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Abstract Sexual and reproductive health (SRH) services are crucial for women especially during disasters, to reduce maternal mortality and morbidity from miscarriages, unsafe abortions, and post-abortion complications. This study explored the SRH interventions provided during disaster response. A systematic review was conducted to identify what menstrual regulation (MR), safe abortion (SA), and post-abortion care (PAC) approaches/interventions exist to promote resilience in the health system in disaster settings; what intervention components were most effective; and challenges and opportunities to meeting SRH rights. Five electronic databases were searched, resulting in 4194 records. Following the screening process, seven publications were included. The intervention-related information in each publication was assessed based on availability, accessibility, acceptability, and quality. Two SRH approaches/interventions were found. The effectiveness of intervention components could not be conducted due to the limited number of relevant studies. Challenges were found at facility and community levels, and opportunities included overcoming them, making MR, SA, and PAC integral to the mitigation phase, and policy change to overcome barriers related to unaffordability and inaccessibility. Recommendations are provided to encourage research and policy towards improving neglected SRH in disaster settings to realize Sustainable Development Goal 3 and the Global Strategy and Sendai Framework’s priority to promote disaster-resilient health systems.

Multidisciplinary meetings (MDMs) are central to clinical decision-making in many areas of cardiology. This study assessed current provision and structure of cardiology MDMs in England in comparison with national guidelines.British Cardiovascular Society (BCS) members were surveyed regarding frequency, core attendees, and organisational aspects of cardiology MDMs for myocardial revascularisation, endocarditis, heart failure, aortic valve, mitral and tricuspid valve MDMs, whether local, regional or outside of the region. Access to electrophysiology (EP), inherited cardiac conditions, and adult congenital heart disease (ACHD) MDMs was also assessed.Survey responses were received from 64 hospitals across England, of which 40 (62%) were secondary care centres and 24 (38%) were tertiary care centres. All units had access to revascularisation MDMs, although 6% of them (all in secondary care centres) lacked any surgical representation. Heart failure MDMs were available in 94% of centres, but 7% reported no attendance by a cardiologist with specialist interest in heart failure, and 23% reported no attendance by a device specialist. 61% of centres had access to dedicated endocarditis MDMs; however, 11% were not attended by a microbiologist or infectious disease physician, and 22% were not attended by a surgeon. Aortic valve MDMs were available in 69% of centres, while mitral and tricuspid valve MDMs were available in 56% of centres. One quarter of centres reported no access to EP, and one third of centres reported no access to ICC or ACHD MDMs.Substantial improvements in provision and structure of cardiology MDMs in England are needed in order to meet national guidance.

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. Therefore, we fully characterized the cumulative fate maps and acute adult expression patterns of all three vesicular glutamate transporters (Slc17a7 (Vglut1), Slc17a6 (Vglut2), and Slc17a8 (Vglut3)) in NA neurons, identifying a novel, dynamic expression pattern for Vglut2 and an undescribed co-expression domain for Vglut3 in the NA system. In contrast to our initial hypothesis that NA-derived glutamate is required to breathing, our functional studies showed that loss of Vglut2 throughout the NA system failed to alter breathing or metabolism under room air, hypercapnia, or hypoxia in unrestrained and unanesthetized mice. These data demonstrate that Vglut2-based glutamatergic signaling within the central NA system is not required for normal baseline breathing and hypercapnic, hypoxic chemosensory reflexes. These outcomes challenge the current understanding of central NA neurons in the control of breathing and suggests that glutamate may not be a critical target to understand NA neuron dysfunction in respiratory diseases.

Introduction: The year 2020 brings in a paradigm shift in medical education with the emergence of the COVID-19 pandemic. Since the government of India initiated the first countrywide lockdown, educational institutions, including medical colleges, have adopted online mode for undergraduate teaching. Medical education is virtually incomplete without appropriate practical exposure. This study was conducted to understand the opinion of the medical students towards online classes as an impact of this pandemic on medical education. Materials and Methods: A descriptive online survey was conducted using a google form among medical undergraduate students from across India. Snowball sampling was used to recruit study participants. The responses were analyzed using numbers and percentages. Continuous variables were expressed as the mean and standard deviation of the mean. Results: The mean age of the 1426 respondents was 20.46 years. The majority of the responses were from Karnataka (412), followed by Odisha (167). While fairly a good number of respondents agreed that online classes provided a conducive environment and independence in learning, a large proportion disagreed or remained neutral in terms of its usefulness. This could be attributed to several reasons, which may be categorized into three important groups: the technical competence of the students, the provision of an enabling environment and the ability of the teachers. Conclusion: Students had varying opinions on online classes, but most emphasized the need for redoing the lessons taught online.

Geometric morphometrics is an efficient way to quantify biological shape variation and its covariation with other biotic or abiotic factors. The geometric information of an object is measured in a non-linear shape space after removing size, orientation, and position-related effects. This study was aimed to determine sexual dimorphism and morphological variation in body shape using landmark-based morphometrics by means of relative warp analysis. The indigenous freshwater fish Puntius sophore (Cyprinidae) was selected as the model organism for the study. Adult male and female individuals were collected during July-August 2019 (breeding season) and March–April 2019 (non-breeding season) from the ponds of Bolpur, West Bengal, India. Prior to analysis, the images were digitised using the appropriate fourteen landmarks and relative wrap analysis was performed using appropriate software. The results were then analysed, and the maximum relative displacements of adjacent landmarks were interpreted using canonical variate analysis (CVA) and principal component analysis (PCA). Significant body shape differences were found to be present in the non-breeding season and breeding season (male and female) populations of the species. Thus, geometric morphometrics can be used to understand the sexual dimorphism in natural populations of small fish species.

This study presents a GIS-based Multi-Criteria Decision Analysis (MCDA) spatial model to assess land suitability for oil palm (OP) cultivation in rainfed conditions. Initially, twelve parameters, viz., rainfall, number of rainy days, mean temperature, RH, ground water level, soil pH, salinity, soil depth, surface texture, stoniness, slope, and drainage, were selected for assessing OP suitability in one of the states (Kerala). However, subsequent ground verification revealed significant discrepancies, which prompted refining the model by focusing on key parameters with greater accuracy and relevance. Accordingly, only five the most critical parameters affecting OP cultivation under rainfed conditions were selected through the rank sum method, and weights were assigned ac-cording to their significance. This study was aimed at creating a comprehensive tool for informed decision making in agricultural planning. District-level spatial data from reliable sources were utilized for Multi-Criteria Decision Analysis. Thematic rasters, representing key factors influencing land suitability, were created in a GIS. Utilizing MCDA techniques, a digital suitability map was generated in ArcGIS 10.3, delineating three distinct classes over an extensive area of 10.5 million hectares. Further, with an aim to focus on actual locations that can be readily planted with oil palm, the suitable locations identified were restricted to eight selected land use/land cover (LULC) classes. This strategic limitation aimed to facilitate the expansion of OP cultivation exclusively to areas deemed most suitable based on the identified criteria. The validation of this developed model involved comparing the suitability map generated with the performance of existing oil palm plantations across diverse locations. The reasonable similarity between the model’s predictions and real-world plantation outcomes validated the effectiveness of this MCDA spatial model. This model not only helps identify suitable locations for rainfed oil palm cultivation but also serves as a valuable tool for strategic decision making in agricultural land use planning.

The way pulsars spin down is not understood in detail, but a number of possible physical mechanisms produce a spin-down rate that scales as a power of the rotation rate ( $\dot{\nu }\propto -{\nu }^{n}$ ), with the power-law index n called the braking index. PSR B0540−69 is a pulsar that in 2011, after 16 yr of spinning down with a constant braking index of 2.1, experienced a giant spin-down change and a reduction of its braking index to nearly zero. Here, we show that, following this episode, the braking index monotonically increased during a period of at least 4 yr and stabilized at ∼1.1. We also present an alternative interpretation of a more modest rotational irregularity that occurred in 2023, which was modeled as an anomalous negative step of the rotation rate. Our analysis shows that the 2023 observations can be equally well described as a transient swing of the spin-down rate (lasting ∼65 days), and the Bayesian evidence indicates that this model is strongly preferred.

We report Bayesian inference of the mass, radius, and hot X-ray emitting region properties—using data from the Neutron Star Interior Composition ExploreR (NICER)—for the brightest rotation-powered millisecond X-ray pulsar, PSR J0437−4715. Our modeling is conditional on informative tight priors on mass, distance, and binary inclination obtained from radio pulsar timing using the Parkes Pulsar Timing Array (PPTA; Reardon et al.), and we use NICER background models to constrain the nonsource background, cross-checking with data from XMM-Newton. We assume two distinct hot emitting regions and various parameterized hot region geometries that are defined in terms of overlapping circles; while simplified, these capture many of the possibilities suggested by detailed modeling of return current heating. For the preferred model identified by our analysis, we infer a mass of M = 1.418 ± 0.037 M _⊙ (largely informed by the PPTA mass prior) and an equatorial radius of $R={11.36}_{-0.63}^{+0.95}$ km, each reported as the posterior credible interval bounded by the 16% and 84% quantiles. This radius favors softer dense matter equations of state and is highly consistent with constraints derived from gravitational wave measurements of neutron star binary mergers. The hot regions are inferred to be nonantipodal and hence inconsistent with a pure centered dipole magnetic field.

We present the discovery, with the Neutron Star Interior Composition Explorer (NICER), that SRGA J144459.2−604207 is a 447.9 Hz accreting millisecond X-ray pulsar (AMXP), which underwent a 4 week long outburst starting on 2024 February 15. The AMXP resides in a 5.22 hr binary, orbiting a low-mass companion donor with M _d > 0.1 M _⊙ . We report on the temporal and spectral properties from NICER observations during the early days of the outburst, from 2024 February 21 through 2024 February 23, during which NICER also detected a type I X-ray burst that exhibited a plateau lasting ∼6 s. The spectra of the persistent emission were well described by an absorbed thermal blackbody and power-law model, with blackbody temperature kT ≈ 0.9 keV and power-law photon index Γ ≈ 1.9. Time-resolved burst spectroscopy confirmed the thermonuclear nature of the burst, where an additional blackbody component reached a maximum temperature of nearly kT ≈ 3 keV at the peak of the burst. We discuss the nature of the companion as well as the type I X-ray burst.

Recently we found compelling evidence for a gravitational-wave background with Hellings and Downs (HD) correlations in our 15 yr data set. These correlations describe gravitational waves as predicted by general relativity, which has two transverse polarization modes. However, more general metric theories of gravity can have additional polarization modes, which produce different interpulsar correlations. In this work, we search the NANOGrav 15 yr data set for evidence of a gravitational-wave background with quadrupolar HD and scalar-transverse (ST) correlations. We find that HD correlations are the best fit to the data and no significant evidence in favor of ST correlations. While Bayes factors show strong evidence for a correlated signal, the data does not strongly prefer either correlation signature, with Bayes factors ∼2 when comparing HD to ST correlations, and ∼1 for HD plus ST correlations to HD correlations alone. However, when modeled alongside HD correlations, the amplitude and spectral index posteriors for ST correlations are uninformative, with the HD process accounting for the vast majority of the total signal. Using the optimal statistic, a frequentist technique that focuses on the pulsar-pair cross-correlations, we find median signal-to-noise ratios of 5.0 for HD and 4.6 for ST correlations when fit for separately, and median signal-to-noise ratios of 3.5 for HD and 3.0 for ST correlations when fit for simultaneously. While the signal-to-noise ratios for each of the correlations are comparable, the estimated amplitude and spectral index for HD are a significantly better fit to the total signal, in agreement with our Bayesian analysis.

Since their first discovery in the late 1960s, gamma-ray bursts have attracted an exponentially growing interest from the international community due to their central role in the most highly debated open questions of the modern research of astronomy, astrophysics, cosmology, and fundamental physics. These range from the intimate nuclear composition of high-density material within the core of ultra-dense neuron stars, to stellar evolution via the collapse of massive stars, the production and propagation of gravitational waves, as well as the exploration of the early universe by unveiling the first stars and galaxies (assessing also their evolution and cosmic re-ionization). GRBs in the past ∼50 years have stimulated the development of cutting-edge technological instruments for observations of high-energy celestial sources from space, leading to the launch and successful operations of many different scientific missions (several of them still in data-taking mode currently). In this review, we provide a brief description of the GRB-dedicated missions from space being designed and developed for the future. The list of these projects, not meant to be exhaustive, shall serve as a reference to interested readers to understand what is likely to come next to lead the further development of GRB research and the associated phenomenology.

Angiotensin receptor/neprilysin inhibitors (ARNI) have become a pillar of heart failure (HF) management. Clinicians gain practical insight into the use of sacubitril/valsartan in patients with HF with reduced ejection fraction (EF) from a comprehensive overview based on clinical experience with ARNI therapy. The objective was to develop a consensus document addressing common concerns regarding the use of ARNI in patients with HF in clinical settings in India. Subject matter experts (SMEs) from India with decision-making expertise in the management of HF were identified to address experiences of ARNI use in Indian patients, its function in reversing myocardial remodeling, improvement in health status, and its safety. In regional meetings, five SMEs from India who consented to participate discussed data from practical experiences and current evidence. ARNI has been shown to substantially enhance EF 5%–10% in a majority of HF patients, although the range of improvement could vary widely in a few patients. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blocker antagonists have been eclipsed by ARNI. Patients who have diminished or declining estimated glomerular filtration rates are more likely than those with normal renal function to experience hyperkalemia. It is prudent to consistently monitor potassium levels in patients with borderline chronic kidney disease. In India, potassium binders may be used to temporarily control hyperkalemia caused by ARNI. Patients with a systolic blood pressure of

Purpose: In cases of eyelid malignancies requiring full thickness excisional biopsy followed by reconstruction of the created defect, the Meibomian glands are lost. Post-operative varying degrees of dry eye disease (DED) are expected in such patients. The aim was to evaluate the objective and subjective statuses of DED in cases of full thickness eyelid reconstruction following excisional biopsy because of malignancies. Methods: This was a cross-sectional pilot study. Objective and subjective dry eye parameters are assessed in cases of full thickness eyelid reconstruction following excisional biopsy because of malignancies in 37 eyes at 6 months post-operative follow-up. Analysis of variance and Chi square test were used for statistical analysis. Results: When compared with fellow eye, all the parameters were found to be statistically significant (P < 0.0). Subjective assessment of dry eye by ocular surface disease index (OSDI) scoring did not corroborate with the objective data (p 0.00). Lower eyelid reconstruction showed a minimum number of dry eye cases (P > 0.05). Conclusion: Prevalence of post-operative dry eye is more with increasing percentage of full thickness upper eyelid reconstruction. Disparity was found between objective and subjective parameters of dry eye in patients requiring varying percentages of upper eyelid reconstruction because of malignancies.

We report a joint experimental and theoretical study of the structural and vibrational properties of C-type bulk Y2O3 under hydrostatic compression. The combination of high-pressure X-ray diffraction and Raman scattering experimental measurements with ab initio theoretical calculations on bulk Y2O3 allows us to confirm the cubic (C-type) – monoclinic (B-type) – trigonal (A-type) phase transition sequence on the upstroke and the trigonal-monoclinic phase transition on the downstroke. This result reconciles with the results already found in related rare-earth sesquioxides of cations with similar ionic radii as Y, such as Ho2O3 and Dy2O3, and ends with the controversy regarding the existence of the intermediate monoclinic phase between the cubic and trigonal phases in pure bulk Y2O3 on the upstroke. As a byproduct, the good agreement between experimental and calculated results allows us to use extensive theoretical data to discuss the structural and vibrational behavior of the three phases of Y2O3 under compression, thus allowing a more detailed understanding of the effect of pressure on rare-earth sesquioxides than previous studies.

XTE J1829−098 is a transient X-ray pulsar with a period of ∼7.8 s. It is a candidate Be star system, although the evidence for this is not yet definitive. We investigated the twenty-year-long X-ray light curve using the Rossi X-ray Timing Explorer Proportional Counter Array (PCA), Neil Gehrels Swift Observatory Burst Alert Telescope, and the Monitor of All-sky X-ray Image. We find that all three light curves are clearly modulated on the ∼244 days orbital period previously reported from PCA monitoring observations, with outbursts confined to a narrow phase range. The light curves also show that XTE J1829−098 was in an inactive state between approximately 2008 December and 2018 April, and no strong outbursts occurred. Such behavior is typical of Be X-ray binary systems, with the absence of outbursts likely related to the dissipation of the Be star's decretion disk. The mean outburst shapes can be approximated with a triangular profile and, from a joint fit of this to all three light curves, we refine the orbital period to 243.95 ± 0.04 days. The mean outburst profile does not show any asymmetry and has a total phase duration of 0.140 ± 0.007. However, the PCA light curve shows that there is considerable cycle-to-cycle variability of the individual outbursts. We compare the properties of XTE J1829−098 with other sources that show short phase-duration outbursts, in particular GS 1843−02 (2S 1845−024), which has a very similar orbital period, but longer pulse period, and whose orbit is known to be highly eccentric.

Recent constraints on neutron star mass and radius have advanced our understanding of the equation of state (EOS) of cold dense matter. Some of them have been obtained by modeling the pulses of three millisecond X-ray pulsars observed by the Neutron Star Interior Composition Explorer (NICER). Here, we present a Bayesian parameter inference for a fourth pulsar, PSR J1231−1411, using the same technique with NICER and XMM-Newton data. When applying a broad mass-inclination prior from radio timing measurements and the emission region geometry model that can best explain the data, we find likely converged results only when using a limited radius prior. If limiting the radius to be consistent with the previous observational constraints and EOS analyses, we infer the radius to be 12.6 ± 0.3 km and the mass to be ${1.04}_{-0.03}^{+0.05}$ M _⊙ , each reported as the posterior credible interval bounded by the 16% and 84% quantiles. If using an uninformative prior but limited between 10 and 14 km, we find otherwise similar results, but ${R}_{\mathrm{eq}}={13.5}_{-0.5}^{+0.3}$ km for the radius. In both cases, we find a nonantipodal hot region geometry where one emitting spot is at the equator or slightly above, surrounded by a large colder region, and where a noncircular hot region lies close to southern rotational pole. If using a wider radius prior, we only find solutions that fit the data significantly worse. We discuss the challenges in finding the better fitting solutions, possibly related to the weak interpulse feature in the pulse profile.

We report an updated analysis of the radius, mass, and heated surface regions of the massive pulsar PSR J0740+6620 using Neutron Star Interior Composition Explorer (NICER) data from 2018 September 21 to 2022 April 21, a substantial increase in data set size compared to previous analyses. Using a tight mass prior from radio-timing measurements and jointly modeling the new NICER data with XMM-Newton data, the inferred equatorial radius and gravitational mass are ${12.49}_{-0.88}^{+1.28}$ km and ${2.073}_{-0.069}^{+0.069}$ M _⊙ , respectively, each reported as the posterior credible interval bounded by the 16% and 84% quantiles, with an estimated systematic error ≲ 0.1 km. This result was obtained using the best computationally feasible sampler settings providing a strong radius lower limit but a slightly more uncertain radius upper limit. The inferred radius interval is also close to the $R={12.76}_{-1.02}^{+1.49}$ km obtained by Dittmann et al., when they require the radius to be less than 16 km as we do. The results continue to disfavor very soft equations of state for dense matter, with R < 11.15 km for this high-mass pulsar excluded at the 95% probability. The results do not depend significantly on the assumed cross-calibration uncertainty between NICER and XMM-Newton. Using simulated data that resemble the actual observations, we also show that our pipeline is capable of recovering parameters for the inferred models reported in this paper.

Pulsar timing arrays (PTAs) are designed to detect low-frequency gravitational waves (GWs). GWs induce achromatic signals in PTA data, meaning that the timing delays do not depend on radio frequency. However, pulse arrival times are also affected by radio-frequency-dependent “chromatic” noise from sources such as dispersion measure (DM) and scattering delay variations. Furthermore, the characterization of GW signals may be influenced by the choice of chromatic noise model for each pulsar. To better understand this effect, we assess if and how different chromatic noise models affect the achromatic noise properties in each pulsar. The models we compare include existing DM models used by the North American Nanohertz Observatory for Gravitational waves (NANOGrav) and noise models used for the European PTA Data Release 2 (EPTA DR2). We perform this comparison using a subsample of six pulsars from the NANOGrav 15 yr data set, selecting the same six pulsars as from the EPTA DR2 six-pulsar data set. We find that the choice of chromatic noise model noticeably affects the achromatic noise properties of several pulsars. This is most dramatic for PSR J1713+0747, where the amplitude of its achromatic red noise lowers from ${\mathrm{log}}_{10}{A}_{\mathrm{RN}}=-{14.1}_{-0.1}^{+0.1}$ to $-{14.7}_{-0.5}^{+0.3}$ , and the spectral index broadens from ${\gamma }_{\mathrm{RN}}={2.6}_{-0.4}^{+0.5}$ to ${\gamma }_{\mathrm{RN}}={3.5}_{-0.9}^{+1.2}$ . We also compare each pulsar's noise properties with those inferred from the EPTA DR2, using the same models. From the discrepancies, we identify potential areas where the noise models could be improved. These results highlight the potential for custom chromatic noise models to improve PTA sensitivity to GWs.

PINT is a pure-Python framework for high-precision pulsar timing developed on top of widely used and well-tested Python libraries, supporting both interactive and programmatic data analysis workflows. We present a new frequentist framework within PINT to characterize the single-pulsar noise processes present in pulsar timing data sets. This framework enables parameter estimation for both uncorrelated and correlated noise processes, as well as model comparison between different timing and noise models in a computationally inexpensive way. We demonstrate the efficacy of the new framework by applying it to simulated data sets as well as a real data set of PSR B1855+09. We also describe the new features implemented in PINT since it was first described in the literature.

A mission to Jupiter's moon Io, the most volcanically active body in the solar system, was suggested as a priority for the New Frontiers program in the 2013 Planetary Science Decadal Survey. We present a New Frontiers–class mission concept, Vulcan, that was designed as an educational exercise through the Jet Propulsion Laboratory’s 2022 Planetary Science Summer School. Vulcan would leverage an instrument suite consisting of wide- and narrow-angle cameras, a thermal infrared spectrometer, two fluxgate magnetometers, and ion and electron electrostatic analyzers to conduct the most thorough investigation of Io to date. Using 78 flybys over a 2 yr primary science mission, Vulcan would characterize the effects of tidal forces on the differentiation state, crustal structure, and volcanism of Io and investigate potential interactions between Io's volcanoes, surface features, and atmosphere. Although Vulcan was developed as an academic exercise, we show that a New Frontiers–class mission to Io could achieve transformative science in both geophysics and plasma physics, unifying typically disparate subfields of planetary science. A dedicated mission to Io, in combination with the Europa Clipper and Jupiter Icy Moons Explorer missions, would address fundamental questions raised by the 2023 Planetary Science Decadal Survey and could complete our understanding of the spectrum of planetary habitability. Lessons learned from Vulcan could be applied to a New Frontiers 5 Io mission concept in the near future.

The Green Bank 820 MHz pulsar survey covers ≃173 deg ^2 in the Cygnus X region of the Galaxy, centered on l = 84.°5 and b = 1.°5. Significant star formation is present in this region, and lines of sight pass through three arms of the Galaxy (Orion–Cygnus, Perseus, and an outer arm). Using the Green Bank Telescope, we recorded 200 MHz of bandwidth for 4.5 minutes at 81.92 μ s resolution for each of 3457 observed survey pointings during 2016 and 2017, covering about two-thirds of the total area. We searched these data for pulsars and report the discovery of six new pulsars—PSRs J2016+3820, J2016+4231, J2019+3810, J2035+3538, J2035+3655, and J2041+4551—and the codiscovery of PSR J2057+4701. PSR J2035+3655 is in a short (4.5 hr) binary orbit; we report the full binary solution and weakly constrain the mass of the pulsar via a marginal (2 σ ) detection of the Shapiro delay. We also searched the survey data for known pulsars to estimate the survey’s sensitivity and measured 820 MHz pulse widths and flux density for 20 detected sources. For sources that were also detected in the Green Bank North Celestial Cap survey at 350 MHz, we measure scattering parameters and compare to expectations for the region. With these results, we revisit the population estimates that motivated this survey and consider the impact of the survey’s yield on their underlying models. We note an apparent underestimate in dispersion measure predictions from typical Galactic electron density models in the survey region, and discuss future observation strategies.

We have searched for radio pulsations toward 49 Fermi Large Area Telescope (LAT) 1FGL Catalog γ -ray sources using the Green Bank Telescope at 350 MHz. We detected 18 millisecond pulsars (MSPs) in blind searches of the data; 10 of these were discoveries unique to our survey. 16 are binaries, with eight having short orbital periods P _B < 1 day. No radio pulsations from young pulsars were detected, although three targets are coincident with apparently radio-quiet γ -ray pulsars discovered in LAT data. Here, we give an overview of the survey and present radio and γ -ray timing results for the 10 MSPs discovered. These include the only isolated MSP discovered in our survey and six short- P _B binary MSPs. Of these, three have very-low-mass companions ( M _c ≪ 0.1 M _⊙ ) and hence belong to the class of black widow pulsars. Two have more massive, nondegenerate companions with extensive radio eclipses and orbitally modulated X-ray emission consistent with the redback class. Significant γ -ray pulsations have been detected from nine of the discoveries. This survey and similar efforts suggest that the majority of Galactic γ -ray sources at high Galactic latitudes are either MSPs or relatively nearby nonrecycled pulsars, with the latter having on average a much smaller radio/ γ -ray beaming ratio as compared to MSPs. It also confirms that past surveys suffered from an observational bias against finding short- P _B MSP systems.

The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational-wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within 1 σ . The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we “extended” each PTA’s data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings–Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA’s Data Release 3, which will involve not just adding in additional pulsars but also including data from all three PTAs where any given pulsar is timed by more than a single PTA.

We present a timing solution for the 5.31 ms spider millisecond pulsar (MSP) J1242−4712, discovered with the GMRT. PSR J1242−4712 orbits a companion of minimum mass 0.08 M _⊙ with an orbital period of 7.7 hr and occupies a relatively unexplored region in the orbital period versus companion mass space. We did not detect gamma-ray pulsations for this MSP, and also could not identify the optical counterpart for PSR J1242–4712 in available optical/near-infrared data. The profile of J1242−4712 evolves with frequency, showing a clear single component at lower frequencies and a three-component profile at 650 MHz. PSR J1242−4712 eclipses for a very short duration near superior conjunction (orbital phase ∼ 0.23−0.25) below 360 MHz. Moreover, significant dispersion measure delays and errors in the pulse times of arrivals are observed near inferior conjunction (orbital phase ∼ 0.7), along with an observed eclipse in one epoch at 650 MHz. Observed eclipses and significant orbital period variability suggest that PSR J1242−4712 is possibly not a helium star−white dwarf binary, but has a semi- or nondegenerate companion, indicating that this is a “spider” MSP lying in a region between typical black widows and redbacks. This system may represent a distinct category of spider MSPs, displaying characteristics that bridge the gap between known black widow and redback MSPs.

The millisecond pulsar J1713+0747 underwent a sudden and significant pulse shape change between 2021 April 16 and 17 (MJDs 59320 and 59321). Subsequently, the pulse shape gradually recovered over the course of several months. We report the results of continued multifrequency radio observations of the pulsar made using the Canadian Hydrogen Intensity Mapping Experiment and the 100 m Green Bank Telescope in a 3 yr period encompassing the shape change event, between 2020 February and 2023 February. As of 2023 February, the pulse shape had returned to a state similar to that seen before the event, but with measurable changes remaining. The amplitude of the shape change and the accompanying time-of-arrival residuals display a strong nonmonotonic dependence on radio frequency, demonstrating that the event is neither a glitch (the effects of which should be independent of radio frequency, ν ) nor a change in dispersion measure alone (which would produce a delay proportional to ν ^−2 ). However, it does bear some resemblance to the two previous “chromatic timing events” observed in J1713+0747, as well as to a similar event observed in PSR J1643−1224 in 2015.

The radio galaxy 3C 66B has been hypothesized to host a supermassive black hole binary (SMBHB) at its center based on electromagnetic observations. Its apparent 1.05 yr period and low redshift (∼0.02) make it an interesting testbed to search for low-frequency gravitational waves (GWs) using pulsar timing array (PTA) experiments. This source has been subjected to multiple searches for continuous GWs from a circular SMBHB, resulting in progressively more stringent constraints on its GW amplitude and chirp mass. In this paper, we develop a pipeline for performing Bayesian targeted searches for eccentric SMBHBs in PTA data sets, and test its efficacy by applying it to simulated data sets with varying injected signal strengths. We also search for a realistic eccentric SMBHB source in 3C 66B using the NANOGrav 12.5 yr data set employing PTA signal models containing Earth term-only as well as Earth+pulsar term contributions using this pipeline. Due to limitations in our PTA signal model, we get meaningful results only when the initial eccentricity e _0 < 0.5 and the symmetric mass ratio η > 0.1. We find no evidence for an eccentric SMBHB signal in our data, and therefore place 95% upper limits on the PTA signal amplitude of 88.1 ± 3.7 ns for the Earth term-only and 81.74 ± 0.86 ns for the Earth+pulsar term searches for e _0 < 0.5 and η > 0.1. Similar 95% upper limits on the chirp mass are (1.98 ± 0.05) × 10 ^9 and (1.81 ± 0.01) × 10 ^9 M _☉ . These upper limits, while less stringent than those calculated from a circular binary search in the NANOGrav 12.5 yr data set, are consistent with the SMBHB model of 3C 66B developed from electromagnetic observations.

We present the results of a Bayesian search for gravitational wave (GW) memory in the NANOGrav 12.5 yr data set. We find no convincing evidence for any gravitational wave memory signals in this data set. We find a Bayes factor of 2.8 in favor of a model that includes a memory signal and common spatially uncorrelated red noise (CURN) compared to a model including only a CURN. However, further investigation shows that a disproportionate amount of support for the memory signal comes from three dubious pulsars. Using a more flexible red-noise model in these pulsars reduces the Bayes factor to 1.3. Having found no compelling evidence, we go on to place upper limits on the strain amplitude of GW memory events as a function of sky location and event epoch. These upper limits are computed using a signal model that assumes the existence of a common, spatially uncorrelated red noise in addition to a GW memory signal. The median strain upper limit as a function of sky position is approximately 3.3 × 10 ^−14 . We also find that there are some differences in the upper limits as a function of sky position centered around PSR J0613−0200. This suggests that this pulsar has some excess noise that can be confounded with GW memory. Finally, the upper limits as a function of burst epoch continue to improve at later epochs. This improvement is attributable to the continued growth of the pulsar timing array.

In 2019 the NICER collaboration published the first mass and radius inferred for PSR J0030+0451, thanks to NICER observations, and consequent constraints on the equation of state characterizing dense matter. Two independent analyses found a mass of ∼1.3–1.4 M _⊙ and a radius of ∼13 km. They also both found that the hot spots were all located on the same hemisphere, opposite to the observer, and that at least one of them had a significantly elongated shape. Here we reanalyze, in greater detail, the same NICER data set, incorporating the effects of an updated NICER response matrix and using an upgraded analysis framework. We expand the adopted models and also jointly analyze XMM-Newton data, which enables us to better constrain the fraction of observed counts coming from PSR J0030+0451. Adopting the same models used in previous publications, we find consistent results, although with more stringent inference requirements. We also find a multimodal structure in the posterior surface. This becomes crucial when XMM-Newton data is accounted for. Including the corresponding constraints disfavors the main solutions found previously, in favor of the new and more complex models. These have inferred masses and radii of ∼[1.4 M _⊙ , 11.5 km] and ∼[1.7 M _⊙ , 14.5 km], depending on the assumed model. They display configurations that do not require the two hot spots generating the observed X-rays to be on the same hemisphere, nor to show very elongated features, and point instead to the presence of temperature gradients and the need to account for them.

Abstract India is one of the oldest maritime nations in the world, and the overseas contacts date back to the third millennium BCE. Besides several archaeological vestiges, numerous stone anchors of various types have been documented during maritime archaeological explorations along the Indian littoral. During a recent maritime archaeological exploration, a broken Indo-Arabian stone anchor, of the Medieval period, was discovered along the Manikapatna coast of Odisha, Indian eastern littoral. In an attempt to determine the provenance of the anchor, we carried out a detailed petrographic, geochemical (major/trace elements) and Sr–Nd isotopic investigation. The results of our study reveal that the stone of the anchor had been cut out of a geologically young, vesicular, subalkalic basalt lava flow. Source fingerprinting done using petrographic, geochemical and isotopic data, suggests that contrary to the general perception, the anchor rock did not come from any local rock formations. All data point to the most likely scenario that the anchor rock was sourced from one of the lava flows of the Deccan Traps at Palitana in the Saurashtra region of Gujarat, western India. This result confirms the existence of Medieval maritime trading between western and eastern Indian states.

Objective: To assess the accessibility of abortion providers across collegiate campuses in the State of Colorado. Participants: Analysis was on secondary data from the Integrated Postsecondary Data System and the U.S. Census Bureau. Methods: We utilized a framework of Reproductive Justice to assess and interpret the accessibility of abortion providers to college students by mapping reproductive health centers and nonprofit institutions of higher education, then using these data to statistically compare racial demographics, female employment, and insurance coverage between institutions with and without access. Results: Of nonprofit postsecondary institutions in Colorado, 11 institutions lack access, serving ?38,900 students. Of these students, 88.7% attend a Minority Serving Institution (MSI). MSIs lacking abortion access had 8% more female enrollment [t(18.32)?=??2.04, p?=?0.027]. Campuses possessing student health centers are less likely to have an MSI designation (50% with vs. 82% without), have greater female Hispanic enrollment by 10% [t(23.72)?=?3.11, p?=?0.005] and lower female multiracial enrollment by 2% [t(37.00)?=?2.20, p?=?0.034]. Analysis of variance (ANOVA) results indicated significant differences in percent composition of Asian, black or African American, Two or More, and Nonresident demographics between collegiate campuses with 30-, 45-, and 60-minute drive-time access. ANOVA results indicated separate patterns of differences for Zip Code Tabulation Area (ZCTA) demographics for Asian, black or African American, Native Hawaiian or Pacific Islander, Other Race, and Nonresident populations. Planned contrasts demonstrated that this difference was greatest at the 30-minute drive-time access, supporting the use of 30-minute drive time as an important indicator of access. Conclusions: The colleges lacking access to a provider are predominantly MSIs in lower income communities. The patterns in campus and ZCTA demographics indicate that collegiate populations are affected by rurality differently than the general population. We recommend that future qualitative research to assess rural students' perceptions on access, campus health center practices, and practices on campuses without dedicated health facilities.

Abstract Background The functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of common alleles that are often commercially produced at great expense, with costs and technical challenges associated with production of intersectional mouse lines hindering customized approaches to many researchers. Here, we present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production. Results Briefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study the way functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase-responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle. Conclusions The lines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.

COVID has drastically impacted organ donation across the world, leading to untold misery for thousands of patients who have been waiting for organs. Early rules on the use of organs from COVID positive or affected donors were stringent due to the fear of spread of disease or thrombotic complications in patients who received these organs. However much has changed in the past two years. Most of our adult population has either been infected with COVID, or has received two doses of vaccine, or both. The current variant, despite being more infective, is associated with mild disease, especially in those who have been vaccinated Our armamentarium against severe COVID has improved dramatically in the past year- we have effective vaccines, monoclonal antibodies for treatment of mild COVID in high risk patients and post exposure and antiviral prophylaxis and treatment which can substantially reduce the risk of severe COVID requiring ICU admission. The risk of transmission of COVID infection has to be balanced against the risk of patients dying with end organ disease. We will have to learn to live with COVID- this also means investigating whether organs from donors who are, or have been COVID positive can be used with acceptable risk –benefit in selected patients with end stage organ failure. This document is a summary of evidence and information regarding donor screening for SARS-CoV-2 and considerations for organ acceptance from donors with a history of COVID-19.

Graft loss and rejections (acute/chronic) continue to remain important concerns in long-term outcomes in kidney transplant despite newer immunosuppressive regimens and increased use of induction agents. Global guidelines identify the risk factors and suggest a framework for management of patients at different risk levels for rejection; however, these are better applicable to deceased donor transplants. Their applicability in Indian scenario (predominantly live donor program) could be a matter of debate. Therefore, a panel of experts discussed the current clinical practice and adaptability of global recommendations to Indian settings. They also took a survey to define risk factors in kidney transplants and provide direction toward evidence- and clinical experience-based risk stratification for donor/recipient and transplant-related characteristics, with a focus on living donor transplantations. Several recipient related factors (dialysis, comorbidities, and age, donor-specific antibodies [DSAs]), donor-related factors (age, body mass index, type – living or deceased) and transplantation related factors (cold ischemia time [CIT], number of transplantations) were assessed. The experts suggested that immunological conflict should be avoided by performing cytotoxic cross match, flow cross match in all patients and DSA-(single antigen bead) whenever considered clinically relevant. HLA mismatches, presence of DSA, along with donor/recipient age, CIT, etc., were associated with increased risk of rejection. Furthermore, the panel agreed that the risk of rejection in living donor transplant is not dissimilar to deceased donor recipients. The experts also suggested that induction immunosuppression could be individualized based on the risk stratification.

The North American Nanohertz Observatory for Gravitational Waves (NANOGrav) has reported evidence for the presence of an isotropic nanohertz gravitational-wave background (GWB) in its 15 yr data set. However, if the GWB is produced by a population of inspiraling supermassive black hole binary (SMBHB) systems, then the background is predicted to be anisotropic, depending on the distribution of these systems in the local Universe and the statistical properties of the SMBHB population. In this work, we search for anisotropy in the GWB using multiple methods and bases to describe the distribution of the GWB power on the sky. We do not find significant evidence of anisotropy. By modeling the angular power distribution as a sum over spherical harmonics (where the coefficients are not bound to always generate positive power everywhere), we find that the Bayesian 95% upper limit on the level of dipole anisotropy is ( C _l _=1 / C _l _=0 ) < 27%. This is similar to the upper limit derived under the constraint of positive power everywhere, indicating that the dipole may be close to the data-informed regime. By contrast, the constraints on anisotropy at higher spherical-harmonic multipoles are strongly prior dominated. We also derive conservative estimates on the anisotropy expected from a random distribution of SMBHB systems using astrophysical simulations conditioned on the isotropic GWB inferred in the 15 yr data set and show that this data set has sufficient sensitivity to probe a large fraction of the predicted level of anisotropy. We end by highlighting the opportunities and challenges in searching for anisotropy in pulsar timing array data.

The NANOGrav 15 yr data set shows evidence for the presence of a low-frequency gravitational-wave background (GWB). While many physical processes can source such low-frequency gravitational waves, here we analyze the signal as coming from a population of supermassive black hole (SMBH) binaries distributed throughout the Universe. We show that astrophysically motivated models of SMBH binary populations are able to reproduce both the amplitude and shape of the observed low-frequency gravitational-wave spectrum. While multiple model variations are able to reproduce the GWB spectrum at our current measurement precision, our results highlight the importance of accurately modeling binary evolution for producing realistic GWB spectra. Additionally, while reasonable parameters are able to reproduce the 15 yr observations, the implied GWB amplitude necessitates either a large number of parameters to be at the edges of expected values or a small number of parameters to be notably different from standard expectations. While we are not yet able to definitively establish the origin of the inferred GWB signal, the consistency of the signal with astrophysical expectations offers a tantalizing prospect for confirming that SMBH binaries are able to form, reach subparsec separations, and eventually coalesce. As the significance grows over time, higher-order features of the GWB spectrum will definitively determine the nature of the GWB and allow for novel constraints on SMBH populations.

Evidence for a low-frequency stochastic gravitational-wave background has recently been reported based on analyses of pulsar timing array data. The most likely source of such a background is a population of supermassive black hole binaries, the loudest of which may be individually detected in these data sets. Here we present the search for individual supermassive black hole binaries in the NANOGrav 15 yr data set. We introduce several new techniques, which enhance the efficiency and modeling accuracy of the analysis. The search uncovered weak evidence for two candidate signals, one with a gravitational-wave frequency of ∼4 nHz, and another at ∼170 nHz. The significance of the low-frequency candidate was greatly diminished when Hellings–Downs correlations were included in the background model. The high-frequency candidate was discounted due to the lack of a plausible host galaxy, the unlikely astrophysical prior odds of finding such a source, and since most of its support comes from a single pulsar with a commensurate binary period. Finding no compelling evidence for signals from individual binary systems, we place upper limits on the strain amplitude of gravitational waves emitted by such systems. At our most sensitive frequency of 6 nHz, we place a sky-averaged 95% upper limit of 8 × 10 ^−15 on the strain amplitude. We also calculate an exclusion volume and a corresponding effective radius, within which we can rule out the presence of black hole binaries emitting at a given frequency.

Pulsar timing array collaborations, such as the North American Nanohertz Observatory for Gravitational Waves (NANOGrav), are seeking to detect nanohertz gravitational waves emitted by supermassive black hole binaries formed in the aftermath of galaxy mergers. We have searched for continuous waves from individual circular supermassive black hole binaries using NANOGrav’s recent 12.5 yr data set. We created new methods to accurately model the uncertainties on pulsar distances in our analysis, and we implemented new techniques to account for a common red-noise process in pulsar timing array data sets while searching for deterministic gravitational wave signals, including continuous waves. As we found no evidence for continuous waves in our data, we placed 95% upper limits on the strain amplitude of continuous waves emitted by these sources. At our most sensitive frequency of 7.65 nHz, we placed a sky-averaged limit of h _0 < (6.82 ± 0.35) × 10 ^−15 , and h _0 < (2.66 ± 0.15) × 10 ^−15 in our most sensitive sky location. Finally, we placed a multimessenger limit of ${ \mathcal M }\lt (1.41\pm 0.02)\times {10}^{9}\,{M}_{\odot }$ on the chirp mass of the supermassive black hole binary candidate 3C 66B.

We report multiple lines of evidence for a stochastic signal that is correlated among 67 pulsars from the 15 yr pulsar timing data set collected by the North American Nanohertz Observatory for Gravitational Waves. The correlations follow the Hellings–Downs pattern expected for a stochastic gravitational-wave background. The presence of such a gravitational-wave background with a power-law spectrum is favored over a model with only independent pulsar noises with a Bayes factor in excess of 10 ^14 , and this same model is favored over an uncorrelated common power-law spectrum model with Bayes factors of 200–1000, depending on spectral modeling choices. We have built a statistical background distribution for the latter Bayes factors using a method that removes interpulsar correlations from our data set, finding p = 10 ^−3 (≈3 σ ) for the observed Bayes factors in the null no-correlation scenario. A frequentist test statistic built directly as a weighted sum of interpulsar correlations yields p = 5 × 10 ^−5 to 1.9 × 10 ^−4 (≈3.5 σ –4 σ ). Assuming a fiducial f ^−2/3 characteristic strain spectrum, as appropriate for an ensemble of binary supermassive black hole inspirals, the strain amplitude is ${2.4}_{-0.6}^{+0.7}\times {10}^{-15}$ (median + 90% credible interval) at a reference frequency of 1 yr ^−1 . The inferred gravitational-wave background amplitude and spectrum are consistent with astrophysical expectations for a signal from a population of supermassive black hole binaries, although more exotic cosmological and astrophysical sources cannot be excluded. The observation of Hellings–Downs correlations points to the gravitational-wave origin of this signal.

We present observations and timing analyses of 68 millisecond pulsars (MSPs) comprising the 15 yr data set of the North American Nanohertz Observatory for Gravitational Waves (NANOGrav). NANOGrav is a pulsar timing array (PTA) experiment that is sensitive to low-frequency gravitational waves (GWs). This is NANOGrav’s fifth public data release, including both “narrowband” and “wideband” time-of-arrival (TOA) measurements and corresponding pulsar timing models. We have added 21 MSPs and extended our timing baselines by 3 yr, now spanning nearly 16 yr for some of our sources. The data were collected using the Arecibo Observatory, the Green Bank Telescope, and the Very Large Array between frequencies of 327 MHz and 3 GHz, with most sources observed approximately monthly. A number of notable methodological and procedural changes were made compared to our previous data sets. These improve the overall quality of the TOA data set and are part of the transition to new pulsar timing and PTA analysis software packages. For the first time, our data products are accompanied by a full suite of software to reproduce data reduction, analysis, and results. Our timing models include a variety of newly detected astrometric and binary pulsar parameters, including several significant improvements to pulsar mass constraints. We find that the time series of 23 pulsars contain detectable levels of red noise, 10 of which are new measurements. In this data set, we find evidence for a stochastic GW background.

Pulsar timing arrays (PTAs) are galactic-scale gravitational wave (GW) detectors. Each individual arm, composed of a millisecond pulsar, a radio telescope, and a kiloparsecs-long path, differs in its properties but, in aggregate, can be used to extract low-frequency GW signals. We present a noise and sensitivity analysis to accompany the NANOGrav 15 yr data release and associated papers, along with an in-depth introduction to PTA noise models. As a first step in our analysis, we characterize each individual pulsar data set with three types of white-noise parameters and two red-noise parameters. These parameters, along with the timing model and, particularly, a piecewise-constant model for the time-variable dispersion measure, determine the sensitivity curve over the low-frequency GW band we are searching. We tabulate information for all of the pulsars in this data release and present some representative sensitivity curves. We then combine the individual pulsar sensitivities using a signal-to-noise ratio statistic to calculate the global sensitivity of the PTA to a stochastic background of GWs, obtaining a minimum noise characteristic strain of 7 × 10 ^−15 at 5 nHz. A power-law-integrated analysis shows rough agreement with the amplitudes recovered in NANOGrav’s 15 yr GW background analysis. While our phenomenological noise model does not model all known physical effects explicitly, it provides an accurate characterization of the noise in the data while preserving sensitivity to multiple classes of GW signals.

The 15 yr pulsar timing data set collected by the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) shows positive evidence for the presence of a low-frequency gravitational-wave (GW) background. In this paper, we investigate potential cosmological interpretations of this signal, specifically cosmic inflation, scalar-induced GWs, first-order phase transitions, cosmic strings, and domain walls. We find that, with the exception of stable cosmic strings of field theory origin, all these models can reproduce the observed signal. When compared to the standard interpretation in terms of inspiraling supermassive black hole binaries (SMBHBs), many cosmological models seem to provide a better fit resulting in Bayes factors in the range from 10 to 100. However, these results strongly depend on modeling assumptions about the cosmic SMBHB population and, at this stage, should not be regarded as evidence for new physics. Furthermore, we identify excluded parameter regions where the predicted GW signal from cosmological sources significantly exceeds the NANOGrav signal. These parameter constraints are independent of the origin of the NANOGrav signal and illustrate how pulsar timing data provide a new way to constrain the parameter space of these models. Finally, we search for deterministic signals produced by models of ultralight dark matter (ULDM) and dark matter substructures in the Milky Way. We find no evidence for either of these signals and thus report updated constraints on these models. In the case of ULDM, these constraints outperform torsion balance and atomic clock constraints for ULDM coupled to electrons, muons, or gluons.

Reprogramming of the cochlea with hair-cell-specific transcription factors such as ATOH1 has been proposed as a potential therapeutic strategy for hearing loss. ATOH1 expression in the developing cochlea can efficiently induce hair cell regeneration but the efficiency of hair cell reprogramming declines rapidly as the cochlea matures. We developed Cre-inducible mice to compare hair cell reprogramming with ATOH1 alone or in combination with two other hair cell transcription factors, GFI1 and POU4F3. In newborn mice, all transcription factor combinations tested produced large numbers of cells with the morphology of hair cells and rudimentary mechanotransduction properties. However, 1 week later, only a combination of ATOH1, GFI1 and POU4F3 could reprogram non-sensory cells of the cochlea to a hair cell fate, and these new cells were less mature than cells generated by reprogramming 1 week earlier. We used scRNA-seq and combined scRNA-seq and ATAC-seq to suggest at least two impediments to hair cell reprogramming in older animals. First, hair cell gene loci become less epigenetically accessible in non-sensory cells of the cochlea with increasing age. Second, signaling from hair cells to supporting cells, including Notch signaling, can prevent reprogramming of many supporting cells to hair cells, even with three hair cell transcription factors. Our results shed light on the molecular barriers that must be overcome to promote hair cell regeneration in the adult cochlea.

Wood-plastic composites (WPCs) are a group of emerging and a sustainable class of high-performance materials, consisting of polymers reinforced with wood particulates, having a wide range of applications in the field of building, infrastructure, and transportation. However, the main drawback of the WPCs is their high flammability. Fire retardants usually enhance WPCs’ flame retardancy but at the expense of mechanical properties. This paper reviews the available literature on flame retardant WPCs in developing an optimum condition between the flammability and mechanical properties, i.e., the addition of wood-flour and flame retardant (FR) in order to find a balance between the flammability resistance and their mechanical properties. It concentrates on the recent advances in the mechanical properties and flammability studies of wood flour-polymer composite products. The applications and durability of these flame retardant WPCs with future remarks are also highlighted.

Background: RIZ1 is one of the tumor-suppressor genes that is silenced in many human cancers. Change in RIZ1 expression has not been reported in ESCC patients. Therefore, the aim of this study was to investigate the role of RIZ1 in ESCC in the Indian population. Methods: Twelve esophageal squamous-cell carcinoma (ESCC) patients in stage IV and 12 healthy individuals were used in this study. Tissue sampling was taken from individuals and total RNA was isolated and then cDNA was synthesized using PCR. RIZ1 primers were then designed, and RIZ1 expression was quantified by qRT-PCR. Mapping of CpG islands in RIZ1 promoter was performed using bioinformatics tools. The promoter methylation status of this gene was studied using u methylation-specific PCR (MSP). T-student test was used to analyze the data. Results: Decreased RIZ1 expression was observed in ESCC compared with healthy controls. The results showed a relatively higher density of CpG dinucleotides in the RIZ1 promoter. No significant difference in promoter methylation was observed in blood and tissue samples. Conclusion: The study showed a significant down-regulation of RIZ-1 gene in the blood and tissue samples of ESCC patients that did not related to the altered promoter methylation.

# Background We previously described experiences of clinicians who published adverse drug reaction reports. We now report on threats and intimidations leveled against clinicians and scientists who received publicly documented threats after communicating safety, efficacy, or data integrity findings contrary to corporate interests. # Methods Data on threats and intimidations were obtained from transcripts of governmental hearings or agencies, university-affiliated reports, media interviews, and investigative journalism articles. Content and timing of threats and intimidation, subsequent harms, numbers of persons seriously injured or who died from individual toxicities, financial payments from sponsors related to safety, efficacy, or data integrity concerns, and civil settlements and criminal findings were evaluated. # Findings Twenty-six individuals who communicated safety, efficacy, or data integrity concerns were targets of threats and intimidation from corporate employees (twenty-three individuals) or regulatory personnel (three). Seventeen individuals identified instances where pharmaceutical sponsors submitted fraudulent data in support of regulatory approval of a drug or device. Scientist and clinician communications were followed by drug/device withdrawals (fourteen drugs/devices), black box warnings (six drugs), withdrawal of a sponsor's application for regulatory approval (one device), and delay of approval of a sponsor's application for regulatory approval (one drug). Actions mainly occurred after persons communicated with pharmaceutical employees (fourteen). Intimidation efforts by corporate personnel included threats of lawsuits (eighteen individuals), hiring private investigators (nine), and public disparagement at conferences (eleven). Related intimidation efforts carried out by academia or regulatory agency superiors included threats of: loss of positions (six), loss of grant funding (two), delays in decisions regarding tenure (two); or reassignment to a low-level position (one). Academic harms included lost: hospital or university appointments (nine and six, respectively), grant funding (two), chairperson title of an international clinical trial group (one), and journal editorial board position (one). Corporate harms included payment of \$1 million to defense attorneys in three cases filed against clinicians. # Interpretation Threats and intimidation carried out by corporate employees and/or academic supervisors followed public communication of concerns regarding patient safety, drug efficacy, or data integrity, including instances where sponsors were identified as having submitted fraudulent data to regulatory or government agencies. Consideration should be given to filing criminal charges against pharmaceutical executives who are discovered by scientists or clinicians to have knowingly submitted fraudulent data to regulatory or governmental agencies, rather than causing the scientists and clinicians who submit such reports to risk losing their reputations and occupations.

The effect of horror sound on electro-cardiac activity is not yet sufficiently explored despite recommendable research on different genres of music and sound. Detecting the impact of these stimuli is a complex task. The current study intends to automatically detect the horror-sound induced cardiac changes using wavelet coefficient-based features extracted from the electrocardiograph signals and several machine learning models. The statistical comparison of these features in the two data groups suggests a significant change in different feature values after exposure to horror sound while watching a horror clip. The statistically discriminative features were employed as input to nine machine learning (ML) models, namely Naïve Bayes, Fast large margin, Logistic regression, generalized linear model, Decision tree, Random Forest, deep learning, gradient boosted tree, and Support vector machine. The performance of these ML models was compared using different performance measures, including accuracy, precision, F-measure, sensitivity, specificity, and area under the curve (AUC). The results suggest the gradient boosted tree is the best performing model in differentiating the horror sound-induced changes in the ECG signals.