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High-precision pulsar timing observations are limited in their accuracy by the jitter noise that appears in the arrival time of pulses. Therefore, it is important to systematically characterise the amplitude of the jitter noise and its variation with frequency. In this paper, we provide jitter measurements from low-frequency wideband observations of PSR J0437$-$4715 using data obtained as part of the Indian Pulsar Timing Array experiment. We were able to detect jitter in both the 300–500 MHz and 1 260–1 460 MHz observations of the upgraded Giant Metrewave Radio Telescope (uGMRT). The former is the first jitter measurement for this pulsar below 700 MHz, and the latter is in good agreement with results from previous studies. In addition, at 300–500 MHz, we investigated the frequency dependence of the jitter by calculating the jitter for each sub-banded arrival time of pulses. We found that the jitter amplitude increases with frequency. This trend is opposite as compared to previous studies, indicating that there is a turnover at intermediate frequencies. It will be possible to investigate this in more detail with uGMRT observations at 550–750 MHz and future high-sensitive wideband observations from next generation telescopes, such as the Square Kilometre Array. We also explored the effect of jitter on the high precision dispersion measure (DM) measurements derived from short duration observations. We find that even though the DM precision will be better at lower frequencies due to the smaller amplitude of jitter noise, it will limit the DM precision for high signal-to-noise observations, which are of short durations. This limitation can be overcome by integrating for a long enough duration optimised for a given pulsar.
Research articles in the clinical and translational science literature commonly use quantitative data to inform evaluation of interventions, learn about the etiology of disease, or develop methods for diagnostic testing or risk prediction of future events. The peer review process must evaluate the methodology used therein, including use of quantitative statistical methods. In this manuscript, we provide guidance for peer reviewers tasked with assessing quantitative methodology, intended to complement guidelines and recommendations that exist for manuscript authors. We describe components of clinical and translational science research manuscripts that require assessment including study design and hypothesis evaluation, sampling and data acquisition, interventions (for studies that include an intervention), measurement of data, statistical analysis methods, presentation of the study results, and interpretation of the study results. For each component, we describe what reviewers should look for and assess; how reviewers should provide helpful comments for fixable errors or omissions; and how reviewers should communicate uncorrectable and irreparable errors. We then discuss the critical concepts of transparency and acceptance/revision guidelines when communicating with responsible journal editors.
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.
We introduce pinta, a pipeline for reducing the upgraded Giant Metre-wave Radio Telescope (uGMRT) raw pulsar timing data, developed for the Indian Pulsar Timing Array experiment. We provide a detailed description of the workflow and usage of pinta, as well as its computational performance and RFI mitigation characteristics. We also discuss a novel and independent determination of the relative time offsets between the different back-end modes of uGMRT and the interpretation of the uGMRT observation frequency settings and their agreement with results obtained from engineering tests. Further, we demonstrate the capability of pinta to generate data products which can produce high-precision TOAs using PSR J1909
$-$
3744 as an example. These results are crucial for performing precision pulsar timing with the uGMRT.
The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a “train the trainer” approach to enable CBs who have successfully completed training to train new staff or faculty.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
Socio-behavioural factors and pathogens associated with childhood diarrhoea are of global public health concern. Our survey in 696 children aged ⩽2 years in rural West Bengal detected rotavirus as sole pathogen in 8% (17/199) of diarrhoeic stool specimens. Other organisms were detected along with rotavirus in 11% of faecal specimens. A third of the children with rotavirus diarrhoea, according to Vesikari score, had severe illness. The top four rotavirus genotypes were G9P[4] (28%), G1P[8] (19%), G2P[4] (14%) and G8P[4] (8%). In the multivariate model, the practice of ‘drawing drinking water by dipping a pot in the storage vessel’ [adjusted odds ratio (aOR) 2·21, 95% confidence interval (CI) 1·03–4·74, P = 0·041], and ‘children aged ⩽6 months with non-exclusive breastfeeding’ (aOR 2·07, 95% CI 1·1–3·82, P = 0·024) had twice the odds of having diarrhoea. Incidence of rotavirus diarrhoea was 24/100 child-years in children aged >6–18 months, 19/100 child-years in children aged >18–24 months and 5/100 child-years in those aged ⩽6 months. Results have translational implications for future interventions including vaccine development.
Intrauterine growth-restricted (IUGR) offspring are at increased risk of adult obesity, as a result of changes in energy balance mechanisms. We hypothesized that impairment of hypothalamic insulin signaling contributes to hyperphagia in IUGR offspring. Study pregnant dams were 50% food restricted from days 10 to 21 to create IUGR newborns. At 5 weeks of age, food intake was measured following intracerebroventricular (icv) injection of vehicle or insulin (10 mU) in control and IUGR pups. At 6 weeks of age, with pups in fed or fasted (48 h) states, pups received icv vehicle or insulin after which they were decapitated, and hypothalamic arcuate (ARC) nucleus dissected for RNA and protein expression. IUGR rats consumed more food than controls under basal conditions, consistent with upregulated ARC phospho AMP-activated protein kinase (pAMPK) and neuropeptide Y (NPY). Insulin acutely reduced food intake in both control and IUGR rats. Consistent with anorexigenic stimulation, central insulin decreased AMP-activated protein kinase and NPY mRNA expression and increased proopiomelanocortin mRNA expression and pAkt, with significantly reduced responses in IUGR as compared with controls. Despite feeding, IUGR offspring exhibit a persistent state of orexigenic stimulation in the ARC nucleus and relative resistance to the anorexigenic effects of icv insulin. These results suggest that impaired insulin signaling contributes to hyperphagia and obesity in IUGR offspring.
This paper reports a case of a non-recurrent laryngeal nerve which was accurately predicted pre-operatively using computed tomography.
Case report:
A 61-year-old man presented with papillary thyroid carcinoma with lymph node metastasis. Computed tomography scans of the neck and chest revealed an ill-defined, hypoattenuating nodule in the right lobe of the thyroid gland, with few upper paratracheal and prevascular nodes, and clear lung fields. The retro-oesophageal course of the right subclavian artery, which was arising from the distal portion of the arch of aorta, was also incidentally revealed in the computed tomography scan. A barium swallow further confirmed the presence of a retro-oesophageal subclavian artery. Total thyroidectomy was performed, with right neck dissection and central compartment clearance. This was carried out with the presence of a non-recurrent laryngeal nerve in mind, and the nerve was accurately localised and preserved.
Conclusion:
To our knowledge this is the first report in the world literature of accurate pre-operative incidental imaging of the right non-recurrent laryngeal nerve in a case of metastatic thyroid cancer, and the subsequent use of computed tomography to guide surgical navigation.
A comparative study of superficial changes on the superalloy Inconel 600, induced by a picosecond Nd:YAG laser operating at 1064, 532, and 266 nm, is presented. All of the laser wavelengths, as well as the used fluences of 2.5 (1064 nm), 4.3 (532 nm), and 0.6 J/cm2 (266 nm) were found to be adequate for inducing surface variations. Quite different surface features were produced depending on the laser wavelength used. The measured surface damage thresholds were 0.25, 0.13 and 0.10 J/cm2 for 1064, 532, and 266 nm, respectively. Drastic differences, in function of the wavelength used, were recorded for the crater depths, as well the appearance of hydrodynamic effects and periodic surface structures. Differences in crater depths were explained via an easier propagation of the first harmonic laser radiation (1064 nm) through the ejected material and plasma compared to a radiation at 532 and 266 nm. Finally, changes in the surface oxygen content caused by ultrashort laser pulses were considered.
The fetal or early origins of adult disease hypothesis states that environmental factors, particularly nutrition, act in early life to program the risks for chronic diseases in adult life. As eating habits can be linked to the development of several diseases including obesity, diabetes and cardiovascular disease, it could be proposed that persistent food preferences across the life-span in people who were exposed to an adverse fetal environment may partially explain their increased risk to develop metabolic disease later in life. In this paper, we grouped the clinical and experimental evidence demonstrating that the fetal environment may impact the individual's food preferences. In addition, we review the feeding preferences development and regulation (homeostatic and hedonic pathways, the role of taste/olfaction and the reward/pleasure), as well as propose mechanisms linking early life conditions to food preferences later in life. We review the evidence suggesting that in utero conditions are associated with the development of specific food preferences, which may be involved in the risk for later disease. This may have implications in terms of public health and primary prevention during early ages.
Maternal undernutrition (MUN) results in growth-restricted newborns with reduced nephron numbers that is associated with increased risk of hypertension and renal disease. The total adult complement of nephrons is set during nephrogenesis suggesting that MUN affects the staged development of nephrons in as yet unknown manner. A possible cause may be the increased renal apoptosis; therefore, we investigated whether apoptotic signaling and cell death were increased in MUN rat kidneys. Pregnant rat dams were fed an ad libitum diet [control] or were 50% food restricted (MUN) starting at embryonic day (E) 10. Male offspring kidneys (n = 5 each, MUN and control) were analyzed for mRNA using quantitative PCR (E20) and for protein expression using Western blotting and immunohistochemistry (E20 and postnatal day 1, P1). Apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Upregulation of pro-apoptotic protein expression was detected at E20 (Fas receptor, caspase 9) and at P1 (caspase 3, Bax). The anti-apoptotic factor Bcl2 was significantly decreased in P1 kidneys. Kidney TUNEL showed apoptotic nuclei significantly increased in the P1 nephrogenic zone (MUN 3.3 + 0.3 v. C 1.6 + 0.5, P = 0.002). The majority of apoptotic nuclei co-localized to mesenchyme and pretubular aggregates in the nephrogenic zone. Differential regulation of apoptosis in mesenchyme and pretubular aggregates following parturition suggests a mechanism for nephropenia in gestational programming of the kidney.
Maternal under-nutrition (MUN) during gestation results in growth-restricted newborns with reduced glomerular number and subsequent hypertension. We investigated dysregulation of glial derived neurotrophic factor (GDNF) and MAPK–ERK (mitogen-activated protein kinase–extracellular signal-regulated protein kinase) signal pathway gene expression following MUN. MUN rats were 50% food restricted from embryonic day 10 till postnatal day 1. Kidneys were harvested at embryonic day (E)20, and postnatal days (P)1 and 21. Kidney protein expression was determined by Western blot. At E20, protein expression of growth factor receptor alpha 1 (GFRα1) and phosphorylated ERK1/2 and mitogen-activated protein kinase kinase (MEK)1/2 were reduced significantly, and immunohistochemistry confirmed reduction of phosphorylated ERK (pERK) with maintenance of pERK localization. Total MEK and ERK were unchanged. At P1, only GFRα1 and pERK1/2 were reduced significantly while at P21, expression of all growth factors except total MEK was unchanged. Total MEK was increased. Glomerular number was decreased by 19% in P21 kidneys and blood pressure was increased in 12-week-old rats. In conclusion, GDNF and MAPK–ERK signaling are dysregulated during active nephrogenesis in fetal and early newborn offspring kidneys in the MUN model. This may be a key mechanism in reduced offspring nephrogenesis and programmed hypertension.
The characteristics of the specularly reflected laser light (1.06 μm) from a copper plasma have been studied experimentally. The diffusivity and depolarization of specularly reflected radiation can be explained by the density contours and self-generated magnetic field at the radiation turning point in the plasma layer.
Laser plasma experiments reveal rich interplay between laser plasma instabilities. The growth of stimulated Brillouin scattering (SBS) is one of the most significant constraints of laser fusion experiments. In this paper, a mechanism of stabilization of SBS process due to magnetic anisotropy has been presented. Magnetic anisotropy induced by the temporally exponentially growing nonoscillating magnetic moment from inverse Faraday effect (IFE) has been studied.It has been shown that for interaction of Nd laser (λ = 1.06 μm) on solid deuterium target the SBS growth rate (y) ∼ 3.45 ps and the phase velocities of the incident and scattered electromagnetic (EM) waves have been shown to decay exponentially (∼e∼λ1) in this SBS process resulting in wave-number mismatch.
The interaction of an Nd:YAG laser, operating at 532 nm with 40 ps pulse duration, with human teeth was studied. The results show that teeth were significantly modified at an energy fluence of about 11 J/cm2. Various surface morphologies of enamel and dentine were recorded. Features on enamel include crater (conical form) in the central part and cauliflower morphology at the periphery, whereas on dentine the crater looks like a stretched dome between sharp edges. The behavior of the enamel-dentine junction area showed different morphology with respect to both tooth enamel and dentine alone. Finally, the junction channel showed a removal of collagen fibers and the formation of a needle-like bottom structure. Generally, this investigation showed that the picosecond Nd:YAG laser can ablate a tooth surface practically instantaneously, implying that large tooth surfaces can be processed in short time.
Interaction of a Nd:YAG laser, operating at wavelengths of 1064 nm (23.6 J cm−2 fluence) or 532 nm (25.9 J cm−2 fluence), and pulse duration of 40 ps, with a titanium-based medical implant Ti6Al4V alloy was studied. Surface damage thresholds were estimated to be 0.9 J cm−2 and 0.25 J cm−2 at laser wavelengths 1064 nm and 532 nm, respectively. At both laser wavelengths, the energy absorbed was mostly converted into thermal energy, forming craters, albeit about 50 times deeper at 1064 nm than at 532 nm. Periodic surface structures (PSS) were also formed with both laser wavelengths, concentric, and radial at micrometer scale (3 µm to 15 µm period), parallel at nanometer scale (800 nm period with the 1064 nm laser, 400 nm with the 532 nm laser). In the case of the 532 nm laser, the concentric structures enlarge their period with accumulating laser pulse count. These features can help roughening of the implant surface and improve bio-compatibility.
Investigations of a high resolution X-ray emission spectrum in the range 0.66–0.75 nm obtained by irradiating a Germanium target with high-power p-polarized, 40 picosecond laser radiation at 532 nm wavelength was done. Spectra in the wavelength region of 2l-4l′ and 2l-5l′ L-shell transitions in F-like, Ne-like and Na-like germanium ions were recorded using the FSSR-2D spectrometer equipped with a spherically bent quartz crystal with a spectral resolution λ/Δλ better than 5000. Spectral lines were compared with theoretical values obtained using the LANL plasma kinetic code ATOMIC. Fair agreement between experimental and theoretical spectral lines has been observed, which allowed to measure enough high bulk electron temperature values of 560 eV and electron density of ∼1021 cm−3 in Ge plasma irradiated by rather small commercial high repetition rate Nd:YAG laser system.