The Indian Pulsar Timing Array (InPTA) employs unique features of the upgraded Giant Metrewave Radio Telescope (uGMRT) to monitor dozens of the International Pulsar Timing Array (IPTA) millisecond pulsars (MSPs), simultaneously in the 300-500 MHz and the 1260-1460 MHz bands. This dual-band approach ensures that any frequency-dependent delays are accurately characterized, significantly improving the timing precision for pulsar observations, which is crucial for pulsar timing arrays. We present details of InPTA’s second data release that involves 7 yrs of data on 27 IPTA MSPs. This includes sub-banded Times of Arrival (ToAs), Dispersion Measures (DM), and initial timing ephemerides for our MSPs. A part of this dataset, originally released in InPTA’s first data release, is being incorporated into IPTA’s third data release which is expected to detect and characterize nanohertz gravitational waves in the coming years. The entire dataset is reprocessed in this second data release providing some of the highest precision DM estimates so far and interesting solar wind related DM variations in some pulsars. This is likely to characterize the noise introduced by the dynamic inter-stellar ionised medium much better than the previous release thereby increasing sensitivity to any future gravitational wave search.

Background: Ischemic stroke often results in long-term motor impairments due to disrupted corticospinal pathways. Transcranial magnetic stimulation (TMS) motor mapping is a non-invasive technique used to assess corticospinal integrity by measuring motor evoked potentials (MEPs). This study investigates whether MEP amplitudes can predict impairment severity and functional performance in chronic stroke. Methods: Four non-human primates (NHPs) with chronic stroke (> six months) following transient right middle cerebral artery occlusion underwent TMS motor mapping using neuronavigation under ketamine anesthesia. Single pulses of TMS (50-70% of maximum stimulator output) were applied to the affected and contralesional primary motor cortices to elicit MEPs and assess cortical excitability. Intramuscular electromyography recorded muscle responses from the biceps, extensor digitorum longus, and abductor pollicis brevis. Neurological dysfunction was evaluated daily for three weeks using the NHP Stroke Scale, NHP Upper Extremity Motor Dysfunction Scale, and the primate Rankin Scale. Results: MEPs were present in NHP1, NHP3, and NHP4 but absent in NHP2. Stronger MEPs correlated with lower impairment severity and better functional performance, while NHP2 exhibited higher impairment and poorer performance. Conclusions: MEP presence and strength can serve as biomarkers of motor recovery potential, highlighting their role in assessing corticospinal integrity and functional outcomes.

Background: We aim to assess the resting state functional connectivity (RSFC) and reactivity with functional near-infrared spectroscopy (fNIRS) in patients with acute stroke compared to age, sex and comorbidity-matched subjects. Methods: Patients with acute anterior circulation stroke syndrome localizing to the right (RH) or left hemisphere (LH) were enrolled. RSFC was assessed using group-level seed-based (Primary Motor cortex,PMC) correlation analysis. Finger-tapping-associated relative oxygen Hemoglobin (ΔHbO) changes were analyzed with generalized linear model regression. Results: 127 participants (RH stroke, 51; LH stroke, 43; control, 33) enrolled at a median of 21 (15,29) hours after symptom onset. Compared to the control group, the RSFC with the affected PMC (LH stroke) was reduced over the affected somatosensory cortex (SSC) in the minor ischemic stroke (IS) (r = -0.14 (-0.3,-0.01)), minor intracerebral hemorrhage (ICH) (-0.48 (-0.78,-0.18)) and major ICH groups (-0.2 (-0.4,-0.01). In the FT task compared to the control groups in LH stroke, ΔHbO was increased over the affected SSC in minor IS (β11.2(1.9,20.5)) and major ICH group (β11.7 (1.4,22.1)). In the FT task in RH stroke, ΔHbO was increased over the unaffected PMC in minor IS (β12.1(2.3,21.8)), major IS (β14.9 (0.3,29.5)), minor ICH (β25.7 (10.1,41.2)) and major ICH (β13.4 (1.1,25.6). Conclusions: Motor cortex dysconnectivity may be worse over the LH stroke. In RH stroke, there is early compensatory increased neuronal activity over the unaffected PMC. These results suggest differential acute remodelling in RH and LH strokes.

NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.

Tight focusing with very small f-numbers is necessary to achieve the highest at-focus irradiances. However, tight focusing imposes strong demands on precise target positioning in-focus to achieve the highest on-target irradiance. We describe several near-infrared, visible, ultraviolet and soft and hard X-ray diagnostics employed in a ∼1022 W/cm2 laser–plasma experiment. We used nearly 10 J total energy femtosecond laser pulses focused into an approximately 1.3-μm focal spot on 5–20 μm thick stainless-steel targets. We discuss the applicability of these diagnostics to determine the best in-focus target position with approximately 5 μm accuracy (i.e., around half of the short Rayleigh length) and show that several diagnostics (in particular, 3$\omega$ reflection and on-axis hard X-rays) can ensure this accuracy. We demonstrated target positioning within several micrometers from the focus, ensuring over 80% of the ideal peak laser intensity on-target. Our approach is relatively fast (it requires 10–20 laser shots) and does not rely on the coincidence of low-power and high-power focal planes.

Adequate nutrition is necessary during childhood and early adolescence for adequate growth and development. Hence, the objective of the study was to assess the association between dietary intake and blood levels of minerals (calcium, iron, zinc, and selenium) and vitamins (folate, vitamin B12, vitamin A, and vitamin D) in urban school going children aged 6–16 years in India, in a multicentric cross-sectional study. Participants were enrolled from randomly selected schools in ten cities. Three-day food intake data was collected using a 24-h dietary recall method. The intake was dichotomised into adequate and inadequate. Blood samples were collected to assess levels of micronutrients. From April 2019 to February 2020, 2428 participants (50⋅2 % females) were recruited from 60 schools. Inadequate intake for calcium was in 93⋅4 % (246⋅5 ± 149⋅4 mg), iron 86⋅5 % (7⋅6 ± 3⋅0 mg), zinc 84⋅0 % (3⋅9 ± 2⋅4 mg), selenium 30⋅2 % (11⋅3 ± 9⋅7 mcg), folate 73⋅8 % (93⋅6 ± 55⋅4 mcg), vitamin B12 94⋅4 % (0⋅2 ± 0⋅4 mcg), vitamin A 96⋅0 % (101⋅7 ± 94⋅1 mcg), and vitamin D 100⋅0 % (0⋅4 ± 0⋅6 mcg). Controlling for sex and socioeconomic status, the odds of biochemical deficiency with inadequate intake for iron [AOR = 1⋅37 (95 % CI 1⋅07–1⋅76)], zinc [AOR = 5⋅14 (95 % CI 2⋅24–11⋅78)], selenium [AOR = 3⋅63 (95 % CI 2⋅70–4⋅89)], folate [AOR = 1⋅59 (95 % CI 1⋅25–2⋅03)], and vitamin B12 [AOR = 1⋅62 (95 %CI 1⋅07–2⋅45)]. Since there is a significant association between the inadequate intake and biochemical deficiencies of iron, zinc, selenium, folate, and vitamin B12, regular surveillance for adequacy of micronutrient intake must be undertaken to identify children at risk of deficiency, for timely intervention.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

An attempt has been made to illustrate the evolution of pelitic granulite from south of the Balaram-Abu road, which lies in the South Delhi Terrane (SDT) of the Aravalli-Delhi Mobile Belt (ADMB), using geochemistry and geochronology. The current work offers a plausible explanation for the protolith of pelitic granulite, nature of the sediments and its provenance. The elemental geochemistry of the pelitic granulites reveals that the protolith is an arkosic to shaley type. The rare earth elements pattern shows that there is a negative Eu anomaly and a small excess of LREE over HREE. This means that the source of sediments probably has the same elements as the upper crust. However, the amounts of Sr, Nd and Pb vary a lot, which shows that the sediments supplied from two different types of sources (felsic and mafic) in different proportions from a Proterozoic terrain. The monazite geochronology indicates that the metamorphic overprint occurred between 797 Ma and 906 Ma. Additionally, the ages correlate to the debris that was formed between the 1188 Ma and 1324 Ma from magmatic/sedimentary sources for pelitic granulite. The present research provides a more in-depth understanding of the evolutionary history of the pelitic granulite that comprises the SDT in the ADMB region during the Proterozoic era.

Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.

Background: Improvements in sleep-onset, maintenance, and daytime functioning, are all important outcomes for the treatment of insomnia. These improvements are usually assessed by objective or patient-reported (subjective) measures or both. Some sleep-promoting drugs do not report consistently aligned subjective and objective outcomes. Therefore, we examined concordance in change from baseline (CFB) in sleep parameters (objective/subjective measures) and daytime functioning (subjective measures) in the clinical program of lemborexant (LEM), a dual-orexin receptor antagonist. Methods: Study E2006-G000-304 (NCT02783729), a 1-month, placebo (PBO)- and active-controlled (zolpidem; not discussed here) study, and Study E2006-G000-303 (NCT02952820), a 12-month, randomized, PBO-controlled study (first 6-months), evaluated the efficacy/safety of LEM 5mg (LEM5) and LEM 10mg (LEM10) in subjects with insomnia disorder. The primary/secondary endpoints in both studies included multiple objective/subjective sleep parameters and patient-reported measures, which were assessed for concordance. Results: In both studies, statistically significant improvements with LEM5/LEM10 were reported in multiple objective and patient-reported measures versus PBO, showing a concordance of results, with observed improvements continuing through 12 months. LEM was well tolerated; most treatment-emergent adverse events were mild/moderate. Conclusions: When deciding which sleep agent to prescribe, it is important that improvement can be demonstrated in both objective and patient-reported measures. LEM treatment showed concordance among observed measures.

Background: Some sleep-promoting medications are associated with cognitive impairment, making treatment of comorbid obstructive-sleep-apnea (OSA) and insomnia (COMISA) challenging. Lemborexant is a dual-orexin-receptor-antagonist approved for insomnia treatment. This post-hoc analysis evaluated cognition in the subgroup of subjects with mild-OSA (apnea-hypopnea-index ≥5–<15 events/h-of-sleep). Methods: Study E2006-G000-304 was a 1-month, randomized, double-blind, placebo (PBO)- and active-comparator (zolpidem-ER 6.25mg [ZOL])-controlled study of lemborexant 5/10mg (LEM5/LEM10). Subjects ≥55y with insomnia disorder/sleep maintenance problems were enrolled (N=1006). A cognitive-performance assessment battery (CPAB) was performed at morning waketime of Days(D)2/3 and D30/31. Change-from-baseline (CFB) for mean power-of-attention (PoA), continuity-of-attention (CoA), quality-of-memory (QoM), and speed-of-memory-retrieval (SoMR) for CPAB tasks was analyzed. Results: The mild-OSA subgroup comprised 410 (40.8%) subjects. On D2/3 and D30/31, CFB for PoA, CoA, QoM, and SoMR for LEM5/LEM10 were not significantly different than PBO. On D2/3, PoA and QoM were significantly worse with ZOL vs PBO; QoM was significantly better with LEM5/LEM10 vs ZOL. On D30/31, SoMR was significantly worse with ZOL vs PBO and significantly better with LEM5/LEM10 vs ZOL. LEM safety in the subgroup was consistent with the overall study population. Conclusions: Memory and attention domains in subjects with COMISA characterized by mild-OSA were not impacted by LEM, unlike ZOL.

Support: Eisai Inc.

Availability of resistance sources among cultivated varieties helps in easy utilization as donor owing to no deleterious linkage drag. In the present investigation, 121 rice varieties were screened for their resistance against a virulent isolate of Fusarium fujikuroi (Ff-10) and genotyped using reported microsatellite markers. Among 121 varieties, only eight varieties, namely Luna Sankhi, Improved Tapaswini, Sarasa, Sadabahar, CR-311, Kshira, Wifa-10 and Binadhan-8, were found to be highly resistant (HR), seven varieties were resistant (R), 31 were moderately resistant (MR), 10 were moderately susceptible (MS), 11 were susceptible (S) and the rest 54 were highly susceptible (HS). The allele diversity of molecular markers classified the population into three clusters. The highly resistant varieties were grouped in major clusters II and III, whereas the remaining genotypes were distributed in all three clusters. Analysis of molecular variance (AMOVA) resulted in 95% of the maximum diversity within the test population and 5% diversity between populations. Population structure analysis grouped the genotypes into two sub-populations based on relatedness, where most of the resistant genotypes were grouped into one sub-population and other genotypes were distributed among sub-populations. Re-examination of reported markers' trait associations with bakanae resistance in the experimental population identified marker RM-3698 as associated with resistance accounting 8.4% explained phenotypic variation. This study shows that simple sequence repeat markers can be used to assess allelic diversity and population structure of bakanae resistance in rice varieties. The highly resistant genotypes, along with resistance markers, could be used as donors in marker-assisted bakanae improvement breeding programmes.

We present the pulse arrival times and high-precision dispersion measure estimates for 14 millisecond pulsars observed simultaneously in the 300$-$500 MHz and 1260$-$1460 MHz frequency bands using the upgraded Giant Metrewave Radio Telescope. The data spans over a baseline of 3.5 years (2018-2021), and is the first official data release made available by the Indian Pulsar Timing Array collaboration. This data release presents a unique opportunity for investigating the interstellar medium effects at low radio frequencies and their impact on the timing precision of pulsar timing array experiments. In addition to the dispersion measure time series and pulse arrival times obtained using both narrowband and wideband timing techniques, we also present the dispersion measure structure function analysis for selected pulsars. Our ongoing investigations regarding the frequency dependence of dispersion measures have been discussed. Based on the preliminary analysis for five millisecond pulsars, we do not find any conclusive evidence of chromaticity in dispersion measures. Data from regular simultaneous two-frequency observations are presented for the first time in this work. This distinctive feature leads us to the highest precision dispersion measure estimates obtained so far for a subset of our sample. Simultaneous multi-band upgraded Giant Metrewave Radio Telescope observations in 300$-$500 MHz and 1260$-$1460 MHz are crucial for high-precision dispersion measure estimation and for the prospect of expanding the overall frequency coverage upon the combination of data from the various Pulsar Timing Array consortia in the near future. Parts of the data presented in this work are expected to be incorporated into the upcoming third data release of the International Pulsar Timing Array.

The Diwani hills are located SE of Balaram–Abu Road in the Banaskantha district of north Gujarat. The crystalline rocks of the Diwani hill area are a diverse assemblage of Precambrian metamorphic and igneous rocks. These rocks are petrologically more complex and date back to the Aravallis or earlier. The mineralogical assemblages such as grt–sp–opx–qz of these rocks indicate their origin in anhydrous or dry conditions, implying metamorphism under pyroxene granulite facies. These granulitic rocks were subjected to Delhi orogenic deformation and were later intruded by the Erinpura granite. Textural and microstructural relationships, mineral chemistry, P–T–X pseudosection modelling and the oxidation state of pelitic granulites from the Diwani hill area of north Gujarat are all part of the current approach. The winTWQ program and pseudosection modelling in the NCKFMASHTO model system utilizing Perple_X software were used to restrict the P–T evolution of these pelitic granulites. The unification of these estimates shows that the pelitic granulites reached their pressure and temperature maxima at 8.6 kbar and 770 °C, respectively. The oxygen fugacity (log fO2) versus temperature computations at 6.2 kbar revealed log fO2–T values of −13.0 and 765 °C, respectively. The electron microprobe dating of monazite grains separated from the granulites of the Diwani hills yields ages ranging from 769 Ma to 855 Ma. The electron microprobe dating presented here from the Diwani hills provides evidence for a Neoproterozoic (Tonian) metamorphic event in the Aravalli–Delhi Mobile Belt.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

OBJECTIVES/GOALS: #NAME? METHODS/STUDY POPULATION: Cell culture & protein identification: human T cells were purified from healthy blood, then activated & cultured for 5d. CAR-T cells were collected from infusion bags of cancer patients undergoing CAR-T. Silver staining of naive & activated healthy T-cell lysates was compared; B-II spectrin was upregulated and confirmed by Western blot. Migration assays: naive & activated T-cells were imaged during migration on ICAM-1 and ICAM-1 + CXCL12 coated plates. T-cells were transfected with BII-spectrin cDNA & the chemokine dependence of migration was compared with controls. In-vivo studies: in a melanoma mouse model, BII-spectrin transfected or control T-cells were injected; tumors were followed with serial imaging. Human patient records were examined to correlate endogenous BII-spectrin levels and CAR-T response. RESULTS/ANTICIPATED RESULTS: Activated T-cells downregulate the cytoskeletal protein B-II spectrin compared to naive cells, leading to chemokine-independent migration in in vitro assays and off-target trafficking when CAR-T cells are given in vivo. Restoration of B-II spectrin levels via transfection restores chemokine-dependence of activated T-cells. In a mouse melanoma model, control mice injected with standard activated T-cells showed fewer cells in the tumor site and more cells in the off-target organs (spleen, lungs) when compared to mice injected with B-II spectrin transfected cells. Furthermore, among 3 human patients undergoing CAR-T therapy, those with higher endogenous B-II spectrin levels experienced fewer side-effects, measured by the neurotoxicity and cytokine release syndrome grades. DISCUSSION/SIGNIFICANCE: A major hurdle to widespread CAR-T therapy for cancer is significant, often fatal side-effects. Our work shows that the protein B-II spectrin is downregulated during CAR-T production, and that restoring B-II spectrin levels decreases side-effects while increasing tumor clearance--hopefully translating to better CAR-T regimens for the future.