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Tracey G Simon,1,2 Sebastian Schneeweiss,2 Richard Wyss,2 Zhigang Lu,2 Lily G Bessette,2 Cassandra York,2 Kueiyu Joshua Lin1,2 1Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 2Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Kueiyu Joshua Lin, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 1620 Tremont St. Suite 3030, Boston, MA, 02120, USA, Tel +1 617 278-0930, Fax +1 617 232-8602, Email jklin@bwh.harvard.eduBackground: The Model for End-Stage Liver Disease (MELD) score predicts disease severity and mortality in cirrhosis. To improve cirrhosis phenotyping in administrative databases lacking laboratory data, we aimed to develop and externally validate claims-based MELD prediction models, using claims data linked to electronic health records (EHR).Methods: We included adults with established cirrhosis in two Medicare-linked EHR networks (training and internal validation; 2007– 2017), and a Medicaid-linked EHR network (external validation; 2000– 2014). Using least absolute shrinkage and selection operator (LASSO) with 5-fold cross-validation, we selected among 146 investigator-specified variables to develop models for predicting continuous MELD and relevant MELD categories (MELD< 10, MELD≥ 15 and MELD≥ 20), with observed MELD calculated from laboratory data. Regression coefficients for each model were applied to the validation sets to predict patient-level MELD and assess model performance.Results: We identified 4501 patients in the Medicare training set (mean age 75.1 years, 18.5% female, mean MELD=13.0), and 2435 patients in the Medicare validation set (mean age: 74.3 years, 31.7% female, mean MELD=12.3). Our final model for predicting continuous MELD included 112 variables, explaining 58% of observed MELD variability; in the Medicare validation set, the area-under-the-receiver operating characteristic curves (AUC) for MELD< 10 and MELD≥ 15 were 0.84 and 0.90, respectively; the AUC for the model predicting MELD≥ 20 (using 27 variables) was 0.93. Overall, these models correctly classified 77% of patients with MELD< 10 (95% CI=0.75– 0.78), 85% of patients with MELD≥ 15 (95% CI=0.84– 0.87), and 87% of patients with MELD≥ 20 (95% CI=0.86– 0.88). Results were consistent in the external validation set (n=2240).Conclusion: Our MELD prediction tools can be used to improve cirrhosis phenotyping in administrative datasets lacking laboratory data.Keywords: cirrhosis, phenotyping, administrative data, claims

While the aviation sector is trying to reach the net zero-carbon status in 2050, sustainable aviation fuel (SAF) is a possible strategy to help achieve this target. The present study compares alternative SAF production routes to meet future demands in the Brazilian and World markets. One possible SAF production chain includes the internationally approved alcohol-to-jet (ATJ) technology using the well-established Brazilian first-generation (1G) sugarcane ethanol as raw material (scenario I). This alternative was compared with technologies that utilize the excess lignocellulosic residues of the 1G sugarcane ethanol production either to produce SAF through gasification and Fischer-Tropsch (FT) synthesis combination (scenario II) or to produce more ethanol in an integrated first- and second-generation plant (1G2G) to serve as input to the ATJ process (scenario III). The assessment and comparison of the proposed SAF production alternatives were performed by adapting and using the models included in the Virtual Biorefinery (VB) platform developed by the LNBR/CNPEM to simulate the various biochemical and thermochemical integrated value chains. The major performed activities were: (i) technical, economic, and environmental assessments of sugarcane production and straw recovery; (ii) simulation of 1G and 1G2G ethanol production processes; (iii) simulation of the SAF production processes considered for the ATJ and FT alternative routes; (iv) economic and Life Cycle Assessment (LCA) of SAF production. The economic assessment results indicated that scenario I has the lower minimum selling price (MSP) for SAF (0.85 US$/L) attributed to the lower investments for the process, while scenarios II (1.10 US$/L) and III (1.07 US$/L) confirmed that the MSP of all scenarios was higher than the fossil fuel price (0.54 US$/L). Nevertheless, the technical results showed that scenario III presented a higher SAF production (135.3 million L/year) than scenarios I and II (98.5 and 114.3 million L/year, respectively). Regarding LCA, it could be mentioned that SAF emissions obtained in all scenarios (the lowest is 20.1 gCO2eq/MJ for scenario II) were lower than fossil fuel (87.5 gCO2eq/MJ). Finally, it can be indicated that the availability of sugarcane in Brazil converts the country into a potentially essential participant for the deployment of large-scale projects for SAF production, which can reduce greenhouse gas emissions compared with the conventional kerosene production chain. Furthermore, the learning curve of new technologies included in scenarios II and III, as well as the implementation of policies associated with the production of biofuels, could strongly reduce the MSP of SAF produced in integrated chains. [ABSTRACT FROM AUTHOR]

This paper analyzes the operation of PowerMOSFETs in the 42-V-PowerNet and shows that very stressful conditions are encountered, which can lead to severe reliability problems. To enable thorough investigations by circuit simulations an accurate physics-based compact model of the devices is proposed: it includes all important electrothermal effects relevant to the description of the observed failure mechanisms. By means of an advanced thermal-modeling approach, multichip assemblies can be accurately described, including mutual heating effects between neighboring devices. Some properly chosen examples demonstrate the validity of the model and its usefulness for reliability investigations. Index Terms--Electrothermal effects, modeling, power metal-oxide semiconductor field-effect transistors (MOSFETs), reliability.

The ability of monitoring the chip temperatures of power semiconductor modules at all times under various realistic working conditions is the basis for investigating the limits of the maximum permissible load. A novel transient thermal model for the fast calculation of temperature fields and hot spot temperature evolution presented recently is extended to include time-dependent boundary conditions for variations of ambient temperature and surface heat flows. For this a Green's function representation of the temperature field is used. Also, general initial temperature conditions are included. The method is exemplified by application to a dc/ac converter module for automotive hybrid drives. The thermal model, which can be represented by a thermal equivalent circuit, then is combined with an electrical PSpice-metal-oxide semiconductor field-effect transistor (MOSFET) model to allow for the fully self-consistent electrothermal circuit simulation of 42-V/14-V dc/dc-converter modules. 670 converter periods with altogether 8000 MOSFET switching cycles in the six-chip module can be simulated within 1-h computing time on a Pentium PC. Various simulation results are presented, which demonstrate the feasibility of the simulation method and allow for the optimization of converter losses. Short circuit modes of converter operation are investigated with a high temperature increase also revealing the thermal interaction between different chips. Index Terms--DC- and ac-converter for automotive, electrothermal simulation, multichip modules, PSpice metal-oxide semiconductor field-effect transistor (MOSFET) model, thermal equivalent circuit, time-dependent boundary conditions.

The sludge generated in sanitary sewage treatment, mainly during all stages of sewage treatment, is a waste that can be used for energy purposes. The sewage sludge can contain many toxic substances, such as pathogens, metals, and organic contaminants, which can cause severe environmental pollution. Therefore, the adequate treatment and possible energy recovery (generation of electricity and/or heat), in addition to representing a noble destination for sanitary sludge, is aligned with the concept of circular economy. To assess the potential for using sewage sludge as an energy source, various analyses were carried out for its characterization, such as proximate and ultimate analysis, calorific value determination, granulometric analysis, and surface adhesion tension. Among the results obtained, the lower heating value (LHV) stands out, with an average value of about 17 MJ/kg, which is a close result to the LHV of conventional biomass. Furthermore, the tests and sludge characterization results show that the drying method proposed in this study is more interesting than the convective method, given that it produces a smaller particle size in the material, for example.

While the aviation sector is trying to reach the net zero-carbon status in 2050, sustainable aviation fuel (SAF) is a possible strategy to help achieve this target. The present study compares alternative SAF production routes to meet future demands in the Brazilian and World markets. One possible SAF production chain includes the internationally approved alcohol-to-jet (ATJ) technology using the well-established Brazilian first-generation (1G) sugarcane ethanol as raw material (scenario I). This alternative was compared with technologies that utilize the excess lignocellulosic residues of the 1G sugarcane ethanol production either to produce SAF through gasification and Fischer-Tropsch (FT) synthesis combination (scenario II) or to produce more ethanol in an integrated first- and second-generation plant (1G2G) to serve as input to the ATJ process (scenario III). The assessment and comparison of the proposed SAF production alternatives were performed by adapting and using the models included in the Virtual Biorefinery (VB) platform developed by the LNBR/CNPEM to simulate the various biochemical and thermochemical integrated value chains. The major performed activities were: (i) technical, economic, and environmental assessments of sugarcane production and straw recovery; (ii) simulation of 1G and 1G2G ethanol production processes; (iii) simulation of the SAF production processes considered for the ATJ and FT alternative routes; (iv) economic and Life Cycle Assessment (LCA) of SAF production. The economic assessment results indicated that scenario I has the lower minimum selling price (MSP) for SAF (0.85 US$/L) attributed to the lower investments for the process, while scenarios II (1.10 US$/L) and III (1.07 US$/L) confirmed that the MSP of all scenarios was higher than the fossil fuel price (0.54 US$/L). Nevertheless, the technical results showed that scenario III presented a higher SAF production (135.3 million L/year) than scenarios I and II (98.5 and 114.3 million L/year, respectively). Regarding LCA, it could be mentioned that SAF emissions obtained in all scenarios (the lowest is 20.1 gCO2eq/MJ for scenario II) were lower than fossil fuel (87.5 gCO2eq/MJ). Finally, it can be indicated that the availability of sugarcane in Brazil converts the country into a potentially essential participant for the deployment of large-scale projects for SAF production, which can reduce greenhouse gas emissions compared with the conventional kerosene production chain. Furthermore, the learning curve of new technologies included in scenarios II and III, as well as the implementation of policies associated with the production of biofuels, could strongly reduce the MSP of SAF produced in integrated chains.

The development of the chick optic lobe was impaired following removal of the optic cup of the early embryo. Tectal cell number is reduced but cell size may be relatively normal. Ther was evidence of neuronal cell death and several neuron-associated proteins and enzymes (nerve-specific protein and acetylcholinesterase) showed selectively impaired maturation. However, other nerve-specific enzymes (choline acetyltransferase, tyrosine hydroxylase), develop normally on a per cell basis. The noninnervated optic lobe had a normal blood-brain barrier but a depressed ability to accumulate amino acids from plasma. Levels of 3':5'-cyclic GMP were also reduced in the nonafferented lobe.

The rate and extent of axoplasmic transport of the brain-specific soluble protein (14-3-2 protein) has been investigated in the avian visual system. 1-day-old chicks were injected monocularly with tritiated proline, Incorporation of the isotope into the 14-3-2 protein synthesized within the retina of the injected eye, as well as the appearance of the labeled protein in the optic lobes was determined at 6 h and 6 days. These time periods were chosen to distinguish between the rapid and slow phases of axophlasmic flowmfollowing preparation of high-speed supernatant fractions, dialysis, chromatography on Sephadex G-150 and immunoprecipitation with specific antiserum, identification of the labeled 14-3-2 protein was carried out by sodium dodecylsulfate-polyacrylamide gel analysis of the radioactive immunoprecipitates; 6 days after isotope administration, approxo% of the 14-3-2 protein synthesized in the chick retina had been transported to the contralateral optic lobe. By contrast, at 6 h no labeled 14-3-2 protein was detectablemthus, transport of this neuronal protein appears to be relatively slow process with little or no rapid component.

This work evaluates the impact of air renewal on energy consumption for indoor environments. For this purpose, an analysis of the problem of air renewal at a Brazilian level was carried out, as well as research into the energy impact of air renewal without energy recovery and the different existing technologies for recovering energy from renewed air. On the other hand, the influence of heat-recovery systems was analyzed in three Brazilian cities (Manaus, São Paulo, and Brasília) for different environments, where a classroom in Manaus has an approximately 50% external air factor and a 42% sensible heat factor. However, classrooms in São Paulo and Brasília have a lower external air factor (27% and 8%, respectively) and a higher sensible heat factor (61% and 78%, respectively). Considering a system with heat recovery, the external air factor decreases to 23%, 10%, and 3% for Manaus, São Paulo, and Brasília, respectively. This allows us to understand the influence of heat-recovery systems, which reduce the external air factor and increase the sensible heat factor.

Abstract Background The Warburg effect is a rare condition in tumor biology, illustrated by significant lactate production in the presence of oxygen. The Warburg effect is associated with very poor prognosis in patients with malignancy. Case presentation We report a 76-year-old Caucasian woman with double-expressor diffuse large B cell lymphoma who presented with severe lactic acidosis and extreme hypoglycemia with normal mentation. Her lactic acidosis was initially controlled with a bicarbonate infusion, and the patient was started promptly on steroids, followed by chemotherapy, but her clinical course was complicated by tumor lysis syndrome, acute renal failure requiring hemodialysis, and progressive liver failure. She manifested a temporary clinical response to chemotherapy but eventually died of complications. Conclusions This case demonstrates the importance of prompt recognition of the Warburg effect, aggressive supportive measures, and early initiation of chemotherapy. Future studies are needed to characterize the role of hemodialysis in this setting.

The on-state current voltage characteristic of thyristors is investigated by numerical simulation. For sufficiently high p-base concentration - as already known - an abrupt increase in on-state voltage is observed above a critical current density. Driving the device to higher currents results in a reduction of on-state voltage. Similar results are obtained for thyristor profiles with very shallow emitters. An analytic model that explains the described phenomena from first principles and leads to a simple criterion for current limiting in terms of Gummel numbers and carrier mobilities is presented.

Abstract Background Whipple's disease is known to cause multiple varied systemic symptoms, and is a well-documented cause of culture-negative endocarditis. Endocarditis secondary to Whipple disease, however, has rarely been known to present primarily as a cause of acute limb ischemia. We describe such a case here. Case presentation A previously healthy 40 year old man presented to the emergency department with acute-onset right arm paresthesias. On exam, he was found to be tachycardic with a VI/VI systolic ejection murmur. He was diagnosed with critical limb ischemia and severe aortic regurgitation, and echocardiography showed a large mass on his bicuspid aortic valve. Thrombectomy was performed urgently, with aortic valve repair the following day. As blood cultures and valvular tissue culture remained unrevealing, the patient remained on empiric vancomycin and ceftriaxone for culture-negative endocarditis. 16 s rRNA nucleic acid amplification testing (NAAT) of his formalin-fixed, paraffin-embedded valvular tissue detected T. whipplei, after which the patient was transitioned to ceftriaxone and trimethoprim-sulfamethoxazole for a year of therapy. He continues to do clinically well. Conclusions We report an unusual presentation of Whipple endocarditis as an acute upper limb ischemia, absent other classic symptoms of Whipple's disease, and with diagnosis made by 16 s rRNA NAAT of valvular tissue in the setting of culture-negative endocarditis.

Buckling strength predictions are presented for a wide range of thin isotropic skew plates. The key studied parameters include the aspect ratio, skew angle, and rotational restraint stiffness on the different edges of the plate. The buckling strengths are evaluated both for isolated plates and for plates that are continuous with other parts of the structure. The assumed loading is uniform, uniaxial compression. The buckling predictions are presented in the form of dimensionless buckling curves, which permit a ready adoption into the 'data sheets' commonly used in current design. The buckling predictions demonstrate the effect of introducing symmetrical combinations of elastic restraints against rotation on the edges of isolated skew plates. Further, they are presented in a manner that allows the benefits of continuity over skew bays to be evaluated. The curves also illustrate the complex character of the buckling mode changes that take place with a change in aspect ratio in skew plate structures. In addition, these mode changes lead to well defined local optima, which the designer can exploit if he has control over the aspect ratio of a skew plate.

In this work, a comprehensive energetic and exergetic comparative assessment is presented for the simple solar organic Rankine cycle (SORC), regenerative solar organic Rankine cycle (RORC), and dual-loop solar organic Rankine cycle (DORC), considering parameters such as the net power produced, exergy destruction, exergy, and energy efficiency in four zones located in Colombia due to their high solar irradiation potential. The energetic and exergetic balances were applied for each system component, using toluene as the working fluid. The RORC system showed a 2% increase in efficiency over the SORC, while the DORC cycle was lower than the SORC (45.85%) and RORC (46.90%) systems. Finally, for the exergy analysis, the results revealed that the SORC (5.3%) and RORC (5.2%) systems had the highest efficiency compared to DORC systems. Additionally, the highest exergy destruction (89%) was related to the collector, followed by the evaporators (1–2%), pumps (0.1%), and turbines (1.12%).

El presente artículo brinda una breve panorámica geográfica, demográfica, económica y política de Colombia, una reseña de la evolución del sector eléctrico, información sobre emisiones de dióxido de carbono, política energética y estrategias para el desarrollo de energías renovables no convencionales en el país. Se muestra de manera detallada el panorama actual del sector eléctrico en Colombia y de manera complementaria se un análisis prospectivo del rol de las fuentes no convencionales de energía en el país. Se brinda información referente a la producción, consumo y demanda de energía, en cuanto a aspectos ambientales se presentan los indicadores de emisiones de gases de efecto invernadero y finalmente se presentan algunos aspectos de la política energética. Se destaca la alta contribución porcentual de la generación de energía hidráulica en la matriz energética, sin dejar a un lado la generación térmica con distintos energéticos. Finalmente, el artículo presente una revisión de las diferentes estrategias realizadas en el país para posibilitar el desarrollo de las Fuentes no convencionales de energía en Colombia.

Background: Assessment of activities of daily living (ADLs) and instrumental ADLs (iADLs) is key to determining the severity of dementia and care needs among older adults. However, such information is often only documented in free-text clinical notes within the electronic health record and can be challenging to find., Objective: This study aims to develop and validate machine learning models to determine the status of ADL and iADL impairments based on clinical notes., Methods: This cross-sectional study leveraged electronic health record clinical notes from Mass General Brigham's Research Patient Data Repository linked with Medicare fee-for-service claims data from 2007 to 2017 to identify individuals aged 65 years or older with at least 1 diagnosis of dementia. Notes for encounters both 180 days before and after the first date of dementia diagnosis were randomly sampled. Models were trained and validated using note sentences filtered by expert-curated keywords (filtered cohort) and further evaluated using unfiltered sentences (unfiltered cohort). The model's performance was compared using area under the receiver operating characteristic curve and area under the precision-recall curve (AUPRC)., Results: The study included 10,000 key-term-filtered sentences representing 441 people (n=283, 64.2% women; mean age 82.7, SD 7.9 years) and 1000 unfiltered sentences representing 80 people (n=56, 70% women; mean age 82.8, SD 7.5 years). Area under the receiver operating characteristic curve was high for the best-performing ADL and iADL models on both cohorts (>0.97). For ADL impairment identification, the random forest model achieved the best AUPRC (0.89, 95% CI 0.86-0.91) on the filtered cohort; the support vector machine model achieved the highest AUPRC (0.82, 95% CI 0.75-0.89) for the unfiltered cohort. For iADL impairment, the Bio+Clinical bidirectional encoder representations from transformers (BERT) model had the highest AUPRC (filtered: 0.76, 95% CI 0.68-0.82; unfiltered: 0.58, 95% CI 0.001-1.0). Compared with a keyword-search approach on the unfiltered cohort, machine learning reduced false-positive rates from 4.5% to 0.2% for ADL and 1.8% to 0.1% for iADL., Conclusions: In this study, we demonstrated the ability of machine learning models to accurately identify ADL and iADL impairment based on free-text clinical notes, which could be useful in determining the severity of dementia., (©John Laurentiev, Dae Hyun Kim, Mufaddal Mahesri, Kuan-Yuan Wang, Lily G Bessette, Cassandra York, Heidi Zakoul, Su Been Lee, Li Zhou, Kueiyu Joshua Lin. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 13.02.2024.)

Importance: There are limited data on discontinuation rates of antipsychotic medications (APMs) used to treat delirium due to acute hospitalization in the routine care of older adults., Objective: To investigate discontinuation rates and patient characteristics of APMs used to treat delirium following infection-related hospitalization among older US adults., Design, Setting, and Participants: This retrospective cohort study was conducted using US claims data (Optum's deidentified Clinformatics Data Mart database) for January 1, 2004, to May 31, 2022. Patients were aged 65 years or older without prior psychiatric disorders and had newly initiated an APM prescription within 30 days of an infection-related hospitalization. Statistical analysis was performed on December 15, 2022., Exposures: New use (no prior use any time before cohort entry) of oral haloperidol and atypical APMs (aripiprazole, olanzapine, quetiapine, risperidone, etc)., Main Outcomes and Measures: The primary outcome was APM discontinuation, defined as a gap of more than 15 days following the end of an APM dispensing. Survival analyses and Kaplan-Meier analyses were used., Results: Our study population included 5835 patients. Of these individuals, 790 (13.5%) were new haloperidol users (mean [SD] age, 81.5 [6.7] years; 422 women [53.4%]) and 5045 (86.5%) were new atypical APM users (mean [SD] age, 79.8 [7.0] years; 2636 women [52.2%]). The cumulative incidence of discontinuation by 30 days after initiation was 11.4% (95% CI, 10.4%-12.3%) among atypical APM users and 52.1% (95% CI, 48.2%-55.7%) among haloperidol users (P < .001 for difference between haloperidol vs atypical APMs). We observed an increasing trend in discontinuation rates from 2004 to 2022 (5% increase [95% CI, 3%-7%] per year) for haloperidol users (adjusted hazard ratio, 1.05 [1.03-1.07]; P < .001) but not for atypical APM users (1.00 [0.99-1.01]; P = .67). Prolonged hospitalization and dementia were inversely associated with the discontinuation of haloperidol and atypical APMs., Conclusions and Relevance: The findings of this cohort study suggest that the discontinuation rate of newly initiated APMs for delirium following infection-related hospitalization was lower in atypical APM users than in haloperidol users, with prolonged hospitalization and dementia as major associated variables. The discontinuation rate was substantially higher in recent years for haloperidol but not for atypical APMs.