Irreversible Stage Research Articles

Microbial Biofilms in the Food Industry-A Comprehensive Review.

Biofilms, present as microorganisms and surviving on surfaces, can increase food cross-contamination, leading to changes in the food industry’s cleaning and disinfection dynamics. Biofilm is an association of microorganisms that is irreversibly linked with a surface, contained in an extracellular polymeric substance matrix, which poses a formidable challenge for food industries. To avoid biofilms from forming, and to eliminate them from reversible attachment and irreversible stages, where attached microorganisms improve surface adhesion, a strong disinfectant is required to eliminate bacterial attachments. This review paper tackles biofilm problems from all perspectives, including biofilm-forming pathogens in the food industry, disinfectant resistance of biofilm, and identification methods. As biofilms are largely responsible for food spoilage and outbreaks, they are also considered responsible for damage to food processing equipment. Hence the need to gain good knowledge about all of the factors favouring their development or growth, such as the attachment surface, food matrix components, environmental conditions, the bacterial cells involved, and electrostatic charging of surfaces. Overall, this review study shows the real threat of biofilms in the food industry due to the resistance of disinfectants and the mechanisms developed for their survival, including the intercellular signalling system, the cyclic nucleotide second messenger, and biofilm-associated proteins.

Unrecognized platelet physiology is the cause of rewarming deaths in accidental hypothermia and neonatal cold injury

BackgroundThe lack of improvement in prognosis of accidental hypothermia and neonatal cold injury suggests that a major cause of mortality has not been appreciated. Aim of the articleTo show that thrombocytopenia that deepens on rewarming under certain conditions is that missing factor. Scientific basisBelow 34 °C the first stage of aggregation is accentuated, the platelets are more sensitive to ADP and aggregation studies show an increased response “first stage hyper aggregation”. We have confirmed that the irreversible second stage of platelet aggregation does not occur below 34 °C. On rewarming, the first stage of aggregation is followed by disaggregation. When platelets are warmed to 34 °C the potential exists for the platelets to undergo an irreversible second stage of aggregation “second stage platelet hyper aggregation” that can cause a further drop in platelet count and a bleeding diathesis. This only occurs if the platelets have been sufficiently primed when cold and may not be appreciated if platelet counts are not followed. Significance of this data and correlation with the literatureThis thesis explains many other open questions. Why has the overall prognosis remained without improvement over the last half century? Why hypothermic cardiac surgery is free of this problem? Why the depth of hypothermia is alone not prognostic? Has following platelet counts been associated with improved prognosis? Why cardiac arrest does not affect prognosis? Why some patients die suddenly after recovering from hypothermia? Why are so many different rewarming techniques used? Why is the prognosis better in hypothermic suicide attempts? What is the pathophysiological explanation for reversible sequestration of platelets to the liver and spleen in hypothermia? Is DIC (diffuse intravascular coagulation) a problem in hypothermia? And how this new approach could improve prognosis? ConclusionPrognosis can be improved by following platelet counts during rewarming. In patients with prolonged hypothermia, this will show a life-threatening drop in such counts easily treated by platelet infusion.

The Predictors of Cardio-renal Syndrome among Patients with ‎COVID-19 Infection‎ ‎

Background and study aim: ‎: Several reports showed that some Covid-19 patients tend to have serious and fatal ‎complications related to the kidney and heart. Rationale and mechanisms inducing this ‎pathogenesis is unclear, but it’s more common to happen in patients with hemodynamic ‎instability and refractory severe hypotension related to cytokine storm. It represents an ‎irreversible stage of a sepsis-like illness that induces simultaneous damage to various organs as ‎the myocardium and renal tubules alike the cardio-renal syndrome. The predictors for this ‎injurious effect of COVID-19 on both myocardium and renal tissues might be related to the co-‎morbidities, late presentation and other factors which need further evaluation‎.The aim of this article is to study the predictors of cardio-renal syndrome in COVID-19 patients‎ Patients and Methods: Our study is a prospective observational study conducted upon confirmed 160 COVID-19 ICU ‎patients admitted from 15th March till 20th May 2020. ‎All patients were subjected to clinical assessment, full laboratory evaluation including PCR for ‎COVID-19 from nasopharyngeal swab and full radiological evaluation.‎. Results: As regards the predictors for cardio-renal syndrome [15-17]; Age showed high statistically ‎significance (P <0.0004). Furthermore, serum creatinine and serum K were statistically ‎significant in patients with cardio-renal affection (P= 0.015, 0.021) whereas GFR, D-dimer, ‎need for mechanical ventilation and vasopressors were highly statistically significant with ‎cardio-renal affected patients (P <0.001)‎‎. Conclusion: Cardio-renal syndrome was common in COVID-19 ICU patients. Hypokalemia, lower ‎GFR on admission, mechanical ventilation, vasopressors, age and D-dimer were significant ‎independent predictors for CRS. Moreover,CRS during hospitalization was associated with an ‎increased risk of in-hospital death‎‎.

Prospects of the Artificial Organs Structures 3D Printing Technology

Transplantation technologies are now highly effective modern methods of medical care for patients with irreversible stage of chronic diseases of vital organs. The success of transplantology allowed to start solving the problems of improving the quality of patients’ life who live with transplanted organ, their adaptation to society, return to work, to authentic family relationships. &#x0D; The aim of the study is to perform analysis of modern literary sources related to the prospects of application of artificial organs structures bioprinting 3D technology.The shortage of donor organs for transplantation, the high cost of traditional transplantation and the problem of immunocompatibility of donor tissues led to the search for alternative, cost-effective and efficient organ replacement technologies. There are different methods of making 3D structures, each of which has its advantages and disadvantages. The technology is selected depending on the properties of the material, the desired characteristics of the finished structure and its application. To date, bioprinters are able to print bone and cartilage implants quickly enough. &#x0D; Thus, 3D bioprinting is now becoming a real breakthrough in regenerative medicine. Every day there are more and more different techniques to improve this technology.

Quantification of soil losses and multivariate statistics of factors controlling water erosion (Allal Al Fassi watershed, Morocco)

In order to preserve water resources and conserve agricultural land and biodiversity, a precise assessment of soil losses is necessary. It is for this reason that the empirical model of revised RUSLE soil loss equation was applied in order to quantify and describe the rate of erosion in Allal Al Fassi watershed, located in the Middle Atlas mountain chain (Morocco). To understand and define the relationships between water erosion and the factors aggravating its dynamics in Allal Al Fassi watershed, the use of multivariate statistics is in fact an integral part. Sub-models have been adopted to calculate factors of R erosivity, K erodibility, LS slope length and steepness, C soil conservation, and P anti-erosion practices using field data, remote sensing, and GIS (geographic information systems). The map of soil losses resulting from RUSLE model allows us to distinguish five classes. The average annual soil losses are estimated to be 624.07 t ha−1 year−1, with a wide range that goes from 3.57 to 3521.07 t ha−1 year−1 and a median equal to 335.48 t ha−1 y−1. They are greater upstream of watershed, mainly in the eastern part, where slopes are steep and long and soil are highly erodible with little or no development despite very variable conservation and very low to low erosion. However, they are low in areas with low to very low erosion, slope length, and steepness and erodibility, with low anti-erosion practices and strong soil conservation. Multivariate statistical analysis has shown that soil losses in Allal Al Fassi watershed are governed by LS slope length and steepness, K erodibility, and P anti-erosion practices and that the percentages of organic matter, sands, and silts have a significant impact on the variation of soil losses. The latter prove to be important for soils type C1 complex, entisols and inceptisols, soils on dolomitic/calcareous substrate, and soils occupied by matorrals and steppes. RUSLE model has proved useful in quantifying erosion and determining the factors controlling it in Allal Al Fassi watershed, highlighting priority areas that require urgent measures (preventive or remedial) and also where erosion risk reaches irreversible stages.

Correlation of Automated Computed Tomography Volumetric Analysis Metrics With Motility Disturbances in Thyroid Eye Disease.

The authors sought to examine relationships between CT metrics derived via an automated method and clinical parameters of extraocular muscle changes in thyroid eye disease (TED). CT images of 204 orbits in the setting of TED were analyzed with an automated segmentation tool developed at the institution. Labels were applied to orbital structures of interest on the study images, which were then registered against a previously established atlas of manually indexed orbits derived from 35 healthy individuals. Point-wise correspondences between study and atlas images were then compared via a fusion algorithm to highlight metrics of interest where TED orbits differed from healthy orbits. Univariate analysis demonstrated several correlations between CT metrics and clinical data. Metrics pertaining to the extraocular muscles-including average diameter, maximum diameter, and muscle volume-were strongly correlated (p < 0.05) with the presence of ocular motility deficits with regards to the superior, inferior, and lateral recti (with exception of superior rectus motility deficits being mildly correlated with muscle volume [p = 0.09]). Motility defects of the medial rectus were strongly correlated with muscle volume, and only weakly correlated with average and maximum muscle diameter. The novel method of automated imaging metrics may provide objective, rapid clinical information which may have utility in prevention and recognition of visual impairments in TED before they reach an advanced or irreversible stage and while they are able to be improved with immunomodulatory treatments.

Defining the metabolomic profile associated with early cardiotoxicity in patients with breast cancer treated with anthracyclines

Abstract Background Anthracycline (ANT) therapy has dramatically improved clinical outcomes for patients with breast cancer, but it causes cardiotoxicity (CTX) in a dose-dependent manner. Current cardiac biomarkers (troponin, brain natriuretic peptide) and 2D echocardiography only detect CTX in advanced and often irreversible stages. Metabolomic analysis may allow early diagnosis of CTX, and prompt initiation of cardio protective therapies. Purpose To diagnose early CTX via speckle tracking echocardiography (STE), and to characterize the metabolomic fingerprint of patients affected by ANT-mediated CTX. Methods In 2019, patients with breast cancer and normal baseline ejection fraction (EF) were enrolled and longitudinally monitored through clinical assessment, blood sample collection and echocardiography, before initiation of ANT therapy and at 180, 270 and 360 mg/m2 of ANT. CTX, defined as &amp;gt;15% reduction in Global Longitudinal Strain (GLS), was monitored at each ANT dose increment. Unsupervised Principal Component Analysis, supervised Partial Least Square and Partial Least-Square Discriminant Analyses were used to compare the metabolomic profiles of patients who did and did not develop CTX during the study period. Results In the study sample (n=33), no patient developed clinical heart failure, but 8 patients (25%) developed CTX by GLS criteria. Patients with CTX had a significant decrease in GLS compared to patients without CTX at 270 mg/m2 (GLS 20.5 vs 17.9, p=0.01) and 360 mg/m2 ANT (GLS 21.6 vs 17.7, p&amp;lt;0.001), but no significant differences in EF or other 2D echocardiographic parameters. The PLS-DA model at 360 mg/m2 ANT (R2=0.92, Q2=0.53, p=0.03) identified a significantly higher prevalence of Krebs cycle intermediates (like fumarate and succinate), and fatty acids (like linoleic acid) in patients with CTX. On the contrary, patients without CTX at 360 mg/m2 ANT had significantly higher levels of cardioprotective metabolites, like tryptophan. Conclusions For the first time in a human population of breast cancer patients, we show that early ANT-induced CTX (diagnosed via asymptomatic GLS reduction) is associated with a unique metabolomic profile, which affects molecular pathways of energy production. Notably, CTX damage upregulates similar metabolites to those previously identified in clinical heart failure and in mouse CTX models. Our results suggest that a metabolomic fingerprint can be leveraged to create prediction models to identify patients at higher risk of developing cardiovascular complications from ANT therapy. This, in turn, will allow to personalize both chemotherapy and cardioprotective treatments. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): University of Cagliari

Osteoarthritis: New Strategies for Transport and Drug Delivery Across Length Scales.

Osteoarthritis (OA) is the fourth leading cause of disability in adults. Yet, few viable pharmaceutical options exist for pain abatement and joint restoration, aside from joint replacement at late and irreversible stages of the disease. From the first onset of OA, as joint pain increases, individuals with arthritis increasingly reach for drug delivery solutions, from taking oral glycosaminoglycans (GAGs) bought over the counter from retail stores (e.g., Costco) to getting injections of viscous, GAG-containing synovial fluid supplement in the doctor's office. Little is known regarding the efficacy of delivery mode and/or treatment by such disease-modulating agents. This Review addresses the interplay of mechanics and biology on drug delivery to affected joints, which has profound implications for molecular transport in joint health and (patho)physiology. Multiscale systems biology approaches lend themselves to understand the relationship between the cell and joint health in OA and other joint (patho)physiologies. This Review first describes OA-related structural and functional changes in the context of the multilength scale anatomy of articular joints. It then summarizes and categorizes, by size and charge, published molecular transport studies, considering changes in permeability induced through inflammatory pathways. Finally, pharmacological interventions for OA are outlined in the context of molecular weights and modes of drug delivery. Taken together, the current state-of-the-art points to a need for new drug delivery strategies that harness systems-based interactions underpinning molecular transport and maintenance of joint structure and function at multiple length scales from molecular agents to cells, tissues, and tissue compartments which together make up articular joints. Cutting edge and cross-length and -time scale imaging represents a key discovery enabling technology in this process.

DS21, a new noninvasive technology, is effective and safe for screening for prediabetes and diabetes in Chinese population

BackgroundScreening for prediabetes and asymptomatic diabetes is important for preventing development to an irreversible stage. The current diagnosis of prediabetes and diabetes is based on blood glucose or HbA1c (an invasive method). The aim of this study was to assess the efficacy and safety of DS21, a new noninvasive technology, for noninvasive screening for prediabetes and diabetes.MethodsA total of 939 subjects were divided into a normal control group (NC, n = 308), impaired glucose regulation group (IGR, n = 312), and diabetes (DM) group (n = 319). All subjects underwent the DS21 test, and mean hands–feet, hand, and feet conductance values were analyzed. The diagnostic accuracy of the conductance value was analyzed by receiver-operating characteristic (ROC) curve.ResultsThe conductance values for hands–feet, hands, and feet in the DM and IGR groups were significantly lower than those in the NC group (all P < 0.01). The area under the ROC curve (AUCROC) for distinguishing NC/IGR was highest when using hands–feet conductance values (0.766 [95% confidence interval, CI 0.730, 0.803]). However, the AUCROCs of distinguishing NC/abnormal glucose metabolism (AGM, including IGR+DM), non-diabetes (NDM)/DM, and IGR/DM were highest when using conductance values for hands at 0.782 [95% CI 0.752, 0.812], 0.688 [95% CI 0.653, 0.723] and 0.573 [95% CI 0.528, 0.617], respectively (all P < 0.01). Hand conductance of values 75.0 (sensitivity 0.769, specificity 0.660), 77.1 (sensitivity 0.718, specificity 0.695), 68.4 (sensitivity 0.726, specificity 0.555), and 58.1 (sensitivity 0.384, specificity 0.744) were recommended as the screening thresholds for NC/AGM, NC/IGR, NDM/DM, and IGR/DM, respectively. A hand conductance value 66.0 was also recommended to distinguish NC/AGM due to its high sensitivity and high PPV. No adverse events occurred in the test.ConclusionsDS21 is fast, noninvasive, low cost, reliable and safe, which makes it a feasible device for screening for prediabetes and diabetes, especially in a large population.

Enabling early detection of osteoarthritis from presymptomatic cartilage texture maps via transport-based learning

Many diseases have no visual cues in the early stages, eluding image-based detection. Today, osteoarthritis (OA) is detected after bone damage has occurred, at an irreversible stage of the disease. Currently no reliable method exists for OA detection at a reversible stage. We present an approach that enables sensitive OA detection in presymptomatic individuals. Our approach combines optimal mass transport theory with statistical pattern recognition. Eighty-six healthy individuals were selected from the Osteoarthritis Initiative, with no symptoms or visual signs of disease on imaging. On 3-y follow-up, a subset of these individuals had progressed to symptomatic OA. We trained a classifier to differentiate progressors and nonprogressors on baseline cartilage texture maps, which achieved a robust test accuracy of 78% in detecting future symptomatic OA progression 3 y prior to symptoms. This work demonstrates that OA detection may be possible at a potentially reversible stage. A key contribution of our work is direct visualization of the cartilage phenotype defining predictive ability as our technique is generative. We observe early biochemical patterns of fissuring in cartilage that define future onset of OA. In the future, coupling presymptomatic OA detection with emergent clinical therapies could modify the outcome of a disease that costs the United States healthcare system $16.5 billion annually. Furthermore, our technique is broadly applicable to earlier image-based detection of many diseases currently diagnosed at advanced stages today.

Diabetic Retinopathy (DR) Severity Level Classification Using Multimodel Convolutional Neural Networks.

Diabetic retinopathy (DR) is a progressive eye disease that affects a large portion of working-age adults. DR, which may progress to an irreversible state that causes blindness, can be diagnosed with a comprehensive dilated eye exam. With the eye dilated, the Doctor takes pictures of the inside of the eye via a medical procedure called Fluorescein Angiography, in which a dye is injected into the bloodstream. The dye highlights the blood vessels in the back of the eye so they can be photographed. In addition, the Doctor may request an Optical Coherence Tomography (OCT) exam, by which cross-sectional photos of the retina are produced to measure the thickness of the retina. Early prognostication is vital in treating the disease and preventing it from progressing into advanced irreversible stages. Skilled medical personnel and necessary medical facilities are required to detect DR in its five major stages. In this paper, we propose a diagnostic tool to detect Diabetic retinopathy from fundus images by using an ensemble of multi-inception CNN networks. Our inception block consists of three Convolutional layers with kernel sizes of 3x3, 5x5, and 1x1 that are concatenated deeply and forwarded to the max-pooling layer. We experimentally compare our proposed method with two pre-trained models: VGG16 and GoogleNets. The experiment results show that the proposed method can achieve an accuracy of 93.2% by an ensemble of 10 random networks, compared to 81% obtained with transfer learning based on VGG19.

Enhancement of zero-field skyrmion density in [Pt/Co/Fe/Ir]2 multilayers at room temperature by the first-order reversal curve

Magnetic skyrmions are novel topological spin textures on the nanoscale, and significant efforts have been taken to improve their zero-field density at room temperature (RT). In this work, we reported an approach of improving zero-field skyrmion density in [Pt/Co/Fe/Ir]2 multilayers at RT by using the first-order reversal curve (FORC) technique to obtain information on the irreversible or reversible behaviors in the magnetization switching process. It was found from the FORC diagram that the magnetization reversal mechanism can be characterized into three stages: (1) reversible labyrinth stripe domains expanding or shrinking stage; (2) irreversible stripe domains fracturing stage; and (3) irreversible skyrmion annihilation stage. Furthermore, the zero-field skyrmion density can be highly improved by choosing reversal fields from the irreversible stripe domains fracturing stage. The highest skyrmion density was approached according to the maximum FORC distribution ρ. Our results have established the FORC measurement as a valuable tool for investigating magnetic multilayers of high skyrmion densities.

Prevalence and Pattern of Pulmonary Manifestation in Patients with Connective Tissue Disorder.

BackgroundA substantial number of deaths and morbidities are caused by pulmonary involvement in connective tissue disorders (CTDs). The majority of patients suffering from CTDs show diverse clinical presentations arising in the lungs, the diaphragm, vasculature, and the pleura during the course of their disease. The clinical course is highly variable ranging from asymptomatic to symptomatic and from reversible to an irreversible stage. The most common occurring pulmonary appearance is the interstitial disease of the lung. In our study, we aim to determine the prevalence and pattern of pulmonary manifestation in patients with CTD presenting at a tertiary care hospital of Karachi, Pakistan.MethodsA descriptive cross-sectional study was conducted in the department of Rheumatology Medical Unit II, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan. All patients having CTD were enrolled. Patients with human immunodeficiency virus (HIV) infection, smokers, chronic obstructive pulmonary disease (COPD), bronchogenic carcinoma and patients with underlying cardiac disease were excluded from the study. Pulmonary manifestations like nonspecific interstitial pneumonia (NSIP), pleural effusion, usual interstitial pneumonia (UIP), interstitial pneumonitis, pulmonary arterial hypertension (PAH), tuberculosis, and pulmonary embolism were observed. In addition to this, treatment history and immunological test findings of these patients were also recorded.ResultsA total of 290 patients with rheumatologic disorders were included in this study, out of which 90.7% (263) were females and the average age of the entire cohort was 35.13 ± 12.53 years. A majority, 71% (206), of the patients were young (≤ 40 years of age). Rheumatoid arthritis (RA) was the most commonly observed rheumatologic disorder in this cohort which was in 70.3% (204) patients. RA was more prevalent in patients above 40 years of age as compared to young patients (≤ 40 years of age) with a frequency of 81% vs. 66%; p=0.012. Pulmonary involvement was observed in 27.2% of the patients while no pulmonary involvement was noted in 72.8% of patients.ConclusionPulmonary manifestations in patients with CTD is not that uncommon (27.2%). PAH and NSIP collectively account for three-fourth of the total prevalent cases of pulmonary involvement in CTD patients.

Home-based inspiratory muscle training in pediatric patients after kidney transplantation: a randomized clinical trial.

Chronic kidney disease (CKD) represents the irreversible stages of renal failure and is a growing worldwide public health issue associated with increases in morbidity, mortality, and decreased quality of life. Kidney transplantation is considered one of the best treatment options in this population. However, even after surgery, respiratory muscle strength is below normal values, and inspiratory muscle training (IMT) improves respiratory muscle function, strength, and endurance. This study aimed to evaluate the effects of IMT regarding respiratory muscle strength, functional capacity, and pulmonary function in pediatric kidney transplant recipients with CKD, and secondarily, to assess the biochemical profile of patients after intervention. This is a randomized, double-blind, placebo-controlled trial. Patients were randomized into two groups, intervention (IG) and control (CG) and performed IMT home-based training for 6weeks. In the IG, the load was adjusted to 40% of the maximal inspiratory pressure and in the CG was adjusted to a minimum placebo load (9cm H2O). Thirty-one patients were randomly allocated to the intervention (n = 16) or control (n = 15) groups. There were no differences at baseline between groups. Increase of 35% in the maximal inspiratory pressure predicted and 26% in the maximal expiratory pressure predicted in the IG were found, compared with 5 and 4% in the CG. There was an increase in hemoglobin and hematocrit values in the IG. Home-based IMT provides a significant increase in respiratory muscle strength, without changes in functional capacity and pulmonary function. Benefits regarding biochemical markers (hemoglobin and hematocrit) were also observed.

COVID-19 interactions with angiotensin-converting enzyme 2 (ACE2) and the kinin system; looking at a potential treatment

The novel coronavirus disease 2019 (COVID-19) is a rapidly expanding infection around the world. The world Health Organization (WHO) in March 2020 announced the Coronavirus pandemic. This infection causes many deaths on daily basis. Therapeutic options are currently limited. It is revealed that COVID-19 binds to human angiotensin-converting enzyme 2 (ACE2) to enter the host cells. One of the activities of ACE2 is hydrolyzing the active bradykinin metabolite [des-Arg973] BK (DABK). A decreased activity or reducing expression of ACE2 by the virus impairs the inactivation of DABK. This enhances its signaling through the bradykinin B1 receptor (BKB1R) and could lead to fluid extravasation and leukocyte recruitment to the lung. Targeting the bradykinin system by either blocking the bradykinin production or blocking bradykinin receptors may open a new potential therapeutic window for the treatment of COVID-19 induced acute respiratory distress syndrome (ARDS) particularly before patients enter the irreversible stages.

The stratification of cirrhosis

Cirrhosis is traditionally seen as an irreversible stage of chronic liver disease although its clinical course may last several years. Overall, the clinical management of cirrhotic patients is based on the observation of clinical events mostly related to complication of portal hypertension. Each event of cirrhosis decompensation has clear prognostic implication although it is not precisely predictable. In practice, the advancement in the knowledge of the mechanisms responsible for disease progression is not yet translated in clinical tools allowing the stratification of the cirrhotic stage according to pathophysiological mechanisms. This article provides a review of the main clinical and histopathogical features of liver cirrhosis that are relevant for its clinical stratification together with the advancements provided by the introduction of non-invasive measures of portal hypertension. Other clinical aspects with a major impact of the quality of life and the possibility of liver transplantation are also discussed.

Stress, strain and electromechanical analyses of (RE)Ba2Cu3Ox conductors using three-dimensional/two-dimensional mixed-dimensional modeling: fabrication, cooling and tensile behavior

High temperature superconducting (HTS) conductors, represented by Rare Earth-Barium-Copper-Oxide (REBCO) conductors, are promising for high energy and high field superconducting applications. In practical applications, however, the HTS conductors experience different stresses and strains, including residual stresses due to thermal mismatch and tensile stresses due to Lorentz forces, resulting in some circumstances to a reduction in the load-carrying capacity as well as the risk of degradation in conductor critical current. In this study a mixed-dimensional high-aspect-ratio laminated composite finite element model for REBCO conductor is developed for stress and strain analyses in the processes of fabricating and cooling, as well as tensile testing. The model includes all the major constituent layers of a typical REBCO conductor and is experimentally validated. First, the thermal residual stresses and strains accumulated during the fabrication and cooling processes are analyzed by a multi-step modeling method that emulates the manufacturing process. Then, with the residual stresses and strains as initial stresses and strains, the mechanical behavior under a tensile load is studied. Lastly, a phenomenological critical current-strain model based on the Ekin power-law formula and the Weibull distribution function is combined with the mixed-dimensional conductor model to predict the strain dependence behavior of critical current in the reversible and irreversible degradation strain ranges. Simulation results show that the multi-step modeling is an effective method for stress and strain analyses of REBCO conductors during the fabrication and cooling processes and under and tensile loads. Compressive thermal residual stress generated on the REBCO layer during fabrication and cooling strongly affects the subsequent mechanical and current-carrying properties. Stress–strain curves generated by tensile loads are analyzed and experimentally validated at both the conductor and constituent-layer levels. Simulation results for the strain dependence of critical current are in good agreement with experiment data in both the reversible and irreversible degradation stages.

The need for implementation of first trimester screening for preeclampsia and fetal growth restriction in low resource settings

Background Preeclampsia [PE] and fetal growth restriction [FGR] is a major cause of perinatal morbidity in both developed and developing countries but the disease leaves a severe impact in developing countries, due to the late presentation of cases where prevention and treatment becomes impossible. Routine antenatal ultrasound and health checkups in periphery are usually done in first trimester for dating and viability scan, in midtrimester for anomaly scan and in third trimester for safe confinement. Underlying disorder of deep placentation which is unidentified can lead to increased maternal morbidity and fetal compromise between 26 to 34 weeks of gestation The complications present at an irreversible stage where there is no sufficient time even for referral to tertiary care center. Frequent antenatal visits as suggested by WHO would definitely bring down maternal mortality but this increased surveillance when offered to all might be a huge burden to health care providers in low resource settings. An acceptable screening test should help in triaging the high risk group in first trimester itself targeting about only one third of the population for prophylactic therapy and increased antenatal surveillance.The objective of this study is to evaluate the performance and feasibility of different screening protocols in low resource settings. Methodology Screening for PE and FGR was done at the 11–14 weeks aneuploidy scan as per FMF guidelines. Group I included 6289 women whose risk prediction was done with maternal characteristics [MC], mean arterial pressure [MAP] and Uterine artery Doppler [UAD]. Group II included 2067 women whose risk was predicted with MC, MAP, UAD and PAPP-A. Group III included 576 women whose risk prediction included all parameters with PLGF. Results Two thousand five hundred fifty-seven cases were screen positive in group I and 602 were screen positive in group II. In group III which included PLGF, 24 were positive for early onset PE and 36 for late onset PE. The number needed to treat [NNT] was 35.9, 29.1 and 10% in Group I, II and III respectively. The detection rate [DR] for PE and FGR was 60% in Group I and DR for FGR in Group II was 85%. In Group III, for early onset PE the DR was 98% and 68% for late onset PE. Conclusion Screening for PE with available resources in the periphery needs to be implemented to avoid its grave complications. Traditional screening for PE by NICE guidelines can be adopted but may have a detection rate of only 30–40%. Though screening by ACOG criteria may have good detection rates but more than two thirds of the population would become screen positive which nullifies this approach as a good screening methodology in low resource settings. Multiparametric approach for screening in first trimester serves as a better screening tool to enable higher detection rate of disease with least false positive rates. Uterine artery Doppler when combined with maternal characteristics and mean arterial pressure could achieve a detection rate of about 60% and would still target only one third of the population for increased antenatal surveillance. This requires training healthcare professionals in the periphery for this approach and this should be our prime focus in the current scenario. Inclusion of serum biochemistry would still bring down the target population to 10% and increase the DR and can be considered as an additional test in economically feasible population. In low resource settings a better screening approach to PE would be a combination of maternal history, biophysical or biochemical parameters whichever is feasible considering the economy and availability of resources.

Kompromitovana čvrstoća kostiju kod pacijenata sa alkoholnom cirozom jetre

Osteoporosis and/or osteopenia are frequently observed complications in alcoholic liver disease patients, especially in its irreversible stage (alcoholic liver cirrhosis - ALC). Current literature review regarding osteoporosis incidence increased fracture risk, bone mineral density changes, micro-structural alteration and pathogenetic mechanisms leading to ALC - induced decrease in bone quality is presented. It has been reported that osteoporosis is influenceing significant number of ALC patients, with particular accent on lumbar spine, as most commonly affected skeletal site. Several risk factors and ethio-pathogenic mechanisms have been associated with the loss of bone mineral density, in patients with ALC and other cirrhosis. Certain authors claim that dominant mechanism in ALC-induced bone loss is decrease in bone formation and osteoblastic function, while other results suggest increased bone remodeling as underlying cause of increased bone fragility in ALC patients. Increased bone fragility and susceptibility to osteoporotic fractures significantly affect life expectancy and quality of life in patients with ALC. Thus, osteological screening and individual fracture risk assessment are highly recommended for all patients with alcoholic liver cirrhosis.

Convex Representations Using Deep Archetypal Analysis for Predicting Glaucoma.

Goal: The purpose of this study was to identify clinically relevant patterns of glaucomatous vision loss through convex representation to predict glaucoma several years prior to disease onset. Methods: We developed a deep archetypal analysis to identify patterns of glaucomatous vision loss, and then projected visual fields over the identified patterns. Projections provided a representation that was more accurate in detecting glaucomatous vision loss, thus, more appropriate for recognizing preclinical signs of glaucoma prior to disease development. To overcome the class imbalance in prediction, we implemented a class-balanced bagging with neural networks. Results: Using original visual field as features of the class-balanced bagging classification provided an area under the receiver-operating characteristic curve (AUC) of 0.55 for predicting glaucoma approximately four years prior to disease development. Using convex representation of the visual fields as input features provided an AUC of 0.61 while using deep convex representation as input features improved the AUC to 0.71. Relevance vector machine (RVM) achieved an AUC of 0.64. Conclusion: Deep archetypal analysis representation of visual functional features with balanced bagging classification could serve as an automated tool for predicting glaucoma. Significance: Glaucoma is the second leading cause of worldwide blindness. Most people with glaucoma have no early symptoms or pain, delaying diagnosis in many patients until they reach late irreversible vision loss stages. In fact, about 50% of people with glaucoma are unaware they have the disease. Deep archetypal analysis models may impact clinical practice in effectively identifying at-risk glaucoma patients well prior to disease development.