, suction, and an oral airway. These 3 items were present 95.4%, 95.9%, and 86.3% of the time respectively. The preparation of other items such as capnography and difficult airway equipment is highly variable and appears to be physician specific rather than clinical situation specific. The most common physician self-reported adverse events associated with PS appear to be hypoxia (Spo2<90%), hypotension (sBP<90), and prolonged sedation which occurred in 10.7%, 8.3%, and 8.1% of PS performed. Conclusion: There appears to be significant practice variability with respect to the clinical setting as well as the equipment ED physicians prefer when administering PS. Given that causal relationships cannot be inferred between airway/monitoring equipment preferences and adverse events, future studies should be targeted at identifying optimal bedside set ups which minimize adverse events.
Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR. We hypothesized that offspring exposed to prenatal hypoxia will exhibit reduced cardiomyocyte proliferation due to reduced Fn-14 expression and that the TWEAK/Fn-14 pathway will be expressed in those adult offspring. We exposed pregnant Sprague Dawley rats to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational days 15 to 21. Ventricular cardiomyocytes were isolated from male and female, control and hypoxic offspring at postnatal day 1. Proliferation was assessed in the presence or absence of r-TWEAK (72 h, 100 ng/ml). Prenatal hypoxia was not associated with differences in Fn-14 protein expression in either male or female offspring. Cardiomyocytes from prenatal hypoxic male, but not female, offspring had decreased proliferation compared with controls. Addition of r-TWEAK increased cardiomyocyte proliferation in all offspring. In adult offspring of all groups, the TWEAK/Fn-14 pathway was not detectable. Cardiomyocyte proliferation was reduced in only male offspring exposed to prenatal hypoxia but this was not due to changes in the Fn-14 pathway. Studies addressing other pathways associated with CVD and prenatal hypoxia are needed.
Numerous advances in surgical techniques and understanding of single-ventricle physiology have resulted in improved survival. We sought to determine the influence of various demographic, perioperative, and patient-specific factors on the survival of single-ventricle patients following stage 1 palliation at our institution.
We conducted a retrospective study of all single-ventricle patients who had undergone staged palliation at our institution over an 8-year period. Data were collected from the Society of Thoracic Surgeons Congenital Heart Surgery database and from patient charts. Information on age, weight at stage 1 palliation, prematurity, genetic abnormalities, non-cardiac anomalies, ventricular dominance, and type of palliation was collected. Information on mortality and unplanned reinterventions was also collected.
A total of 72 patients underwent stage 1 palliation over an 8-year period. There were 12 deaths before and one death after stage 2 palliation. There was no hospital mortality following Glenn or Fontan procedures. On univariate analysis, low weight at the time of stage 1 palliation and prematurity were found to be risk factors for mortality following stage 1 palliation. However, multivariable Cox regression analysis revealed weight at stage 1 palliation to be a strong predictor of mortality. The type of stage 1 palliation did not have any influence on the outcome. No difference in survival was noted following the Glenn procedure.
Low weight has a deleterious impact on survival following stage 1 palliation. This is mitigated by stage 2 palliation. The type of stage 1 palliation itself has no bearing on the outcome.
The Numeniini is a tribe of 13 wader species (Scolopacidae, Charadriiformes) of which seven are Near Threatened or globally threatened, including two Critically Endangered. To help inform conservation management and policy responses, we present the results of an expert assessment of the threats that members of this taxonomic group face across migratory flyways. Most threats are increasing in intensity, particularly in non-breeding areas, where habitat loss resulting from residential and commercial development, aquaculture, mining, transport, disturbance, problematic invasive species, pollution and climate change were regarded as having the greatest detrimental impact. Fewer threats (mining, disturbance, problematic native species and climate change) were identified as widely affecting breeding areas. Numeniini populations face the greatest number of non-breeding threats in the East Asian-Australasian Flyway, especially those associated with coastal reclamation; related threats were also identified across the Central and Atlantic Americas, and East Atlantic flyways. Threats on the breeding grounds were greatest in Central and Atlantic Americas, East Atlantic and West Asian flyways. Three priority actions were associated with monitoring and research: to monitor breeding population trends (which for species breeding in remote areas may best be achieved through surveys at key non-breeding sites), to deploy tracking technologies to identify migratory connectivity, and to monitor land-cover change across breeding and non-breeding areas. Two priority actions were focused on conservation and policy responses: to identify and effectively protect key non-breeding sites across all flyways (particularly in the East Asian- Australasian Flyway), and to implement successful conservation interventions at a sufficient scale across human-dominated landscapes for species’ recovery to be achieved. If implemented urgently, these measures in combination have the potential to alter the current population declines of many Numeniini species and provide a template for the conservation of other groups of threatened species.
We compared the cost-effectiveness (CE) of an active case-finding (ACF) programme for household contacts of tuberculosis (TB) cases enrolled in first-line treatment to routine passive case-finding (PCF) within an established national TB programme in Peru. Decision analysis was used to model detection of TB in household contacts through: (1) self-report of symptomatic cases for evaluation (PCF), (2) a provider-initiated ACF programme, (3) addition of an Xpert MTB/RIF diagnostic test for a single sputum sample from household contacts, and (4) all strategies combined. CE was calculated as the incremental cost-effectiveness ratio (ICER) in terms of US dollars per disability-adjusted life years (DALYs) averted. Compared to PCF alone, ACF for household contacts resulted in an ICER of $2155 per DALY averted. The addition of the Xpert MTB/RIF diagnostic test resulted in an ICER of $3275 per DALY averted within a PCF programme and $3399 per DALY averted when an ACF programme was included. Provider-initiated ACF of household contacts in an urban setting of Lima, Peru can be highly cost-effective, even including costs to seek out contacts and perform an Xpert/MTB RIF test. ACF including Xpert MTB/RIF was not cost-effective if TB cases detected had high rates of default from treatment or poor outcomes.