Open-Source Implementations of the Reactive Asset Administration Shell: A Survey.

The use of open-source software is crucial for the digitalization of manufacturing, including the implementation of Digital Twins as envisioned in Industry 4.0. This research paper provides a comprehensive comparison of free and open-source implementations of the reactive Asset Administration Shell (AAS) for creating Digital Twins. A structured search on GitHub and Google Scholar was conducted, leading to the selection of four implementations for detailed analysis. Objective evaluation criteria were defined, and a testing framework was created to test support for the most common AAS model elements and API calls. The results show that all implementations support at least a minimal set of required features while none implement the specification in all details, which highlights the challenges of implementing the AAS specification and the incompatibility between different implementations. This paper is therefore the first attempt at a comprehensive comparison of AAS implementations and identifies potential areas for improvement in future implementations. It also provides valuable insights for software developers and researchers in the field of AAS-based Digital Twins.

Perioperative use of glucose containing solutions in infants less than 6 months of age: A clinical practice survey among US academic centers.

BACKGROUND: Although there is a wide breadth of literature on glucose homeostasis in infants, standardization of perioperative hypoglycemia diagnosis and management is lacking. AIMS: Survey of academic pediatric anesthesiology departments across the USA to evaluate institutional policies regarding the perioperative use of glucose containing solutions in infants less than 6 months of age. METHODS: A questionnaire was sent to 20 United States university affiliated academic pediatric anesthesiology departments. RESULTS: The responses suggest that, in the centers surveyed, glucose administration in infants is largely practitioner dependent. Two respondents (10%) claim to have a departmental policy regarding glucose administration in infants less than 6 months of age. In premature infants, 75% of respondents administer glucose. When administering glucose, 75% of physicians surveyed replete infants at their maintenance intravenous fluid rate. There was discrepancy among practitioners regarding initiation of hypoglycemia treatment, 35% treat infants at a blood glucose level of 70 mg/dl, 30% at BG 60 mg/dl, 25% at 50 mg/dl, and 10% are unsure. DISCUSSION: This survey highlights the lack of consensus, at least among pediatric anesthesiologists working in US academic centers, regarding blood glucose management in infants less than 6 months of age. There is a need to define the indications for using glucose containing solutions in infants during the perioperative period, their ideal content, the appropriate thresholds for hypo- and hyperglycemia as well as the optimal point-of care glucose monitoring intervals.

Poor socioeconomic status is associated with delayed femoral fracture fixation in adolescent patients.

INTRODUCTION: Healthcare disparities continue to exist in pediatric orthopedic care. Femur fractures are the most common diaphyseal fracture and the leading cause of pediatric orthopedic hospitalization. Prompt time to surgical fixation of femur fractures is associated with improved outcomes. OBJECTIVE: The objective of this study was to evaluate associations between socioeconomic status and timing of femoral fixation in adolescents on a nationwide level. METHODS: The 2016-2020 National Inpatient Sample (NIS) database was queried using International Classification of Disease, 10th edition (ICD-10) codes for repair of femur fractures. Patients between the ages of 10 and 19 years of age with a principal diagnosis of femur fracture were selected. Patients transferred from outside hospitals were excluded. Baseline demographics and characteristics were described. Patients were categorized as poor socioeconomic status (PSES) if they were classified in the Healthcare Cost and Utilization Project's (HCUP) lowest 50th percentile median income household categories and on Medicaid insurance. The primary outcome studied was timing to femur fixation. Delayed fixation was defined as fixation occurring after 24 h of admission. Secondary outcomes included length of stay (LOS) and discharge disposition. RESULTS: From 2016-2020, 10,715 adolescent patients underwent femur fracture repair throughout the United States. Of those, 765 (7.1 %) underwent late fixation. PSES and non-white race were consistently associated with late fixation, even when controlling for injury severity. Late fixation was associated with decreased rate of routine discharge (p < 0.01), increased LOS (p < 0.01) and increased total charges (p < 0.01). CONCLUSION: Patients of PSES or non-white race were more likely to experience delayed femoral fracture fixation. Delayed fixation led to worse outcomes and increased healthcare resource utilization. Research studying healthcare disparities may provide insight for improved provider education, implicit bias training, and comprehensive standardization of care.

Carotid Artery Dissection and Hemorrhagic Stroke in the Setting of Multisystem Inflammatory Syndrome in Children.

An alarming and distressing delayed inflammatory response to Coronavirus Disease 2019 (COVID-19) has emerged in children and adolescents, a population previously thought to have been largely spared by this global pandemic. In April 2020, clinicians in the United Kingdom identified eight cases of previously healthy children testing positive for current or recent infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presenting with Kawasaki disease-like features. From April 16 to May 4, 2020, New York City reported that 15 patients aged 2-15 years were hospitalized with a similar multisystem inflammatory syndrome, many requiring intensive care unit (ICU) admission. This syndrome is referred to either as pediatric inflammatory multisystem syndrome, or multisystem inflammatory syndrome in children (MIS-C). We present the case of an eight-year-old with MIS-C who developed carotid artery dissection following venoarterial extracorporeal membrane oxygenation (VA-ECMO) cannulation, followed by a subsequent hemorrhagic stroke in the basal ganglia.

Acute Liver Failure in a Pediatric Patient with Tetralogy of Fallot following Cardiac Catheterization.

A 4-month-old female with Tetralogy of Fallot (TOF) developed acute liver failure (ALF) following a cardiac catheterization procedure to correct severe stenosis of her right ventricular outflow tract (RVOT) conduit via balloon angioplasty. Cardiac history included TOF, heterotaxy syndrome, ipsilateral pulmonary veins, interrupted inferior vena cava (IVC) with azygos continuation, patent ductus arteriosus (PDA), and pulmonary atresia that was repaired with a right ventricle (RV) to pulmonary artery (PA) conduit. This is the first case described of its kind to our knowledge. Consent was obtained from the patient's family to publish this case report.

Acute stroke care in a neurologically underserved state: lessons learned from the Iowa Stroke Survey.

Prior studies have suggested that stroke care is more fragmented in rural or neurologically underserved areas. The purpose of this study was to determine the availability of diagnostic and treatment services for acute stroke care in Iowa and to identify factors influencing care. Each of the 118 facilities in Iowa with emergency departments was surveyed by telephone. This survey consisted of 10 questions, focusing on the existence of pre-hospital and emergency room acute stroke protocols and the availability of essential personnel and diagnostic and treatment modalities essential for acute stroke care. Of the 118 hospitals with emergency departments, 109 (92.4%) had CT available. Within the subset having CT capabilities, 89.9% (98/109) had intravenous tissue plasminogen activator (IV t-PA) available. Of those facilities with both CT and IV t-PA, 46% (45/98) had around-the-clock in-house physician coverage. Further, 31% (14/45) of sites with CT, t-PA, and an in-house physician had a radiology technician on site. Only 12% (14/118) of centers could offer all essential components. Despite 88% of Iowa hospitals not providing all of these components, only 31% of these hospitals reported protocols for stabilization and immediate transfer of acute stroke patients. These findings indicate that the development of a stroke system is still in its infancy in Iowa. Collaborative efforts are needed to address barriers in rural Iowa and to assist facilities in providing the best possible care. Creativity will be paramount in establishing a functional statewide system to ensure optimum care for all Iowans.

Anesthesia for Pygopagus Conjoined Twins During Single-Twin and Simultaneous Pneumoperitoneum: A Case Report.

We present the case of the first stage of separation of 9-month-old pygopagus conjoined twins who demonstrated minimal shared vasculature on preoperative imaging and no cross-sedation or cross-neuromuscular blockade during separate inductions of anesthesia. Laparoscopy was implemented in 1 twin at a time, then in both twins simultaneously. Despite insufflation of a single-twin's abdomen, both twins demonstrated hypercapnia and signs of a concomitant respiratory acidosis because of carbon dioxide diffusion through a shared peritoneal membrane. This is the first documented case of simultaneous laparoscopy-induced pneumoperitoneum in pygopagus conjoined twins.

Calmodulin methionine residues are targets for one-electron oxidation by hydroxyl radicals: formation of S[therefore]N three-electron bonded radical complexes.

The one-electron oxidation of calmodulin, studied on the microsecond timescale by pulse radiolysis, leads to methionine sulfide radical cations, which complex to adjacent amide groups to form three-electron bonded intermediates.

Tissue plasminogen activator use: evaluation and initial management of ischemic stroke from an Iowa hospital perspective.

Despite its efficacy for acute ischemic stroke, tissue plasminogen activator (rt-PA) is reported as used in less than 5% of patients with stroke. This study assessed the rate of intravenous rt-PA use in a community hospital and identified factors influencing rt-PA use. A retrospective chart review revealed a total of 464 patients presenting to the emergency department with a primary diagnosis of stroke from January 2000 through June 2002. Records were sorted into 3 groups: those presenting to the emergency department within 3 hours, 3 to 6 hours, and 6 hours or more of symptom onset. Each record was reviewed using National Institute of Neurologic Disorders and Stroke thrombolytic therapy criteria. Primary measures were rate of intravenous rt-PA use and reasons for not receiving rt-PA. Of the 464 patients with stroke who presented to the emergency department during the 30-month period, 99 arrived in less than 3 hours, 22 between 3 and 6 hours, and 343 greater than 6 hours. A total of 13 (2.8% of all patients with stroke or 13% of those presenting within 3 hours) received rt-PA. All patients meeting criteria received rt-PA. Rapidly improving or minor symptoms and difficult to control or elevated blood pressure were the most common reasons for not using rt-PA. Of the patients arriving within the 3-hour window, 14 were excluded by time factors. We conclude from this study that rt-PA can be effectively used in community hospitals and that use likely exceeds previously quoted national rates when based on a more appropriate measure of eligibility criteria as opposed to total presenting patients with stroke.

Patient considerations in the use of tapentadol for moderate to severe pain.

Poorly controlled acute and chronic pain can increase morbidity, impair quality of life and prolong disability. Over 80 percent of post surgical patients report moderate to severe uncontrolled postoperative pain. Over-reliance on potent opioid agonists can lead to several opioid related side effects such as gastrointestinal intolerability, respiratory depression and cognitive impairment. A recently approved dual acting central analgesic tapentadol may offer improved tolerability over traditional opioid agonists while having multimodal opioid and nonopioid analgesic benefits. Tapentadol, classified by the US Food and Drug Administration as a class 2 opioid, is currently marketed in the United States as immediate release (IR) NUCYNTA® for moderate to severe acute pain in tablets of 50 mg, 75 mg, and 100 mg, and as extended release (ER) NUCYNTA ER® for the treatment of chronic moderate to severe pain in tablets of 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg. Tapentadol is a low affinity mu opioid receptor agonist and a norepinephrine reuptake inhibitor. Tapentadol has no active metabolites and this property makes it useful in patients with hepatic and renal failure. Clinical trials with tapentadol IR showed that there was improved gastrointestinal tolerability and similar pain relief as compared to oxycodone IR. Tapentadol ER allows for twice daily dosing. Clinical trials showed that tapentadol ER could effectively relieve moderate to severe chronic pain and was associated with significantly fewer gastrointestinal adverse effects as compared to oxycodone controlled release. Tapentadol ER is indicated and has Food and Drug Administration approval for the treatment of chronic painful diabetic neuropathy. The most common side effects of tapentadol are nausea (30%), vomiting (18%), dizziness (24%), and somnolence (15%). Tapentadol, due to its potential synergistic effects on norepinephrine levels, is contraindicated in patients who have taken monoamine oxidase inhibitors within the last 14 days. Caution has to be exercised with the use of tapentadol IR and tapentadol ER in the presence of other central nervous system depressants such as neuroleptics, opioids, illicit drugs, muscle relaxants, sedatives, and anxiolytics.

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. METHODS: We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid ß (Aß)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). FINDINGS: 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aß(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aß(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. INTERPRETATION: Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease.

Identification of methionine sulfoxide diastereomers in immunoglobulin gamma antibodies using methionine sulfoxide reductase enzymes.

Light-induced formation of singlet oxygen selectively oxidizes methionines in the heavy chain of IgG2 antibodies. Peptide mapping has indicated the following sensitivities to oxidation: M252 > M428 > M397. Irrespective of the light source, formulating proteins with the free amino acid methionine limits oxidative damage. Conventional peptide mapping cannot distinguish between the S- and R-diastereomers of methionine sulfoxide (Met[O]) formed in the photo-oxidized protein because of their identical polarities and masses. We have developed a method for identification and quantification of these diastereomers by taking advantage of the complementary stereospecificities of the methionine sulfoxide reductase (Msr) enzymes MsrA and MsrB, which promote the selective reduction of S- and R-diastereomers of Met(O), respectively. In addition, an MsrBA fusion protein that contains both Msr enzyme activities permitted the quantitative reduction of all Met(O) diastereomers. Using these Msr enzymes in combination with peptide mapping, we were able to detect and differentiate diastereomers of methionine sulfoxide within the highly conserved heavy chain of an IgG2 that had been photo-oxidized, as well as those in an IgG1 oxidized with peroxide. The rapid identification of the stereospecificity of methionine oxidation by Msr enzymes not only definitively differentiates Met(O) diastereomers, which previously has been indistinguishable using traditional techniques, but also provides an important tool that may contribute to understanding of the mechanisms of protein oxidation and development of new formulation strategies to stabilize protein therapeutics.

Efficacy and cost-effectiveness of a high-powered parallel waterjet for wound debridement.

Current concepts of wound healing acknowledge the essential role of wound bed preparation in achieving a wound with good healing potential. Critical to wound bed preparation is the removal of necrosis, unhealthy tissue, foreign matter, and infection. One of the accepted methods of wound bed preparation is surgery. The high-power parallel waterjet is a new surgical device, which allows the operator to remove very precisely undesirable tissue and debris with maximal preservation of viable tissue. A retrospective study was performed to evaluate the efficacy, safety, and economic impact of using this technique of surgical debridement. Forty patients who had waterjet debridements were compared with 22 patients with matched wounds who had conventional surgical debridement. The waterjet group had significantly fewer procedures (p<0.002) than the conventional group. Based on these outcomes, the use of the new device in appropriate patients is expected to lead to cost savings of approximately 1,900 dollars per patient.

Tertiary structural rearrangements upon oxidation of Methionine145 in calmodulin promotes targeted proteasomal degradation.

The selectivity underlying the recognition of oxidized calmodulin (CaM) by the 20S proteasome in complex with Hsp90 was identified using mass spectrometry. We find that degradation of oxidized CaM (CaMox) occurs in a multistep process, which involves an initial cleavage that releases a large N-terminal fragment (A1-F92) as well as multiple smaller carboxyl-terminus peptides ranging from 17 to 26 amino acids in length. These latter small peptides are enriched in methionine sulfoxides (MetO), suggesting a preferential degradation around MetO within the carboxyl-terminal domain. To confirm the specificity of CaMox degradation and to identify the structural signals underlying the preferential recognition and degradation by the proteasome/Hsp90, we have investigated how the oxidation of individual methionines affect the degradation of CaM using mutants in which all but selected methionines in CaM were substituted with leucines. Substitution of all methionines with leucines except Met144 and Met145 has no detectable effect on the structure of CaM, permitting a determination of how site-specific substitutions and the oxidation of Met144 and Met145 affects the recognition and degradation of CaM by the proteasome/Hsp90. Comparable rates of degradation are observed upon the selective oxidation of Met144 and Met145 in CaM-L7 relative to that observed upon oxidation of all nine methionines in wild-type CaM. Substitution of leucines for either Met144 or Met145 promotes a limited recognition and degradation by the proteasome that correlates with decreases in the helical content of CaM. The specific oxidation of Met144 has little effect on rates of proteolytic degradation by the proteasome/Hsp90 or the structure of CaM. In contrast, the specific oxidation of Met145 results in both large increases in the rate of degradation by the proteasome/Hsp90 and significant circular dichroic spectral shape changes that are indicative of changes in tertiary rather than secondary structure. Thus, tertiary structural changes resulting from the site-specific oxidation of a single methionine (i.e., Met145) promote the degradation of CaM by the proteasome/Hsp90, suggesting a mechanism to regulate cellular metabolism through the targeted modulation of CaM abundance in response to oxidative stress.