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The aim of this study was to assess which machine, Radixact or CyberKnife, can deliver better treatment for lung and prostate stereotactic body radiation therapy (SBRT) with the use of Synchrony® real-time motion tracking system. Ten and eight patients treated with lung and prostate SBRT, respectively, using the CyberKnife system were selected for the assessment. For each patient, a retrospective Radixact plan was created and compared with the original CyberKnife plan. There was no statistically significant difference in the new conformity index of the Radixact plans and that of the Cyberknife plans in both lung and prostate SBRT. The average homogeneity index in the Radixact plans was better in both lung and prostate SBRT with statistical significance (p = 0·04 for lung and p = 0·02 for prostate). In lung SBRT, the dose to lungs was lower in Cyberknife plans (p = 0·002). In prostate SBRT, there was no statistically significant difference in organs at risk sparing between Cyberknife plans and Radixact plans. In conclusion, CyberKnife was better in lung SBRT while Radixact was better in prostate SBRT.
We investigated real-world vaccine effectiveness for Oxford-AstraZeneca (ChAdOx1) and CoronaVac against laboratory-confirmed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare workers (HCWs).
Methods:
We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil between January 1, 2021 and August 3, 2021, to assess vaccine effectiveness. We calculated vaccine effectiveness as 1 − rate ratio (RR), with RR determined by adjusting Poisson models with the occurrence of SARS-CoV-2 infection as the outcome and the vaccination status as the main variable. We used the logarithmic link function and simple models adjusting for sex, age, and job types.
Results:
In total, 13,813 HCWs met the inclusion criteria for this analysis. Among them, 6,385 (46.2%) received the CoronaVac vaccine, 5,916 (42.8%) received the ChAdOx1 vaccine, and 1,512 (11.0%) were not vaccinated. Overall, COVID-19 occurred in 6% of unvaccinated HCWs, 3% of HCWs who received 2 doses of CoronaVac vaccine, and 0.7% of HCWs who received 2 doses of ChAdOx1 vaccine (P < .001). In the adjusted analyses, the estimated vaccine effectiveness rates were 51.3% for CoronaVac, and 88.1% for ChAdOx1 vaccine. Both vaccines reduced the number of hospitalizations, the length of hospital stay, and the need for mechanical ventilation. In addition, 19 SARS-CoV-2 samples from 19 HCWs were screened for mutations of interest. Of 19 samples, 18 were the γ (gamma) variant.
Conclusions:
Although both COVID-19 vaccines (viral vector and inactivated virus) can significantly prevent COVID-19 among HCWs, CoronaVac was much less effective. The COVID-19 vaccines were also effective against the dominant γ variant.
To investigate the downstream rim seal gas ingestion characteristics of a 1.5-stage turbine, the URANS equations were solved numerically using the SST turbulence model. The effects of different purge flow rates and the second vane on the ingestion characteristics of the aft cavity and the nonuniform fluctuations of the main gas path pressure are analysed. The results showed that the aft cavity is affected by the combined effects of the blade and the second vane, and the potential field at the leading edge of the second vane greatly influence the airflow variation in the aft cavity, which enhances the ingress of the mainstream into the wheel-space. The front purge flow weakens the egress between the suction side of the blade and the suction side of the second vane. The potential field at the leading edge of the second vane suppresses the nonuniform distribution of airflow in the aft cavity caused by the rotational effect of the blade.
The epidemic of tuberculosis has posed a serious burden in Qinghai province, it is necessary to clarify the epidemiological characteristics and spatial-temporal distribution of TB for future prevention and control measures. We used descriptive epidemiological methods and spatial statistical analysis including spatial correlation and spatial-temporal analysis in this study. Furthermore, we applied an exponential smoothing model for TB epidemiological trend forecasting. Of 43 859 TB cases, the sex ratio was 1.27:1 (M:F), and the average annual TB registered incidence was 70.00/100 000 of 2009–2019. More cases were reported in March and April, and the worst TB stricken regions were the prefectures of Golog and Yushu. High TB registered incidences were seen in males, farmers and herdsmen, Tibetans, or elderly people. 7132 cases were intractable, which were recurrent, drug resistant, or co-infected with other infections. Three likely cases clusters with significant high risk were found by spatial-temporal scan on data of 2009–2019. The exponential smoothing winters' additive model was selected as the best-fitting model to forecast monthly TB cases in the future. This research indicated that TB in Qinghai is still a serious threaten to the local residents' health. Multi-departmental collaboration and funds special for TB treatments and control are still needed, and the exponential smoothing model is promising which could be applied for forecasting of TB epidemic trend in this high-altitude province.
In 2015, an international outbreak of Mycobacterium chimaera infections among patients undergoing cardiothoracic surgeries was associated with exposure to contaminated LivaNova 3T heater-cooler devices (HCDs). From June 2017 to October 2020, the Centers for Disease Control and Prevention was notified of 18 patients with M. chimaera infections who had undergone cardiothoracic surgeries at 2 hospitals in Kansas (14 patients) and California (4 patients); 17 had exposure to 3T HCDs. Whole-genome sequencing of the clinical and environmental isolates matched the global outbreak strain identified in 2015.
Methods:
Investigations were conducted at each hospital to determine the cause of ongoing infections. Investigative methods included query of microbiologic records to identify additional cases, medical chart review, observations of operating room setup, HCD use and maintenance practices, and collection of HCD and environmental samples.
Results:
Onsite observations identified deviations in the positioning and maintenance of the 3T HCDs from the US Food and Drug Administration (FDA) recommendations and the manufacturer’s updated cleaning and disinfection protocols. Additionally, most 3T HCDs had not undergone the recommended vacuum and sealing upgrades by the manufacturer to decrease the dispersal of M. chimaera–containing aerosols into the operating room, despite hospital requests to the manufacturer.
Conclusions:
These findings highlight the need for continued awareness of the risk of M. chimaera infections associated with 3T HCDs, even if the devices are newly manufactured. Hospitals should maintain vigilance in adhering to FDA recommendations and the manufacturer’s protocols and in identifying patients with potential M. chimaera infections with exposure to these devices.
During emergency responses, public health leaders frequently serve in incident management roles that differ from their routine job functions. Leaders’ familiarity with incident management principles and functions can influence response outcomes. Therefore, training and exercises in incident management are often required for public health leaders. To describe existing methods of incident management training and exercises in the literature, we queried 6 English language databases and found 786 relevant articles. Five themes emerged: (1) experiential learning as an established approach to foster engaging and interactive learning environments and optimize training design; (2) technology-aided decision support tools are increasingly common for crisis decision-making; (3) integration of leadership training in the education continuum is needed for developing public health response leaders; (4) equal emphasis on competency and character is needed for developing capable and adaptable leaders; and (5) consistent evaluation methodologies and metrics are needed to assess the effectiveness of educational interventions.
These findings offer important strategic and practical considerations for improving the design and delivery of educational interventions to develop public health emergency response leaders. This review and ongoing real-world events could facilitate further exploration of current practices, emerging trends, and challenges for continuous improvements in developing public health emergency response leaders.
We conducted the first detailed mineral magnetic investigation of more than nine loess–paleosol couplets of the composite Titel-Stari Slankamen loess section in Serbia, which provides one of the longest and most complete terrestrial record of paleoclimatic changes in Europe since ~1.0 Ma. The results show that the ferrimagnetic mineral assemblage of the loess units is dominated by partially oxidized multidomain (MD) and pseudo-single domain (PSD) magnetite; however, with an increasing degree of pedogenesis, the eolian contribution is gradually masked by pedogenic superparamagnetic(SP) and single-domain (SD) ferrimagnets (mainly maghemite). The overall consistency of ferrimagnetic grain-size parameters indicates an absence of dissolution of the fine-grained ferrimagnetic fraction despite changes in climate regime over the past 1.0 Ma. The variations of normalized dJ/dT@120K and normalized χheating@530°C reflect a long-term stepwise increase in aridity during glacials with a major step at ~0.6–0.5 Ma, over the last 1.0 Ma. Overall, the results provide an improved basis for the future use of the magnetic properties of Serbian loess deposits for paleoclimatic reconstruction.
This work is the first in situ U–Pb geochronological study of perovskite and calcic garnet (andradite) from the Guli complex in the Maimecha–Kotuy alkaline province (Polar Siberia, Russia). The U–Pb isotopic compositions of perovskite from contact zones of the two carbonatite stocks (Southern and Northern) and from jacupirangite separating the stocks were determined by laser-ablation inductively-coupled-plasma mass-spectrometry (LA-ICPMS) and isotope-dilution thermal-ionisation mass-spectrometry (ID-TIMS). The LA-ICPMS and ID-TIMS data for perovskite from the Northern carbonatite stock are in good agreement, yielding 206Pb/238U ages of 250.4 ± 1.1 Ma and 249 ± 2 Ma, respectively. These ages are also within the analytical uncertainty from the ID-TIMS results for perovskite from jacupirangites (250 ± 1 Ma). The LA-ICPMS results for perovskite from the Southern carbonatite stock indicate its somewhat older age (255.3 ± 2.4 Ma), implying the possibility of small-volume mantle magmatism predating the eruption of the Siberian flood basalts at ca. 252–251 Ma. This interpretation is supported by reports of pre-flood magmatism elsewhere in eastern Siberia. Andradite crystals from the contact between the Southern stock and metasomatised melilitolite were analysed by ID-TIMS. These measurements are inconclusive (247 ± 6 Ma) and could not be used to constrain further the timing of carbonatitic magmatism in the southern part of the complex. The present contribution also presents a refined methodology for LA-ICPMS geochronological studies of perovskite with elevated levels of common lead, and addresses some of the problems with previously proposed calibration standards.
Global health disasters are on the rise and can occur at any time with little advance warning, necessitating preparation. The authors created a comprehensive evidence-based Emergency Preparedness Training Program focused on long-term retention and sustained learner engagement.
Method:
A prospective observational study was conducted of a simulation-based mass casualty event training program designed using an outcomes-based logic model. A total of 25 frontline healthcare workers from multiple hospital sites in the New York metropolitan area participated in an 8-hour immersive workshop. Data was collected from assessments, and surveys provided to participants 3 weeks prior to the workshop, immediately following the workshop, and 3 months after completion of the workshop.
Results:
The mean percentage of total knowledge scores improved across pre-workshop, post-workshop and retention (3 months post-workshop) assessments (53.2% vs. 64.8% vs. 67.6%, P < 0.05). Average comfort scores in the core MCI competencies increased across pre-workshop, post-workshop and retention self-assessments (P < 0.01). Of the participants assessed at 3 months retention (n = 14, 56%), 50.0% (n = 7) assisted in updating their hospital’s emergency operations plan and 50.0% (n = 7) pursued further self-directed learning in disaster preparedness medicine.
Conclusions:
The use of the logic model provided a transparent framework for the design, implementation, and evaluation of a competency-based EPT program at a single academic center.
Ventriculo-ventricular interactions are known to exist, though not well quantified. We hypothesised that the ventricular–vascular coupling ratio assessed by cardiovascular MRI would provide insight into this relationship. We also sought to compare MRI-derived ventricular–vascular coupling ratio to echocardiography and patient outcomes.
Methods:
Children with cardiac disease and biventricular physiology were included. Sanz’s and Bullet methods were used to calculate ventricular–vascular coupling ratio by MRI and echocardiography, respectively. Subgroup analysis was performed for right and left heart diseases. Univariate and multivariate regressions were performed to determine associations with outcomes.
Results:
A total of 55 patients (age 14.3 ± 2.5 years) were included. Biventricular ventricular–vascular coupling ratio by MRI correlated with each other (r = 0.41; p = 0.003), with respect to ventricle’s ejection fraction (r = −0.76 to −0.88; p < 0.001) and other ventricle’s ejection fraction (r = −0.42 to −0.47; p < 0.01). However, biventricular ejection fraction had only weak correlation with each other (r = 0.31; p = 0.02). Echo underestimated ventricular–vascular coupling ratio for the left ventricle (p < 0.001) with modest correlation to MRI-derived ventricular–vascular coupling ratio (r = 0.43; p = 0.002). There seems to be a weak correlation between uncoupled right ventricular–vascular coupling ratio with the need for intervention and performance on exercise testing (r = 0.33; p = 0.02).
Conclusion:
MRI-derived biventricular ventricular–vascular coupling ratio provides a better estimate of ventriculo-ventricular interaction in children and adolescents with CHD. These associations are stronger than traditional parameters and applicable to right and left heart conditions.
ABSTRACT IMPACT: Understanding gene expression changes after viral vaccination and booster may help predict vaccine efficacy. OBJECTIVES/GOALS: Utilize a systems biology approach to identify gene expression changes after administration of Zaire Ebola virus glycoprotein expressed in a Chimp Adeno3 vector (ChAd3-EBOZ) and either boosted ˜7 weeks later with modified vaccinia Ankara MVA expressing Zaire and Marburg GPs plus Tai forest NP (MVA-BN ®Filo) or given saline (placebo). METHODS/STUDY POPULATION: As part of the phase 1b, open-label vaccination trial of ChAd3-EBO-Z in Mali, West Africa, peripheral blood mononuclear cells were isolated from eight volunteers for whole genome transcriptomics analysis. Four subjects received the MVA-BN ®-Filo booster and four received saline. Samples were taken prior to receipt of the booster or placebo, as well as 1, 7, and 14 days afterwards. Significant differentially expressed genes were identified using RNA-seq between baseline and post-MVA-BN ®Filo. Functional enrichment analysis against the GO Ontology Database and the Immune Signatures C7 collection of MSigDB (ImmuneSigDB) was performed. These differentially expressed genes were also examined for associations with Ebola antibody titers and cell-mediated immune responses. RESULTS/ANTICIPATED RESULTS: The majority of gene expression changes occurred on day 1 post-MVA-BN ®-Filo administration. 870 genes had significantly different expression when day 1 samples were compared to pre-booster baseline (791 upregulated/79 downregulated). Those upregulated genes are mainly involved type I interferon and regulation of viral life cycle pathways. The downregulated genes are involved in regulation of cellular defense response, lymphocyte mediated immunity. Comparing to the C7 Immune Signatures collection datasets, we identified more than 100 upregulated genes from 6 studies of yellow fever vaccination that were also significantly upregulated in our study. The top enriched ontological pathway of those genes is cellular response to type I Interferon. DISCUSSION/SIGNIFICANCE OF FINDINGS: The use of a systems biology approach to compare gene expression changes among vaccine studies utilizing whole genome transcriptomics data allows the identification of genes involved in the immune response to vaccination and might aid in predicting vaccine efficacy.
To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies.
Design:
Quasi-experimental study.
Setting and population:
Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States.
Methods:
Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014–May 2016) and after the intervention (June 2016–December 2018). These data were compared using interrupted time series analysis.
Results:
In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality.
Conclusions:
Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.
Retrospective observational study to determine diagnostic yield and utility of genetic testing in children with epilepsy attending the Epilepsy Clinic at Children’s Hospital, London, Ontario, Canada.
Methods:
Children (birth–18 years) with epilepsy, who were seen in a 10-year period (January 1, 2008–March 31, 2018), were selected using defined inclusion criteria and by combining clinic datasets and laboratory records.
Results:
In total, 105 children (52.38% male and 47.61% female) with a variety of seizures were included in the analysis. Developmental delay was documented in the majority (83; 79.04%). Overall, a genetic diagnosis was established in 24 (22.85%) children. The diagnostic yield was highest for whole-exome sequencing (WES), at 35.71%. The yield from microarray was 8.33%. Yields of single-gene testing (18.60%) and targeted multigene panel testing (19.23%) were very similar. Several likely pathogenic and pathogenic variants not previously reported were identified and categorized using ACMG criteria. All diagnosed patients underwent a review of anti-seizure medication management and received counseling on natural history of their disease, possible complications, recurrence risks, and possibilities of preimplantation or prenatal genetic diagnosis.
Conclusions:
Our study confirms the multiple benefits of detecting a genetic etiology in children with epilepsy. Similar yields in single versus multigene testing underscore the importance of accurate clinical phenotyping. Patients with epilepsy and their caregivers in Ontario would undoubtedly benefit from repatriation of multigene panels and WES to the province.
Robust personal protective equipment is essential in preventing the transmission of coronavirus disease 2019 to head and neck surgeons who are routinely involved in aerosol generating procedures.
Objective
This paper describes the collective experience, across 3 institutes, of using a reusable half-face respirator in 72 head and neck surgery cases.
Method
Cost analysis was performed to demonstrate the financial implications of using a reusable respirator compared to single-use filtering facepiece code 3 masks.
Conclusion
The reusable respirator is a cost-effective alternative to disposable filtering facepiece code 3 respirators. Supplying reusable respirators to individual staff members may increase the likelihood of them having appropriate personal protective equipment during their clinical duties.
This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = −0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
The aim of this study was to examine whether the presence of risk alleles of the norepinephrine transporter gene (SLC6A2) polymorphisms is associated with differences in regional cerebral blood flow (rCBF) measured by 99mTc-HMPAO single photon emission computerized tomography in a Korean sample of ADHD.
Methods
The present study included 24 children with ADHD (9.5±2.4 years), consisting of 20 boys and 4 girls, aged 6-16 years. We investigated the G1287A and -3081(A/T) polymorphisms of the SLC6A2. The rCBF was compared between the ADHD subjects with and without risk alleles at the G1287A polymorphism and at the -3081(A/T) polymorphism. Image analyses were performed with voxelwise t-statistics using SPM2.
Results
1) The ADHD subjects with the A allele (risk allele) at the G1287A polymorphism showed reduced perfusion in the left middle frontal gyrus, left inferior parietal lobule, precuneus, right superior frontal gyrus, and right superior parietal lobule as compared with ADHD subjects without the A allele (p< 0.001).
2) The ADHD subjects with the A allele at the G1287A polymorphism showed increased perfusion in the right middle frontal gyrus, right middle temporal gyrus, right superior temporal gyrus, right fusiform gyrus, right precentral gyrus, and right anterior lobe of cerebellum as compared with ADHD subjects without the A allele (p< 0.001).
3) No significant perfusion differences were found between ADHD subjects with and without the T allele (risk allele) at the -3081(A/T) polymorphism.
Conclusion
Our findings suggest that the SLC6A2 G1287A polymorphism might exert differential effects on rCBF in children with ADHD.
Many family characteristics were reported to increase the risk of bipolar disorder (BPD). The development of BPD may be mediated through different pathways, involving diverse risk factor profiles. We evaluated the associations of family characteristics to build influential causal-pie models to estimate their contributions on the risk of developing BPD at the population level. We recruited 329 clinically diagnosed BPD patients and 202 healthy controls to collect information in parental psychopathology, parent-child relationship, and conflict within family. Other than logistic regression models, we applied causal-pie models to identify pathways involved with different family factors for BPD. The risk of BPD was significantly increased with parental depression, neurosis, anxiety, paternal substance use problems, and poor relationship with parents. Having a depressed mother further predicted early onset of BPD. Additionally, a greater risk for BPD was observed with higher numbers of paternal/maternal psychopathologies. Three significant risk profiles were identified for BPD, including paternal substance use problems (73.0%), maternal depression (17.6%), and through poor relationship with parents and conflict within the family (6.3%). Our findings demonstrate that different aspects of family characteristics elicit negative impacts on bipolar illness, which can be utilized to target specific factors to design and employ efficient intervention programs.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Methods:
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
Results:
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Conclusions:
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.