For many modern biopharmaceutical processes, manufacturers develop data-driven models using data analytics/machine learning (DA/ML) methods. The challenge is how to select the best methods for a specific dataset to construct the most accurate and reliable model. This article describes the application of smart process data analytics software to industrial end-to-end biomanufacturing datasets for monoclonal antibody production to automate the determination of the best DA/ML tools for model construction and process understanding. The application demonstrates that smart process data analytics software captures product- and process-specific characteristics for two different monoclonal antibody productions. This study provides tools that can be widely applied to biomanufacturing processes for root cause analysis, prediction, and control.

Objectives: To assess the willingness of patients to remove urinary catheters by themselves after anterior / posterior vaginal wall repairs done as day cases Design: This was a non-randomized, single centre, prospective pilot study where we included patients who have had anterior and/or posterior colporrhaphy as day cases between November 2020 and September 2022. Setting - UK DGH hospital urogynaecology department Population: all patients who had anterior/ posterior colporrhaphy as day cases between nov 2020 and sept 2022 Methods :Non-randomized, single centre, prospective pilot study Main Outcome: Majority of patients were able to remove their urinary catheters post operatively without complications Measures: Outcomes were evaluated using patients’ feedback respones Results: The data obtained was over 22 month peroid.The total was a total of 81 patients with 61% of them having anterior repairs and 39% having posterior repairs. Ages of the participants ranged from 42 years to 89 years. 79 % of questionnaires were returned. 98% of the enrolled patients would not prefer to wait for another admission date where a bed will be available. 97% of our patients removed the urinary catheter by themselves and found it to be easy. 88% of our patients would not prefer to come to the hospital or have a nurse sent to their homes to remove the catheter. 89 % of our patients would recommend this service to a friend. Conclusion: Our Study demonstrated that removal of patient’s own catheter following vaginal wall repairs is cost-saving and highly acceptable to this cohort of patients

The aim of this study was to evaluate the bond strength of three different calcium silicate based cements (Biodentine, NeoPutty and MTA Cem LC) with two different bulk fill composites (fiber-reinforced and non-fiber-reinforced). Plexiglas molds with a diameter of 4 mm and a thickness of 2 mm were prepared (n=60). Each CBC was mixed according to the manufacturer’s instructions and placed in plexiglass molds. The BD, NP, and MTA Cem LC samples were then randomly divided into 2 subgroups containing 10 samples each. The surfaces of the samples were air dried and Single Bond universal adhesive was applied. Then, cylindrical plastic capsules of 2 mm height and 2 mm inner diameter belonging to Filtek Bulk fill and EverX Posterior composite resin groups were centered on the coating material and polymerized for 20 seconds. After SBS testing, all samples were examined by scanning electron microscopy (SEM) to identify failure patterns. Three samples, one from each group, were prepared to evaluate the chemical compositions of the materials. Samples were prepared using plexiglass molds with a diameter of 10 mm and a thickness of 2 mm. The materials were then examined with an energy dispersive X-ray spectroscopy for surface elemental analysis. The values obtained from the tests were evaluated as statistically significant (p < 0.05). After SBS testing, the difference between all CBCs was statistically significant in both compound groups. According to the findings obtained from this study, it was concluded that MTA Cem LC had the highest SBS values in both composite groups.

A 30-year-old man presented with sudden chest pain and evidence of multiple cystic lesions in both long and left-sided pneumothorax in HRCT. H&E stained section and IHC for CD1a and S100 were positive in lung samples. The patient was treated with the diagnosis of Isolated pulmonary langerhans cell histiocytosis.

Key Clinical Message: An elevated middle cerebral artery peak systolic velocity in the setting of non-diabetic hypertrophic cardiomyopathy may portend an especially poor prognosis.

Spinal intramedullary lipoma within the craniovertebral region is extremely rare. These lesions are often associated with spinal dysraphism. Here we present a non-dysraphic one. Our patient was a 56-year-old female who presented with progressive right shoulder pain and gait disturbance.

The Klein-Gordon-Maxwell system has received great attention in the community of mathematical physics. Under a special superlinear condition on the nonlinear term, the existence of solution for critical Klein-Gordon-Maxwell system with steep potential well has been solved. In this paper, under two general superlinear conditions, we obtain the existence of ground state solution for the critical Klein-Gordon-Maxwell system with steep potential well. The general superlinear conditions bring challenge in proving the boundedness of Cerami sequence, which is a key step in the proof of the existence. To solve this, we construct a Pohožaev identity and adopt some analytical techniques. Our results extend the previous results in the literature.

Background: Information and communication technologies (ICTs) improve patient-centered care and are routinely used in Allergic Rhinitis (AR), but patients’ preferences and attitudes are unexplored. This study examines AR-related information preferences and ICT use by AR patients. Methods: A survey-based cross-sectional study was carried out in Ecuador in seven centers of reference of allergic disease. Participants were 18 or older, diagnosed with AR, and had access to ICT and the internet. Descriptive and binomial logistic regression were done. A value of less than 0.05 was considered statistically significant. Results: 217 patients were included. 47% used ICTs to learn about AR, 38.2% found it useful. 75% disagreed that ICTs reduce doctor’s appointments. Individuals with poorer quality of life were 27% more likely to utilize ICTs to contact their doctor and 23% more likely to be interested in AR-related content. Patients with long-term AR or other allergies were less likely to use ICTs. Higher education and lower quality of life may increase AR app adoption by 4.8 times. Academic preparation five-fold increased ICT use for health provider communication. Mild-persistent allergic rhinitis 12 times enhanced the probabilities of using ICTs to share experiences and communicate with other patients. Conclusions: Our study found that moderate-to-severe AR individuals are not interested in information despite ICTs’ potential benefits. Consequently, allergists should use evidence-based resources and establish new technological options for content, follow-up, and emotional support for AR patients in Ecuador.

Background: As the global prevalence of allergy increases, it is clear that more individuals are presenting with complex and multiple allergies. The impact of various demographic and clinical risk factors on developing allergies has not been explored at a population level. Objectives: To ascertain if age, gender, ethnicity, UK geographical region of residence and being diagnosed with another allergy affect the risk of having allergies. Methods: A retrospective analysis was performed using cross-sectional data for the year 2018 extracted from the from the health improvement network (THIN) database. THIN is a live primary care database which holds entries about 6% of the UK population. A logistic regression analysis was carried out using demographic data and allergy diagnoses as independent variables. Results: Of the 3.03 million records analysed, 49.8% were male and 19.7% were children (aged < 18 yrs). There were gender, ethnicity and region-based differences in the prevalence of GP diagnosed allergic diseases in the UK. The odds of developing anaphylaxis are highest in individuals with food allergy [OR: 54.57 (95%CI: 45.65-65.22); p<0.001 for children and OR:18.05 (95% CI:16.79-19.41); p<0.001 for adults respectively]. Individuals with any diagnosed allergy had significantly higher odds of being diagnosed with others. Conclusions: Having an allergy significantly increases the odds of being diagnosed with others. There are age, gender, ethnicity and region based differences in the prevalence of allergies. These data suggest that the number of individuals with multiple allergies is increasing and that the needs of increasingly cosmopolitan populations should be taken into account when planning allergy services.

Papillary thyroid carcinoma of the pyramidal lobe is rare. We describe a case of a 77-year-old woman who corroborates current literature findings, namely greater presence of adverse prognostic factors. Upper Neck Papillary Thyroid Cancer is a new entity, proposed to group these tumors with potential clinical and therapeutic implications.

Cystic fibrosis has seen a multitude of therapeutic advances targeting its downstream effects. This has led to a steady increase in survival over the past few decades. The recent development of disease-modifying drugs targeting the underlying CFTR mutation has revolutionized treatment for CF. Despite these advances, individuals with CF who are racial and ethnic minorities, from low socioeconomic status, or female sex have worse clinical outcomes. The inequitable access to CFTR modulators from cost and/or genetic eligibility has the potential to further worsen the existing health disparities seen within the CF community.

In this note, we prove that the Erdös-Straus conjecture holds true. Similarly, the Sierpinski conjecture follows. A relax extension of the restricted Hagedorn equation is presented.

Non-invasive sensory stimulation in the range of the brain’s gamma rhythm (30-100 Hz) is emerging as a new potential therapeutic strategy for the treatment of Alzheimer’s disease (AD). Here we investigated the effect of repeated combined exposure to 40 Hz synchronized sound and light stimuli on hippocampal long-term potentiation (LTP) in vivo in three rat models of early AD. We employed a very complete model of AD amyloidosis, amyloid precursor protein (APP)-overexpressing transgenic McGill-R-Thy1-APP rats at an early pre-plaque stage, systemic treatment of transgenic APP rats with corticosterone modelling certain environmental AD risk factors and, importantly, intracerebral injection of highly disease-relevant AD patient-derived synaptotoxic beta-amyloid and tau in wild-type animals. We found that daily sessions of 40 Hz sensory stimulation fully abrogated the inhibition of LTP in all three models. Moreover, there was a negative correlation between the magnitude of LTP and the level of active caspase-1 in the hippocampus of transgenic APP animals which suggests that the beneficial effect of 40 Hz stimulation was dependent on modulation of pro-inflammatory mechanisms. Our findings support ongoing clinical trials of gamma-patterned sensory stimulation in early AD.

Safety of Biologicals In Severe Asthma Patients Having COVID-19Running title: COVID-19, biologicals and severe asthma

As implantable medical electronics (IMEs) developed for healthcare monitoring and biomedical therapy are extensively explored and deployed clinically, the demand for non-invasive implantable biomedical electronics is rapidly surging. Current rigid and bulky implantable microelectronic power sources are prone to immune rejection and incision, or cannot provide enough energy for long-term use, which greatly limits the development of implantable medical devices. Herein, a comprehensive review of the historical development of IMEs and the applicable miniaturised power sources along with advantages and limitations is given. Despite recent advances in microfabrication techniques, biocompatible materials have facilitated the development of IMEs system toward non-invasive, ultra-flexible, bioresorbable, wireless and multifunctional, progress in the development of minimally invasive power sources in implantable systems has remained limited. Here we summarise three promising minimally invasive power sources, including energy storage devices (biodegradable primary batteries, rechargeable batteries and supercapacitors), human body energy harvesters (nanogenerators and biofuel cells) and wireless power transfer (far-field radiofrequency radiation, near-field wireless power, ultrasonic and photovoltaic power). The energy storage and harvesting mechanism, configurational design, output power and applications in vivo are discussed. It is expected to give a comprehensive understanding of the IMEs for painless health monitoring and biomedical therapy with long-term stable function

The simultaneous consideration of various economic, social, and environmental factors in determining the proper location for constructing a sports complex for traditional games is crucial to the continuation of such events. This research takes a two-stage approach when studying where to locate such infrastructure. In the first stage, namely, that of ranking the locations, the criteria influencing the evaluation are categorized based on the research literature and on interviews with experts well-versed in social, economic, and environmental questions. The criteria identified in this stage are divided into two broad categories: intra-city (selecting the most suitable city) and inter-city (identifying the most suitable geographic area). The best geographical area for constructing a sports complex is found using intra-city criteria based on expert opinions. These opinions were obtained using an online questionnaire prepared according to the Best Worst Method (BWM), giving the weights of both categories. In an effort to assess the desirability of the cities under consideration, we apply piecewise linear pereference functions (PLPFs) to determine the ranges in which each of the items achieve their best score. In the second stage, i.e., the geographical area selection stage, and according to the weighting of inter-city criteria and the ideal distance to each criterion (e.g., fire stations and hospitals), the best geographical area for constructing a sports complex is selected using geographical information system (GIS). The results of this research confirm that social factors are more important than economic and environmental ones in the evaluation phase of the candidates and PLPFs produce different results vis- à-vis the existing linear methods.

By employing thiazole and 4-chlorothiazole as the A′ units, two A-D-A′-D-A type nonfused-ring electron acceptors (NFREAs) Tz-H and Tz-Cl were designed and synthesized. Replacing thiazole in Tz-H with 4-chlorothiazole can not only remarkably shorten the synthetic route through C-H direct arylation but also enhance molecular planarity with the simultaneous incorporation of S···N and S···Cl non-covalently conformational locks (NoCLs). The photovoltaic devices based on PM6:Tz-Cl exhibited a power conversion efficiency as high as 11.10%, much higher than that of PM6:Tz-H (6.41%), mainly due to more efficient exciton dissociation, better and more balanced carrier mobility, less charge recombination, and more favorable morphology. These findings demonstrate the great potential of NoCLs in achieving low-cost and high-performance NFREAs.

The utilization of cyclobutanones as the synthon in transition metal catalysis has been made great success. Because C(carbonyl)−C bond of cyclobutanones can be cleaved through strain release. Despite those advancements, the main catalysts in literature are Rh catalysts or Ni catalysts and the reaction with C–H bond is still underdeveloped. Herein, we realized the first palladium-catalyzed skeletal reorganisation of cyclobutanones invoving successive cleavage of C(carbonyl)−C bonds and C−H bond cleavage, which con-stitutes an rapid access to diverse indanones.

Background and aim: It has been reported GIMAP6 was crucial for autophagy. But it is unknown the role of GIMAP6 in occurrence and tumor-immunity of lung adenocarcinoma. Methods: Comprehensive analyses for datasets from TCGA and GTEx databases were conducted by R software. Basic experiments including RT-qPCR, CCK-8 assays, colony formation assay and transwell assays were applied to explore the role of GIMAP6 in vivo and vitro. Prognostic features and GIMAP6 were applied to construct nomogram. Potential mechanism of GIMAP6 in lung adenocarcinoma was investigated by GO, KEGG and GESA. The correlation between GIMAP6 and immune landscape has also been explored using scRNA sequencing datasets from Timer 2.0 and TISCH. Results: The OS and DSS of lung adenocarcinoma patients with high GIMAP6 expression was better than that with low GIMAP6 expression. The nomogram based on T stage, N stage, and GIMAP6 had predictive significance for prognosis, which was identified by ROC and calibration curve. Functional enrichment analysis suggested that GIMAP6 was mainly involved in T-cell receptor signaling pathway, chemokine signaling pathway, cytokine and cytokine receptor interaction. Single cell sequencing and TIMER2.0 analysis illustrated that GIMAP6 was positively correlated with the infiltration of immune cells and immune-relate molecules including CTLA4, PD-L1, and TIGIT. Basic experiments confirmed the role of GIMAP6 in the proliferation, invasion and migration of lung adenocarcinoma cells. Conclusion: We confirmed that GIMAP6 was an effective prognostic molecule and involved in the regulation of the immune microenvironment of lung adenocarcinoma, which may become a predictor for the efficacy of immunotherapy.

Moving targets are a real threat to pulse compression radars, especially those operating with Doppler-intolerant waveforms. As the Doppler frequency increases, the radar system performance degrades accordingly. In the case of high-speed targets, the Doppler frequency is high enough to distort the received signal, and consequently, the matched filter output is distorted. Therefore, no target information could be extracted. In this paper, we introduce a new Doppler compensation (DC) and estimation technique for phase-coded pulse compression radars to allow the detection of high-speed targets. Moreover, their Doppler frequency value is estimated without ambiguity from one burst and without the need for a range-Doppler module. In addition, the proposed method does not require a synchronization system to perform its function. As such, the implementation of the proposed method is simple and inexpensive. The performance evaluation of the new method shows its superiority in compensation and estimation when examined under higher Doppler frequency and noise compared to a conventional radar.

Use of ethanol is attracting increasing attention both as primary feedstock and as an alternative to increase the feedstock flexibility in a given unit. However, steam reforming of ethanol is not a straight forward process. Equilibrium of the reaction is shifted towards the production of hydrogen even at low temperature. However, in practice, ethanol is also converted to ethylene. The present study is focused primarily upon the production of hydrogen in fixed-bed reactors by steam-ethanol reforming under different temperature conditions. Computational fluid dynamics is used to model fluid flow, heat and mass transfer, and chemical reactions. The governing integral equations are solved for the conservation of mass, momentum, and energy and other scalars such as laminar flow and chemical species. Steady-state analyses are performed using computational fluid dynamics. The reaction rates are computed by the laminar finite-rate model. The present study aims to explore how to effectively produce hydrogen in fixed-bed reactors by steam-ethanol reforming at different temperatures. Particular emphasis is placed upon the effect of temperature on the transport and reaction characteristics of fixed-bed reactors for polymer electrolyte membrane fuel cell applications. The results indicate that under a thermodynamic point of view, high temperatures and steam-ethanol molar ratios promote hydrogen yield. Low ethylene content is obtained at high pressure and low temperature. At high temperatures the contribution of steam reforming reactions results in a marked increasing of overall enthalpy, enhancing process endothermicity, whereas the exothermic contribution of water-gas shift and methanation reactions reduces the external heat supply and the overall energy penalty at lower temperature. Although the equilibrium of the water-gas shift reaction favors the products formation at lower temperatures, reaction kinetics are faster at higher temperatures. The typical products distribution of ethanol steam reforming reaction, according to thermodynamic evaluations, results in considerable hydrogen production rates at higher temperatures and high methane yields at lower temperatures. The majority of supported metals as catalysts expresses better performance at high temperatures, and the production of oxygenated products increases and the formation of coke is thermodynamically favored at low temperatures. Low reaction temperatures generally favor the Boudouard reaction mechanism while methane decomposition is the main route at high temperatures.Keywords: Hydrogen; Ethanol; Reformers; Burners; Reforming; Combustion

Changing oxygen availability in lakes and reservoirs is a fundamental limnological challenge of our time, with massive consequences for freshwater ecosystem functioning and water quality. Cross-lake surveys, paleolimnological studies, and long-term monitoring records indicate that many lakes are exhibiting declines in both surface and bottom-water oxygen availability due to climate and land use change, though a few lakes are exhibiting increases in oxygen. By analyzing time series of oxygen monitoring data from ~400 lakes, I find that some lakes may be experiencing a decoupling of surface and bottom oxygen dynamics: variability in surface oxygen concentrations is decreasing in some lakes while variability in bottom oxygen concentrations is increasing. Changes in both oxygen concentrations and variability have many implications for lake functioning because oxygen concentrations control many ecosystem processes. Consequently, lake ecosystem provisioning and cultural services (e.g., drinking water, fisheries, recreation) will likely be impaired by declining oxygen, whereas the effects of changing oxygen on regulatory and supporting ecosystem services (e.g., nitrate removal through denitrification,

When chicks in a brood hatch asynchronously, the first to hatch gets fed sooner, creating a hierarchy of asymmetries in the brood. In species that suffer from brood reduction, this asymmetry can facilitate the death of one chick during periods of low food availability. The aim of this study was to analyze the effect of initial asymmetries on the growth and survival of Magellanic penguin Spheniscus magellanicus chicks, after disentangling the effects of parental condition, during four breeding seasons. We manipulated chicks' asymmetries within the brood by performing a cross-fostering experiment, creating broods with different weight ratios in a colony located in Isla Quiroga, Santa Cruz, Argentina. We found that weight ratio determines the asymmetry within the brood throughout the entire breeding season, and that final asymmetry also depends on the study season. Chicks that hatch last have a greater chance of survival when the weight ratio with their older sibling is closer to 1. Parental body condition affects chick growth but not asymmetry. To conclude, parents do not reverse the effect of initial asymmetry in post-hatching stages, even during breeding seasons of high reproductive success.

AbstractWater levels in the Laurentian Great Lakes have fluctuated dramatically over recent decades. Since 2015, each of the lakes has reached a record high, often following a recent record or near-record low. These exceptional swings have motivated examinations of changes in lake level variability, particularly given the known climate change-driven intensification of the hydrologic cycle. Recent studies have presented evidence of rising lake level variability and changing water balance components (i.e., overlake precipitation, overlake evaporation, and basin runoff), however a full characterization of trends in variability is needed. Here, we build on previous analyses by quantitatively answering the question: are trends in hydrologic interannual variability over the Great Lakes over recent decades – both lake levels and individual hydrologic components – statistically robust, or simply the result of random chance? Using two non-parametric trend tests, we find that interannual variability of lake levels is significantly increasing in Lakes Superior, Michigan-Huron, and Erie, while decreasing in well-regulated Lake Ontario. We also find robust increasing variability in overlake precipitation, overlake evaporation, and basin runoff for the vast majority of lakes. These results suggest that critical work must follow to both attribute causes of detected trends and to determine if trends will continue increasing in the future with continued anthropogenic climate change. 1. IntroductionRecent extraordinary shifts in Great Lakes water levels have prompted questions about potential changes in year-over-year lake level variability. Changes in the variability of Great Lake levels, namely, how quickly lake levels fluctuate between higher and lower water levels, can have dramatic environmental and societal impacts. Examples include shifts in shoreline erosion patterns (Gronewold and Stow, 2014; Davidson-Arnott, 2016), shipping costs (Millerd, 2010; Lindeberg and Albercook, 2000; Wang et al., 2012), tourism and recreation (Wall, 1998; Hartmann, 1990), and risks to critical infrastructure like water resource management (de Loe and Kreutzwiser, 2000), hydropower (Meyer et al., 2017), and toxic waste facilities (Environmental Law and Policy Center, 2022). Researchers and the public alike have thus been captivated by the rapid transition of Great Lake levels between record low and high lake levels and the resultant impacts (e.g., Gronewold et al., 2021; Egan, 2021). This interest is further motivated by the observed and projected intensification of the hydrologic cycle due to anthropogenic climate change (IPCC, 2021; Seager, 2014). Within this context, Gronewold et al. (2021) presented evidence of rising lake level variability and described the situation caused by this hydrologic cycle intensification as a “continental-scale hydrological tug-of-war” between changing water balance components.Lake levels of large lakes are dominated by three net basin supply (NBS) components: overlake precipitation, overlake evaporation, and basin runoff, where the collective balance of these three components largely determine Great Lakes levels (Δlake storage = poverlake + rbasin - eoverlake) (Gronewold et al., 2021). Note that we define runoff here as the amount of water entering the lake from all incoming river systems in a respective Great Lakes basin, excepting flow from any upstream lakes. These components are all expected to change with the amplification of anthropogenic climate change and trends in these components have already been well observed. For instance, Javed et al. (2019) find increasing evaporation, spatially mixed results on precipitation, and no change in runoff, over Lakes Michigan and Huron. Harp and Horton (2022) characterize an increase in wet day precipitation intensity of ~5% over the U.S.-portion of the Great Lakes basin from 1951 to the present. Looking forward, Mailhot et al. (2019) found increases in net basin supply components with an intensifying annual cycle, but claimed “no long-term changes can be confidently estimated for lake levels.” Kayastha et al. (2022) used a regionally downscaled model to project future Great Lake levels and found a rise in both water levels and net basin supply components, particularly overlake precipitation and runoff. The climate change-driven increase in Great Lake levels was similarly projected by Van De Weghe et al. (2022). These findings differ with earlier work by Hayhoe et al. (2010) which projected falling Great Lakes levels based on increasing evaporation rates with increasing regional temperatures. Examining individual hydrologic components, Wang et al. (2018) project a 16% increase in lake evaporation by the end of the 21st century in a high greenhouse gas emissions scenario (RCP8.5). However, despite examination of trends of lake levels, little attention has been given to statistically characterizing observed trends in variability for either Great Lakes levels or their net basin supply components. Here, we address this knowledge gap by providing a statistically rigorous assessment of changes in interannual variability over the past five decades.