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Future carbon-neutral power systems impose many challenges; one is the urgent need for a simulation platform that allows replicating the complex systems' actual dynamic performance. This paper shows the results of implementing a cyber-physical testbed co-simulation in real-time to analyse the system frequency response considering primary frequency control and emergency frequency control: under-frequency load-shedding (UFLS) protection schemes. The proposed testbed uses a physical layer of two real-time simulators from different vendors in a closed loop, Opal-RT OP4510 and Typhoon HIL 604, being the first simulator for test system modelling and the remainder used to implement the UFLS protection scheme. Two connections of the real-time simulators are considered: physical connection using wires to exchange analogue signals and cybernetic digital communication using ANSI C37.118 communication protocol. The cybernetic layer of the testbed models a test system, controls the real-time simulation, and implements digital communication between the simulators. A modified version of the P.M. Anderson 9-bus systems is used for testing purposes, including phasor measurement units (PMUs). Results of the real-time simulation show the appropriate performance of the proposed testbed.

Spinal cord stimulation (SCS) is an effective treatment modality for chronic pain conditions for which other treatment modalities have failed to provide relief. Ample prospective studies exist supporting its indications for use and overall efficacy. However, less is known about how SCS is used at the population level. Our objective is to understand the demographics, clinical characteristics, and utilization patterns of open and percutaneous SCS procedures.

Introduction Acute respiratory distress syndrome (ARDS) is a known predictor of poor outcomes in critically ill patients. We sought to examine the role ARDS plays in outcomes in subarachnoid hemorrhage (SAH) patients. Prior studies investigating the incidence of ARDS in SAH patients did not control for SAH severity. Hence, we sought to determine the incidence ARDS in patients diagnosed with aneurysmal SAH and investigate the predisposing risk factors and impact upon outcomes.Methods A retrospective cohort study was conducted using the National Inpatient Sample (NIS) database for the years 2008 to 2014. Multivariate stepwise regression analysis was performed to identify the risk factors and outcome associated with developing ARDS in the setting of SAH.Results We identified 170,869 patients with non-traumatic subarachnoid hemorrhage, of whom 6962 were diagnosed with ARDS and of those 4829 required mechanical ventilation. ARDS more frequently developed in high grade SAH patients (1.97 ± 0.05 vs. 1.15 ± 0.01; p < 0.0001). Neurologic predictors of ARDS included cerebral edema (OR 1.892, CI 1.180–3.034, p = 0.0035) and medical predictors included cardiac arrest (OR 4.642, CI 2.273–9.482, p < 0.0001) and cardiogenic shock (OR 2.984, CI 1.157–7.696, p = 0.0239). ARDS was associated with significantly worse outcomes (15.5% vs. 52.9% discharged home, 63.0% vs. 40.8% discharged to rehabilitation facility and 21.5% vs. 6.3% in-hospital mortality).Conclusion Patients with SAH who developed ARDS were less likely to be discharged home, more likely to need rehabilitation and had a significantly higher risk of mortality. The identification of risk factors contributing to ARDS is helpful for improving outcomes and resource utilization.

Purpose: To evaluate the utility of 5-Item Modified Frailty Index (mFI-5) as compared to chronological age in predicting outcomes of spinal osteotomy in Adult Spinal Deformity (ASD) patients. Methods: Using Current Procedural and Terminology (CPT) codes, the American College of Surgeons National Surgery Quality Improvement Program (ACS-NSQIP) database was queried for adult patients undergoing spinal osteotomy from 2015 to 2019. Multivariate regression analysis was performed to evaluate the effect of baseline frailty status, measured by mFI-5 score, and chronological age on postoperative outcomes. Receiver-operating characteristic (ROC) curve analysis was performed to analyze the discriminative performance of age versus mFI-5. Results: A total of 1,789 spinal osteotomy patients (median age 62 years) were included in the analysis. Among the patients assessed, 38.5% (n= 689) were pre-frail, 14.6% frail (n= 262), and 2.2% (n= 39) severely frail using the mFI-5. Based on the multivariate analysis, increasing frailty tier was associated with worsening outcomes, and higher odds ratios (OR) for poor outcomes were found for increasing frailty tiers as compared to age. Severe frailty was associated with the worst outcomes, e.g., unplanned readmission (OR 9.618, [95% CI 4.054–22.818], p&lt; 0.001) and major complications (OR 5.172, [95% CI 2.271–11.783], p&lt; 0.001). In the ROC curve analysis, mFI-5 score (AUC 0.838) demonstrated superior discriminative performance than age (AUC 0.601) for mortality. Conclusions: The mFI5 frailty score was found to be a better predictor than age of worse postoperative outcomes in ASD patients. Incorporating frailty in preoperative risk stratification is recommended in ASD surgery.

The risk of tuberculosis (TB) is variable among individuals with latent Mycobacterium tuberculosisinfection (LTBI), but validated estimates of personalized risk are lacking. In pooled data from 18 systematically identified cohort studies from 20 countries, including 80,468 individuals tested for LTBI, 5-year cumulative incident TB risk among people with untreated LTBI was 15.6% (95%?confidence interval (CI), 8.0–29.2%) among child contacts, 4.8% (95% CI, 3.0–7.7%) among adult contacts, 5.0% (95% CI, 1.6–14.5%) among migrants and 4.8% (95% CI, 1.5–14.3%) among immunocompromised groups. We confirmed highly variable estimates within risk groups, necessitating an individualized approach to risk stratification. Therefore, we developed a personalized risk predictor for incident TB (PERISKOPE-TB) that combines a quantitative measure of T cell sensitization and clinical covariates. Internal–external cross-validation of the model demonstrated a random effects meta-analysis C-statistic of 0.88 (95% CI, 0.82–0.93) for incident TB. In decision curve analysis, the model demonstrated clinical utility for targeting preventative treatment, compared to treating all, or no, people with LTBI. We challenge the current crude approach to TB risk estimation among people with LTBI in favor of our evidence-based and patient-centered method, in settings aiming for pre-elimination worldwide.

Drug-resistant tuberculosis (TB) represents a substantial threat to the global efforts to control this disease. After decades of stagnation, the treatment of drug-resistant TB is undergoing major changes: two drugs with a new mechanism of action, bedaquiline and delamanid, have been approved by stringent regulatory authorities and are recommended by the WHO. This narrative review summarizes the evidence, originating from both observational studies and clinical trials, which is available to support the use of these drugs, with a focus on special populations. Areas of uncertainty, including the use of the two drugs together or for prolonged duration, are discussed. Ongoing clinical trials are aiming to optimize the use of bedaquiline and delamanid to shorten the treatment of drug-resistant TB.

Background Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH.Objective We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score.Methods This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality.Results We identified 6496 patients with ruptured AVMs comparing them to 627,185 admitted with ICH. Mortality was lower for ruptured AVMs (11%) compared to ICH (22%) [p< 0.01]. Mortality associated factors were liver disease (OR 2.64, CI 1.81–3.85, p< .001), diabetes mellitus (OR 2.42, CI 1.38–4.22, p= 0.002), alcohol abuse (OR 1.81, CI 1.31–2.49, p= 0.001), hydrocephalus (OR 3.35 CI 2.81–4.00, p< 0.001), cerebral edema (OR 1.5, 1.25–1.85, p< 0.001), cardiac arrest (OR 15, CI 7.9–30, p< 0.001), and pneumonia (OR 1.93, CI 1.51–2.47, p< 0.001). A 0–5 ruptured AVM mortality score was developed: Cardiac arrest (=3), age >60 (=1), Black race (=1), chronic liver failure (=1) diabetes mellitus (=1), pneumonia (=1), alcohol abuse (=1) and cerebral edema (=1). Mortality increased with score. No patient with 5 or more points survived.Conclusion The Ruptured AVM Mortality Score allows for risk stratification on patients with ICH due to ruptured AVM. This scale could prove useful in prognostication and patient education.

Background: Intracranial aneurysms (IAs) are life-threatening lesions known within the literature to be found incidentally during routine angiographic workup for carotid artery stenosis (CAS). As IAs are associated with vascular shear stress, it is reasonable to expect that altered flow demands within the anterior circulation, such as with CAS, increase compensatory flow demands via the Circle of Willis (COW) and may induce similar stress at the basilar apex. Objective: We present a series of nine unruptured basilar apex aneurysms (BAA) with CAS and a comparative radiographic analysis to BAA without CAS. Methods: Twenty-three patients with BAA were retrospectively identified using records from 2011 to 2016. CAS by North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria, morphology of BAA, competency of COW, and anatomic relationships within the posterior circulation were examined independently by a neuroradiologist using angiographic imaging. Results: Nine (39%) of the twenty-three BAA patients had CAS, with six having stenosis ≥50%. Four (67%) of the patients with ≥50% CAS demonstrated aneurysm flow angles contralateral to the side with highest CAS. Additionally, the angle between the basilar artery (BA) trajectory and aneurysm neck was observed to be smaller in patients with ≥50% CAS (61 vs 74 degrees). No significant differences in COW patency, posterior circulation morphology, and degree of stenosis were observed. Conclusion: Changes in the cervical carotid arteries may lead to blood flow alterations in the posterior circulation that increase the propensity for BAA formation. Posterior circulation imaging can be considered in CAS patients to screen for BAA.

Single-incision laparoscopic cholecystectomy has emerged as an alternative to conventional multiport laparoscopic cholecystectomy (LC). Technical difficulty, prolonged surgical times and increased complication rates have been reported in single-incision laparoscopic surgery. One of the concerns is lack of triangulation of instruments. The SPIDER®surgical system is a single-incision laparoscopic device that utilizes flexible instruments with the purpose of achieving adequate triangulation. The purpose of this study is to compare the outcomes of SPIDER versus LC. A retrospective chart review of patients who underwent LC and SPIDER cholecystectomy by a single surgeon during a concurrent 44-month period at Baptist Health South Florida hospitals was performed focusing on demographics, indication for surgery, complications and incisional hernia rates. Exclusion criteria were concomitant surgery and hernia repair at the time of surgery. A total of 612 patients underwent minimally invasive cholecystectomy: 279 cases for SPIDER cholecystectomy and 333 for multiport LC. Baseline differences in patient characteristics between the SPIDER and LC groups were statistically significant. The SPIDER group had younger and healthier patients (lower ASA classification scores) with predominant diagnosis of cholelithiasis (69 %) compared to the LC group which had more complex cases. Total complications rate for both SPIDER and LC were 0.4 % (n= 1) and 3 % (n= 10), respectively. Conversion to open cholecystectomy occurred in one patient from the LC group (0.3 %). Conversion rate from SPIDER to additional ports or LC was performed in 5 cases (1.8 %) with no conversions to open surgery. Hemoperitoneum was reported in 2 cases, one for each approach, requiring reoperation. Single-incision laparoscopic cholecystectomy with SPIDER is a safe and feasible technique with similar outcomes to multiport LC. However, statistical significant difference was reported in baseline characteristics of both groups. No incisional hernias were reported in this case series for either technique.

With the growth of the discipline of laparoscopic surgery, technology has been further developed to facilitate the performance of minimally invasive hernia repair. Most of the published literature regarding robotic inguinal hernia repair has been performed by urologists who have dealt with this entity in a concomitant way during radical prostatectomies. General surgeons, who perform the vast majority of inguinal herniorrhaphies worldwide, have yet to describe the role of robotic inguinal hernia repair. Here, we describe our initial experience and create the foundation for future research questions regarding robotic inguinal hernia repair. A retrospective chart review was performed in 78 patients who underwent robotic transabdominal preperitoneal TAPP inguinal hernia repair with a prosthetic mesh using the da Vinci platform (Intuitive Surgical Inc). Data collected included patient demographics, past medical history, previous surgeries, details related to the surgical procedure, perioperative outcomes and complications. A total of 123 hernias were repaired. Forty-five patients had bilateral robotic inguinal herniorrhaphies, and the mean age was 55.1 years (SD 15.1), with a mean BMI of 27.6 (SD 6.1). There were 71 male and 7 female patients. Surgical complications included hematoma in three patients (3.9 %), two seromas (2.6 %) and one superficial surgical site infection at a trocar site (1.3 %), which resolved with oral antibiotics. Chronic postoperative complications (>30 days post-surgery) included the persistence of hematomas in two patients (2.6 %). Same day discharge was achieved in 60 patients (76.9 %) with a mean length of stay of 8 h (SD 2.65). Neither mortality nor conversion to open surgery occurred. Our early experience has demonstrated that the robotic transabdominal preperitoneal (TAPP) inguinal hernia repair is a safe and versatile approach that allows the general surgeon to perform this procedure in more complex cases such as those involving incarcerated and/or recurrent hernias.

Respiratory failure following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a known complication, and requirement of tracheostomy is associated with worse outcomes. Our objective is to evaluate characteristics associated with tracheostomy timing in AIS patients treated with MT.

•Cervical stenosis represents a progressive pathology with great variation in trajectory.•Anterior cervical discectomy and fusion (ACDF) may modify the course of one's disease.•There are significant disparities in accessibility and outcomes of ACDF.•Research and policymaking should be prioritized on more equitable application of ACDF.

La tuberculosis continúa siendo una de las enfermedades transmisibles causantes de mayor morbimortalidad en el mundo. España con una tasa de incidencia de 13,04 por 100.000 habitantes ocupa el tercer lugar entre los países europeos más afectados. Estos datos muestran una tendencia a su disminución, pudiendo pasar desapercibida y hacer que no se realicen las medidas de prevención adecuadas ante un enfermo sospechoso. El personal sanitario que trabaja en un centro donde se atiende a pacientes con tuberculosis presenta riesgo de transmisión, siendo este riesgo superior en determinadas áreas o unidades de trabajo. Desde los Servicios de Prevención de Riesgos Laborales, encargados de vigilar la salud de los trabajadores sanitarios, se elaboran diferentes estrategias de abordaje con el objetivo de evitar la infección en estos trabajadores y detectar la infección tuberculosa reciente. Las guías nacionales existentes hasta la actualidad incluyen la prueba de la tuberculina como prueba de cribado de la infección tuberculosa, con referencia a las nuevas pruebas diagnósticas basadas en la detección in vitrode interferón-gamma (IGRA) para determinados casos. El objetivo de la presente guía ha sido consensuar y establecer unos criterios comunes para incluir las pruebas IGRA, como una ayuda complementaria a la prueba de la tuberculina en el personal sanitario, a partir de la evidencia disponible en la actualidad. Las recomendaciones de su utilización se han adaptado a las diferentes situaciones en que se pueden encontrar los profesionales que participan en la vigilancia de la salud de los trabajadores sanitarios.

Aspartic proteases (AP) are a family of important hydrolytic enzymes in medicinal chemistry, since many of its members have become therapeutical targets for a wide variety of diseases from AIDS to Alzheimer. The enzymatic activity of these proteins is driven by the Asp dyad, a pair of active site Asp residues that participate in the hydrolysis of peptides. Hence, the protonation state of these and other acidic residues present in these enzymes determines the catalytic rate and the affinity for an inhibitor at a given pH. In the present work we have reviewed the effect of the protonation states of the titratable residues in AP’s both on catalysis and inhibition in this family of enzymes. The first section focuses on the details of the catalytic reaction mechanism picture brought about by a large number of kinetic, crystallographic and computational chemistry analyses. The results indicate that although the mechanism is similar in both retroviral and eukaryotic enzymes, there are some clear differences. For instance, while in the former family branch the binding of the substrate induces a mono-ionic charge state for the Asp dyad, this charge state seems to be already present in the unbound state of the eukaryotic enzymes. In this section we have explored as well the possible existence of low barrier hydrogen bonds (LBHB’s) in the enzymatic path. Catalytic rate enhancement in AP’s could in part be explained by the lowering of the barrier for proton transfer in a hydrogen bond from donor to acceptor, which is a typical feature of LBHB’s. Review of the published work indicates that the experimental support for this type of bonds is rather scarce and it may be more probable in the first stages of the hydrolytic mechanism in retroviral proteases. The second section deals with the effect of active site protonation state on inhibitor binding. The design of highly potent AP inhibitors, that could be the basis for drug leads require a deep knowledge of the protonation state of the active site residues induced by their presence. This vital issue has been tackled by experimental techniques like NMR, X-ray crystallography, calorimetric and binding kinetic techniques. Recently, we have developed a protocol that combines monitoring the pH effect on binding affinities by SPR methods and rationalization of the results by molecular mechanics based calculations. We have used this combined method on BACE-1 and HIV-1 PR, two important therapeutic targets. Our calculations are able to reproduce the inhibitor binding trends to either enzyme upon a pH increase. The results indicate that inhibitors that differ in the Asp dyad binding fragments will present different binding affinity trends upon a pH increase. Our calculations have enabled us to predict the protonation states at different pH values that underlie the above mentioned trends. We have found out that these results have many implications not only for in silico hit screening campaigns aimed at finding high affinity binders, but also (in the case of BACE-1) for the discovery of cell active compounds.

An approach based on noncovalent interactions of single-walled carbon nanotubes (SWCNTs) with amphiphilic block copolymers (BCs) containing polyethylenoxide has been undertaken for developing efficiently reinforced nanocomposite materials. The SWCNT dispersion in BC aqueous solutions provides highly purified and unbundled SWCNTs, a material particularly suitable for the reinforcement of epoxy matrices. The effect of SWCNT oxidation prior to wrapping was also explored, and it was determined that oxidized SWCNTs wrapped in BC present higher purity and debundling than their as-grown counterpart. Epoxy nanocomposites containing BC-wrapped SWCNTs exhibit improved mechanical and electrical properties, which depend on the choice of the wrapping BC and SWCNT surface chemistry.

Neoplastic cells exhibit defects in their ability to differentiate; therefore, differentiation therapy represents a viable option to control cancer growth and progression. Rhabdomyosarcomas (RMS), a malignant tumor of skeletal muscle, is the most common soft tissue sarcoma in children and is characterized by its poor response to cytotoxic treatment and significant morbidity. Since modulation of -tubulin and human leukocyte antigen (HLA) class I expression has been detected during malignant transformation, we analyzed in this study the expression pattern of both kinds of proteins after the treatment with 5-FU derivatives in the human RMS RD cell line. Cytotoxic assays, scanning and transmission electron microscopy, flow cytometry and immunocytochemical analyses were used. The compounds analyzed belonged to the following three categories: (a) symmetrical bis(5-fluorouracil-1-yl) derivatives with a linker that connects the N1 atoms of both pyrimidine moieties by means of two amide bonds; and (b) an ester with the 5-FU base. The whole structure corresponds to the terminal fragment of the molecules included in (a) and (c) 5-fluorouracil acyclonucleoside-like structures. 1- {[3-(3-Chloro-2-hydroxypropoxy)-1-methoxy]propoxy]propyl}-5-fluorouracil (2), that belongs to the class (a) produced the highest increment of tubulin and its intense capillary distribution throughout the cytoplasm. On the other hand, N,Nbis[ 3-(5-fluorouracil-1-yl)-3-methoxypropanoyl]-, diamino-m-xylene (5) and 2 that are included in the class (c) caused the major percentage of marked cells by the HLA class I proteins. In short, our results showed that the 5-FU derivatives increase HLA class I expression and showed greater microtubule stability with an important network of tubulin beams related with the degree of differentiation of RD cells. These results could mean a more favorable prognosis of the patients affected with these tumors.

This paper presents MiiSD, a Methodology for integrated information System Design that can also be used to identify information to be standardized to develop partial standard models. It proposes a meeting point between scientific developments, centred on the definition of standards for information exchange and on the commercial development of management programmes for business information. Applying the proposed methodology the amount and complexity of the data to be standardized are reduced. Additionally, this methodology helps companies to define what its information structure systems should be. On the other hand, it can also be used to carry out an audit of the information system already running within a company, identifying the main areas that are lacking. MiiSD outlines a new perspective over the problem of information integration in manufacturing companies.

. There are known classifications that describe thoracolumbar (TL) burst type injury but it is unclear which have the most influence on management. Our objective is to investigate the association of classification publications on the quantity and type of the most influential articles on TL burst fractures.