Analog and Neuromorphic computing with a framework on a reconfigurable platform

The objective of the research is to demonstrate energy-efficient computing on a configurable platform, the Field Programmable Analog Array (FPAA), by leveraging analog strengths, along with a framework, to enable real-time systems on hardware. By taking inspiration from biology, fundamental blocks of neurons and synapses are built, understanding the computational advantages of such neural structures. To enable this computation and scale up from these modules, it is important to have an infrastructure that adapts by taking care of non-ideal effects like mismatches and variations, which commonly plague analog implementations. Programmability, through the presence of floating gates, helps to reduce these variations, thereby ultimately paving the path to take physical approaches to build larger systems in a holistic manner.Ph.D

A COMPARATIVE STUDY OF DEXMEDETOMIDINE AND CLONIDINE AS AN ADJUVANT TO ROPIVACAINE IN SUPRACLAVICULAR BRACHIAL PLEXUS BLOCK

Objectives: Ultrasound-guided supraclavicular brachial plexus block is the most commonly performed approach for the upper limb surgeries and perioperative pain relief. This study was conducted to compare the post-operative analgesic efficacy of dexmedetomidine and clonidine as an adjuvant to ropivacaine in supraclavicular brachial plexus block in patients undergoing upper limb surgeries. Methods: This was a prospective, randomized, and double-blinded comparative research that included 60 ASA PS I and II patients who were scheduled for the upper limb surgery. The patients were randomized into two groups, namely, Group C and Group D, with 30 patients each. The patients in Group D were given USG-guided supraclavicular brachial plexus block with 30 ml of 0.5% ropivacaine and dexmedetomidine 1 μg/kg and patients in Group C received 30 ml of 0.5% ropivacaine and clonidine 1 μg/kg. The patients were monitored for post-operative and interpreted by visual analog score and duration of analgesia. The Student’s independent t-test was employed for comparing continuous variables. Chi-square test or Fisher’s exact test, whichever is appropriate, was applied for comparing categorical variables. Results: The mean duration of analgesia was longer and the mean consumption of rescue analgesics was lower in Group D as compared to Group C. No significant post-operative complications or local side effects related to the block were noted. Conclusion: Dexmedetomidine prolongs the duration of sensory and motor block as well as the duration of post-operative analgesia as compared to clonidine when used as an adjuvant to ropivacaine in supraclavicular brachial plexus block

Artificial Bio-inspired Tactile Receptive Fields for Edge Orientation Classification

Robots and users of hand prosthesis could easily manipulate objects if endowed with the sense of touch. Towards this goal, information about touched objects and surfaces has to be inferred from raw data coming from the sensors. An important cue for objects discrimination is the orientation of edges, that is used both in artificial vision and touch as pre-processing stage. We present a spiking neural network, inspired on the encoding of edges in human first order tactile afferents. The network uses three layers of Leaky Integrate and Fire neurons to distinguish different edge orientations of a bar pressed on the artificial skin of the iCub robot. The architecture is successfully able to discriminate eight different orientations (from 0o to 180o), by implementing a structured model of overlapping receptive fields. We demonstrate that the network can learn the appropriate connectivity through unsupervised spike based learning, and that the number and spatial distribution of sensitive areas within the receptive fields are important in edge orientation discrimination

Identification of the DNA-Binding Domains of Human Replication Protein A That Recognize G-Quadruplex DNA

Replication protein A (RPA), a key player in DNA metabolism, has 6 single-stranded DNA-(ssDNA-) binding domains (DBDs) A-F. SELEX experiments with the DBDs-C, -D, and -E retrieve a 20-nt G-quadruplex forming sequence. Binding studies show that RPA-DE binds preferentially to the G-quadruplex DNA, a unique preference not observed with other RPA constructs. Circular dichroism experiments show that RPA-CDE-core can unfold the G-quadruplex while RPA-DE stabilizes it. Binding studies show that RPA-C binds pyrimidine- and purine-rich sequences similarly. This difference between RPA-C and RPA-DE binding was also indicated by the inability of RPA-CDE-core to unfold an oligonucleotide containing a TC-region 5′ to the G-quadruplex. Molecular modeling studies of RPA-DE and telomere-binding proteins Pot1 and Stn1 reveal structural similarities between the proteins and illuminate potential DNA-binding sites for RPA-DE and Stn1. These data indicate that DBDs of RPA have different ssDNA recognition properties

Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis

Monocyte miRNAs govern both protective and pathological responses during tuberculosis (TB) through their differential expression and emerged as potent targets for biomarker discovery and host-directed therapeutics. Thus, this study examined the miRNA profile of sorted monocytes across the TB disease spectrum [drug-resistant TB (DR-TB), drug-sensitive TB (DS-TB), and latent TB] and in healthy individuals (HC) to understand the underlying pathophysiology and their regulatory mechanism

Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children

INTRODUCTION: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases. METHODS: To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations). RESULTS: Children with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84–100% and specificity 80–100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels. DISCUSSION: Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation

Unique cellular immune signatures of multisystem inflammatory syndrome in children

The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8(+) T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4(+) and CD8(+) T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6–9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely