Genetic testing for nephrotic syndrome and FSGS in the era of next-generation sequencing

The haploid human genome is composed of three billion base pairs, about one percent of which consists of exonic regions, the coding sequence for functional proteins, also now known as the “exome”. The development of next-generation sequencing makes it possible from a technical and economic standpoint to sequence an individual’s exome but at the cost of generating long lists of gene variants that are not straightforward to interpret. Various public consortiums such as the 1000 Genomes Project and the NHLBI Exome Sequencing Project have sequenced the exomes and a subset of entire genomes of over 2500 control individuals with ongoing efforts to further catalogue genetic variation in humans.1 The use of these public databases facilitates the interpretation of these variant lists produced by exome sequencing and, as a result, novel genetic variants linked to disease are being discovered and reported at a record rate. However, the interpretation of these results and their bearing on diagnosis, prognosis, and treatment is becoming ever more complicated. Here, we discuss the application of genetic testing to individuals with focal and segmental glomerulosclerosis (FSGS), taking a historical perspective on gene identification and its clinical implications along with the growing potential of next-generation sequencing

Evaluation of the efficacy of tamsulosin with or without deflazacort for stone clearance after extracorporeal shockwave lithotripsy for upper ureteral and renal calculi

Background: Medical expulsive therapy in the form of alpha blockers, corticosteroids, calcium channel blockers is being used with success for medical treatment of lower ureteric calculus. Adjunctive use of these therapeutic agents in post extracorporeal shockwave lithotripsy period is also being tried.With this background, we evaluated the efficacy of tamsulosin with or without deflazacort for various outcome factors after ESWL of upper ureteral and renal calculi.Methods: A Prospecive study during period from February 2014 to April 2015 including a total of 90 patients with solitary upper ureteral or renal calculus who underwent ESWL was conducted. Patients were divided into three groups. Group A(30 patients) were given standard therapy (analgesics and antibiotics for 5 days), Group B (30 patients) were given standard plus tamsulosin (0.4 mg once daily) for 4 weeks and Group C (30 patients) were given standard therapy plus tamsulosin (0.4 mg once daily) and deflazacort (6 mg twice daily) for 4 weeks . Patients were evaluated at 2 and 4 weeks post ESWL with X ray KUB and USG.Results: At the end of 4 weeks, 10, 17, and 26 patients in group A, B and C respectively cleared their stones. Out of these 2, 6 and 19 patients in group A, B and C respectively cleared their stones in first 2 weeks. Clearance in group C was significantly higher as compared to group A and B.Conclusions: Addition of alpha-blocker tamsulosin along with deflazacort post ESWL for renal and upper ureteric calculi increases the stone expulsion rate and reduces the expulsion duration as shown by highly statistically significant results in group C.

CaveSeg: Deep Semantic Segmentation and Scene Parsing for Autonomous Underwater Cave Exploration

In this paper, we present CaveSeg - the first visual learning pipeline for semantic segmentation and scene parsing for AUV navigation inside underwater caves. We address the problem of scarce annotated training data by preparing a comprehensive dataset for semantic segmentation of underwater cave scenes. It contains pixel annotations for important navigation markers (e.g. caveline, arrows), obstacles (e.g. ground plain and overhead layers), scuba divers, and open areas for servoing. Through comprehensive benchmark analyses on cave systems in USA, Mexico, and Spain locations, we demonstrate that robust deep visual models can be developed based on CaveSeg for fast semantic scene parsing of underwater cave environments. In particular, we formulate a novel transformer-based model that is computationally light and offers near real-time execution in addition to achieving state-of-the-art performance. Finally, we explore the design choices and implications of semantic segmentation for visual servoing by AUVs inside underwater caves. The proposed model and benchmark dataset open up promising opportunities for future research in autonomous underwater cave exploration and mapping.Comment: submitted for review in ICRA 2024. 10 pages, 9 figure

Anti-inflammatory effect of low intensity ultrasound (LIUS) on complete Freund's adjuvant-induced arthritis synovium

SummaryObjectivesArthritis with intra-articular inflammation was accompanied by joint pain, swelling, and stiffness leading to significant functional impairment. Thus, regulation of joint inflammation is a good therapeutic approach for patients with arthritis. In this study, the effect of low intensity ultrasound (LIUS) applied to an adjuvant-induced arthritic rat model on the synovium was investigated.DesignSynovial inflammation was induced by complete Freund's adjuvant (CFA)-injection into the rat knee joint. LIUS (200 mW/cm2) was applied on the ipsilateral knee everyday for 10 min beginning 1 day after inflammation induction. The expression of proinflammatory factors and immunohistochemical staining pattern of the synovium were assessed.ResultsCFA induced an increase of the knee circumference that was significantly diminished by LIUS. Synovial membrane hyperplasia in the ipsilateral joint was also affected by LIUS. The inflammatory mediators, COX-1/2, IL-1β, and iNOS, but not TNF-α, in the synovial membrane were induced after 3 days, and they closely correlated with the degree of edema. In the synovial membrane, the expression of inflammatory mediators was reduced by LIUS. The chemoattractant chemokine receptor CCR5 also was involved. On immunohistochemical analysis, CFA caused increased infiltration of CD11b-positive cells in the synovium. After 3 days, neutrophils, myeloperoxidase (MPO)-positive cells filled the inflammatory core; later, monocytes and macrophages, ionized calcium binding adaptor molecule 1 (Iba1)-positive cells in the periphery infiltrated the core by day 5. LIUS markedly reduced CFA-induced inflammatory cells infiltration.ConclusionLIUS showed a potent anti-inflammatory effect in this animal arthritis model with reduced infiltration of inflammatory cells into the synovium

Validation of a low field Rheo-NMR instrument and application to shear-induced migration of suspended non-colloidal particles in Couette flow.

Nuclear magnetic resonance rheology (Rheo-NMR) is a valuable tool for studying the transport of suspended non-colloidal particles, important in many commercial processes. The Rheo-NMR imaging technique directly and quantitatively measures fluid displacement as a function of radial position. However, the high field magnets typically used in these experiments are unsuitable for the industrial environment and significantly hinder the measurement of shear stress. We introduce a low field Rheo-NMR instrument (1H resonance frequency of 10.7MHz), which is portable and suitable as a process monitoring tool. This system is applied to the measurement of steady-state velocity profiles of a Newtonian carrier fluid suspending neutrally-buoyant non-colloidal particles at a range of concentrations. The large particle size (diameter >200μm) in the system studied requires a wide-gap Couette geometry and the local rheology was expected to be controlled by shear-induced particle migration. The low-field results are validated against high field Rheo-NMR measurements of consistent samples at matched shear rates. Additionally, it is demonstrated that existing models for particle migration fail to adequately describe the solid volume fractions measured in these systems, highlighting the need for improvement. The low field implementation of Rheo-NMR is complementary to shear stress rheology, such that the two techniques could be combined in a single instrument

Artificial intelligence assisted tools for the detection of anxiety and depression leading to suicidal ideation in adolescents: a review

Epidemiological studies report high levels of anxiety and depression amongst adolescents. These psychiatric conditions and complex interplays of biological, social and environmental factors are important risk factors for suicidal behaviours and suicide, which show a peak in late adolescence and early adulthood. Although deaths by suicide have fallen globally in recent years, suicide deaths are increasing in some countries, such as the US. Suicide prevention is a challenging global public health problem. Currently, there aren’t any validated clinical biomarkers for suicidal diagnosis, and traditional methods exhibit limitations. Artificial intelligence (AI) is budding in many fields, including in the diagnosis of medical conditions. This review paper summarizes recent studies (past 8 years) that employed AI tools for the automated detection of depression and/or anxiety disorder and discusses the limitations and effects of some modalities. The studies assert that AI tools produce promising results and could overcome the limitations of traditional diagnostic methods. Although using AI tools for suicidal ideation exhibits limitations, these are outweighed by the advantages. Thus, this review article also proposes extracting a fusion of features such as facial images, speech signals, and visual and clinical history features from deep models for the automated detection of depression and/or anxiety disorder in individuals, for future work. This may pave the way for the identification of individuals with suicidal thoughts

A Search for X-ray/UV Correlation in the Reflection-Dominated Seyfert 1 Galaxy Mrk 1044

Correlated variability between coronal X-rays and disc optical/UV photons provides a very useful diagnostic of the interplay between the different regions around an active galactic nucleus (AGN) and how they interact. AGN that reveal strong X-ray reflection in their spectra should normally exhibit optical/UV to X-ray correlation consistent with reprocessing -- where the optical/UV emission lag behind the X-rays. While such correlated delay has been seen in some sources, it has been absent in others. \rm{Mrk~1044} is one such source that has been known to reveal strong X-ray reflection in its spectra. In our analysis of three long \textit{XMM-Newton} and several \textit{Swift} observations of the source, we found no strong evidence for correlation between its UV and X-ray lightcurves both on short and long time scales. Among other plausible causes for the non-detection, we posit that higher X-ray variability than UV and strong general relativistic effects close to the black hole may also be responsible. We also present results from the spectral analysis based on \textit{XMM-Newton} and \textit{NuSTAR} observations, which show the strong soft X-ray excess and iron K$\alpha$ line in the 0.3--50 keV spectrum that can be described by relativistic reflection.Comment: Accepted for Publication in APJ, 13 pages, 11 figures, 2 table

The relationship between web enjoyment and student perceptions and learning using a web-based tutorial

Web enjoyment has been regarded as a component of system experience. However, there has been little targeted research considering the role of web enjoyment alone in student learning using web-based systems. To address this gap, this study aims to examine the influence of web enjoyment on learning performance and perceptions by controlling system experience as a variable in the study. 74 students participated in the study, using a web-based tutorial covering subject matter in the area of 'Computation and algorithms'. Their learning performance was assessed with a pre-test and a post-test and their learning perceptions were evaluated with a questionnaire. The results indicated that there are positive relationships between the levels of web enjoyment and perceived usefulness and non-linear navigation for users with similar, significant levels of system experience. The implications of these findings in relation to web-based learning are explored and ways in which the needs of students who report different levels of web enjoyment might be met are discussed