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Introduction: Physicians who practice emergency medicine (EM) often perform procedural interventions, which can occasionally result in unintended patient harm. Our study's objective was to identify and describe the interventions and contributing factors associated with medico-legal (ML) cases involving emergency physicians performing procedural interventions. Methods: The Canadian Medical Protective Association (CMPA) is a not-for-profit, ML organization which represented over 99,000 physicians at the time of this study. We extracted five years (2014-2018) of CMPA data describing closed ML cases involving procedural interventions (e.g. suturing, reducing a dislocated joint) and excluding interventions related to pharmacotherapy (e.g. injection of local anesthetic), diagnosis (electrocardiograms) and physical assessments (e.g. ear exams), performed by physicians practicing EM. We then applied an internal contributing factor framework to identify themes. We analysed the data using descriptive statistics. Results: We identified 145 cases describing 145 patients who had 205 procedures performed in the course of their EM care. The three most common interventions were orthopedic injury management (47/145, 32.4%), wound management (43/145, 29.7%), and Advanced Cardiac Life Support (24/145, 16.6%). Out of 145 patients, 93.8% (136/145) experienced a patient safety event, and 55.9% (76/136) suffered an avoidable harmful incident. One quarter of patients suffered mild harm (34/76, 25.0%), 18.4% of patients died, 14.5% suffered severe harm, and 13.2% moderate harm. Peer experts were critical of 86/145 cases (59.3%) where the following provider contributing factors were found: a lack of situational awareness (20/68, 29.4%), and deficient physician clinical decision-making (54/68, 79.7%). Clinical decision-making issues included a lack of thoroughness of assessment (33/54, 61.1%), failure to perform tests or interventions (21/54, 38.9%), and a delay or failure to seek help from another physician (17/54, 31.2%). Peer experts were also critical of 48.8% of cases containing team factors (42/86) due to deficient medical record keeping (26/42, 61.9%), and communication breakdown with patients or other team members (25/42, 59.5%). Conclusion: Both provider and team factors contributed to ML cases involving EM physicians performing procedural interventions. Addressing these factors may improve patient safety and reduce ML risk for physicians.
This report is on the synthesis by electrospinning of multiferroic core-shell nanofibers of strontium hexaferrite and lead zirconate titanate or barium titanate and studies on magneto-electric (ME) coupling. Fibers with well-defined core–shell structures showed the order parameters in agreement with values for nanostructures. The strength of ME coupling measured by the magnetic field-induced polarization showed the fractional change in the remnant polarization as high as 21%. The ME voltage coefficient in H-assembled films showed the strong ME response for the zero magnetic bias field. Follow-up studies and potential avenues for enhancing the strength of ME coupling in the core–shell nanofibers are discussed.
Sexual dysfunction occurs in 40%-60% of patients with major depressive disorder (MDD), due to either the illness itself and/or the effects of antidepressant treatment. The phase-2 CLARITY trial recently demonstrated the efficacy of adjunctive pimavanserin (PIM) for MDD when added to ongoing selective serotonin or serotonin–norepinephrine reuptake inhibitor (SSRI/SNRI) treatment. No new safety observations were reported in this study. This post-hoc analysis examines the potential impact of PIM treatment on sexual function.
Study methodology has been presented previously (APA 2019). Adult male and female patients with moderate-to-severe MDD were randomized to PIM 34 mg/day (n=51) or placebo (PBO, n=152) added to ongoing SSRI/SNRI treatment. Massachusetts General Hospital–Sexual Functioning Inventory (MGH-SFI) and Hamilton Depression Rating Scale, 17-item version (HAMD-17) item 14 (sexual interest) scores were examined by analysis of covariance.
Adjunctive PIM resulted in significantly greater 5-week reduction (improvement) relative to SSRI/SNRI treatment plus placebo on mean MGH-SFI scores (difference –0.634, SE 0.167; P<0.001; effect size [ES], Cohen’s d 0.614). Similarly, PIM resulted in greater improvement compared with placebo on individual MGH-SFI items that applied to both males and females: Interest in Sex (P=0.006; ES=0.483), Ability to Get Sexually Aroused/Excited (P=0.001; ES=0.560), Ability to Achieve Orgasm (P<0.001; ES=0.609), Overall Sexual Satisfaction (P=0.003; ES=0.524). HAMD-17 item 14 scores were also significantly more reduced (improved) with PIM (P<0.001; ES=0.574).
These results underscore the potential of adjunctive PIM for improving sexual function in patients with MDD and inadequate response to SSRIs/SNRIs. Potential benefits should be confirmed in further studies.
Depression is the leading cause of disability worldwide, with fewer than 50% of treated patients achieving full remission. This study (“CLARITY,” ACP-103-042: NCT03018340) examined the 5-HT2A inverse agonist pimavanserin (PIM) as a potential adjunctive treatment for major depressive disorder (MDD).
Adult female and male subjects with a DSM-5 primary diagnosis of a major depressive episode as part of MDD, inadequate response to ongoing SSRIs or SNRIs of adequate dose and duration as confirmed by the Massachusetts General Hospital Antidepressant Treatment History Questionnaire, and a MADRS total score >20 were randomized to PIM 34 mg/day or placebo (PBO) added to their SSRI/SNRI treatment. A sequential parallel comparison design was used, consisting of two 5-week stages. PBO nonresponders in Stage-1 who met prespecified criteria were re-randomized to PIM or PBO for the second period (Stage-2). The primary efficacy measure was the weighted average of Stage-1 and Stage-2 total scores of the HAMD-17.
Of the 207 patients enrolled, 52 received PIM, and 155 received PBO in Stage 1. Mean age was 46.2 years, and 72.9% of patients were female. Baseline MADRS total (mean [SD]: 31.5 [0.4]) and HAMD-17 total scores (22.2 [0.3]) indicated a moderate overall severity of illness. PIM met the primary endpoint, reducing the weighted Stage-1/Stage-2 HAMD-17 total score relative to PBO (least-square means [LSM] difference, –1.7; standard error [SE], 0.9; P=0.04). Stage-1 PIM patients demonstrated highly significant 5-week improvement on the HAMD-17 (LSM difference=–4.0, SE=1.1; P<0.001; effect size, Cohen’s d: 0.626), separating from placebo by the end of Week 1 (LSM difference=–1.7, SE=0.8; P=0.04). Stage-2 results showed no significant separation among Stage-1 placebo nonresponders (P=0.69). In Stage 2, a substantively smaller number of subjects (n=58) were rerandomized than planned, likely due to restrictive criteria for re-randomization. Greater overall improvement was seen with PIM relative to PBO on the key secondary endpoint, the Sheehan Disability Scale (LSM difference=–0.8, SE=0.3; P=0.004), and positive results were also seen on 7 of the 11 other secondary endpoints, including responder rate (≥50% reduction in HAMD-17 total; P=0.007), Massachusetts General Hospital Sexual Functioning Index (P<0.001), and Karolinska Sleepiness Scale for daytime sleepiness (P=0.02). Discontinuations due to adverse events were low (PIM 1.2%, PBO 3.2%). One serious adverse event was reported in each treatment group, deemed unrelated to treatment. No deaths were reported. Laboratory assessments, electrocardiography, and changes in vital signs were unremarkable, and no new safety signals were reported.
Study data provide evidence of the efficacy, safety, and tolerability of adjunctive PIM in treating MDD inadequately responsive to SSRI or SNRI therapy. Efforts to confirm these results are ongoing in a Phase 3 program.
Restless legs syndrome (RLS) is a neurological disorder characterized by an urge to move and uncomfortable sensations. Genetic studies have identified polymorphisms in up to 19 risk loci, including MEIS1 and BTBD9. Rodents deficient in either homolog show RLS-like phenotypes. However, whether MEIS1 and BTBD9 interact in vivo is unclear. Here, with C. elegans, we observed that the hyperactive egg-laying behavior caused by loss of BTBD9 homolog was counteracted by knockdown of MEIS1 homolog. This was further investigated in mutant mice with Btbd9, Meis1, or both knocked out. The double knockout mice showed an earlier onset of the motor deficit in a wheel running test but did not have increased sensitivity to heat stimuli as observed in single knock outs. Meis1 protein level was not influenced by Btbd9 deficiency, and Btbd9 transcription was not affected by Meis1 haploinsufficiency. Our results demonstrate that MEIS1 and BTBD9 do not regulate each other.
California has a large population of people experiencing homelessness (PEH) that is characterised by a high proportion of people who are unsheltered and chronically homeless. PEH are at increased risk of communicable diseases due to multiple, intersecting factors, including increased exposures, comorbid conditions including substance use disorder and mental illness and lack of access to hygiene and healthcare facilities. Data available for several communicable diseases show that PEH in California experiences an increased burden of communicable diseases compared to people not experiencing homelessness. Public health agencies face unique challenges in serving this population. Efforts to reduce homelessness, increase access to health care for PEH, enhance data availability and strengthen partnerships among agencies serving PEH can help reduce the disparity in communicable disease burden faced by PEH.
Contact guidance is vital to many physiological processes, yet is still poorly understood. This is partly due to the variability of experimental platforms, making comparisons difficult. To combat this, a multiplexed approach was used to fabricate topographical cues on single quartz coverslips for high-throughput screening. Furthermore, this method offers control of surface roughness and protein adsorption characterization, two critical aspects to the in vitro environment often overlooked in contact guidance platforms. The quartz surface can be regenerated, is compatible with versatile microscopy modes, and can scale up for manufacturing offering a novel platform that could serve as a potential standard assay.
Tuberculosis (TB) is generally considered a disease that principally afflicts the low-income segments of a population. In the Nanshan District of Shenzhen, China, with the economic transformation and a new Headquarters Economy (HE) emerging, there are now more cases in office workers than in manufacturing workers. To illustrate this trend, we describe a small TB outbreak in an office building located in the centre of the rapidly growing HE district. Two active pulmonary tuberculosis cases were found in workers who shared an office, and whole genome sequencing showed that the genetic distance between the strains of the two cases was just one single nucleotide polymorphism, consistent with intra-office transmission. Investigation of 30 other workers in the same or adjacent offices with interviews, interferon-gamma release assays (IGRAs) and chest X-rays, identified one new TB case and latent tuberculosis infection (LTBI) in 40.0% (12/30) of the contacts. The offices were under-ventilated. None of the IGRA positive, asymptomatic contacts agreed to receive treatment for LTBI, presumably due to TB stigma, and over the next 2 years 69.0% (20/29) of the contacts were lost to follow-up. Treatment for LTBI and stigma of TB remain challenges here. Office workers in the HE of rapidly economic developing areas should be targeted with increased vigilance by TB control programmes.
Particle-in-Cell (PIC) simulation is an interpolation-based method on the Newton–Maxwell (N–M) system. Its well-known drawback is its shape/interpolation functions often causing the violation of continuity equations (CEs) at mesh nodes and that of Maxwell equations (MEs) at particles' positions. Whether this drawback can be overcome by choosing/solving suitable shape/interpolation functions is of fundamental importance for the PIC simulation. Until now, these shape/interpolation functions are usually subjectively chosen and, hence, always invoke the drawback. Here, we first investigate whether these shape/interpolation functions can be self-consistently solved by considering under what condition the CEs and the MEs can be satisfied anywhere. Strict mathematical analysis reveals that strict self-consistent shape/interpolation functions are unavailable. Only few approximately self-consistent shape/interpolation functions are luckily found by some authors. This fact drives us to present another universal interpolation-free strict method on the N–M system.
Crop insurance is the cornerstone program of domestic farm policy in most developed countries. Although most countries’ rating methodology corrects for time-varying movements in the first two moments, it is unclear whether using the entire yield series remains appropriate. We use distributional tests and an out-of-sample retain-cede rating game to answer whether governments/insurers should historically trim yields in estimating their premium rates. Despite small sample sizes and the need to estimate tail probabilities, the historical data appear to be sufficiently different such that trimming is justified.
Depth-integrated mathematical models for simulating waves and currents from deep to shallow water are presented. These models are derived from Euler’s equations in the
-coordinate system, mapping the total water depth in Cartesian coordinates onto a specified range of
-coordinates. The horizontal velocity is approximated as a truncated infinite series of products of prescribed shape functions of
and unknown functions of horizontal coordinates and time. Adopting the method of weighted residuals, the new models are obtained by minimizing the residuals of the horizontal momentum equations with either the Galerkin method or the subdomain method. These models’ linear and nonlinear water wave properties are investigated. The new models are implemented numerically. A hierarchy of numerical models with different degree of polynomial approximation is developed and checked against several benchmarked experiments and a new set of experiments of self-focusing wave groups. For both the Galerkin and subdomain models, excellent agreements are observed for both the free surface elevations and the velocity profiles. The new models are superior to the existing Boussinesq-type models for their applicability to a wide range of physical scenarios, including the interactions between a wave package of multiple frequency components and a linearly sheared current. The new Galerkin models have similar characteristics and accuracy as the Green–Naghdi models, but the new models are more efficient computationally. Finally, for the same degree of polynomial approximation the subdomain models perform better than the Galerkin models and require less computational time.
Sketching is a natural and intuitive communication tool used for expressing concepts or ideas which are difficult to communicate through text or speech alone. Sketching is therefore used for a variety of purposes, from the expression of ideas on two-dimensional (2D) physical media, to object creation, manipulation, or deformation in three-dimensional (3D) immersive environments. This variety in sketching activities brings about a range of technologies which, while having similar scope, namely that of recording and interpreting the sketch gesture to effect some interaction, adopt different interpretation approaches according to the environment in which the sketch is drawn. In fields such as product design, sketches are drawn at various stages of the design process, and therefore, designers would benefit from sketch interpretation technologies which support these differing interactions. However, research typically focuses on one aspect of sketch interpretation and modeling such that literature on available technologies is fragmented and dispersed. In this paper, we bring together the relevant literature describing technologies which can support the product design industry, namely technologies which support the interpretation of sketches drawn on 2D media, sketch-based search interactions, as well as sketch gestures drawn in 3D media. This paper, therefore, gives a holistic view of the algorithmic support that can be provided in the design process. In so doing, we highlight the research gaps and future research directions required to provide full sketch-based interaction support.
While child self-regulation is shaped by the environment (e.g., the parents’ caregiving behaviors), children also play an active role in influencing the care they receive, indicating that children's individual differences should be integrated in models relating early care to children's development. We assessed 409 children's observed temperamental behavioral inhibition (BI), effortful control (EC), and the primary caregiver's parenting at child ages 3 and 5. Parents reported on child behavior problems at child ages 3, 5, and 8. Mediation analyses were conducted to examine relations between child temperament and parenting in predicting child problems. BI at age 3 was positively associated with structured parenting at age 5, which was negatively related to child internalizing and attention-academic problems at age 8. In contrast, parenting at child age 3 did not predict child BI or EC at age 5, nor did age 3 EC predict parenting at age 5. Findings indicate that child behavior may shape the development of caregiving and, in turn, long-term child adjustment, suggesting that studies of caregiving and child outcomes should consider the role of child temperament toward developing more informative models of child–environment interplay.
Reflection is an important component in design skill development that helps designers better understand their design problem, develop better solutions, and improve their design approaches. This study explored the information that a student design team reflected on as part of a needs finding experience and the outcomes from these reflections. During the needs finding experience, the team exhibited reflection-in- action behavior as they used available data to form and iterate on explanatory hypotheses about potential community needs. After the needs finding experience, the team exhibited reflection-on-action behavior as they drew connections between their interview approaches and stakeholder responses and discussed changes they might make in the future. The team also identified situations where contextual factors of the stakeholder impacted their interviews, but during these reflections did not indicate how they might adapt their approaches to account for such factors in the future. These findings show that student designers can use reflection as a tool to improve their needs finding process but would benefit from pedagogical structures that might help them reflect more effectively.
Estimating the feed intake of grazing herbivores is critical for determining their nutrition, overall productivity and utilization of grassland resources. A 17-day indoor feeding experiment was conducted to evaluate the potential use of Medicago sativa as a natural supplement for estimating the total feed intake of sheep. A total of 16 sheep were randomly assigned to four diets (four sheep per diet) containing a known amount of M. sativa together with up to seven forages common to typical steppes. The diets were: diet 1, M. sativa + Leymus chinensis + Puccinellia distans; diet 2, species in diet 1 + Phragmites australis; diet 3, species in diet 2 + Chenopodium album + Elymus sibiricus; and diet 4, species in diet 3 + Artemisia scoparia + Artemisia tanacetifolia. After faecal marker concentrations were corrected by individual sheep recovery, treatment mean recovery or overall recovery, the proportions of M. sativa and other dietary forages were estimated from a combination of alkanes and long-chain alcohols using a least-square procedure. Total intake was the ratio of the known intake of M. sativa to its estimated dietary proportion. Each dietary component intake was obtained using total intake and the corresponding dietary proportions. The estimated values were compared with actual values to assess the estimation accuracy. The results showed that M. sativa exhibited a distinguishable marker pattern in comparison to the other dietary forage species. The accuracy of the dietary composition estimates was significantly (P < 0.001) affected by both diet diversity and the faecal recovery method. The proportion of M. sativa and total intake across all diets could be accurately estimated using the individual sheep or the treatment mean recovery methods. The largest differences between the estimated and observed total intake were 2.6 g and 19.2 g, respectively, representing only 0.4% and 2.6% of the total intake. However, they were significantly (P < 0.05) biased for most diets when using the overall recovery method. Due to the difficulty in obtaining individual sheep recovery under field conditions, treatment mean recovery is recommended. This study suggests that M. sativa, a natural roughage instead of a labelled concentrate, can be utilized as a dietary supplement to accurately estimate the total feed intake of sheep indoors and further indicates that it has potential to be used in steppe grassland of northern China, where the marker patterns of M. sativa differ markedly from commonly occurring plant species.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Music or other background sounds are often played in barns as environmental enrichment for animals on farms or to mask sudden disruptive noises. Previous studies looking at the effects of this practice on non-human animal well-being and productivity have found contradictory results. However, there is still a lack of discussion on whether piglets have the ability to distinguish different types of music. In this study, we exposed piglets to different music conditions to investigate whether the piglets preferred certain music types, in which case those types would have the potential to be used as environmental enrichment. In total, 30 piglets were tested for music type preference to determine whether growing pigs respond differently to different types of music. We used music from two families of instruments (S: string, W: wind) and with two tempos (S: slow, 65 beats/min (bpm); F: fast, 200 bpm), providing four music-type combinations (SS: string-slow; SF: string-fast; WS: wind-slow; WF: wind-fast). The piglets were given a choice between two chambers, one with no music and the other with one of the four types of music, and their behaviour was observed. The results showed that SS and WF music significantly increased residence time (P<0.01) compared with the other music conditions. Compared with the control group (with no music), the different music conditions led to different behavioural responses, where SS music significantly increased lying (P<0.01) and exploration behaviour (P<0.01); SF music significantly increased tail-wagging behaviour (P<0.01); WS music significantly increased exploration (P<0.01); and WF music significantly increased walking, lying, standing and exploration (all P<0.01). The results also showed that musical instruments and tempo had little effect on most of the behaviours. Fast-tempo music significantly increased walking (P=0.02), standing (P<0.01) and tail wagging (P=0.04) compared with slow-tempo music. In conclusion, the results of this experiment show that piglets are more sensitive to tempo than to musical instruments in their response to musical stimulation and seem to prefer SS and WF music to the other two types. The results also suggest a need for further research on the effect of music types on animals.
Community-acquired pneumonia (CAP) results in substantial numbers of hospitalisations and deaths in older adults. There are known lifestyle and medical risk factors for pneumococcal disease but the magnitude of the additional risk is not well quantified in Australia. We used a large population-based prospective cohort study of older adults in the state of New South Wales (45 and Up Study) linked to cause-specific hospitalisations, disease notifications and death registrations from 2006 to 2015. We estimated the age-specific incidence of CAP hospitalisation (ICD-10 J12-18), invasive pneumococcal disease (IPD) notification and presumptive non-invasive pneumococcal CAP hospitalisation (J13 + J18.1, excluding IPD), comparing those with at least one risk factor to those with no risk factors. The hospitalised case-fatality rate (CFR) included deaths in a 30-day window after hospitalisation. Among 266 951 participants followed for 1 850 000 person-years there were 8747 first hospitalisations for CAP, 157 IPD notifications and 305 non-invasive pneumococcal CAP hospitalisations. In persons 65–84 years, 54.7% had at least one identified risk factor, increasing to 57.0% in those ⩾85 years. The incidence of CAP hospitalisation in those ⩾65 years with at least one risk factor was twofold higher than in those without risk factors, 1091/100 000 (95% confidence interval (CI) 1060–1122) compared with 522/100 000 (95% CI 501–545) and IPD in equivalent groups was almost threefold higher (18.40/100 000 (95% CI 14.61–22.87) vs. 6.82/100 000 (95% CI 4.56–9.79)). The CFR increased with age but there were limited difference by risk status, except in those aged 45 to 64 years. Adults ⩾65 years with at least one risk factor have much higher rates of CAP and IPD suggesting that additional risk factor-based vaccination strategies may be cost-effective.
Heading date (HD) and flowering date (FD) are critical for yield potential and stability, so understanding their genetic foundation is of great significance in wheat breeding. Three related recombinant inbred line populations with a common female parent were developed to identify quantitative trait loci (QTL) for HD and FD in four environments. In total, 25 putative additive QTL and 20 pairwise epistatic effect QTL were detected in four environments. The additive QTL were distributed across 17 wheat chromosomes. Of these, QHd-1A, QHd-1D, QHd-2B, QHd-3B, QHd-4A, QHd-4B and QHd-6D were major and stable QTL for HD. QFd-1A, QFd-2B, QFd-4A and QFd-4B were major and stable QTL for FD. In addition, an epistatic interaction test showed that epistasis played important roles in controlling wheat HD and FD. Genetic relationships between HD/FD and five yield-related traits (YRTs) were characterized and ten QTL clusters (C1–C10) simultaneously controlling YRTs and HD/FD were identified. The present work laid a genetic foundation for improving yield potential in wheat molecular breeding programmes.
A multichannel calorimeter system is designed and constructed which is capable of delivering single-shot and broad-band spectral measurement of terahertz (THz) radiation generated in intense laser–plasma interactions. The generation mechanism of backward THz radiation (BTR) is studied by using the multichannel calorimeter system in an intense picosecond laser–solid interaction experiment. The dependence of the BTR energy and spectrum on laser energy, target thickness and pre-plasma scale length is obtained. These results indicate that coherent transition radiation is responsible for the low-frequency component (
1 THz) of BTR. It is also observed that a large-scale pre-plasma primarily enhances the high-frequency component (
3 THz) of BTR.