Perinatal optimisation for periviable birth and outcomes: a 4-year network analysis (2018-2021) across a change in national guidance.

Introduction: The British Association of Perinatal Medicine (BAPM) released their revised framework for extremely preterm infant management in 2019. This revised framework promotes consideration of perinatal optimisation and survival-focused care from 22 weeks gestation onwards. This was a departure from the previous BAPM framework which recommended comfort care as the only recommended management for infants <23 + 0 weeks. Methods: Our study evaluates the clinical impact that this updated framework has had across the Northwest of England. We utilised anonymised network data from periviable infants delivered across the region to examine changes in perinatal optimisation practices and survival outcomes following the release of the latest BAPM framework. Results: Our data show that after the introduction of the updated framework there has been an increase in perinatal optimisation practices for periviable infants and an 80% increase in the number of infants born at 22 weeks receiving survival-focused care and admission to a neonatal unit. Discussion: There remain significant discrepancies in optimisation practices by gestational age, which may be contributing to the static survival rates that were observed in the lowest gestational ages.

Evidence for the earliest structural use of wood at least 476,000 years ago.

Wood artefacts rarely survive from the Early Stone Age since they require exceptional conditions for preservation; consequently, we have limited information about when and how hominins used this basic raw material1. We report here on the earliest evidence for structural use of wood in the archaeological record. Waterlogged deposits at the archaeological site of Kalambo Falls, Zambia, dated by luminescence to at least 476 ± 23 kyr ago (ka), preserved two interlocking logs joined transversely by an intentionally cut notch. This construction has no known parallels in the African or Eurasian Palaeolithic. The earliest known wood artefact is a fragment of polished plank from the Acheulean site of Gesher Benot Ya'aqov, Israel, more than 780 ka (refs. 2,3). Wooden tools for foraging and hunting appear 400 ka in Europe4-8, China9 and possibly Africa10. At Kalambo we also recovered four wood tools from 390 ka to 324 ka, including a wedge, digging stick, cut log and notched branch. The finds show an unexpected early diversity of forms and the capacity to shape tree trunks into large combined structures. These new data not only extend the age range of woodworking in Africa but expand our understanding of the technical cognition of early hominins11, forcing re-examination of the use of trees in the history of technology12,13.

Posterior Cruciate Ligament Reconstruction With Quadriceps Tendon-Patellar Bone Autograft.

Multiple surgical techniques for posterior cruciate ligament reconstruction have been described and subsequently scrutinized. We describe a surgical technique using full-thickness quadriceps tendon-patellar bone autograft in single-bundle, all-inside posterior cruciate ligament reconstruction that offers the following advantages over traditional technique: This technique mitigates the risk of tunnel widening and convergence while preserving bone stock, eliminating the killer turn, allowing for suspensory cortical fixation to optimize stabilization, and using a bone plug that allows for faster graft incorporation.

MELAS: Phenotype Classification into Classic-versus-Atypical Presentations.

BACKGROUND AND PURPOSE: An increased number of pathogenic variants have been described in mitochondrial encephalomyopathy lactic acidosis and strokelike episodes (MELAS). Different imaging presentations have emerged in parallel with a growing recognition of clinical and outcome variability, which pose a diagnostic challenge to neurologists and radiologists and may impact an individual patient's response to therapeutic interventions. By evaluating clinical, neuroimaging, laboratory, and genetic findings, we sought to improve our understanding of the sources of potential phenotype variability in patients with MELAS. MATERIALS AND METHODS: This retrospective single-center study included individuals who had confirmed mitochondrial DNA pathogenic variants and a diagnosis of MELAS and whose data were reviewed from January 2000 through November 2021. The approach included a review of clinical, neuroimaging, laboratory, and genetic data, followed by an unsupervised hierarchical cluster analysis looking for sources of phenotype variability in MELAS. Subsequently, experts identified "victory-variables" that best differentiated MELAS cohort clusters. RESULTS: Thirty-five patients with a diagnosis of mitochondrial DNA-based MELAS (median age, 12 years; interquartile range, 7-24 years; 24 female) were eligible for this study. Fifty-three discrete variables were evaluated by an unsupervised cluster analysis, which revealed that two distinct phenotypes exist among patients with MELAS. After experts reviewed the variables, they selected 8 victory-variables with the greatest impact in determining the MELAS subgroups: developmental delay, sensorineural hearing loss, vision loss in the first strokelike episode, Leigh syndrome overlap, age at the first strokelike episode, cortical lesion size, regional brain distribution of lesions, and genetic groups. Ultimately, 2-step differentiating criteria were defined to classify atypical MELAS. CONCLUSIONS: We identified 2 distinct patterns of MELAS: classic MELAS and atypical MELAS. Recognizing different patterns in MELAS presentations will enable clinical and research care teams to better understand the natural history and prognosis of MELAS and identify the best candidates for specific therapeutic interventions.

Enhanced stimulated Raman scattering during intense laser propagation.

Stimulated Raman scattering is ubiquitous in many high-intensity laser environments. Parametric four-wave mixing between the pump and Raman sidebands can affect the Raman gain, but stringent phase matching requirements and strongly nonlinear dynamics obscure clear understanding of its effects at high laser powers. Here we investigate four-wave mixing in the presence of strong self-focusing and weak ionization at laser powers above the Kerr critical power. Theoretical analysis shows that the plasma generated at focus naturally leads to phase matching conditions suitable for enhanced Raman gain, almost without regard to the initial phase mismatch. Multidimensional nonlinear optical simulations with multiphoton and collisional ionization confirm the enhancement and suggest that it may lead to significantly higher Raman losses in some high-intensity laser environments.

Ultrafast visualization of incipient plasticity in dynamically compressed matter.

Plasticity is ubiquitous and plays a critical role in material deformation and damage; it inherently involves the atomistic length scale and picosecond time scale. A fundamental understanding of the elastic-plastic deformation transition, in particular, incipient plasticity, has been a grand challenge in high-pressure and high-strain-rate environments, impeded largely by experimental limitations on spatial and temporal resolution. Here, we report femtosecond MeV electron diffraction measurements visualizing the three-dimensional (3D) response of single-crystal aluminum to the ultrafast laser-induced compression. We capture lattice transitioning from a purely elastic to a plastically relaxed state within 5 ps, after reaching an elastic limit of ~25 GPa. Our results allow the direct determination of dislocation nucleation and transport that constitute the underlying defect kinetics of incipient plasticity. Large-scale molecular dynamics simulations show good agreement with the experiment and provide an atomic-level description of the dislocation-mediated plasticity.

eDNA in subterranean ecosystems: Applications, technical aspects, and future prospects.

Monitoring of biota is pivotal for the assessment and conservation of ecosystems. Environments worldwide are being continuously and increasingly exposed to multiple adverse impacts, and the accuracy and reliability of the biomonitoring tools that can be employed shape not only the present, but more importantly, the future of entire habitats. The analysis of environmental DNA (eDNA) metabarcoding data provides a quick, affordable, and reliable molecular approach for biodiversity assessments. However, while extensively employed in aquatic and terrestrial surface environments, eDNA-based studies targeting subterranean ecosystems are still uncommon due to the lack of accessibility and the cryptic nature of these environments and their species. Recent advances in genetic and genomic analyses have established a promising framework for shedding new light on subterranean biodiversity and ecology. To address current knowledge and the future use of eDNA methods in groundwaters and caves, this review explores conceptual and technical aspects of the application and its potential in subterranean systems. We briefly introduce subterranean biota and describe the most used traditional sampling techniques. Next, eDNA characteristics, application, and limitations in the subsurface environment are outlined. Last, we provide suggestions on how to overcome caveats and delineate some of the research avenues that will likely shape this field in the near future. We advocate that eDNA analyses, when carefully conducted and ideally combined with conventional sampling techniques, will substantially increase understanding and enable crucial expansion of subterranean community characterisation. Given the importance of groundwater and cave ecosystems for nature and humans, eDNA can bring to the surface essential insights, such as study of ecosystem assemblages and rare species detection, which are critical for the preservation of life below, as well as above, the ground.

Propylene glycol toxicity from compulsive corn starch ingestion.

INTRODUCTION: Propylene glycol (PG) is usually considered safe, however, toxicity can develop with high doses or when used for prolonged periods of time. PG can be found in some medications as well as some food products. We report a case of likely PG toxicity that occurred after compulsive daily ingestion of large amounts of corn starch. CASE REPORT: Our patient initially presented to an outside hospital (OSH) via ambulance for altered mental status. Her mental status improved after her blood sugar of 25 was corrected. On admission to OSH Emergency Department her initial vital signs included a heart rate of 115 bpm, blood pressure 113/59 mm/hg, temperature 35.8C. Pertinent labs included: sodium 119 mEq/L, bicarbonate 9 mEq/L, anion gap 29 mEq/L, creatinine 2.5 mg/dL and lactic acid 20 mEq/L. On transfer to our hospital her repeat lactic acid was 20 mEq/L, osmolar gap was 20. Her PG level, which was drawn several hours after her initial presentation, was 11 mg/dL. Our patient noted that she ingested a 16 oz. package of corn starch mixed with baking soda approximately every 2 days. Given the concerns for PG she was underwent intermittent hemodialysis. PG and lactic acid levels improved, however, she ultimately died due to complications from her hospitalization. DISCUSSION: PG causes toxicity through metabolism to lactic acid. While there are small amounts in food products and medications, under the right circumstances, PG can accumulate and lead to significant toxicity.

Magnetic Field Amplification by a Nonlinear Electron Streaming Instability.

Magnetic field amplification by relativistic streaming plasma instabilities is central to a wide variety of high-energy astrophysical environments as well as to laboratory scenarios associated with intense lasers and electron beams. We report on a new secondary nonlinear instability that arises for relativistic dilute electron beams after the saturation of the linear Weibel instability. This instability grows due to the transverse magnetic pressure associated with the beam current filaments, which cannot be quickly neutralized due to the inertia of background ions. We show that it can amplify the magnetic field strength and spatial scale by orders of magnitude, leading to large-scale plasma cavities with strong magnetic field and to very efficient conversion of the beam kinetic energy into magnetic energy. The instability growth rate, saturation level, and scale length are derived analytically and shown to be in good agreement with fully kinetic simulations.

The data-driven future of high-energy-density physics.

High-energy-density physics is the field of physics concerned with studying matter at extremely high temperatures and densities. Such conditions produce highly nonlinear plasmas, in which several phenomena that can normally be treated independently of one another become strongly coupled. The study of these plasmas is important for our understanding of astrophysics, nuclear fusion and fundamental physics-however, the nonlinearities and strong couplings present in these extreme physical systems makes them very difficult to understand theoretically or to optimize experimentally. Here we argue that machine learning models and data-driven methods are in the process of reshaping our exploration of these extreme systems that have hitherto proved far too nonlinear for human researchers. From a fundamental perspective, our understanding can be improved by the way in which machine learning models can rapidly discover complex interactions in large datasets. From a practical point of view, the newest generation of extreme physics facilities can perform experiments multiple times a second (as opposed to approximately daily), thus moving away from human-based control towards automatic control based on real-time interpretation of diagnostic data and updates of the physics model. To make the most of these emerging opportunities, we suggest proposals for the community in terms of research design, training, best practice and support for synthetic diagnostics and data analysis.

Transcriptomic Response in the Spleen after Whole-Body Low-Dose X-Ray Irradiation.

As the use of medical radiation procedures continues to rise, it is imperative to further our understanding of the effects of this exposure. The spleen is not known as a particularly radiosensitive organ, although its tolerance to radiation is not well understood. Low-dose radiation exposure has been implicated in beneficial responses, particularly in cell death and DNA damage repair. In this study, adult male rats received 2, 20, 200 mGy or 4 Gy whole-body X-ray irradiation and the transcriptional response in the spleen was analyzed at 0.5, 4 and 24 h postirradiation. We analyzed expression of genes involved in apoptosis, cell cycle progression and DNA damage repair. As expected, 4 Gy irradiated animals demonstrated elevated expression of genes related to apoptosis at 0.5, 4 and 24 h postirradiation in the spleen. These animals also showed upregulation of DNA damage repair genes at 24 h postirradiation. Interestingly, the spleens of 20 mGy irradiated animals showed reduced apoptosis and cell cycle arrest compared to the spleens of sham-irradiated animals. These results further reveal that the cellular response in the spleen to whole-body irradiation differs between low- and high-dose irradiation.

Extremely Dense Gamma-Ray Pulses in Electron Beam-Multifoil Collisions.

Sources of high-energy photons have important applications in almost all areas of research. However, the photon flux and intensity of existing sources is strongly limited for photon energies above a few hundred keV. Here we show that a high-current ultrarelativistic electron beam interacting with multiple submicrometer-thick conducting foils can undergo strong self-focusing accompanied by efficient emission of gamma-ray synchrotron photons. Physically, self-focusing and high-energy photon emission originate from the beam interaction with the near-field transition radiation accompanying the beam-foil collision. This near field radiation is of amplitude comparable with the beam self-field, and can be strong enough that a single emitted photon can carry away a significant fraction of the emitting electron energy. After beam collision with multiple foils, femtosecond collimated electron and photon beams with number density exceeding that of a solid are obtained. The relative simplicity, unique properties, and high efficiency of this gamma-ray source open up new opportunities for both applied and fundamental research including laserless investigations of strong-field QED processes with a single electron beam.

Postnatally acquired CMV meningitis diagnosed via BioFire FilmArray: A case report.

Postnatally acquired cytomegalovirus (CMV) is commonly acquired via breast milk, with premature infants more frequently developing symptoms of CMV infection in comparison to term infants. Meningitis is a rare clinical manifestation of CMV infection. The diagnosis of meningitis is difficult to make in infants, particularly those who are preterm. Consequentially, broad-spectrum empiric antimicrobial coverage is often administered for several days while waiting for current gold standard CSF testing to result. The BioFire FilmArray (BFA) simultaneously tests for 14 different pathogens, including CMV, allowing for quicker diagnosis and shorter time to definitive treatment. Here, we report a very low birth weight infant with postnatally acquired CMV meningitis, the first to our knowledge to be diagnosed using the BioFire FilmArray.

Mechanisms of resistance to selective RET tyrosine kinase inhibitors in RET fusion-positive non-small-cell lung cancer.

BACKGROUND: Rearranged during transfection (RET) gene fusions are a validated target in non-small-cell lung cancer (NSCLC). RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently demonstrated favorable antitumor activity and safety profiles in advanced RET fusion-positive NSCLC, and both have received approval by the US Food and Drug Administration for this indication. Insights into mechanisms of resistance to selective RET inhibitors remain limited. PATIENTS AND METHODS: This study was performed at five institutions. Tissue and/or cell-free DNA was obtained from patients with RET fusion-positive NSCLC after treatment with selpercatinib or pralsetinib and assessed by next-generation sequencing (NGS) or MET FISH. RESULTS: We analyzed a total of 23 post-treatment tissue and/or plasma biopsies from 18 RET fusion-positive patients who received an RET-selective inhibitor (selpercatinib, n = 10; pralsetinib, n = 7; pralsetinib followed by selpercatinib, n = 1, with biopsy after each inhibitor). Three cases had paired tissue and plasma samples, of which one also had two serial resistant tissue specimens. The median progression-free survival on RET inhibitors was 6.3 months [95% confidence interval 3.6-10.8 months]. Acquired RET mutations were identified in two cases (10%), both affecting the RET G810 residue in the kinase solvent front. Three resistant cases (15%) harbored acquired MET amplification without concurrent RET resistance mutations, and one specimen had acquired KRAS amplification. No other canonical driver alterations were identified by NGS. Among 16 resistant tumor specimens, none had evidence of squamous or small-cell histologic transformation. CONCLUSIONS: RET solvent front mutations are a recurrent mechanism of RET inhibitor resistance, although they occurred at a relatively low frequency. The majority of resistance to selective RET inhibition may be driven by RET-independent resistance such as acquired MET or KRAS amplification. Next-generation RET inhibitors with potency against RET resistance mutations and combination strategies are needed to effectively overcome resistance in these patients.

Nonlinear underwater propagation of picosecond ultraviolet laser beams.

Meter-scale nonlinear propagation of a picosecond ultraviolet laser beam in water, sufficiently intense to cause stimulated Raman scattering (SRS), nonlinear focusing, pump-Stokes nonlinear coupling, and photoexcitation, was characterized in experiments and simulations. Pump and SRS Stokes pulse energies were measured, and pump beam profiles were imaged at propagation distances up to 100 cm for a range of laser power below and above self-focusing critical power. Simulations with conduction band excitation energy UCB=9.5eV, effective electron mass meff=0.2me, Kerr nonlinear refractive index n2=5×10-16cm2/W, and index contribution due to SRS susceptibility n2r=1.7×10-16cm2/W produced the best agreement with experimental data.

Radiation therapy strategies for skull-base malignancies.

INTRODUCTION: The management of skull base malignancies continues to evolve with improvements in surgical technique, advances in radiation delivery and novel systemic agents. METHODS: In this review, we aim to discuss in detail the management of common skull base pathologies which typically require multimodality therapy, focusing on the radiotherapeutic aspects of care. RESULTS: Technological advances in the administration of radiation therapy have led to a wide variety of different treatment strategies for the treatment of skull base malignances, with outcomes summarized herein. CONCLUSION: Radiation treatment plays a key and critical role in the management of patients with skull base tumors. Recent advancements continue to improve the risk/benefit ratio for radiotherapy in this setting.

Catching and killing of airborne SARS-CoV-2 to control spread of COVID-19 by a heated air disinfection system.

Airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via air-conditioning systems poses a significant threat for the continued escalation of the current coronavirus disease (COVID-19) pandemic. Considering that SARS-CoV-2 cannot tolerate temperatures above 70 °C, here we designed and fabricated efficient filters based on heated nickel (Ni) foam to catch and kill SARS-CoV-2. Virus test results revealed that 99.8% of the aerosolized SARS-CoV-2 was caught and killed by a single pass through a novel Ni-foam-based filter when heated up to 200 °C. In addition, the same filter was also used to catch and kill 99.9% of Bacillus anthracis, an airborne spore. This study paves the way for preventing transmission of SARS-CoV-2 and other highly infectious airborne agents in closed environments.

Constitutive Model for Time-Dependent Flows of Shear-Thickening Suspensions.

We develop a tensorial constitutive model for dense, shear-thickening particle suspensions subjected to time-dependent flow. Our model combines a recently proposed evolution equation for the suspension microstructure in rate-independent materials with ideas developed previously to explain the steady flow of shear-thickening ones, whereby friction proliferates among compressive contacts at large particle stresses. We apply our model to shear reversal, and find good qualitative agreement with particle-level, discrete-element simulations whose results we also present.

High-Pressure Melt Curve and Phase Diagram of Lithium.

We investigate the phase diagram of lithium at temperatures of 200 to 400 K, to pressures over 100 GPa using x-ray diffraction in diamond anvil cells, covering the region in which the melting curve is disputed. To overcome degradation of the diamond anvils by dense lithium we utilize a rapid compression scheme taking advantage of the high flux available at modern synchrotrons. Our results show the hR1 and cI16 phases to be stable to higher temperature than previously reported. The melting minima of lithium is found to be close to room temperature between 40 and 60 GPa, below which the solid is crystalline. Analysis of the stability fields of the cI16 and oC88 phases suggest the existence of a triple point between these and an undetermined solid phase at 60 GPa between 220 and 255 K.

First Documented Pathologies in Tenontosaurus tilletti with Comments on Infection in Non-Avian Dinosaurs.

In 2001, a nearly complete sub-adult Tenontosaurus tilletti was collected from the Antlers Formation (Aptian-Albian) of southeastern Oklahoma. Beyond its exceptional preservation, computed tomography (CT) and physical examination revealed this specimen has five pathological elements with four of the pathologies a result of trauma. Left pedal phalanx I-1 and left dorsal rib 10 are both fractured with extensive callus formation in the later stages of healing. Left dorsal rib 7 (L7) and right dorsal rib 10 (R10) exhibit impacted fractures compressed 26 mm and 24 mm, respectively. The fracture morphologies in L7 and R10 indicate this animal suffered a strong compressive force coincident with the long axis of the ribs. All three rib pathologies and the pathological left phalanx I-1 are consistent with injuries sustained in a fall. However, it is clear from the healing exhibited by these fractures that this individual survived the fall. In addition to traumatic fractures, left dorsal rib 10 and possibly left phalanx I-1 have a morphology consistent with post-traumatic infection in the form of osteomyelitis. The CT scans of left metacarpal IV revealed the presence of an abscess within the medullary cavity consistent with a subacute form of hematogenous osteomyelitis termed a Brodie abscess. This is only the second reported Brodie abscess in non-avian dinosaurs and the first documented occurrence in herbivorous dinosaurs. The presence of a Brodie abscess, known only in mammalian pathological literature, suggest mammalian descriptors for bone infection may be applicable to non-avian dinosaurs.