Enhancing grid resiliency in distributed energy systems through a comprehensive review and comparative analysis of islanding detection methods.

Reduction of fossil fuel usage, clean energy supply, and dependability are all major benefits of integrating distributed energy resources (DER) with electrical utility grid (UG). Nevertheless, there are difficulties with this integration, most notably accidental islanding that puts worker and equipment safety at risk. Islanding detection methods (IDMs) play a critical role in resolving this problem. All IDMs are thoroughly evaluated in this work, which divides them into two categories: local approaches that rely on distributed generation (DG) side monitoring and remote approaches that make use of communication infrastructure. The study offers a comparative evaluation to help choose the most efficient and applicable IDM, supporting well-informed decision-making for the safe and dependable operation of distributed energy systems within electrical distribution networks. IDMs are evaluated based on NDZ outcomes, detection duration, power quality impact, multi-DG operation, suitability, X/R ratio reliance, and efficient functioning.

Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial.

BACKGROUND: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days. METHODS: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient (r) with 95% CI. RESULTS: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase (P=0.10). Older age (P<0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale (P<0.01), and longer stroke onset-to-needle time (P=0.004) were associated with lower EQ5D index and VAS scores. There was a strong association (r, 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index (r, 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores (r, 0.42 [95% CI, 0.37-0.46]). CONCLUSIONS: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Nanobiosensors for detection of opioids: A review of latest advancements.

Opioids are generally used as analgesics in pain treatment. Like many drugs, they have side effects when overdosed and can causeaddiction problems.Illegal drug use and misuse are becoming a major concern for authorities worldwide; thus, it is critical to have precise procedures for detecting them in confiscated samples, biological fluids, and wastewaters. Routine blood and urine tests are insufficient for highly selective determinations and can cause cross-reactivities. For this purpose, nanomaterial-based biosensors are great tools to determine opioid intakes, continuously monitoring the drugs with high sensitivity and selectivity even at very low sample volumes.Nanobiosensors generally comprise a signal transducer nanostructure in which a biological recognition molecule is immobilized onto its surface. Lately, nanobiosensors have been extensively utilized for the molecular detection of opioids. The usage of novel nanomaterials in biosensing has impressed researchers who work on developing biosensors. Nanomaterials with a large surface area have been used to develop nanobiosensors with shorter reaction times and higher sensitivity than conventional biosensors. Colorimetric and fluorescence sensing methods are two kinds of optical sensor systems based on nanomaterials. Noble metal nanoparticles (NPs), such as silver and gold, are the most frequently applied nanomaterials in colorimetric techniques, owing to their unique optical feature of surface plasmon resonance. Despite the progress of an extensive spectrum of nanobiosensors over the last two decades, the future purpose of low-cost, high-throughput, multiplexed clinical diagnostic Lab-on-a-Chip instruments has yet to be fulfilled. In this review, a concise overview of opioids (such as tramadol and buprenorphine, oxycodone and fentanyl, methadone and morphine) is provided as well as information on their classification, mechanism of action, routine tests, and new opioid sensing technologies based on various NPs. In order to highlight the trend of nanostructure development in biosensor applications for opioids, recent literature examples with the nanomaterial type, target molecules, and their limits of detection are discussed.

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial.

BACKGROUND: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care. METHODS: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual. FINDINGS: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis. FUNDING: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Ultrasensitive probeless capacitive biosensor for amyloid beta (Aß1-42) detection in human plasma using interdigitated electrodes.

Progressive aggregation and protein misfolding are the initial fundamental indicators of neurodegenerative disorders such as Alzheimer's disease (AD). In this study, a highly sensitive and novel method to detect amyloid beta (Aß) biomarkers, which are a hallmark of AD, using an immunoassay platform-based interdigitated capacitive biosensor, has been explored. For several decades, aptamers have classified as a novel class of molecular recognition probes comprising single-stranded complementary DNA sequences that bind to their identified targets with high specificity and affinity by an in vitro technique called SELEX (systematic evolution of exponential and enrichment). Aptamers, often referred to as "chemical antibodies", possess several highly obvious features for clinical use. The proposed sensing bio-device was fabricated and glazed with oligomeric Aß (oAß) aptamer and anti-oAß antibody, functionalized onto a Pt/Ti-featured SiO2 substrate. Subsequently, analytical studies were conducted to confirm that the specificity, sensitivity, and selective detection of the oAß-based bioengineered surfaces facilitate a label-free approach. The bionic capacitive sensor achieved real-time detection within 5 s (faster response than ELISA) under the femto-molar range concentrations of oAß peptide in plasma using anti-oAß antibody and oAß aptamer with ultra-high affinity. Furthermore, the prepared capacitive biochip was selective against plasma-borne antigens and standby for 100 days at 4 °C. The developed biosensor is suitable for point-of-care (POC) diagnostic applications owing to its portability and scalability. Furthermore, the superior efficacy of oAß in identifying AD has huge potential for biomedical applications.

Positron emission tomographic imaging in drug discovery.

Positron emission tomography (PET) is an extensively used nuclear functional imaging technique, especially for central nervous system (CNS) and oncological disorders. Currently, drug development is a lengthy and costly pursuit. Imaging with PET radiotracers could be an effective way to hasten drug discovery and advancement, because it facilitates the monitoring of key facets, such as receptor occupancy quantification, drug biodistribution, pharmacokinetic (PK) analyses, validation of target engagement, treatment monitoring, and measurement of neurotransmitter concentrations. These parameters demand careful analyses for the robust appraisal of newly formulated drugs during preclinical and clinical trials. In this review, we discuss the usage of PET imaging in radiopharmaceutical development; drug development approaches with PET imaging; and PET developments in oncological and cardiac drug discovery.

Ultrasensitive and Reusable Graphene Oxide-Modified Double-Interdigitated Capacitive (DIDC) Sensing Chip for Detecting SARS-CoV-2.

This research reveals the promising functionalization of graphene oxide (GrO)-glazed double-interdigitated capacitive (DIDC) biosensing platform to detect severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike (S1) proteins with enhanced selectivity and rapid response. The DIDC bioactive surface consisting of Pt/Ti featured SiO2 substrate was fabricated using GrO/EDC-NHS/anti-SARS-CoV-2 antibodies (Abs) which is having layer-by-layer interface self-assembly chemistry method. This electroactive immune-sensing platform exhibits reproducibility and sensitivity with reference to the S1 protein of SARS-CoV-2. The outcomes of analytical studies confirm that GrO provided a desired engineered surface for Abs immobilization and amplified capacitance to achieve a wide detection range (1.0 mg/mL to 1.0 fg/mL), low limit of detection (1 fg/mL) within 3 s of response time, good linearity (18.56 nF/g), and a high sensitivity of 1.0 fg/mL. Importantly, the unique biochip was selective against blood-borne antigens and standby for 10 days at 5 °C. Our developed DIDC-based SARS-CoV-2 biosensor is suitable for point-of-care (POC) diagnostic applications due to portability and scaling-up ability. In addition, this sensing platform can be modified for the early diagnosis of severe viral infections using real samples.

Nanotechnology Facilitated Cultured Neuronal Network and Its Applications.

The development of a biomimetic neuronal network from neural cells is a big challenge for researchers. Recent advances in nanotechnology, on the other hand, have enabled unprecedented tools and techniques for guiding and directing neural stem cell proliferation and differentiation in vitro to construct an in vivo-like neuronal network. Nanotechnology allows control over neural stem cells by means of scaffolds that guide neurons to reform synaptic networks in suitable directions in 3D architecture, surface modification/nanopatterning to decide cell fate and stimulate/record signals from neurons to find out the relationships between neuronal circuit connectivity and their pathophysiological functions. Overall, nanotechnology-mediated methods facilitate precise physiochemical controls essential to develop tools appropriate for applications in neuroscience. This review emphasizes the newest applications of nanotechnology for examining central nervous system (CNS) roles and, therefore, provides an insight into how these technologies can be tested in vitro before being used in preclinical and clinical research and their potential role in regenerative medicine and tissue engineering.

Pre-hospital triage of suspected acute stroke patients in a mobile stroke unit in the rural Alberta.

Mobile Stroke Unit (MSU) expedites the delivery of intravenous thrombolysis in acute stroke patients. We further evaluated the functional outcome of patients shipped to a tertiary care centre or repatriated to local hospitals after triage by MSU in acute stroke syndrome in rural northern Alberta. Consecutive patients with suspected acute stroke syndrome were included. On the basis of neurology consultation and, Computed Tomography findings, patients, who were thrombolysed or needed advanced care were transported to the Comprehensive stroke center (CSC) (Triage to CSC group). Other patients were repatriated to local hospital care (Triage to LHC group). A total of 156 patients were assessed in MSU, 73 (46.8%) were female and the mean age was 66.6 ± 15 years. One hundred and eight (69.2%) patients, including 41 (26.3%) treated with thrombolysis were transported to the CSC (Triage to CSC group) and 48 (30.8%) were repatriated to local hospital care. The diagnosis made in MSU and final diagnosis were matching in 88% (95) and 91.7% (44, p = 0.39) in Triage to CSC and Triage to LHC groups respectively. Prehospital triage by MSU of acute stroke syndrome can reliably repatriate patients to the home hospital. The proposed model has the potential to triage patients according to their medical needs by enabling treatment in home hospitals whenever reasonable.

Neurophysiological Correlates of Cognition as Revealed by Virtual Reality: Delving the Brain with a Synergistic Approach.

The synergy of perceptual psychology, technology, and neuroscience can be used to comprehend how virtual reality affects cognition of human brain. Numerous studies have used neuroimaging modalities to assess the cognitive state and response of the brain with various external stimulations. The virtual reality-based devices are well known to incur visual, auditory, and haptic induced perceptions. Neurophysiological recordings together with virtual stimulations can assist in correlating humans' physiological perception with response in the environment designed virtually. The effective combination of these two has been utilized to study human behavior, spatial navigation performance, and spatial presence, to name a few. Moreover, virtual reality-based devices can be evaluated for the neurophysiological correlates of cognition through neurophysiological recordings. Challenges exist in the integration of real-time neuronal signals with virtual reality-based devices, and enhancing the experience together with real-time feedback and control through neuronal signals. This article provides an overview of neurophysiological correlates of cognition as revealed by virtual reality experience, together with a description of perception and virtual reality-based neuromodulation, various applications, and existing challenges in this field of research.

Comparison of wearable sensor to traditional methods in functional outcome measures: A systematic review.

Traditional methods of collecting functional outcome measures are widely used for lower extremity arthroplasty outcome assessment. Wearable sensors are emerging as viable tools for functional outcome measures in monitoring of postarthroplasty recovery. The objective of this review was to compare the efficacy of wearable sensors with traditional methods for monitoring postarthroplasty functional recovery. Articles were searched for inclusion in this review that used both traditional and wearable sensor functional outcome measures to assess lower extremity function before and after lower extremity arthroplasty. Two independent screeners reviewed all articles, and resolved differences through consensus and consultation with the senior author. Studies that met inclusion criteria were evaluated for methodologic quality using performed risk of bias assessments. Results from several traditional and wearable sensor functional outcome measures from baseline through follow-up were normalized across studies. Fourteen articles met the inclusion criteria. Six studies used statistical methods to directly compare functional outcome measures and eight studies used qualitative description of comparisons. This review found evidence that wearable sensors detected nuanced functional outcome information on the specific biomechanics and timing of recovery, which were unaccounted for using traditional methods. Wearable sensors have shown promising utility in providing additional recovery information from lower extremity arthroplasty compared with traditional functional outcome measures, but future research is needed to assess the clinical significance of this additional information. Wearable sensor technology is an emerging clinical tool providing advanced and determinative data with the potential for advancing the assessment of lower extremity arthroplasty outcomes.

Targeted pancreatic beta cell imaging for early diagnosis.

Pancreatic beta cells are important in blood glucose level regulation. As type 1 and 2 diabetes are getting prevalent worldwide, we need to explore new methods for early detection of beta cell-related afflictions. Using bioimaging techniques to measure beta cell mass is crucial because a decrease in beta cell density is seen in diseases such as diabetes and thus can be a new way of diagnosis for such diseases. We also need to appraise beta cell purity in transplanted islets for type 1 diabetes patients. Sufficient amount of functional beta cells must also be determined before being transplanted to the patients. In this review, indirect imaging of beta cells will be discussed. This includes membrane protein on pancreatic beta cells whereby specific probes are designed for different imaging modalities mainly magnetic resonance imaging, positron emission tomography and fluorescence imaging. Direct imaging of insulin is also explored though probes synthesized for such function are relatively fewer. The path for successful pancreatic beta cell imaging is fraught with challenges like non-specific binding, lack of beta cell-restricted targets, the requirement of probes to cross multiple lipid layers to bind to intracellular insulin. Hence, there is an urgent need to develop new imaging techniques and innovative probing constructs in the entire imaging chain of bioengineering to provide early detection of beta cell-related pathology.

Dealing with PET radiometabolites.

Positron emission tomography (PET) offers the study of biochemical, physiological, and pharmacological functions at a cellular and molecular level. The performance of a PET study mostly depends on the used radiotracer of interest. However, the development of a novel PET tracer is very difficult, as it is required to fulfill a lot of important criteria. PET radiotracers usually encounter different chemical modifications including redox reaction, hydrolysis, decarboxylation, and various conjugation processes within living organisms. Due to this biotransformation, different chemical entities are produced, and the amount of the parent radiotracer is declined. Consequently, the signal measured by the PET scanner indicates the entire amount of radioactivity deposited in the tissue; however, it does not offer any indication about the chemical disposition of the parent radiotracer itself. From a radiopharmaceutical perspective, it is necessary to quantify the parent radiotracer's fraction present in the tissue. Hence, the identification of radiometabolites of the radiotracers is vital for PET imaging. There are mainly two reasons for the chemical identification of PET radiometabolites: firstly, to determine the amount of parent radiotracers in plasma, and secondly, to rule out (if a radiometabolite enters the brain) or correct any radiometabolite accumulation in peripheral tissue. Besides, radiometabolite formations of the tracer might be of concern for the PET study, as the radiometabolic products may display considerably contrasting distribution patterns inside the body when compared with the radiotracer itself. Therefore, necessary information is needed about these biochemical transformations to understand the distribution of radioactivity throughout the body. Various published review articles on PET radiometabolites mainly focus on the sample preparation techniques and recently available technology to improve the radiometabolite analysis process. This article essentially summarizes the chemical and structural identity of the radiometabolites of various radiotracers including [11C]PBB3, [11C]flumazenil, [18F]FEPE2I, [11C]PBR28, [11C]MADAM, and (+)[18F]flubatine. Besides, the importance of radiometabolite analysis in PET imaging is also briefly summarized. Moreover, this review also highlights how a slight chemical modification could reduce the formation of radiometabolites, which could interfere with the results of PET imaging.

Tailored Biofunctionalized Biosensor for the Label-Free Sensing of Prostate-Specific Antigen.

The increase in the demand and popularity of smart biosensors has brought a novel and innovative concept to develop a diverse range of semen mutual biomarker (i.e., prostate-specific antigen, PSA)-based biodevices for our daily life applications. Using a versatile strategy, here we have developed a next-generation miniaturized capacitive biomarker-based sensor, which facilitates a direct, rapid quantitation and ultrafast detection of prostate-specific antigen (PSA) selectively. To fabricate an affordable PSA biosensor, an interdigitated capacitor (IDC) was functionalized and to detect PSA at concentrations varying from 0.1 to 10 µL/mL, with a response time of 3 s. Moreover, the PSA biosensor showed a high level of selectivity due to the successful probing of the capacitive response-generated biomolecular interactions using external stimuli at the bioelectrode. The resulting IDC-based PSA biosensors are capable of excellent reproducibility and reusability, which are required for real-time biosensing of any targeted biomolecules where low-concentration detection is a key for point-of-care, on-site sensing applications. We anticipate that this research could open exciting opportunities for PSA detection at a low concentration level.

Blood brain barrier: A tissue engineered microfluidic chip.

With the increasing concern of neurological diseases, the improvised therapy for neurodegenerative disorders such as Alzheimer's disease is crucial. Yet, the efficacious delivery of drug across blood-brain barrier (BBB) remains a formidable challenge. BBB acts as a gate keeper to prevent the ingress of harmful foreign agents into the brain. It has built a great interest in designing BBB models to boost the field of neurotherapeutics. Recently, microfluidic systems are gaining ground in cell culture and bio-system analysis. It creates a new era of micro engineered laboratory onto a chip by combining the benefits of both in vitro and in vivo models. The high-fidelity microfluidic BBB-on-a-Chip possess the engineered physiological microenvironment for real time monitoring of barrier properties with human derived stem cells. These emerging models have intrinsic merits of regulating micro-scale fluid delivery and versatile fabrication. Moreover, the progress of 3D printing technology and versatility of stem cells assist in fabricating these robust and reproducible models. This review revolves around the various approaches of modelling microfluidic BBBs and emphasises on the limitations of existing models and technology. It contributes to the interdisciplinary engineering aspects of BBB research and its magnificent impact on drug development.

Flood inundation mapping and monitoring using SAR data and its impact on Ramganga River in Ganga basin.

Remote sensing-based flood inundation mapping and monitoring is very crucial input before, during, and after floods. Ganga-Ramganga doab is one of the prolonged flood-affected area in middle Ganga plain due to seasonal monsoon which leads to rise in water levels of Ganga and Ramganga rivers. The focus of the present study is to map severe flood condition captured through synthetic aperture radar (SAR) data during August-September 2018, and to explain the impact on Ramganga river morphology. SAR data is preferred for flood mapping and real-time monitoring in all weather conditions. In this study, dual-polarized (VV and VH) Sentinel-1 SAR images coupled with hydrological data (river water level) were used to produce flood inundation maps. Thresholding technique has been applied to determine the flood mapping through Sentinel-1 data. VH and VV polarisation methods have been applied for a comparison of their respective accuracies in delineating surface water. Results have been validated against a Sentinel-2 optical image, and both polarisations produced a total accuracy of more than 93%. VV polarisation has high accuracies than VH polarisation as similar results are observed in previous studies as well. The finding reveals that severe bank erosion took place in the Ramganga channel which significantly affected the channel morphology, mainly the massive mobilisation of channel sediments. The results show that the average channel width increased from 46 to 336 m. The proposed approach demonstrates that the microwave remote sensing data along with GIS can be used efficiently for flood inundation mapping, monitoring, and analysing its effect on channel morphology. Therefore, the results of this study will help to take the initiative to reduce the flood hazard impact in the doab area and increase the flexibility in the process of flood management.

Peripheral Biomarkers for Early Detection of Alzheimer's and Parkinson's Diseases.

Neurological disorders are found to be influencing the peripheral tissues outside CNS. Recent developments in biomarkers for CNS have emerged with various diagnostic and therapeutic shortcomings. The role of central biomarkers including CSF-based and molecular imaging-based probes are still unclear for early diagnosis of major neurological diseases. Current trends show that early detection of neurodegenerative diseases with non-invasive methods is a major focus of researchers, and the development of biomarkers aiming peripheral tissues is in demand. Alzheimer's and Parkinson's diseases are known for the progressive loss in neural structures or functions, including the neural death. Various dysfunctions of metabolic and biochemical pathways are associated with early occurrence of neuro-disorders in peripheral tissues including skin, blood cells, and eyes. This article reviews the peripheral biomarkers explored for early detection of Alzheimer's and Parkinson's diseases including blood cells, skin fibroblast, proteomics, saliva, olfactory, stomach and colon, heart and peripheral nervous system, and others. Graphical Abstract.

Misfolded Protein Linked Strategies Toward Biomarker Development for Neurodegenerative Diseases.

The progressive loss of structure and function of neurons causes various neurodegenerative diseases which need to be examined using measurable indicators, known as biomarkers. Proteins are the building blocks for the cell and are essential as they participate in many processes in the cells. When biologically essential proteins are impaired, it leads to devastating consequences in humans and mammals among which the most prominent is neurodegenerative disease. Proteins conform to three-dimensional structures to enable their functions. Besides, some proteins have the tendency to form self-assembly structures. When these self-assembly proteins assume abnormal conformation, they accumulate and cause pathological conditions. The genetic and molecular origins of protein misfolding in association with their relationship with neurodegeneration and aging are being studied to better understand and develop treatments. Accumulations of these misfolded proteins form aggregates which is considered as the most prominent cause of many neurodegenerative diseases. This article reviews the misfolded proteins in various neurodegenerative diseases and analyzes the diverse aspects of protein misfolding as a potential agent of biomarkers with an approach for finding an inhibitor for misfolding.

Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke.

Importance: Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design. Objective: To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase. Design, Setting, and Participants: Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA). Exposures: Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA. Main Outcomes and Measures: Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion]). Results: Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]). Conclusions and Relevance: In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke.