Gestation-wise Reference Ranges of Neutrophil Counts in Indian Newborns

Objectives: Blood counts are commonly performed tests in neonatal intensive care units with the results having various clinical ramifications. Interpreting blood counts as normal or abnormal requires reference ranges as per gestation. Studies on reference ranges for neonatal neutrophil counts are already scarce, and data is lacking in the Asian context. We sought to formulate gestation-wise reference ranges of neutrophil counts in an Indian setting. Methods: Healthy, newborn babies of either gender, aged between 30 to 41 weeks gestation were included in the study. Gestational age was corroborated through first trimester dating scan and postnatally by the New Ballard Score. Single venous blood samples were drawn on day three and day five for estimation of total leukocyte count, differential count (neutrophils, lymphocytes), and peripheral blood smear examination. Results: We evaluated the data of 420 newborns. The normative values were compiled week-wise for gestational ages of 30 to 41 weeks at birth. We observed a clustering of neutrophil count values below 8000 cells/μL on day three and below 5000 cells/μL on day five. No gender-based differences in counts were observed. We were able to generate reference range curves for neutrophil counts as per gestational age. Conclusions: The absolute neutrophil counts of term and preterm Indian newborns are higher than the values depicted in the standard reference chart used currently. This indicates that a different standard chart as per gestation should be used in Indo-Asian countries to differentiate ‘normal’ from ‘abnormal’

Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers

Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers

Laser structured micro-targets generate MeV electron temperature at 4 x10^16 W/cm^2

Relativistic temperature electrons higher than 0.5 MeV are generated typically with laser intensities of about 10^18 W/cm^2. Their generation with high repetition rate lasers that operate at non-relativistic intensities (~10^16W/cm^2) is cardinal for the realization of compact, ultra-short, bench-top electron sources. New strategies, capable of exploiting different aspects of laser-plasma interaction, are necessary for reducing the required intensity. We report here, a novel technique of dynamic target structuring of microdroplets, capable of generating 200 keV and 1 MeV electron temperatures at 1/100th of the intensity required by ponderomotive scaling(10^18 W/cm^2) to generate relativistic electron temperature. Combining the concepts of pre-plasma tailoring, optimized scale length and micro-optics, this method achieves two-plasmon decay boosted electron acceleration with "non-ideal" ultrashort (25 fs) pulses at 4 x10^16 W/cm^2 only. With shot repeatability at kHz, this precise in-situ targetry produces directed, imaging quality beam-like electron emission up to 6 MeV with milli-joule class lasers, that can be transformational for time-resolved, microscopic studies in all fields of science

Shaped liquid drops generate MeV temperature electron beams with millijoule class laser

MeV temperature electrons are typically generated at laser intensities of 1018 W cm−2. Their generation at non-relativistic intensities (~1016 W cm−2) with high repetition rate lasers is cardinal for the realization of compact, ultra-fast electron sources. Here we report a technique of dynamic target structuring of micro-droplets using a 1 kHz, 25 fs, millijoule class laser, that uses two collinear laser pulses; the first to create a concave surface in the liquid drop and the second, to dynamically-drive electrostatic plasma waves that accelerate electrons to MeV energies. The acceleration mechanism, identified as two plasmon decay instability, is shown to generate two beams of electrons with hot electron temperature components of 200 keV and 1 MeV, respectively, at an intensity of 4 × 1016 Wcm−2, only. The electron beams are demonstrated to be ideal for single shot high resolution (tens of μm) electron radiography

Shaped liquid drops generate MeV temperature electron beams with millijoule class laser

MeV temperature electrons are typically generated at laser intensities of 1018 W cm−2. Their generation at non-relativistic intensities (~1016 W cm−2) with high repetition rate lasers is cardinal for the realization of compact, ultra-fast electron sources. Here we report a technique of dynamic target structuring of micro-droplets using a 1 kHz, 25 fs, millijoule class laser, that uses two collinear laser pulses; the first to create a concave surface in the liquid drop and the second, to dynamically-drive electrostatic plasma waves that accelerate electrons to MeV energies. The acceleration mechanism, identified as two plasmon decay instability, is shown to generate two beams of electrons with hot electron temperature components of 200 keV and 1 MeV, respectively, at an intensity of 4 × 1016 Wcm−2, only. The electron beams are demonstrated to be ideal for single shot high resolution (tens of μm) electron radiography

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure