Epidermal electronics for noninvasive, wireless, quantitative assessment of ventricular shunt function in patients with hydrocephalus

2018 ◽  
Vol 10 (465) ◽  
pp. eaat8437 ◽  
Author(s):  
Siddharth R. Krishnan ◽  
Tyler R. Ray ◽  
Amit B. Ayer ◽  
Yinji Ma ◽  
Philipp Gutruf ◽  
...  
Keyword(s):  
High Performance ◽  
Standard Of Care ◽  
Rechargeable Batteries ◽  
Operating Conditions ◽  
Diagnostic Tools ◽  
Shunt Failure ◽  
Current Standard ◽  
Sensors And Actuators ◽  
Magnetic Resonance Imaging Mri ◽  
Wireless Architectures

Hydrocephalus is a common and costly neurological condition caused by the overproduction and/or impaired resorption of cerebrospinal fluid (CSF). The current standard of care, ventricular catheters (shunts), is prone to failure, which can result in nonspecific symptoms such as headaches, dizziness, and nausea. Current diagnostic tools for shunt failure such as computed tomography (CT), magnetic resonance imaging (MRI), radionuclide shunt patency studies (RSPSs), and ice pack–mediated thermodilution have disadvantages including high cost, poor accuracy, inconvenience, and safety concerns. Here, we developed and tested a noninvasive, skin-mounted, wearable measurement platform that incorporates arrays of thermal sensors and actuators for precise, continuous, or intermittent measurements of flow through subdermal shunts, without the drawbacks of other methods. Systematic theoretical and experimental benchtop studies demonstrate high performance across a range of practical operating conditions. Advanced electronics designs serve as the basis of a wireless embodiment for continuous monitoring based on rechargeable batteries and data transmission using Bluetooth protocols. Clinical studies involving five patients validate the sensor’s ability to detect the presence of CSF flow (P= 0.012) and further distinguish between baseline flow, diminished flow, and distal shunt failure. Last, we demonstrate processing algorithms to translate measured data into quantitative flow rate. The sensor designs, fabrication schemes, wireless architectures, and patient trials reported here represent an advance in hydrocephalus diagnostics with ability to visualize flow in a simple, user-friendly mode, accessible to the physician and patient alike.

scholarly journals Assessment of Prognostic Value of Cystic Features in Glioblastoma Relative to Sex and Treatment with Standard-of-Care

2019 ◽  
Author(s):  
Lee Curtin ◽  
Paula Whitmire ◽  
Cassandra R. Rickertsen ◽  
Gina L. Mazza ◽  
Peter Canoll ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Prognostic Impact ◽  
Current Standard ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Cystic Component ◽  
Potential Link ◽  
Magnetic Resonance Imaging Mri

AbstractGlioblastoma (GBM) is the most aggressive primary brain tumor and can have cystic components, identifiable through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7-23% of GBMs and report mixed results regarding their prognostic impact. Using our retrospective cohort of 493 patients with first-diagnosis GBM, we carried out an exploratory analysis on this potential link between cystic GBM and survival. Using pretreatment MRIs, we manually identified 88 patients with GBM that had a significant cystic component at presentation and 405 patients that did not. Patients with cystic GBM had significantly longer overall survival and were significantly younger at presentation. Within patients who received the current standard of care (SOC) (N=184, 40 cystic), we did not observe a survival benefit of cystic GBM. Unexpectedly, we did not observe a significant survival benefit between this SOC cystic cohort and patients with cystic GBM diagnosed before the standard was established (N=40 with SOC, N=19 without SOC); this significant SOC benefit was clearly observed in patients with noncystic GBM (N=144 with SOC, N=111 without SOC). When stratified by sex, this significant survival benefit was only preserved in male patients (N=303, 47 cystic). We report differences in the absolute and relative sizes of imaging abnormalities on MRI and the prognostic implication of cysts based on sex. We discuss hypotheses for these differences, including the possibility that the presence of a cyst could indicate a less aggressive tumor.

scholarly journals Application of Operando X-ray Diffractometry in Various Aspects of the Investigations of Lithium/Sodium-Ion Batteries

Energies ◽  
2018 ◽  
Vol 11 (11) ◽  
pp. 2963 ◽  
Author(s):  
Wen Zhu ◽  
Yuesheng Wang ◽  
Dongqiang Liu ◽  
Vincent Gariépy ◽  
Catherine Gagnon ◽  
...  
Keyword(s):  
High Performance ◽  
Electrode Materials ◽  
Rechargeable Batteries ◽  
Operating Conditions ◽  
Cycle Life ◽  
Side Reactions ◽  
X Ray ◽  
The Impact ◽  
Working Mechanisms

The main challenges facing rechargeable batteries today are: (1) increasing the electrode capacity; (2) prolonging the cycle life; (3) enhancing the rate performance and (4) insuring their safety. Significant efforts have been devoted to improve the present electrode materials as well as to develop and design new high performance electrodes. All of the efforts are based on the understanding of the materials, their working mechanisms, the impact of the structure and reaction mechanism on electrochemical performance. Various operando/in-situ methods are applied in studying rechargeable batteries to gain a better understanding of the crystal structure of the electrode materials and their behaviors during charge-discharge under various conditions. In the present review, we focus on applying operando X-ray techniques to investigate electrode materials, including the working mechanisms of different structured materials, the effect of size, cycling rate and temperature on the reaction mechanisms, the thermal stability of the electrodes, the degradation mechanism and the optimization of material synthesis. We demonstrate the importance of using operando/in-situ XRD and its combination with other techniques in examining the microstructural changes of the electrodes under various operating conditions, in both macro and atomic-scales. These results reveal the working and the degradation mechanisms of the electrodes and the possible side reactions involved, which are essential for improving the present materials and developing new materials for high performance and long cycle life batteries.

Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives

2020 ◽  
Vol 26 (28) ◽  
pp. 3468-3496
Author(s):  
Emilio Rodrigo ◽  
Marcio F. Chedid ◽  
David San Segundo ◽  
Juan C.R. San Millán ◽  
Marcos López-Hoyos
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Rescue Therapy ◽  
Standard Of Care ◽  
Rejection Rate ◽  
New Drugs ◽  
High Dose ◽  
Current Standard ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.

scholarly journals Use of Machine Learning to Investigate the Quantitative Checklist for Autism in Toddlers (Q-CHAT) towards Early Autism Screening

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 574
Author(s):  
Gennaro Tartarisco ◽  
Giovanni Cicceri ◽  
Davide Di Pietro ◽  
Elisa Leonardi ◽  
Stefania Aiello ◽  
...  
Keyword(s):  
Machine Learning ◽  
High Performance ◽  
Behavioral Science ◽  
Autistic Traits ◽  
Classification Performance ◽  
Recursive Feature Elimination ◽  
Diagnostic Tools ◽  
Support Vector ◽  
K Nearest Neighbors ◽  
Autism Screening

In the past two decades, several screening instruments were developed to detect toddlers who may be autistic both in clinical and unselected samples. Among others, the Quantitative CHecklist for Autism in Toddlers (Q-CHAT) is a quantitative and normally distributed measure of autistic traits that demonstrates good psychometric properties in different settings and cultures. Recently, machine learning (ML) has been applied to behavioral science to improve the classification performance of autism screening and diagnostic tools, but mainly in children, adolescents, and adults. In this study, we used ML to investigate the accuracy and reliability of the Q-CHAT in discriminating young autistic children from those without. Five different ML algorithms (random forest (RF), naïve Bayes (NB), support vector machine (SVM), logistic regression (LR), and K-nearest neighbors (KNN)) were applied to investigate the complete set of Q-CHAT items. Our results showed that ML achieved an overall accuracy of 90%, and the SVM was the most effective, being able to classify autism with 95% accuracy. Furthermore, using the SVM–recursive feature elimination (RFE) approach, we selected a subset of 14 items ensuring 91% accuracy, while 83% accuracy was obtained from the 3 best discriminating items in common to ours and the previously reported Q-CHAT-10. This evidence confirms the high performance and cross-cultural validity of the Q-CHAT, and supports the application of ML to create shorter and faster versions of the instrument, maintaining high classification accuracy, to be used as a quick, easy, and high-performance tool in primary-care settings.

scholarly journals Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 864
Author(s):  
Christopher L. Cioffi
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Therapeutic Potential ◽  
Opioid Analgesic ◽  
Critical Role ◽  
Analgesic Efficacy ◽  
Standard Of Care ◽  
Current Standard ◽  
Glycine Transporters ◽  
Pathological Pain

Among the myriad of cellular and molecular processes identified as contributing to pathological pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired glycinergic neurotransmission develops in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models and is a key maladaptive mechanism causing mechanical hyperalgesia and allodynia. Thus, it has been hypothesized that pharmacological agents capable of augmenting glycinergic tone within the dorsal horn may be able to blunt or block aberrant nociceptor signaling to the brain and serve as a novel class of analgesics for various pathological pain states. Indeed, drugs that enhance dysfunctional glycinergic transmission, and in particular inhibitors of the glycine transporters (GlyT1 and GlyT2), are generating widespread interest as a potential class of novel analgesics. The GlyTs are Na+/Cl−-dependent transporters of the solute carrier 6 (SLC6) family and it has been proposed that the inhibition of them presents a possible mechanism by which to increase spinal extracellular glycine concentrations and enhance GlyR-mediated inhibitory neurotransmission in the dorsal horn. Various inhibitors of both GlyT1 and GlyT2 have demonstrated broad analgesic efficacy in several preclinical models of acute and chronic pain, providing promise for the approach to deliver a first-in-class non-opioid analgesic with a mechanism of action differentiated from current standard of care. This review will highlight the therapeutic potential of GlyT inhibitors as a novel class of analgesics, present recent advances reported for the field, and discuss the key challenges associated with the development of a GlyT inhibitor into a safe and effective agent to treat pain.

scholarly journals Updated Insights on EGFR Signaling Pathways in Glioma

2021 ◽  
Vol 22 (2) ◽  
pp. 587
Author(s):  
Alexandru Oprita ◽  
Stefania-Carina Baloi ◽  
Georgiana-Adeline Staicu ◽  
Oana Alexandru ◽  
Daniela Elise Tache ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Egfr Signaling ◽  
Current Standard ◽  
Egfr Amplification ◽  
Epidermal Growth ◽  
New Diagnosis ◽  
Clear Clinical Benefit

Nowadays, due to recent advances in molecular biology, the pathogenesis of glioblastoma is better understood. For the newly diagnosed, the current standard of care is represented by resection followed by radiotherapy and temozolomide administration, but because median overall survival remains poor, new diagnosis and treatment strategies are needed. Due to the quick progression, even with aggressive multimodal treatment, glioblastoma remains almost incurable. It is known that epidermal growth factor receptor (EGFR) amplification is a characteristic of the classical subtype of glioma. However, targeted therapies against this type of receptor have not yet shown a clear clinical benefit. Many factors contribute to resistance, such as ineffective blood–brain barrier penetration, heterogeneity, mutations, as well as compensatory signaling pathways. A better understanding of the EGFR signaling network, and its interrelations with other pathways, are essential to clarify the mechanisms of resistance and create better therapeutic agents.

A comparison between 25-gauge and 22-gauge Franseen needles for endoscopic ultrasound-guided sampling of pancreatic and peripancreatic masses: a randomized non-inferiority study

Endoscopy ◽  
2021 ◽  
Author(s):  
Dongwook Oh ◽  
Joonseog Kong ◽  
Sung Woo Ko ◽  
Seung-Mo Hong ◽  
Hoonsub So ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Endoscopic Ultrasound ◽  
Care Center ◽  
Tertiary Care ◽  
Standard Of Care ◽  
Fine Needle Biopsy ◽  
Needle Aspiration ◽  
Adverse Event Rate ◽  
Current Standard ◽  
Fine Needle

Abstract Background Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) and fine-needle biopsy (FNB) are the current standard of care for sampling pancreatic and peripancreatic masses. Recently, a 22G EUS-FNB needle with Franseen geometry was developed, and this device was also introduced in a 25G platform. We compared the performance of the 25G and 22G Franseen needles for EUS-guided sampling of pancreatic and peripancreatic solid masses. Methods We conducted a parallel-group randomized non-inferiority trial at a tertiary-care center from November 2018 to May 2019. The primary outcome was the quality of the histologic core assessed using the Gerke score. The optimal histologic core is indicated by a Gerke score of 4 or 5, which enables optimal histologic interpretation. The overall diagnostic accuracy and adverse event rate were also evaluated. Results 140 patients were enrolled and randomized (1:1) to the 25G and 22G groups. Tissue acquisition by EUS-FNB was successful in all patients. The optimal histologic core procurement rate was 87.1 % (61/70) for the 25G needle vs. 97.1 % (68/70) for the 22G; difference −10 % (95 % confidence interval −17.35 % to −2.65 %). High quality specimens were more frequently obtained in the 22G group than in the 25G group (70.0 % [49/70] vs. 28.6 % [20 /70], respectively; P < 0.001). The overall diagnostic accuracy did not differ between the groups (97.4 % for 25G vs. 100 % for 22G). Conclusions The 25G Franseen needle was inferior to the 22G needle in histologic core procurement. Therefore, for cases in which tissue architecture is pivotal for diagnosis, a 22G needle, which procures relatively higher quality specimens than the 25G needle, should be used.

scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

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