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Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
Our study objective was to describe the Canadian emergency medicine (EM) research community landscape prior to the initiation of a nationwide network.
A two-phase electronic survey was sent to 17 Canadian medical schools. The Phase 1 Environmental Scan was administered to department chairs/hospital EM chiefs, to identify EM physicians conducting clinical or educational research. The Phase 2 Survey was sent to the identified EM researchers to assess four themes: 1) geographic distribution, 2) training/career satisfaction, 3) time/financial compensation, and 4) research facilitators/barriers. Descriptive analyses were conducted, and results were stratified by Canadian regions.
A total of 92 EM researchers were identified in Phase 1; 67 (73%) responded to the Phase 2 Survey. Of those, 42 (63%) reported being clinical researchers, and 19 (45%) had a graduate degree. Three provinces encompassed most of the researchers (n = 35). Of the respondents, 61% had a research degree, 66% felt adequately trained for their research career, 73% had financial support, 83% had access to office spaces, 52% had no mentor during their first years of their career, 69% felt satisfied with their research career, and 82% suggested that they will still be conducting research in 5 years.
EM researchers reported being adequately trained, even though only a little over half had a graduate degree. Only two-thirds had financial support, and mentorship was lacking in one-third of the participants. Not all respondents had a form of infrastructure, but most felt optimistic about their careers. The Canadian EM research environment could be improved to ensure better research capacity.
This retrospective, case series audit assessed the clinical and health-economic impact of long-term treatment with quetiapine (‘Seroquel’), a new atypical antipsychotic, in patients with chronic schizophrenia.
The study design was of a case series format, comprising patients entered from one centre into the open-label extension of a multicentre 6-week efficacy study. Twenty-one patients (15 male, six female; mean age 39 years) were studied, of whom 17 (81%) had been rated as ‘partially responsive’ to previous antipsychotics. Data on hospitalisations and information on symptoms were collected retrospectively for the 12 months before quetiapine treatment was initiated and for the 12 months after.
Quetiapine was effective in reducing psychotic symptoms with mean BPRS scores reducing significantly, from 38 to 21 (P < 0.005). Motor function was also significantly improved with mean Simpson scale scores reducing from 15 to 12 (P < 0.005). Average inpatient days were reduced by 11% in year two (97 compared with 109 days) while the overall costs of treatment, including drug costs, fell by 5% (I£20,843 to I£19,827).
Four patients had been hospitalised for longer than 5 years before starting quetiapine; these chronically institutionalised patients remained in hospital, despite improved clinical outcomes (mean BPRS scores after treatment of 34, compared with 43 before), for the full 12 months of quetiapine treatment. Were the data from this audit to be re-analysed excluding these four patients then average inpatient days would have been reduced by 33% (45 to 30 days) and overall cost of treatment by 19% (I£8617 to I£7011).
This audit suggests that treatment with quetiapine over this 1-year period was associated with both clinical improvements and a decreased usage of inpatient services. The reduction in hospitalisation costs would appear to compensate for the increased cost of drug treatment. Significantly, potential savings appear to be greatest for those patients with a ‘revolving door’ pattern of repeated readmission.
Antidepressant use has risen x3-5 in Western countries since the early 1990s, outstripping changes in depression incidence or prevalence. This represents a major public health challenge.
Nationally-collected antidepressant data were used to assess the impact of "Doing Well", (DW) a novel depression care programme operating in Renfrewshire, Scotland. "Doing Well" implemented a model of “stepped collaborative care”, practitioner education and significant service redesign. Prescribing was compared for three groups: "DW" (76,000 population; clinical and educational intervention), "DW neighbours” (101,000 population; educational interventions only), and Scotland (no specific intervention).
A national rise in antidepressant prescriptions was stabilised for the "DW" group (graph). Antidepressant cost/item fell by 42% and 40% in both “DW” and “DW neighbours” groups but rose by 8% nationally.
Access to clinical interventions are required to reduce antidepressant prescriptions, but cost savings may be made with educational interventions alone.
A main objective of EPOS is to provide a valid multifactorial model for the prediction of psychosis. One major element of such a model should be the clinical state.
In a European multicentre study, persons fulfilling clinical criteria thought to indicate an increased risk for psychosis (PAR) were assessed amongst others with different psychopathological instruments covering the whole spectrum from basic symptoms to frank psychotic symptoms. Inclusion criteria comprised attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), cognitive basic symptoms (CogDis) and a combination of family risk and reduced functioning (S&T).
246 PAR were included into the study, mostly by APS or CogDis. Analysis of demographical data showed a high amount of functional impairment, resulting e.g. in low mean GAF scores (51.0 ± 11.8 SD), and of non-psychotic axis-I disorders. In September 2006, the hazard rate for a conversion to psychosis was 15.3 at 12 and 20.0 at 18 months after baseline assessment. According to the inclusion criteria, the highest rate of conversion was observed among PAR with BLIPS. On a dimensional level, a low GAF score was among the best predictors of conversion.
The transition rates of EPOS were in line with recent studies. A first analysis of clinical data supports the notion that the functional state should be an inherent part of any set of clinical risk criteria. Further analysis will consider the contribution of single symptoms or symptom combinations and the impact of symptom duration.
One aim of the European prediction of psychosis study (EPOS) has been to evaluate the clinical course of putatively prodromal patients in terms of psychopathology.
245 patients at risk for psychosis defined by attenuated positive symptoms, brief limited psychotic symptoms, a state/ trait combination or cognitive-perceptive basic symptoms was recruited in six centres in four countries. The Structured Interview for Prodromal Syndromes (SIPS) and the Bonn Scale for the Assessment of Basic Symptoms – Prediction List (BSABS-P) were employed. Follow-up was scheduled after 9 months (t1) and 18 months.
In total, 40 patients developed a psychosis (P). Compared to those without a transition (NP), P showed significantly higher SIPS scores at baseline. The same applied to the BSABS-P sub-scores 'cognitive perception disturbances' and 'cognitive motor disturbances'. The P sub-group developing psychosis after t1 showed no significant change of the SIPS positive (SIPS-P) sub-score or of any BSABS-P score from baseline to t1, whereas all scores improved in the NP group. At t1, SIPS-P and BSABS-P sub-score 'cognitive thought disturbances' were significantly lower in those later becoming psychotic.
Patients at risk showing a transition to psychosis during exhibited a pronounced psychopathology at baseline. Also, the positive symptom scores did not significantly improve during 1st follow-up, whereas those patients with no transition during the complete follow-up showed an improvement of all scores. As EPOS is a naturalistic study, different treatments have been performed in a considerable portion of the patients and association with course awaits further analysis.
Autism spectrum disorder (ASD) and schizophrenia (SCZ) are separate neurodevelopmental disorders that are both characterized by difficulties in social cognition and social functioning. Due to methodological confounds, the degree of similarity in social cognitive impairments across these two disorders is currently unknown. This study therefore conducted a comprehensive comparison of social cognitive ability in ASD and SCZ to aid efforts to develop optimized treatment programs.
In total, 101 individuals with ASD, 92 individuals with SCZ or schizoaffective disorder, and 101 typically developing (TD) controls, all with measured intelligence in the normal range and a mean age of 25.47 years, completed a large battery of psychometrically validated social cognitive assessments spanning the domains of emotion recognition, social perception, mental state attribution, and attributional style.
Both ASD and SCZ performed worse than TD controls, and very few differences were evident between the two clinical groups, with effect sizes (Cohen's d) ranging from 0.01 to 0.34. For those effects that did reach statistical significance, such as greater hostility in the SCZ group, controlling for symptom severity rendered them non-significant, suggesting that clinical distinctions may underlie these social cognitive differences. Additionally, the strength of the relationship between neurocognitive and social cognitive performance was of similar, moderate size for ASD and SCZ.
Findings largely suggest comparable levels of social cognitive impairment in ASD and SCZ, which may support the use of existing social cognitive interventions across disorders. However, future work is needed to determine whether the mechanisms underlying these shared impairments are also similar or if these common behavioral profiles may emerge via different pathways.
Introduction: 9-1-1 telecommunicators receive minimal education on agonal breathing, often resulting in unrecognized out-of-hospital cardiac arrest (OHCA). We successfully piloted an educational intervention that significantly improved telecommunicators’ OHCA recognition and bystander CPR rates in Ottawa. We sought to better understand the operations of Canadian 9-1-1 communications centers (CC) in preparation for a multi-centre study of this intervention. Methods: We conducted a National survey of all Canadian CCs. Survey domains included information on organizational structure, dispatch system used, education curriculum, and performance monitoring. It was peer-reviewed, translated in French, pilot-tested, and distributed electronically using a modified Dillman method. We designated respondents in each CC before distribution and used targeted follow-up and small incentives to increase response rate. Respondents also described functioning of neighboring CCs if known. Results: We received information from 51/51 provincial and 1/25 territorial CCs, representing 99.7% of the Canadian population. CCs largely utilize the Medical Dispatch Priority System (MPDS) platform (93%), many are Province/Ministry regulated (50%) and most require a High School diploma as minimum entry level education (78%). Telecommunicators receive initial in-class training (median 1.3 months, IQR 0.3-1.9; range 0.1-2.2), often followed by a preceptorship (84.4%) (median 1.0 months, IQR 0.7-1.7; range 0.4-6.0). Educational curriculum includes information on agonal breathing in 41% of CC, without audio examples in 34%. Among responding CCs, over 39,000 suspected OHCA 9-1-1 calls are received annually. Few CCs maintain local performance statistics on OHCA recognition (25%), bystander CPR rates (25%) or survival rates (50%). Most (97%) expressed interest in future research collaborations. Conclusion: Most Canadian telecommunicators receive no or minimal education in recognizing agonal breathing. Further training and improved OHCA monitoring may assist recognition and enhance outcomes.
High-intensity laser–plasma interactions produce a wide array of energetic particles and beams with promising applications. Unfortunately, the high repetition rate and high average power requirements for many applications are not satisfied by the lasers, optics, targets, and diagnostics currently employed. Here, we aim to address the need for high-repetition-rate targets and optics through the use of liquids. A novel nozzle assembly is used to generate high-velocity, laminar-flowing liquid microjets which are compatible with a low-vacuum environment, generate little to no debris, and exhibit precise positional and dimensional tolerances. Jets, droplets, submicron-thick sheets, and other exotic configurations are characterized with pump–probe shadowgraphy to evaluate their use as targets. To demonstrate a high-repetition-rate, consumable, liquid optical element, we present a plasma mirror created by a submicron-thick liquid sheet. This plasma mirror provides etalon-like anti-reflection properties in the low field of 0.1% and high reflectivity as a plasma, 69%, at a repetition rate of 1 kHz. Practical considerations of fluid compatibility, in-vacuum operation, and estimates of maximum repetition rate are addressed. The targets and optics presented here demonstrate a potential technique for enabling the operation of laser–plasma interactions at high repetition rates.
Emergency physicians are using bolus-dose vasopressors to temporize hypotensive patients until more definitive blood pressure support can be established. Despite a paucity of clinical outcome data, emergency department applications are expanding into the prehospital setting. This series presents two cases of field expedient vasopressor use by emergency medicine providers for preflight stabilization during aeromedical evacuation to a hospital ship as part of the United States Navy disaster response in Puerto Rico. A critical approach and review of the literature are discussed.
Two critically ill patients were managed in an austere environment as a result of the devastation from Hurricane Maria (Yabucoa, Puerto Rico; 2017). They both exhibited signs of respiratory distress, hemodynamic instability, and distributive shock requiring definitive airway management and hemodynamic support prior to aeromedical evacuation.
The novel use of field expedient vasopressors prior to induction for rapid sequence intubation was successfully and safely employed in both cases. Both patients had multiple risk factors for peri-induction cardiac arrest given their presenting hemodynamics. Despite their illness severity, both patients were induced, transported, and ultimately admitted to the intensive care unit (ICU) in stable condition following administration of the field expedient vasopressors.
Field expedient vasopressors were safely and effectively employed in an austere field environment during a disaster response. This case series contributes to the growing body of literature of safe bolus-dose vasopressor use by emergency physicians to temporize hypotensive patients in resource-constrained situations.
HardwickJM, MurnanSD, Morrison-PonceDP, DevlinJJ. Field Expedient Vasopressors During Aeromedical Evacuation: A Case Series from the Puerto Rico Disaster Response. Prehosp Disaster Med. 2018;33(6):668–672.
The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH MB using immunohistochemical analysis as well as transcriptome data across 763 primary tumors. Characterization of CD271+ and CD271- cells by RNA sequencing revealed that these two subpopulations are molecularly distinct, co-existing cellular subsets both in vitro and in vivo. MAPK/ERK signaling is upregulated in the CD271+ population and inhibiting this pathway reduced CD271 levels, stem/progenitor cell proliferation and cell survival as well as cell migration in vitro. Importantly, the MEK inhibitor selumetinib extends survival and reduces CD271 levels in vivo. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH MB tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH MB cells.
Hamiltonian extended magnetohydrodynamics (XMHD) is restricted to respect helical symmetry by reducing the Poisson bracket for the three-dimensional dynamics to a helically symmetric one, as an extension of the previous study for translationally symmetric XMHD (Kaltsas et al., Phys. Plasmas, vol. 24, 2017, 092504). Four families of Casimir invariants are obtained directly from the symmetric Poisson bracket and they are used to construct Energy–Casimir variational principles for deriving generalized XMHD equilibrium equations with arbitrary macroscopic flows. The system is then cast into the form of Grad–Shafranov–Bernoulli equilibrium equations. The axisymmetric and the translationally symmetric formulations can be retrieved as geometric reductions of the helically symmetric one. As special cases, the derivation of the corresponding equilibrium equations for incompressible plasmas is discussed and the helically symmetric equilibrium equations for the Hall MHD system are obtained upon neglecting electron inertia. An example of an incompressible double-Beltrami equilibrium is presented in connection with a magnetic configuration having non-planar helical magnetic axis.
Introduction: Medical journals are an essential venue for knowledge translation. Skilled reviewers and editors are required to ensure quality standards in research publications and yet postgraduate programs rarely include this training in their curricula. Imparting appropriate skills and developing capacity in journalship has thus proved challenging. The Canadian Journal of Emergency Medicine (CJEM) is the national journal for Emergency Medicine (EM) in Canada. The CJEM editorial board recently decided to provide longitudinal mentorship for junior academic faculty members and trainees through an editorial internship. The internship had three goals for participants: (1) introduce and develop the responsibilities and skills of a good editor; (2) enhance a career in academic EM; and, (3) galvanize future participation as a reviewer or editor in scientific publications. Methods: The senior editorial board of CJEM and the inaugural intern developed a one-year Editorial Internship that was launched in June 2017. The curricular framework was designed by current and prior CJEM senior editors from four Canadian universities, and was informed by similar programs in the United States. The curriculum was refined iteratively based on feedback and discussion between the senior editors and intern. The internship was designed for a single individual in the Canadian EM community, including residents, pediatric fellows and practicing emergency physicians. Results: To develop the responsibilities and skills of being a good editor, the intern performed six mentored reviews of manuscripts either under current review at CJEM or previous submissions identified as difficult peer review decisions. In addition, the intern learned about CJEM values and norms by participating in monthly videoconference meetings and quarterly editorial board meetings. To enhance an academic career, the intern was assigned two writing projects under the guidance of senior editors for publication in CJEM, and completed an online critical appraisal course. Conclusion: The inaugural editorial intern gained experience as an editor and produced scholarly work. We feel the internship met its first two goals, and CJEM has committed to continue the internship annually. The ultimate determination of whether the internship achieved its third goal will only be known after longitudinal tracking of participants career involvement in academic publishing and editing.
An outbreak of mumps within a student population in Scotland was investigated to assess the effect of previous vaccination on infection and clinical presentation, and any genotypic variation. Of the 341 cases, 79% were aged 18–24. Vaccination status was available for 278 cases of whom 84% had received at least one dose of mumps containing vaccine and 62% had received two. The complication rate was 5·3% (mainly orchitis), and 1·2% were admitted to hospital. Genetic sequencing of mumps virus isolated from cases across Scotland classified 97% of the samples as genotype G. Two distinct clusters of genotype G were identified, one circulating before the outbreak and the other thereafter, suggesting the virus that caused this outbreak was genetically different from the previously circulating virus. Whilst the poor vaccine effectiveness we found may be due to waning immunity over time, a contributing factor may be that the current mumps vaccine is less effective against some genotypes. Although the general benefits of the measles–mumps–rubella (MMR) vaccine should continue to be promoted, there may be value in reassessing the UK vaccination schedule and the current mumps component of the MMR vaccine.
Complications related to methamphetamine use and abuse are common presentations seen in the emergency department. Standard management focuses on addressing the central nervous system and cardiovascular effects with the use of sedation and hemodynamic support. We describe a case report of a patient with methamphetamine toxicity and subsequent severe cardiomyopathy refractory to conventional management that responded to cardiovascular support with extracorporeal membrane oxygenation therapy (ECMO). A 22-year-old female was admitted in severe cardiogenic shock following intravenous administration of methamphetamine and oral fentanyl use. Despite aggressive treatment with benzodiazepines, intravenous fluids, vasopressors, vasodilators, antibiotics and inotropes, the patient’s clinical status deteriorated, and she suffered a cardiac arrest. The patient was successfully resuscitated, and following the return of spontaneous circulation, ECMO was initiated. After 82 hours the patient was successfully weaned from ECMO with the recovery of her left ventricular function and no neurologic sequelae. The patient developed leg ischemia requiring embolectomy and open repair as a complication of ECMO cannulation. In our case, ECMO was used successfully in treating severe cardiac dysfunction from acute methamphetamine-induced cardiomyopathy and was used as a bridge to recovery. The complications seen in this patient emphasize the potential risks associated with this intervention and highlight the need for careful patient selection.
Cardiometabolic diseases exhibit changes in lipid biology, which is important as lipids have critical roles in membrane architecture, signalling, hormone synthesis, homoeostasis and metabolism. However, Developmental Origins of Health and Disease studies of cardiometabolic disease rarely include analysis of lipids. This short review highlights some examples of lipid pathology and then explores the technology available for analysing lipids, focussing on the need to develop imaging modalities for intracellular lipids. Analytical methods for studying interactions between the complex endocrine and intracellular signalling pathways that regulate lipid metabolism have been critical in expanding our understanding of how cardiometabolic diseases develop in association with obesity and dietary factors. Biochemical methods can be used to generate detailed lipid profiles to establish links between lifestyle factors and metabolic signalling pathways and determine how changes in specific lipid subtypes in plasma and homogenized tissue are associated with disease progression. New imaging modalities enable the specific visualization of intracellular lipid traffic and distribution in situ. These techniques provide a dynamic picture of the interactions between lipid storage, mobilization and signalling, which operate during normal cell function and are altered in many important diseases. The development of methods for imaging intracellular lipids can provide a dynamic real-time picture of how lipids are involved in complex signalling and other cell biology pathways; and how they ultimately regulate metabolic function/homoeostasis during early development. Some imaging modalities have the potential to be adapted for in vivo applications, and may enable the direct visualization of progression of pathogenesis of cardiometabolic disease after poor growth in early life.
To assess the impact of farm management on herd fertility, a survey of 105 beef farms in Northern Ireland was conducted to establish the relationship between management variables and fertility. Each herd's average calving interval (CI) and the proportion of cows with a CI > 450 days (extended calving interval, ECI) was calculated to establish herd fertility. The relationship between each response variable (CI and proportion ECI) and each explanatory variable (respondents’ answers to questionnaire) was examined using univariate linear regression analyses. All response variables found to be associated with the explanatory variables were modelled against each group in turn using a fully automated multivariate stepwise regression algorithm employing the method of forward selection with backward elimination. The optimum 365-day CI and a proportion of 0 cows per hundred calved ECI targets were not widely attained in the current study. The distribution of CI and proportion ECI in the current study suggests more realistic targets would be a 379-day CI and 5 cows per hundred calved with ECI in commercial beef breeding herds. Six management factors were found to be associated with herd fertility: herd vaccination, bull selection, fertility management, breeding female management, perception of extension service (rural education provided by the government) and record keeping. It was found that respondents who vaccinated cows had a reduction of 5 cows per hundred calved in the proportion of cows with ECI, and as the number of vaccines administered to a cow increased, the CI decreased. Regular vaccination of breeding bulls was associated with a 9-day reduction in CI. Bull selection strategy had several associations with herd fertility; most notable was that respondents who used visual selection rather than estimated breeding values (EBVs) to select bulls were found to have a 15-day longer CI and 7 cows per hundred calved higher proportion of cows with ECI. For each 0·01 increase in the proportion of cows served by artificial insemination, CI increased by 0·16 days. Respondents who rated their beef breeding herd fertility as ‘very good’ had lower ECI and CI than those who rated beef breeding herd fertility as poor or satisfactory. Condition scoring of cows at weaning lowered ECI by 5 cows per hundred calved. Those who perceived the extension service to be very useful had the lowest CI and lowest ECI. Respondents who did not keep a record of CI to assess herd fertility had an 11-day longer CI and 6 cows per hundred calved higher proportion ECI than those who did not. In conclusion, the survey found a number of important variables linked to improved fertility including selecting sires based on EBVs and using a robust vaccination programme.