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The methodology for production of biologics is going through a paradigm shift from batch‐wise operation to continuous production. Lot of efforts are focused on integration, intensification, and continuous operation for decreased foot‐print, material, equipment, and increased productivity and product quality. These integrated continuous processes with on‐line analytics become complex processes, which requires automation, monitoring, and control of the operation, even unmanned or remote, which means bioprocesses with high level of automation or even autonomous capabilities. The development of these digital solutions becomes an important part of the process development and needs to be assessed early in the development chain. This work discusses a platform that allows fast development, advanced studies, and validation of digital solutions for integrated continuous downstream processes. It uses an open, flexible, and extendable real‐time supervisory controller, called Orbit, developed in Python. Orbit makes it possible to communicate with a set of different physical setups and on the same time perform real‐time execution. Integrated continuous processing often implies parallel operation of several setups and network of Orbit controllers makes it possible to synchronize complex process system. Data handling, storage, and analysis are important properties for handling heterogeneous and asynchronous data generated in complex downstream systems. Digital twin applications, such as advanced model‐based and plant‐wide monitoring and control, are exemplified using computational extensions in Orbit, exploiting data and models. Examples of novel digital solutions in integrated downstream processes are automatic operation parameter optimization, Kalman filter monitoring, and model‐based batch‐to‐batch control. [ABSTRACT FROM AUTHOR]

Ducted rotor-only low-pressure axial fans play an integral role in automotive thermal management. The tightly packed under-hood region and down-stream heat-exchanger shape limit the fan diameter. In order to circumvent this limitation, multiple cooling fans of small diameters are tightly packaged and placed in parallel. Currently, there is limited scientific work, that study the aerodynamics of low-pressure axial fans when installed in parallel. This work aims to quantify the aerodynamic performance and the flow-field as a result of installing low-pressure axial fans in parallel through computational fluid dynamics (CFD). Publicly available experimental data from Friedrich-Alexander University is used for the validation of the numerical setup. Three-dimensional, full-annulus, unsteady Reynolds-averaged Navier-Stokes (URANS) analysis has been performed for both a single-fan and two-fans installed in parallel and their respective aerodynamic performance has been compared for the operation condition identified as the best efficiency point in experiments. Only small differences are observed in the overall aerodynamic performance of the two-fans in parallel compared to a single-fan. A circumferential nonuniformity in the form of a local high-pressure zone at the inlet of the fan is observed when the two-fans are placed in parallel. The resulting circumferential nonuniformity is quantified, both in space and time. A strong correlation is found between the pressure fields of the two-fans installed in parallel. [ABSTRACT FROM AUTHOR]

Background Reports suggest that the potential long-lasting health consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may involve persistent dysregulation of some immune populations, but the potential clinical implications are unknown. We investigated the associated risk of hospitalization due to non–coronavirus disease 2019 (COVID-19) infectious diseases following the postacute phase of SARS-CoV-2 infection. Methods By cross-linking data from the comprehensive Danish test and surveillance system for COVID-19 together with nationwide healthcare and demographic registers, we established a study cohort of 2 430 694 individuals aged ≥50 years, from 1 January 2021 to 10 December 2022, with no evidence of SARS-CoV-2 infection prior to study entry. Using Poisson regression, we compared the outcome rates of non-COVID-19 infectious disease hospitalizations following the acute phase of (a first) SARS-CoV-2 infection (defined as ≥29 days since the day of infection) in recovered individuals with rates among SARS-CoV-2–uninfected individuals. Results Among 2 430 694 included individuals (mean age, 66.8 [standard deviation, 11.3] years), 930 071 acquired SARS-CoV-2 infection during follow-up totaling 4 519 913 person-years. The postacute phase of SARS-CoV-2 infection was associated with an incidence rate ratio (IRR) of 0.90 (95% confidence interval [CI]:.88–.92) for any infectious disease hospitalization. Findings (IRR [95% CI]) were similar for upper respiratory tract (1.08 [.97–1.20]), lower respiratory tract (0.90 [.87–.93]), influenza (1.04 [.94–1.15]), gastrointestinal (1.28 [.78–2.09]), skin (0.98 [.93–1.03]), urinary tract (1.01 [.96–1.08]), certain invasive bacterial (0.96 [.91–1.01]), and other (0.96 [.92–1.00]) infectious disease hospitalizations and in subgroups. Conclusions Our study does not support an increased susceptibility to non-COVID-19 infectious disease hospitalization following SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Hyponatremia is a known adverse effect of thiazide antihypertensive medications, but its frequency is uncertain and believed to be very uncommon to rare. This population-based study emulates a target trial to characterize the incidence of hyponatremia after treatment initiation with thiazide medication compared with nonthiazide alternatives. Visual Abstract. Cumulative Incidence of Thiazide-Induced Hyponatremia: Hyponatremia is a known adverse effect of thiazide antihypertensive medications, but its frequency is uncertain and believed to be very uncommon to rare. This population-based study emulates a target trial to characterize the incidence of hyponatremia after treatment initiation with thiazide medication compared with nonthiazide alternatives. Background: According to drug labels, the frequency of thiazide-induced hyponatremia is unknown or uncommon to very rare (that is, <1 in 10 000 to <1 in 100), but the exact burden remains unclear. Objective: To estimate the increase in the cumulative incidence of hyponatremia using thiazide diuretics compared with nonthiazide antihypertensive drugs in routine clinical practice. Design: Population and register-based cohort study using target trial emulation. Setting: Denmark, 1 January 2014 to 31 October 2018. Participants: Two target trials were emulated among persons aged 40 years or older who had no recent prescription for any antihypertensive drug, had no previous hyponatremia, and were eligible for the studied antihypertensive treatments. The first target trial emulation compared new use of bendroflumethiazide (BFZ) versus a calcium-channel blocker (CCB). The second target trial emulation compared new use of hydrochlorothiazide plus a renin–angiotensin system inhibitor (HCTZ–RASi; that is, combination pill) versus a RASi alone. Measurements: Two-year cumulative incidences of sodium levels less than 130 mmol/L using stabilized inverse probability of treatment–weighted survival curves. Results: The study compared 37 786 new users of BFZ with 44 963 of a CCB and 11 943 new users of HCTZ–RASi with 85 784 of a RASi. The 2-year cumulative incidences of hyponatremia were 3.83% for BFZ and 3.51% for HCTZ–RASi. The risk differences were 1.35% (95% CI, 1.04% to 1.66%) between BFZ and CCB and 1.38% (CI, 1.01% to 1.75%) between HCTZ–RASi and RASi; risk differences were higher with older age and higher comorbidity burden. The respective hazard ratios were 3.56 (CI, 2.76 to 4.60) and 4.25 (CI, 3.23 to 5.59) during the first 30 days since treatment initiation and 1.26 (CI, 1.09 to 1.46) and 1.29 (CI, 1.05 to 1.58) after 1 year. Limitation: The study assumed that filled prescriptions equaled drug use, and residual confounding is likely. Conclusion: Treatment initiation with thiazide diuretics suggests a more substantial excess risk for hyponatremia, particularly during the first months of treatment, than indicated by drug labeling. Primary Funding Source: Independent Research Fund Denmark. [ABSTRACT FROM AUTHOR]

Background Data about the clinical benefit from initial low-density lipoprotein cholesterol (LDL-C) reduction with lipid lowering treatment for secondary prevention and risk of major vascular events amongst older as compared with younger individuals treated during routine clinical care are limited. We investigated this in a nationwide cohort. Methods Individuals aged ≥ 50 years with a first-time hospitalisation for a cardiovascular event (index event, including acute coronary syndrome, non-haemorrhagic stroke, transient ischaemic attack and coronary revascularisation), 1 January 2008 to 31 October 2018, who subsequently used lipid lowering treatment, and had an LDL-C measurement before and after the event were included. Hazard ratios (HRs) for major vascular events per 1 mmol/L reduction in LDL-C were estimated for the included 21,751 older and 22,681 younger individuals (≥/<70 years old) using Cox regression. Results LDL-C lowering was associated with a 12% lower risk of major vascular events in older individuals per 1 mmol/L reduction in LDL-C (HR 0.88, 95% confidence interval [CI] 0.84–0.93), with no significant difference compared with the risk reduction amongst younger individuals (HR 0.88, 95% CI 0.83–0.93; P -value for difference between age groups: 0.86). The risk reduction was more pronounced when post hoc restricting, as a proxy for compliance, to new users with an LDL-C reduction above the lowest decile for both older (0.81, 95% CI 0.73–0.90) and younger (0.81, 95% CI 0.72–0.91) individuals. Conclusions This study strongly supports a similar relative clinical benefit of LDL-C reduction with lipid lowering treatment for secondary prevention of major vascular events amongst individuals aged ≥70 and <70 years. [ABSTRACT FROM AUTHOR]