we report a case of lower extremity hemorrhage refractory to usual methods of bleeding control, which was controlled using a Folley catheter which was placed in to external iliac artery.

This work considers a seeded fesoterodine fumarate (FF) cooling crystallization and presents the methodology and implementation of a real-time machine learning modeling-based predictive controller to handle batch-to-batch (B2B) parametric drift. Specifically, an autoencoder recurrent neural network-based model predictive controller (AERNN-MPC) is developed to optimize product yield, crystal size, and energy consumption while accounting for the physical constraints on cooling jacket temperature. Deviations in the kinetic parameters are considered in the closed-loop simulations to account for the B2B parametric drift, and two error-triggered online update mechanisms are proposed to address issues pertaining to the availability of real-time crystal property measurements and are incorporated into the AERNN-MPC to improve the model prediction accuracy. Closed-loop simulation results demonstrate that the proposed AERNN-MPC with online update, irrespective of the accessibility to real-time crystal property data, achieves a desired closed-loop performance in terms of maximizing product yield and minimizing energy consumption.

Aim: Advanced age is an important risk factor for adverse events during procedural sedation. Remimazolam is safe and effective in adults’ gastroscopy sedation. The ideal dose and availability for elderly patients are not well known. We aim to investigate its 95% effective dose (ED95) for elderly patients undergoing gastroscopy, and to assess its safety and efficacy, with propofol as the comparison. Methods: The trial consists of two parts, patients who are over 65 and scheduled for elective outpatient painless gastroscopy were enrolled. In the first part, Dixon’s up-and-down methodology was used to determine the ED95 of remimazolam and propofol for inhibiting body movement during gastroscopic insertion, in combination with 0.2μg/kg remifentanil. In the second part, patients in each group received 0.2μg/kg remifentanil and the ED95 dose of the study drug for sedation induction, adding supplemental doses to maintain sedation depth when necessary. The primary outcome was the incidence of adverse events. The secondary outcome was the recovery time. Results: The ED95 of remimazolam and propofol induction dose were 0.204mg/kg [95% CI (0.175–0.390) mg/kg] and 1.994 mg/kg [95% CI (1. 739–5.955) mg/kg] respectively in gastroscopy. Adverse events were reported in 40.6% of patients in the remimazolam group and 83.1% in the propofol group (p<0.001), whereas the remimazolam group showed a higher incidence of hiccup(p=0.017). A shorter time to awakening (p<0.05) in the remimazolam group was observed. Conclusion: For elderly patients undergoing gastroscopy, the ED95 dose of remimazolam is a safer alternative than propofol when inducing the same sedation depth.

Aim To undertake a scoping review of pharmacists’ activities in opioid medicines management in primary care settings, including those developed or led by pharmacists, or in which pharmacists were members of broader multi-disciplinary teams; and to collate the activities, models of care and settings, and reported outcomes. Methods The bibliographic databases MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, SCOPUS and Web of Science were searched. Studies with quantitative evaluation and published in English were eligible. Participants were patients with any pain category or an opioid use disorder, and healthcare providers. Studies originating in hospitals or involving supply functions were not included. Screening of literature and data charting of results were undertaken by two researchers. Results The 47 studies included in the scooping review occurred in primary care settings collated into four categories: general practice or primary care clinics; healthcare organisations; community pharmacies and outreach services. Studies were primarily of opioid use in chronic, non-cancer pain. Other indications were opioid use disorder, cancer and dental pain. Pharmacist activities targeted risk-mitigation, patient and provider education and broader, strategic approaches. Patient-related outcomes included reduced opioid load, improved functionality and symptom management, enhanced access to services and medication-assisted treatments, and engagement in risk-mitigation strategies. Behaviour change of providers was demonstrated. Conclusion The review has identified the significant contribution that pharmacists working in primary care settings can make to minimise harm from opioids. Strategies implemented in isolation have the potential to further reduce adverse clinical outcomes with greater collaboration and coordination, such as opioid stewardship.

Compounds with (NHC)→E coordination bond are being generated and their chemistry is being explored over the past 15 years (NHC= N-heterocyclic carbenes, E = main group elements). Many examples of species with N-heterocyclic olefins (NHOs) are known, which exhibit umpolung chemistry. Increasing number of chemical species, which carry NHC as a functional unit, are being reported. There is a need to understand their electronic structure. Alkylated imidazole oximes (cationic, found useful in medicinal chemistry) ((NHC)-C(H)=N-OH(+)) carry NHC unit as a functional group. Similarly, the corresponding nitroso-N-heterocyclic olefins ((NHC)=C(R)-N=O) also carry NHC as a functional unit. It is important to establish the interaction between the NHC unit and the rest part of the molecule in these species. Density functional (DFT) study has been carried out to explore the electronic structure details of a few oximes and nitroso NHOs. The results indicate that a structure with NHC→C coordination interaction can be considered as one of the resonance structures of these species.

BACKGROUND: Workplace burnout can result in negative consequences for clinicians and patients. We assessed burnout prevalence and sources among pediatric hematology/oncology inpatient nurses, ambulatory nurses, physicians (MDs), and advanced practice providers (APPs) by evaluating effects of job demands and involvement in patient safety events (PSEs). METHODS: A cross-sectional survey (Maslach Burnout Inventory) measured emotional exhaustion, depersonalization, and reduced personal accomplishment. The NASA Task Load Index measured mental demand, physical demand, temporal demand, effort, and frustration. Relative weights analyses estimated the unique contributions of tasks and PSEs on burnout. Post-hoc analyses evaluated open-response comments for burnout factors. RESULTS: Burnout prevalence was 33%, 20%, 34% and 33% in inpatient nurses, ambulatory nurses, and MD, and APPs respectively (N=481, response rate 69%). Reduced personal accomplishment was significantly higher in inpatient nurses than MDs & APPs. Job frustration was the most significant predictor of burnout across all four cohorts. Other significant predictors of burnout included temporal demand (nursing groups & MDs) effort (inpatient nurses & MDs) and PSE involvement (ambulatory nurses). Open-response comments identified time constraints, lack of administrator support, insufficient institutional support for self-care, and inadequate staffing and/or turnover as sources of frustration. CONCLUSIONS: All four clinician groups reported substantial levels of burnout, and job demands predicted burnout. The body of knowledge on job stress and workplace burnout supports targeting organizational-level sources, versus individual-level factors, as the most effective prevention and reduction strategy. This study elaborates on this evidence by identifying structural drivers of burnout within a multidisciplinary context of pediatric hematology/oncology clinicians.

This is the first report of a case of COVID-19 after allogeneic stem cell transplantation. Our case suggests that COVID-19 may exist without characteristic CT images, especially in immunocompromised hosts, such as patients after transplantation.

Peptides that bind to and are presented on the cell surface by Human Leukocyte Antigens (HLA) molecules play a critical role in adaptive immunity. For a long time, it was believed all of the HLA bound peptides were generated through simple proteolysis of linear sequences of cellular proteins, and therefore, are templated in the genome and proteome. However, evidence for untemplated peptide ligands of HLA molecules has accumulated over the last two decades, with a recent global analysis of HLA-bound peptides suggesting that a considerable proportion of HLA bound peptides are potentially generated through splicing/fusion of discontinuous peptide segments from one or two distinct proteins. In this review, we will review recent discoveries and debates on the contribution of spliced peptides to the HLA class I immunopeptidome, consider biochemical rules for splicing, and the potential role of these spliced peptides in immune recognition.

Background: Chest X-rays are routinely obtained after removal of chest drains in patients undergoing cardiac and thoracic surgical procedures. However, a lack of guidelines and evidence could question the practice. Routine chest X-rays increase exposure to ionising radiation, increase healthcare costs and lead to overutilisation of available resources. This review aims to explore the evidence in the literature regarding the routine use of chest X-rays following the removal of chest drains. Materials & Method: A systematic literature search was conducted in PubMed, Medline via Ovid, Cochrane central register of control trials (CENTRAL) and ClinicalTrials.gov without any limit on the publication year. The references of the included studies are manually screened to identify potentially eligible studies. Results: A total of 375 studies were retrieved through the search and 18 studies were included in the review. Incidence of pneumothorax remains less than 10% across adult cardiac, and paediatric cardiac and thoracic surgical populations. The incidence may be as high as 50% in adult thoracic surgical patients. However, the re-intervention rate remains less than 2% across the populations. Development of respiratory and cardiovascular symptoms can adequately guide for a chest X-ray following the drain removal. As an alternative, bedside ultrasound can be used to detect pneumothorax in the thorax after the removal of a chest drain without the need for ionising radiation. Conclusion: A routine chest X-ray following chest drain removal in adult and paediatric patients undergoing cardiac and thoracic surgery is not necessary. It can be omitted without compromising patient safety. Obtaining a chest X-ray should be clinically guided. Alternatively, bedside ultrasound can be used for the same purpose without the need for radiation exposure.

The era of "big data'' promises to provide new hydrologic insights, and open web-based platforms are being developed and adopted by the hydrologic science community to harness these datasets and data services. This shift accompanies advances in hydrology education and the growth of web-based hydrology learning modules, but their capacity to utilize emerging open platforms and data services to enhance student learning through data-driven activities remains largely untapped. Given that generic equations may not easily translate into local or regional solutions, teaching students to explore how well models or equations work in particular settings or to answer specific problems using real data is essential. This paper introduces an open web-based learning module developed to advance data-driven hydrologic process learning, targeting upper level undergraduate and early graduate students in hydrology and engineering. The module was developed and deployed on the HydroLearn open educational platform, which provides a formal pedagogical structure for developing effective problem-based learning activities. We found that data-driven learning activities utilizing collaborative open web platforms like HydroShare and CUAHSI JupyterHub computational notebooks allowed students to access and work with datasets for systems of personal interest and promoted critical evaluation of results and assumptions. Initial student feedback was generally positive, but also highlights challenges including trouble-shooting and future-proofing difficulties and some resistance to open-source software and programming. Opportunities to further enhance hydrology learning include better articulating the myriad benefits of open web platforms upfront, incorporating additional user-support tools, and focusing methods and questions on implementing and adapting notebooks to explore fundamental processes rather than tools and syntax. The profound shift in the field of hydrology toward big data, open data services and reproducible research practices requires hydrology instructors to rethink traditional content delivery and focus instruction on harnessing these datasets and practices in the preparation of future hydrologists and engineers.

Long isolation period for suspected child cases was proposed based in one case. New evidence suggests that children are not as dangerous as they seemed, as a vehicle for this infection. We must be cautious when making recommendations for a disease that affects millions of people, based on just one case.

A 16-year-old male with past medical history of congenital atrial septal defect surgical repair presented with recurrent pericarditis secondary to post-cardiotomy injury syndrome (PCIS). After failing medical therapy, he ultimately underwent pericardiectomy for symptom resolution. PCIS is underdiagnosed in children and should be considered in patients with recurrent chest pain.

Background: Despite recent advancements in prevention, treatment, and management options, cardiovascular diseases contribute to one of the leading causes of morbidity and mortality. Several studies highlight the compelling evidence for the existence of healthcare inequities and disparities in the treatment and management control of cardiovascular diseases. Aims: To explore the role of racial disparities in the treatment of various cardiovascular diseases, highlighting the role of socioeconomic and cultural factors, and ultimately postulate solutions to eliminate the disparities. Methods: A comprehensive review of literature was conducted using appropriate keywords on search engines of SCOPUS, Wiley, PubMed, and SAGE Journals. Conclusion: By continued research to eliminate healthcare inequalities, there exists a potential to improve health-related outcomes in minority populations.

Background: It is common practice to observe patients during an overnight stay (ONS) following a catheter ablation procedure for the treatment of atrial fibrillation (AF). Objectives: To investigate the safety and economic impact of a same day discharge (SDD) protocol after cryoballoon ablation for treatment of AF in high-volume, geographically diverse US hospitals. Methods: We retrospectively reviewed 2,374 consecutive patients (1,119 SDD and 1,180 ONS) who underwent cryoballoon ablation for AF at three US centers. Baseline characteristics and longer-term safety were recorded during follow-up. The mean cost of an ONS was used to evaluate yearly cost savings as a function of the percentage of SDD cases/yearr. Results: There was no difference between SDD and ONS in the 30 day total complication rate [n=15 (1.26%) versus n=24 (2.03%); p=0.136 respectively]. The most common complication was hematoma in both the SDD (n=8; 0.67%) and ONS (n=11; 0.93%) cohorts. Sensitivity analysis demonstrated that when 50% of every 100 patients treated were discharged the same day, hospital cost savings ranged from $45,825 to $83,813 per year across US hospitals. Conclusions: SDD following cryoballoon ablation for AF appears to be safe and is associated with cost savings across different US hospitals.

Significant amounts of soluble product aggregates were observed in the low-pH viral inactivation (VI) opertion during an initial scale-up run for an IgG4 monoclonal antibody (mAb IgG4-N1). Being earlier in development, a scale-down model did not exist, nor was it practical to use costly Protein A eluate (PAE) for testing the VI process at scale, thus, a computational fluid dynamics (CFD)-based high molecular weight (HMW) prediction model was developed for troubleshooting and risk mitigation. It was previously reported that the IgG4-N1 molecules upon exposure to low pH tend to change into transient and partially unfolded monomers during VI acidification (i.e., VIA) and form aggregates after neutralization (i.e., VIN) (Jin et al. 2019). Therefore, the CFD model reported here focuses on the VIA step. The model mimics the continuous addition of acid to PAE and tracks acid distribution during VIA. Based on the simulated low-pH zone (≤ pH 3.3) profiles and PAE properties, the integrated low-pH zone (ILPZ) value was obtained to predict HMW level at the VI step. The simulations were performed to examine the operating parameters, such as agitation speed, acid addition rate, and protein concentration of PAE, of the pilot scale (50-200L) runs. The conditions with predictions of no product aggregation risk were recommended to the real scale-up runs, resulted in 100% success rate of the consecutive 12 pilot-scale runs. This work demonstrated that the CFD-based HMW prediction model could be used as a tool to facilitate the scale up of the low-pH VI process directly from bench to pilot/production scale.

Rationale, Aims and Objectives: Guidelines recommend inviting family members of intensive care unit (ICU) patients to rounds. We aimed to create a toolkit to support family participation in ICU bedside rounds, based upon evidence from research and in collaboration with ICU family member representatives and healthcare providers. Methods: A multi-method qualitative research program was conducted to provide an evidence-base. Ethnographic observations of rounds and interviews and focus groups with family members and ICU healthcare providers were analyzed for key themes, barriers and facilitators of participation, and suggestions. A full day workshop with family representatives and providers (physicians, nurses, social workers, and unit managers) from a diverse range of adult ICUs in Western Canada, including several community ICUs and a majority of large, urban ICUs enabled the collaborative development of key toolkit elements. Results: We have developed an evidence-informed approach to patient-and-family-centered rounds that highlights the importance of 6 key elements foundational to patient and family centered rounds: Invitation, Orientation, Engagement, Summary, Questions, and Communication Follow-Up. We describe strategies, techniques, and templates to optimize these elements and interactions so that communication is more meaningful, and to facilitate the ability of family members to adopt a meaningful role as contributing members of the care team. Conclusion: There is consensus on general strategies for facilitating family participation in rounds and meaningful communication between family and the healthcare team during rounds as an important element of the continuum of communication in the ICU. The incorporation of these elements should be standardized, though tailored to user needs.

Abstract Objectives: In most cases, suspension laryngoscopy (SL) is efficient, bloodless and with minimal post-procedure discomfort. We aimed to identify predictive patient factors for acceptable surgical views at SL as well as quantify our tertiary airway unit’s complication rates. Design: Prospective cohort study of 150 consecutive microlaryngoscopy procedures involving SL over an 8-month period between November 2019 and July 2020. Patients were assessed pre-operatively for pre-existing oral, temporomandibular, dental, pharyngeal or laryngeal pathology, interincisor distance and qualitative gross limitations to neck extension and forward head posture. Intraoperatively, the laryngoscopic view was graded by anesthetic and surgical teams, and complications were recorded on patient interview in recovery. Setting: Tertiary adult airway service for predominantly benign pathology. Results: Adequate surgical views were obtained in 149/150 procedures. BMI and limitations to chin and neck movement had mild positive correlations with more difficult views in their own rights, but did not correlate with a statistically significant increase in complications. There was a negative correlation between age and interincisor gap (p=0.014), and wider mouth opening correlated with a lower incidence of sore throat (p=0.023). Macroglossia showed a statistically significant positive correlation with tongue symptoms (p=1.611x10-8). Conclusion: In the context of an experienced airway unit with a high caseload of predominantly benign pathology, SL is very effective and safe with low associated morbidity and no mortality. Patient-reported neck and chin movement were found to correlate well with the surgical view obtained. The most common complication of SL is temporary sore throat and there remain recognized risks of temporary tongue and dental symptoms.

The sharp rise in anthropogenic activities and climate change have caused the extensive degradation of grasslands worldwide, jeopardising ecosystem function and threatening human well-being. Toxic weeds have been constantly spreading in recent decades; indeed, their occurrence is considered to provide an early sign of land degeneration. Policy makers and scientific researchers often focus on the negative effects of toxic weeds, such as how they inhibit forage growth, kill livestock and cause economic losses. However, toxic weeds can have several potentially positive ecological impacts on grasslands, such as promoting soil and water conservation, improving nutrient cycling and biodiversity conservation, and protecting pastures from excessive damage by livestock. We reviewed the literature to detail the adaptive mechanisms underlying toxic weeds and to provide new insight into their roles in degraded grassland ecosystems. The findings highlight that the establishment of toxic weeds may provide a self-protective strategy of degenerated pastures that does not require special interventions. Consequently, policy makers, managers and other personnel responsible for managing grasslands need to take appropriate actions to assess the long-term trade-offs between the development of animal husbandry and the maintenance of ecological services provided by grasslands.