Rate of Urinary Tract Infections, Bacteremia, and Meningitis in Preterm and Term Infants.

BACKGROUND AND OBJECTIVES: There are very limited data on the rate of urinary tract infections (UTI), bacteremia, and meningitis in preterm infants with fever. Many of the studies on the incidence of these infections excluded preterm infants. This study compared the rate of these infections in preterm infants born at 32-36 weeks to term infants born at 37-42 weeks. METHODS: A multicenter observational cohort study was conducted to evaluate rates of UTI, bacteremia, and meningitis in term and preterm infants 8-60 days of age with a diagnosis of fever from 2016 through 2022 using encounter data from children's hospitals in the Pediatric Health Information System. RESULTS: There were 19 507 total febrile infants identified, of which 2162 were preterm and 17 345 were term. Preterm infants had a lower rate of UTI than term infants (1.8% confidence interval [CI] [1.3-2.5] vs 3.0% CI [2.7-3.2], P = .001). Preterm and term infants did not have statistically different rates of bacteremia (1.5% CI [1.3-1.7] vs 1.2% CI [0.8-1.8], P = .44) or meningitis (0.16% CI [0.1-0.2] vs 0.05% CI [0-0.2], P = .36). CONCLUSIONS: There was no difference in the rate of bacteremia or meningitis between term and preterm infants in a large multicenter cohort of febrile infants. Preterm infants had a lower rate of UTI than term infants. This is the first multicenter study to compare UTI, bacteremia, and meningitis between term and preterm febrile infants.

Self-Shielding of X-ray Emission from Ultrafast Laser Processing Due to Geometrical Changes of the Interaction Zone.

Materials processing with ultrashort laser pulses is one of the most important approaches when it comes to machining with very high accuracy. High pulse repetition rates and high average laser power can be used to attain high productivity. By tightly focusing the laser beam, the irradiances on the workpiece can exceed 1013 W/cm2, and thus cause usually unwanted X-ray emission. Pulsed laser processing of micro holes exhibits two typical features: a gradual increase in the irradiated surface within the hole and, with this, a decrease in the local irradiance. This and the shielding by the surrounding material diminishes the amount of ionizing radiation emitted from the process; therefore, both effects lead to a reduction in the potential X-ray exposure of an operator or any nearby person. The present study was performed to quantify this self-shielding of the X-ray emission from laser-drilled micro holes. Percussion drilling in standard air atmosphere was investigated using a laser with a wavelength of 800 nm a pulse duration of 1 ps, a repetition rate of 1 kHz, and with irradiances of up to 1.1·1014 W/cm. The X-ray emission was measured by means of a spectrometer. In addition to the experimental results, we present a model to predict the expected X-ray emission at different angles to the surface. These calculations are based on raytracing simulations to obtain the local irradiance, from which the local X-ray emission inside the holes can be calculated. It was found that the X-ray exposure measured in the surroundings strongly depends on the geometry of the hole and the measuring direction, as predicted by the theoretical model.

Compact 20-pass thin-disk multipass amplifier stable against thermal lensing effects and delivering 330 mJ pulses with M2 < 1.17.

We report on an Yb:YAG thin-disk multipass amplifier delivering 100 ns long pulses at a central wavelength of 1030 nm with an energy of 330 mJ at a repetition rate of 100 Hz. The beam quality factor at the maximum energy was measured to be M2 < 1.17. The small signal gain is 21.7, and the gain at 330 mJ was measured to be 6.9. The 20-pass amplifier is designed as a concatenation of stable resonator segments in which the beam is alternately Fourier transformed and relay-imaged back to the disk by a 4f-imaging optical scheme stage. The Fourier transform propagation makes the output beam robust against spherical phase front distortions, while the 4f-stage is used to compensate the thermal lens of the thin-disk and to reduce the footprint of the amplifier.

Enhancing heat transfer at low temperatures by laser functionalization of the inner surface of metal pipes.

The latent heat transfer during vapour condensation in the condenser section of passive heat transport devices such as the two-phase closed thermosiphon is limited by film condensation. Dropwise condensation provides an increase of the heat transfer coefficient by up to one order of magnitude and can be achieved with a water-repellant surface. The inner surface of pipes made from stainless steel was functionalized by laser surface texturing with ultrashort laser pulses and subsequent storage in a liquid containing long-chained hydrocarbons. The pipes were separated into half-pipes by wire eroding to enable laser texturing of the inner surface, and were then joined by electron beam welding after laser texturing. As a result, superhydrophobic and water-repellent surfaces with a contact angle of 153° were obtained on the inner surface of the pipes with a length of up to 1 m. The functionalized pipes were used in the condenser section of a two-phase closed thermosiphon to demonstrate a heat transfer rate of 0.92 kW at 45 °C, which is approximately three times the heat transfer rate of 0.31 kW of a smooth reference pipe.

Data-Driven Prediction and Uncertainty Quantification of Process Parameters for Directed Energy Deposition.

Laser-based directed energy deposition using metal powder (DED-LB/M) offers great potential for a flexible production mainly defined by software. To exploit this potential, knowledge of the process parameters required to achieve a specific track geometry is essential. Existing analytical, numerical, and machine-learning approaches, however, are not yet able to predict the process parameters in a satisfactory way. A trial-&-error approach is therefore usually applied to find the best process parameters. This paper presents a novel user-centric decision-making workflow, in which several combinations of process parameters that are most likely to yield the desired track geometry are proposed to the user. For this purpose, a Gaussian Process Regression (GPR) model, which has the advantage of including uncertainty quantification (UQ), was trained with experimental data to predict the geometry of single DED tracks based on the process parameters. The inherent UQ of the GPR together with the expert knowledge of the user can subsequently be leveraged for the inverse question of finding the best sets of process parameters by minimizing the expected squared deviation between target and actual track geometry. The GPR was trained and validated with a total of 379 cross sections of single tracks and the benefit of the workflow is demonstrated by two exemplary use cases.

Detrimental effects of period-chirped gratings in pulse compressors.

We present a comprehensive simulative and experimental investigation of how period-chirped pulse compression gratings affect the compressed pulses. A specifically developed ray-tracing tool was used for the simulative investigations. It is shown that the chirp creates a characteristic spatio-spectral error pattern, which leads to a degradation of the beam quality and an increase of the pulse duration. The experimental investigations, for which both a narrow-bandwidth continuous-wave and a pulsed laser beam were guided through a Treacy-compressor comprised of period-chirped gratings, confirm the simulation results and present methods on how to identify the chirp's characteristic error pattern in practice.

BCL11B and the NuRD complex cooperatively guard T-cell fate and inhibit OPA1-mediated mitochondrial fusion in T cells.

The nucleosome remodeling and histone deacetylase (NuRD) complex physically associates with BCL11B to regulate murine T-cell development. However, the function of NuRD complex in mature T cells remains unclear. Here, we characterize the fate and metabolism of human T cells in which key subunits of the NuRD complex or BCL11B are ablated. BCL11B and the NuRD complex bind to each other and repress natural killer (NK)-cell fate in T cells. In addition, T cells upregulate the NK cell-associated receptors and transcription factors, lyse NK-cell targets, and are reprogrammed into NK-like cells (ITNKs) upon deletion of MTA2, MBD2, CHD4, or BCL11B. ITNKs increase OPA1 expression and exhibit characteristically elongated mitochondria with augmented oxidative phosphorylation (OXPHOS) activity. OPA1-mediated elevated OXPHOS enhances cellular acetyl-CoA levels, thereby promoting the reprogramming efficiency and antitumor effects of ITNKs via regulating H3K27 acetylation at specific targets. In conclusion, our findings demonstrate that the NuRD complex and BCL11B cooperatively maintain T-cell fate directly by repressing NK cell-associated transcription and indirectly through a metabolic-epigenetic axis, providing strategies to improve the reprogramming efficiency and antitumor effects of ITNKs.

Injection-seeded high-power Yb:YAG thin-disk laser stabilized by the Pound-Drever-Hall method.

We demonstrate an injection-seeded thin-disk Yb:YAG laser at 1030 nm, stabilized by the Pound-Drever-Hall (PDH) method. We modified the PDH scheme to obtain an error signal free from Trojan locking points, which allowed robust re-locking of the laser and reliable long-term operation. The single-frequency pulses have 50 mJ energy (limited to avoid laser-induced damage) with a beam quality of M2 < 1.1 and an adjustable length of 55-110 ns. Heterodyne measurements confirmed a spectral linewidth of 3.7 MHz. The short pulse build-up time (850 ns) makes this laser suitable for laser spectroscopy of muonic hydrogen, pursued by the CREMA collaboration.

CEBPA phase separation links transcriptional activity and 3D chromatin hubs.

Cell identity is orchestrated through an interplay between transcription factor (TF) action and genome architecture. The mechanisms used by TFs to shape three-dimensional (3D) genome organization remain incompletely understood. Here we present evidence that the lineage-instructive TF CEBPA drives extensive chromatin compartment switching and promotes the formation of long-range chromatin hubs during induced B cell-to-macrophage transdifferentiation. Mechanistically, we find that the intrinsically disordered region (IDR) of CEBPA undergoes in vitro phase separation (PS) dependent on aromatic residues. Both overexpressing B cells and native CEBPA-expressing cell types such as primary granulocyte-macrophage progenitors, liver cells, and trophectoderm cells reveal nuclear CEBPA foci and long-range 3D chromatin hubs at CEBPA-bound regions. In short, we show that CEBPA can undergo PS through its IDR, which may underlie in vivo foci formation and suggest a potential role of PS in regulating CEBPA function.

3D chromatin reprogramming primes human memory TH2 cells for rapid recall and pathogenic dysfunction.

Memory T cells provide long-lasting defense responses through their ability to rapidly reactivate, but how they efficiently "recall" an inflammatory transcriptional program remains unclear. Here, we show that human CD4+ memory T helper 2 (TH2) cells carry a chromatin landscape synergistically reprogrammed at both one-dimensional (1D) and 3D levels to accommodate recall responses, which is absent in naive T cells. In memory TH2 cells, recall genes were epigenetically primed through the maintenance of transcription-permissive chromatin at distal (super)enhancers organized in long-range 3D chromatin hubs. Precise transcriptional control of key recall genes occurred inside dedicated topologically associating domains ("memory TADs"), in which activation-associated promoter-enhancer interactions were preformed and exploited by AP-1 transcription factors to promote rapid transcriptional induction. Resting memory TH2 cells from patients with asthma showed premature activation of primed recall circuits, linking aberrant transcriptional control of recall responses to chronic inflammation. Together, our results implicate stable multiscale reprogramming of chromatin organization as a key mechanism underlying immunological memory and dysfunction in T cells.

Carm1-arginine methylation of the transcription factor C/EBPα regulates transdifferentiation velocity.

Here, we describe how the speed of C/EBPα-induced B cell to macrophage transdifferentiation (BMT) can be regulated, using both mouse and human models. The identification of a mutant of C/EBPα (C/EBPαR35A) that greatly accelerates BMT helped to illuminate the mechanism. Thus, incoming C/EBPα binds to PU.1, an obligate partner expressed in B cells, leading to the release of PU.1 from B cell enhancers, chromatin closing and silencing of the B cell program. Released PU.1 redistributes to macrophage enhancers newly occupied by C/EBPα, causing chromatin opening and activation of macrophage genes. All these steps are accelerated by C/EBPαR35A, initiated by its increased affinity for PU.1. Wild-type C/EBPα is methylated by Carm1 at arginine 35 and the enzyme's perturbations modulate BMT velocity as predicted from the observations with the mutant. Increasing the proportion of unmethylated C/EBPα in granulocyte/macrophage progenitors by inhibiting Carm1 biases the cell's differentiation toward macrophages, suggesting that cell fate decision velocity and lineage directionality are closely linked processes.

Simple spatially resolved period measurement of chirped pulse compression gratings.

We present an easy-to-implement and low-cost setup for the precise measurement of the period chirp of diffraction gratings offering a resolution of 15 pm and reasonable scan speeds of 2 seconds per measurement point. The principle of the measurement is illustrated on the example of two different pulse compression gratings, one fabricated by laser interference lithography (LIL) and the other by scanning beam interference lithography (SBIL). A period chirp of 0.22 pm/mm2 at a nominal period of 610 nm was measured for the grating fabricated with LIL, whereas no chirp was observed for the grating fabricated by SBIL, which had a nominal period of 586.2 nm.

General mathematical model for the period chirp in interference lithography.

We present a general analytical model for the calculation of the spatial distribution of the grating period, enabling the unification of all configurations of classical laser interference lithography (LIL) and scanning-beam interference lithography (SBIL) into one formalism. This is possible due to the consideration of Gaussian beams instead of point sources which allow for the accurate description of not only the laser's far-field but also its near-field. The proposed model enables the calculation of the grating period, the inclination and the slant of the grating lines on arbitrarily shaped substrates, originating from the interference of arbitrarily orientated and positioned Gaussian beams.

Pound-Drever-Hall locking scheme free from Trojan operating points.

The Pound-Drever-Hall (PDH) technique is a popular method for stabilizing the frequency of a laser to a stable optical resonator or, vice versa, the length of a resonator to the frequency of a stable laser. We propose a refinement of the technique yielding an "infinite" dynamic (capture) range so that a resonator is correctly locked to the seed frequency, even after large perturbations. The stable but off-resonant lock points (also called Trojan operating points), present in conventional PDH error signals, are removed by phase modulating the seed laser at a frequency corresponding to half the free spectral range of the resonator. We verify the robustness of our scheme experimentally by realizing an injection-seeded Yb:YAG thin-disk laser. We also give an analytical formulation of the PDH error signal for arbitrary modulation frequencies and discuss the parameter range for which our PDH locking scheme guarantees correct locking. Our scheme is simple as it does not require additional electronics apart from the standard PDH setup and is particularly suited to realize injection-seeded lasers and injection-seeded optical parametric oscillators.

Diagnostic testing for evaluation of brief resolved unexplained events.

BACKGROUND: Since the publication of the American Academy of Pediatrics (AAP) clinical practice guideline for brief resolved unexplained events (BRUEs), a few small, single-center studies have suggested low yield of diagnostic testing in infants presenting with such an event. We conducted this large retrospective multicenter study to determine the role of diagnostic testing in leading to a confirmatory diagnosis in BRUE patients. METHODS: Secondary analysis from a large multicenter cohort derived from 15 hospitals participating in the BRUE Quality Improvement and Research Collaborative. The study subjects were infants < 1 year of age presenting with a BRUE to the emergency departments (EDs) of these hospitals between October 1, 2015, and September 30, 2018. Potential BRUE cases were identified using a validated algorithm that relies on administrative data. Chart review was conducted to confirm study inclusion/exclusion, AAP risk criteria, final diagnosis, and contribution of test results. Findings were stratified by ED or hospital discharge and AAP risk criteria. For each patient, we identified whether any diagnostic test contributed to the final diagnosis. We distinguished true (contributory) results from false-positive results. RESULTS: Of 2036 patients meeting study criteria, 63.2% were hospitalized, 87.1% qualified as AAP higher risk, and 45.3% received an explanatory diagnosis. Overall, a laboratory test, imaging, or an ancillary test supported the final diagnosis in 3.2% (65/2036, 95% confidence interval [CI] 2.7%-4.4%) of patients. Out of 5163 diagnostic tests overall, 1.1% (33/2897, 95% CI 0.8%-1.5%) laboratory tests and 1.5% (33/2266, 95% CI 1.0%-1.9%) of imaging and ancillary studies contributed to a diagnosis. Although 861 electrocardiograms were performed, no new cardiac diagnoses were identified during the index visit. CONCLUSIONS: Diagnostic testing to explain BRUE including for those with AAP higher risk criteria is low yield and rarely contributes to an explanation. Future research is needed to evaluate the role of testing in more specific, at-risk populations.

SEGCOND predicts putative transcriptional condensate-associated genomic regions by integrating multi-omics data.

MOTIVATION: The compartmentalization of biochemical reactions, involved in the activation of gene expression in the eukaryotic nucleus, leads to the formation of membraneless bodies through liquid-liquid phase separation. These formations, called transcriptional condensates, appear to play important roles in gene regulation as they are assembled through the association of multiple enhancer regions in 3D genomic space. To date, we are still lacking efficient computational methodologies to identify the regions responsible for the formation of such condensates, based on genomic and conformational data. RESULTS: In this work, we present SEGCOND, a computational framework aiming to highlight genomic regions involved in the formation of transcriptional condensates. SEGCOND is flexible in combining multiple genomic datasets related to enhancer activity and chromatin accessibility, to perform a genome segmentation. It then uses this segmentation for the detection of highly transcriptionally active regions of the genome. At a final step, and through the integration of Hi-C data, it identifies regions of putative transcriptional condensates (PTCs) as genomic domains where multiple enhancer elements coalesce in 3D space. SEGCOND identifies a subset of enhancer segments with increased transcriptional activity. PTCs are also found to significantly overlap highly interconnected enhancer elements and super enhancers obtained through two independent approaches. Application of SEGCOND on data from a well-defined system of B-cell to macrophage transdifferentiation leads to the identification of previously unreported genes with a likely role in the process. AVAILABILITY AND IMPLEMENTATION: Source code and details for the implementation of SEGCOND is available at https://github.com/AntonisK95/SEGCOND. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Theoretical investigation on the elimination of the period chirp by deliberate substrate deformations.

We present a theoretical investigation on the approach of deliberately bending the substrate during the exposure within laser interference lithography to compensate for the period chirp. It is shown that the yet undiscovered function of the surface geometry, necessary to achieve the zero-chirp case (i.e. having a perfectly constant period over the whole substrate) is determined by a first-order differential equation. As the direct analytical solution of this differential equation is difficult, a numerical approach is developed, based on the optimization of pre-defined functions towards the unknown analytical solution of the differential equation by means of a Nelder-Mead simplex algorithm. By applying this method to a concrete example, we show that an off-center placement of the substrate with respect to the point sources is advantageous both in terms of achievable period and substrate curvature and that a fourth-order polynomial can greatly satisfy the differential equation leading to a root-mean-square deviation of only 1.4 pm with respect to the targeted period of 610 nm.

Experimental analysis on CPA-free thin-disk multipass amplifiers operated in a helium-rich atmosphere.

We present an experimental investigation on the benefits of helium as an atmospheric gas in CPA-free thin-disk multipass amplifiers (TDMPAs) for the amplification to average powers exceeding 1 kW and pulse peak powers reaching 5 GW. Both the performance of the amplifier and the properties of the amplified sub-400 fs laser pulses centred at a wavelength of 1030 nm are compared for different helium concentrations in air, outlining and quantifying the benefits of a helium-rich atmosphere. The amplification of 100 µJ pulses in an atmosphere with 60% helium instead of air led to a maximum increase in efficiency from 24% to 29%. This translated into an increase of average output power and pulse energy of 34 W (i.e +19%) and 0.34 mJ (i.e. +19%) respectively. At the same time an improvement of the beam quality from M2 = 1.18 to M2 = 1.14 was achieved. For the amplification of 10 µJ pulses to over 1 kW of average power an atmosphere with 33% helium led to an improved beam pointing stability by a factor of 2. Moreover, the beam propagation factor M2 improved by 0.1, and the power stability improved by approximately 10%.