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Background: Intravenous immunoglobulin (IVIG) may benefit many inflammatory central nervous system (CNS) disorders based on multiple immunomodulatory effects. IVIg is being used in inflammatory CNS conditions however robust evidence and guidelines are lacking in many disorders. Over the last 5 years, the percentage of IVIg used for CNS indications within neurology almost doubled in British Columbia (BC), Canada. Clear local guidelines may guide rational use. Methods: Consensus guidelines for IVIG use for CNS indications were developed by a panel of subspecialty neurologists and the Provincial Blood Coordinating Office, informed by focused literature review. Guidelines were structured similarly to existing BC peripheral nervous system guidelines and Australian Consensus Guidelines. Utilization and efficacy will be monitored provincewide on an ongoing basis. Results: Categories of conditions for Conditionally Approved (N=11) and Exceptional Circumstance Use (N=5) were created based on level of evidence for efficacy. Dosing and monitoring recommendations were made and outcomes measures defined. Rationale for Not Indicated conditions (N=2) was included. Guidelines were distributed to BC neurologists for feedback. This system will be re-evaluated after 1 year. Conclusions: IVIG use in CNS inflammatory conditions has an emerging role. Guidelines for use and monitoring of outcomes will help improve resource utilization and provide further evidence regarding effectiveness.
The Murchison Widefield Array (MWA) is a low-frequency aperture array capable of high-time and frequency resolution astronomy applications such as pulsar studies. The large field-of-view of the MWA (hundreds of square degrees) can also be exploited to attain fast survey speeds for all-sky pulsar search applications, but to maximise sensitivity requires forming thousands of tied-array beams from each voltage-capture observation. The necessity of using calibration solutions that are separated from the target observation both temporally and spatially makes pulsar observations vulnerable to uncorrected, frequency-dependent positional offsets due to the ionosphere. These offsets may be large enough to move the source away from the centre of the tied-array beam, incurring sensitivity drops of
in Phase II extended array configuration. We analyse these offsets in pulsar observations and develop a method for mitigating them, improving both the source position accuracy and the sensitivity. This analysis prompted the development of a multi-pixel beamforming functionality that can generate dozens of tied-array beams simultaneously, which runs a factor of ten times faster compared to the original single-pixel version. This enhancement makes it feasible to observe multiple pulsars within the vast field of view of the MWA and supports the ongoing large-scale pulsar survey efforts with the MWA. We explore the extent to which ionospheric offset correction will be necessary for the MWA Phase III and the low-frequency square kilometre array (SKA-low).
Laboratory tests were carried out in order to examine the population growth of Prostephanus truncatus (Horn) (Coleoptera: Bostrychidae) and Sitophilus oryzae (L.) (Coleoptera: Curculionidae) on maize. These two species were placed either simultaneously or one species was allowed to colonize the kernels 7 days earlier than the other, at two temperatures, 26 and 30 °C for 65 days. Apart from progeny production, grain quality parameters, such as insect-damaged kernels (IDK) and undamaged kernels (NDK), the weight of frass and kernel weight were measured. Our data confirms that temperature plays a key role in the competition of these two species; P. truncatus seems to perform better at the higher temperature (30 °C), regardless of the presence of an additional species. Moreover, the results of the present study demonstrates that P. truncatus outcompetes S. oryzae. Sitophilus oryzae produced fewer progeny than P. truncatus in all combinations. Given the outcome of a competition, we hypothesize that most of the kernel damage was due to feeding by P. truncatus. Based on these data, we surmise that P. truncatus has a competitive advantage as an invasive species in new areas with stored maize, even in the presence of S. oryzae.
Background: Intravenous immunoglobulin (IVIG) may benefit many inflammatory central nervous system (CNS) disorders based on multiple immunomodulatory effects. IVIG is being used in inflammatory CNS conditions however robust evidence and guidelines are lacking in many disorders. Over the last 5 years, the percentage of IVIG used for CNS indications within neurology almost doubled in British Columbia (BC), Canada. Clear local guidelines may guide rational use. Methods: Consensus guidelines for IVIG use for CNS indications were developed by a panel of subspecialty neurologists and the Provincial Blood Coordinating Office, informed by focused literature review. Guidelines were structured similarly to existing BC peripheral nervous system guidelines and Australian Consensus Guidelines. Utilization and efficacy will be monitored provincewide on an ongoing basis. Results: Categories of conditions for Possible Indication (N=11) and Exceptional Circumstance Use (N=4) were created based on level of evidence for efficacy. Dosing and monitoring recommendations were made and outcomes measures defined. Rationale for Not Indicated conditions (N=3) was included. Guidelines will be distributed to BC neurologists for feedback and re-evaluated after 1 year. Conclusions: IVIG use in CNS inflammatory conditions has an emerging role. Guidelines for use and monitoring of outcomes will help improve resource utilization and provide further evidence regarding effectiveness.
We present a second-personal account of corporate moral agency. This approach is in contrast to the first-personal approach adopted in much of the existing literature, which concentrates on the corporation’s ability to identify moral reasons for itself. Our account treats relationships and communications as the fundamental building blocks of moral agency. The second-personal account rests on a framework developed by Darwall. Its central requirement is that corporations be capable of recognizing the authority relations that they have with other moral agents. We discuss the relevance of corporate affect, corporate communications, and corporate culture to the second-personal account. The second-personal account yields a new way to specify first-personal criteria for moral agency, and it generates fresh insights into the reasons those criteria matter. In addition, a second-personal analysis implies that moral agency is partly a matter of policy, and it provides a fresh perspective on corporate punishment.
Diet is a modifiable risk factor for chronic disease and a potential modulator of telomere length (TL). The study aim was to investigate associations between diet quality and TL in Australian adults after a 12-week dietary intervention with an almond-enriched diet (AED). Participants (overweight/obese, 50–80 years) were randomised to an AED (n 62) or isoenergetic nut-free diet (NFD, n 62) for 12 weeks. Diet quality was assessed using a Dietary Guideline Index (DGI), applied to weighed food records, that consists of ten components reflecting adequacy, variety and quality of core food components and discretionary choices within the diet. TL was measured by quantitative PCR in samples of lymphocytes, neutrophils, and whole blood. There were no significant associations between DGI scores and TL at baseline. Diet quality improved with AED and decreased with NFD after 12 weeks (change from baseline AED + 9·8 %, NFD − 14·3 %; P < 0·001). TL increased in neutrophils (+9·6 bp, P = 0·009) and decreased in whole blood, to a trivial extent (–12·1 bp, P = 0·001), and was unchanged in lymphocytes. Changes did not differ between intervention groups. There were no significant relationships between changes in diet quality scores and changes in lymphocyte, neutrophil or whole blood TL. The inclusion of almonds in the diet improved diet quality scores but had no impact on TL mid-age to older Australian adults. Future studies should investigate the impact of more substantial dietary changes over longer periods of time.
This study aimed to evaluate hearing outcomes and device safety in a large, single-surgeon experience with the totally implantable active middle-ear implants.
This was a retrospective case series review of 116 patients with moderate-to-severe sensorineural hearing loss undergoing implantation of active middle-ear implants.
Mean baseline unaided pure tone average improved from 57.6 dB before surgery to 34.1 dB post-operatively, signifying a mean gain in pure tone average of 23.5 dB (p = 0.0002). Phonetically balanced maximum word recognition score improved slightly from 70.5 per cent to 75.8 per cent (p = 0.416), and word recognition score at a hearing level of 50 dB values increased substantially from 14.4 per cent to 70.4 per cent (p < 0.0001). Both revision and explant rates were low and dropped with increasing surgeon experience over time.
This study showed excellent post-operative hearing results with active middle-ear implants with regard to pure tone average and word recognition score at a hearing level of 50 db. Complication rates in this case series were significantly lower with increasing experience of the surgeon. Active middle-ear implants should be considered in appropriate patients with moderate-to-severe sensorineural hearing loss who have struggled with conventional amplification and are good surgical candidates.
Medical care is predicated on ‘do no harm’, yet the urgency to find drugs and vaccines to treat or prevent COVID-19 has led to an extraordinary effort to develop and test new therapies. Whilst this is an essential cornerstone of a united global response to the COVID-19 pandemic, the absolute requirements for meticulous efficacy and safety data remain. This is especially pertinent to the needs of pregnant women; a group traditionally poorly represented in drug trials, yet a group at heightened risk of unintended adverse materno-fetal consequences due to the unique physiology of pregnancy and the life course implications of fetal or neonatal drug exposure. However, due to the complexities of drug trial participation when pregnant (be they vaccines or therapeutics for acute disease), many clinical drug trials will exclude them. Clinicians must determine the best course of drug treatment with a dearth of evidence from either clinical or preclinical studies, where at least in the short term they may be more focused on the outcome of the mother than of her offspring.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
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.
There is a long history in Lucretian scholarship of finding conflict in the DRN between its philosophical content and its poetic form. Recent criticism has emphasized rather how the poem’s poetic form complements its Epicurean message. This chapter argues for important differences between literary and philosophical approaches to the poem, in particular with regard to its relationship with other texts, in order to identify some important differences in common modes of reading the poem. The chapter examines a ‘master-text’ model of reading, in which the DRN is related in strong fashion to another text on which it is dependent. The precise nature and identity of this ‘master-text’ can vary, according to the purpose or use to which the DRN is put. The approach of such ‘master-text’ readings is strikingly different from the dominant intertextual mode. In the examples of intertextual reading examined, the relationship to the other text is not one of subordination, but a tool used by the DRN to serve a particular function within the poem itself. The modes of reading explored in this chapter can lead to real differences in interpretation: e.g., on the end of the DRN, or on how uncompromising or sympathetic we should view certain parts of the poem. One important consequence is the need to acknowledge the differences in our reading practices and theoretical assumptions.
OBJECTIVES/GOALS: We have recently shown that mice exposed to six days of 60% caloric restriction acutely display reduced hypoglycemia-induced glucagon release following refeeding, and that this effect is concurrent with low leptin levels. The current study was conducted to ascertain if leptin treatment during caloric restriction would reverse this effect. METHODS/STUDY POPULATION: Three groups of mice were used, an ad libitum (Ad-lib) fed group and two caloric restriction (CR) groups, one of which received twice daily leptin injection (0.5-1μg/g; IP) and the other vehicle (saline) during their caloric restriction. CR mice were placed on 60% caloric restriction for 6 consecutive days. Ad lib mice were housed in an identical manner but fed ad libitum during this same period. Following 6 days of restriction, CR mice were given ad lib access to food for 16 h. After the 16 h period of refeeding, both CR and ad lib mice began a 6 h fast which was immediately followed by a hypoglycemic insulin tolerance test (ITT). ITTs consisted of a variable dose of insulin intended to achieve a blood glucose of ~45 mg/dL within 60 minutes, at which time blood was collected for glucagon and corticosterone assays. RESULTS/ANTICIPATED RESULTS: The mean blood glucose levels during the ITT at 45 and 60 minutes post injection across all three groups were 46.8 + 3.1 and 37.0 + 2.4, respectively. There were no significant differences in glucose levels between the three groups at these two time points. As expected, saline treated CR mice displayed significantly reduced serum glucagon levels in response to the ITT relative to Ad-lib mice (23.5 + 10.9 vs. 91.7 + 20.8 pg/mL, p = 0.009). In contrast, leptin-treated CR mice maintained their hypoglycemia-induced glucagon response to the ITT (78.0 + 16.8 pg/mL, p>0.99 vs. Ad-lib group). In addition, although corticosterone levels in saline treated CR mice were numerically lower than in Ad-lib mice, this difference was not statistically significance (3928 + 277 vs. 4571 + 178 pg/mL, p = 0.179). DISCUSSION/SIGNIFICANCE OF IMPACT: Diabetes patients on insulin therapy often develop impaired hypoglycemic counter-regulation which can lead to life-threatening hypoglycemic complications. Our results suggest that leptin may hold promise as a therapeutic intervention for the prevention of impaired hypoglycemic counter-regulation in persons with diabetes.
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.
Introduction: Prognostication is a significant challenge early in the post-cardiac arrest period. Common prognostic factors for neurological survival are unreliable (high false positive rates) until 72 hours post-cardiac arrest. It is not known whether there are a combination of factors that can be utilized earlier in the post-cardiac arrest period to accurately predict patient outcome. Our objective was to predict neurological outcome utilizing a novel combination of patient factors early in the post-cardiac arrest period. Methods: We conducted a retrospective cohort study using data from our local cardiac arrest registry. We included adult patients who obtained a return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). We excluded patients who did not survive for at least 24 hours post-ROSC and those who had a do not resuscitate (DNR) order within 2 hours of ROSC. We performed an ordinal regression analysis using the proportional odds model to predict neurological outcome (modified rankin score (mRS)). We included a good neurological outcome (mRS 0-2), poor neurological outcome (mRS 3-5), and dead (mRS 6) as an ordinal outcome. We included a number of patient demographics, intra- and post-cardiac arrest factors as covariates in our model. The predictive performance of our model was analyzed using receiver operating characteristic (ROC) curves for discrimination and Brier statistic for calibration. Results: We included 3448 patients in our analysis. We found that an initial shockable rhythm (odds ratio (OR) 4.1; 95% confidence interval (CI) 3.6, 5.4), the absence of pupillary reflexes (OR 3.5; 95% CI 2.4,4.8) and maximum motor score on the Glasgow Coma Scale (GCS) (OR 1.5; 95% CI 1.4,1.6) had the greatest association with improved neurologic outcome. Longer duration of resuscitation was associate with worse outcomes (OR 0.84, 95% CI 0.82,0.87). The overall performance of our model was excellent with an area under the ROC curve of 0.89 and a Brier statistic of 0.13. Conclusion: Our model predicted good neurological outcome with a high rate of accuracy, however external validation of the model is required. This model may be useful in providing initial risk stratification of patients in clinical practice and future research on post-cardiac arrest care.
Introduction: Despite recent advances in resuscitation, some patients remain in ventricular fibrillation (VF) after multiple defibrillation attempts during out-of-hospital cardiac arrest (OHCA). Vector change defibrillation (VC) and double sequential external defibrillation (DSED) have been proposed as alternate therapeutic strategies for OHCA patients with refractory VF. The primary objective was to determine the feasibility, safety and sample size required for a future cluster randomized controlled trial (RCT) with crossover comparing VC or DSED to standard defibrillation for patients experiencing refractory VF. Secondary objectives were to evaluate the intervention effect on VF termination and return of spontaneous circulation (ROSC). Methods: We conducted a pilot cluster RCT with crossover in four Canadian paramedic services and included all treated adult OHCA patients who presented in VF and received a minimum of three defibrillation attempts. In addition to standard cardiac arrest care, each EMS service was randomly assigned to provide continued standard defibrillation (control), VC or DSED. Services crossed over to an alternate defibrillation strategy after six months. Prior to the launch of the trial, 2,500 paramedics received in-person training for VC and DSED defibrillation using a combination of didactic, video and simulated scenarios. Results: Between March 2018 and September 2019, 152 patients were enrolled. Monthly enrollment varied from 1.4 to 6.1 cases per service. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no reported cases of defibrillator malfunction, skin burns, difficulty with pad placement or concerns expressed by paramedics, patients, families, or ED staff about the trial. In the standard defibrillation group, 66.6% of cases resulted in VF termination, compared to 82.0% in VC and 76.3% of cases in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. Conclusion: Findings from our pilot RCT suggest the DOSE VF protocol is feasible and safe. VF termination and ROSC were higher with VC and DSED compared to standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact patient-centered, clinical outcomes
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.