Tripled yield in direct-drive laser fusion through statistical modelling.

Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.

Shigella sonnei utilises colicins during inter-bacterial competition.

The mammalian colon is one of the most densely populated habitats currently recognised, with 1011-1013 commensal bacteria per gram of colonic contents. Enteric pathogens must compete with the resident intestinal microbiota to cause infection. Among these enteric pathogens are Shigella species which cause approximately 125 million infections annually, of which over 90 % are caused by Shigella flexneri and Shigella sonnei. Shigella sonnei was previously reported to use a Type VI Secretion System (T6SS) to outcompete E. coli and S. flexneri in in vitro and in vivo experiments. S. sonnei strains have also been reported to harbour colicinogenic plasmids, which are an alternative anti-bacterial mechanism that could provide a competitive advantage against the intestinal microbiota. We sought to determine the contribution of both T6SS and colicins to the anti-bacterial killing activity of S. sonnei. We reveal that whilst the T6SS operon is present in S. sonnei, there is evidence of functional degradation of the system through SNPs, indels and IS within key components of the system. We created strains with synthetically inducible T6SS operons but were still unable to demonstrate anti-bacterial activity of the T6SS. We demonstrate that the anti-bacterial activity observed in our in vitro assays was due to colicin activity. We show that S. sonnei no longer displayed anti-bacterial activity against bacteria that were resistant to colicins, and removal of the colicin plasmid from S. sonnei abrogated anti-bacterial activity of S. sonnei. We propose that the anti-bacterial activity demonstrated by colicins may be sufficient for niche competition by S. sonnei within the gastrointestinal environment.

Disparities in adverse impacts of the COVID-19 pandemic by disability status in metropolitan Texas.

BACKGROUND: This article addresses the urgent need for more evidence-based research using primary data to document how the COVID-19 pandemic affected the health and social wellbeing of disabled individuals. Our study sought to determine if adults with disabilities, and with specific types of disability, were more likely to suffer adverse health and social impacts related to COVID-19 than nondisabled adults in metropolitan Texas, during the first 18 months of the pandemic. METHODS: We collected primary data from randomly selected residents in eight Texas metropolitan areas through a bilingual telephone survey in July 2021. Statistical analysis comprised multivariable generalized estimating equations that control for relevant sociodemographic and COVID-related risk factors, and spatial clustering. RESULTS: Disabled survey respondents had been more adversely affected by COVID-19 than nondisabled respondents, in terms of mental and physical health, health care access, living conditions and social life. Significant disparities were also found for almost all COVID-19 impacts when the disabled category was disaggregated by disability type. Respondents experiencing cognitive and independent living difficulties were negatively impacted in all five areas of life examined. CONCLUSIONS: Findings emphasize the need to consider a wide range of impacts associated with the COVID-19 pandemic that negatively affect the health and social wellbeing of disabled persons, as well as develop disability-inclusive policies that provide adequate protections.

Proof-of-Principle Experiment on the Dynamic Shell Formation for Inertial Confinement Fusion.

In the dynamic-shell (DS) concept [V. N. Goncharov et al., Novel Hot-Spot Ignition Designs for Inertial Confinement Fusion with Liquid-Deuterium-Tritium Spheres, Phys. Rev. Lett. 125, 065001 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.065001] for laser-driven inertial confinement fusion the deuterium-tritium fuel is initially in the form of a homogeneous liquid inside a wetted-foam spherical shell. This fuel is ignited using a conventional implosion, which is preceded by a initial compression of the fuel followed by its expansion and dynamic formation of a high-density fuel shell with a low-density interior. This Letter reports on a scaled-down, proof-of-principle experiment on the OMEGA laser demonstrating, for the first time, the feasibility of DS formation. A shell is formed by convergent shocks launched by laser pulses at the edge of a plasma sphere, with the plasma itself formed as a result of laser-driven compression and relaxation of a surrogate plastic-foam ball target. Three x-ray diagnostics, namely, 1D spatially resolved self-emission streaked imaging, 2D self-emission framed imaging, and backlighting radiography, have shown good agreement with the predicted evolution of the DS and its stability to low Legendre mode perturbations introduced by laser irradiation and target asymmetries.

Direct-drive laser fusion: status, plans and future.

Laser-direct drive (LDD), along with laser indirect (X-ray) drive (LID) and magnetic drive with pulsed power, is one of the three viable inertial confinement fusion approaches to achieving fusion ignition and gain in the laboratory. The LDD programme is primarily being executed at both the Omega Laser Facility at the Laboratory for Laser Energetics and at the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. LDD research at Omega includes cryogenic implosions, fundamental physics including material properties, hydrodynamics and laser-plasma interaction physics. LDD research on the NIF is focused on energy coupling and laser-plasma interactions physics at ignition-scale plasmas. Limited implosions on the NIF in the 'polar-drive' configuration, where the irradiation geometry is configured for LID, are also a feature of LDD research. The ability to conduct research over a large range of energy, power and scale size using both Omega and the NIF is a major positive aspect of LDD research that reduces the risk in scaling from OMEGA to megajoule-class lasers. The paper will summarize the present status of LDD research and plans for the future with the goal of ultimately achieving a burning plasma in the laboratory. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Changes in cellular Ca2+ and Na+ regulation during the progression towards heart failure in the guinea pig.

KEY POINTS: During compensated hypertrophy in vivo fractional shortening (FS) remains constant until heart failure (HF) develops, when FS decreases from 70% to 39%. Compensated hypertrophy is accompanied by an increase in INa,late and a decrease in Na+ ,K+ -ATPase current. These changes persist as HF develops. SR Ca2+ content increases during compensated hypertrophy then decreases in HF. In healthy cells, increases in SR Ca2+ content and Ca2+ transients can be achieved by the same amount of inhibition of the Na+ ,K+ -ATPase as measured in the diseased cells. SERCA function remains constant during compensated hypertrophy then decreases in HF, when there is also an increase in spark frequency and spark-mediated Ca2+ leak. We suggest an increase in INa,late and a decrease in Na+ ,K+ -ATPase current and function alters the balance of Ca2+ flux mediated by the Na+ /Ca2+ exchange that limits early contractile impairment. ABSTRACT: We followed changes in cardiac myocyte Ca2+ and Na+ regulation from the formation of compensated hypertrophy (CH) until signs of heart failure (HF) are apparent using a trans-aortic pressure overload (TAC) model. In this model, in vivo fractional shortening (FS) remained constant despite HW:BW ratio increasing by 39% (CH) until HF developed 150 days post-TAC when FS decreased from 70% to 39%. Using live and fixed fluorescence imaging and electrophysiological techniques, we found an increase in INa,late from -0.34 to -0.59 A F-1 and a decrease in Na+ ,K+ -ATPase current from 1.09 A F-1 to 0.54 A F-1 during CH. These changes persisted as HF developed (INa,late increased to -0.82 A F-1 and Na+ ,K+ -ATPase current decreased to 0.51 A F-1 ). Sarcoplasmic reticulum (SR) Ca2+ content increased during CH then decreased in HF (from 32 to 15 µm l-1 ) potentially supporting the maintenance of FS in the whole heart and Ca2+ transients in single myocytes during the former stage. We showed using glycoside blockade in healthy myocytes that increases in SR Ca2+ content and Ca2+ transients can be driven by the same amount of inhibition of the Na+ ,K+ -ATPase as measured in the diseased cells. SERCA function remains constant in CH but decreases (τ for SERCA-mediated Ca2+ removal changed from 6.3 to 3.0 s-1 ) in HF. In HF there was an increase in spark frequency and spark-mediated Ca2+ leak. We suggest an increase in INa,late and a decrease in Na+ ,K+ -ATPase current and function alters the balance of Ca2+ flux mediated by the Na+ /Ca2+ exchange that limits early contractile impairment.

Cryptic lineage differentiation among Indo-Pacific bottlenose dolphins (Tursiops aduncus) in the northwest Indian Ocean.

Phylogeography can provide insight into the potential for speciation and identify geographic regions and evolutionary processes associated with species richness and evolutionary endemism. In the marine environment, highly mobile species sometimes show structured patterns of diversity, but the processes isolating populations and promoting differentiation are often unclear. The Delphinidae (oceanic dolphins) are a striking case in point and, in particular, bottlenose dolphins (Tursiops spp.). Understanding the radiation of species in this genus is likely to provide broader inference about the processes that determine patterns of biogeography and speciation, because both fine-scale structure over a range of kilometers and relative panmixia over an oceanic range are known for Tursiops populations. In our study, novel Tursiops spp. sequences from the northwest Indian Ocean (including mitogenomes and two nuDNA loci) are included in a worldwide Tursiops spp. phylogeographic analysis. We discover a new 'aduncus' type lineage in the Arabian Sea (off India, Pakistan and Oman) that diverged from the Australasian lineage ∼261 Ka. Effective management of coastal dolphins in the region will need to consider this new lineage as an evolutionarily significant unit. We propose that the establishment of this lineage could have been in response to climate change during the Pleistocene and show data supporting hypotheses for multiple divergence events, including vicariance across the Indo-Pacific barrier and in the northwest Indian Ocean. These data provide valuable transferable inference on the potential mechanisms for population and species differentiation across this geographic range.

First Observation of Cross-Beam Energy Transfer Mitigation for Direct-Drive Inertial Confinement Fusion Implosions Using Wavelength Detuning at the National Ignition Facility.

Cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces ablation pressure and implosion velocity in direct-drive inertial confinement fusion. Mitigating CBET is demonstrated for the first time in inertial-confinement implosions at the National Ignition Facility by detuning the laser-source wavelengths (±2.3 Å UV) of the interacting beams. We show that, in polar direct-drive, wavelength detuning increases the equatorial region velocity experimentally by 16% and alters the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation-hydrodynamic simulations that indicate a 10% increase in the average ablation pressure.

A tutorial on model informed approaches to cardiovascular safety with focus on cardiac repolarisation.

Drugs can affect the cardiovascular (CV) system either as an intended treatment or as an unwanted side effect. In both cases, drug-induced cardiotoxicities such as arrhythmia and unfavourable hemodynamic effects can occur, and be described using mathematical models; such a model informed approach can provide valuable information during drug development and can aid decision-making. However, in order to develop informative models, it is vital to understand CV physiology. The aims of this tutorial are to present (1) key background biological and medical aspects of the CV system, (2) CV electrophysiology, (3) CV safety concepts, (4) practical aspects of development of CV models and (5) regulatory expectations with a focus on using model informed and quantitative approaches to support nonclinical and clinical drug development. In addition, we share several case studies to provide practical information on project strategy (planning, key questions, assumptions setting, and experimental design) and mathematical models development that support decision-making during drug discovery and development.

Publisher's Note: Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA [Phys. Rev. Lett. 117, 025001 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.025001.

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA.

A record fuel hot-spot pressure P_{hs}=56±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, 011201(R) (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

The Hispanic health paradox across generations: the relationship of child generational status and citizenship with health outcomes.

OBJECTIVES: In examining the Hispanic health paradox, researchers rarely determine if the paradox persists across immigrant generations. This study examines immigrant respiratory health disparities among Hispanic children in terms of current asthma, bronchitis, and allergies using an expanded six-group immigrant cohort framework that includes citizenship and the fourth-plus generation. STUDY DESIGN: Cross-sectional primary survey data from 1568 caretakers of Hispanic schoolchildren in El Paso, Texas (USA), were utilized. METHODS: Data were analyzed using generalized linear models. RESULTS: Results indicate that a healthy immigrant advantage lasts until the 2.5 generation for bronchitis and allergies (P < 0.05), and until the third generation for asthma (P < 0.10). Citizenship was not an influence on the likelihood of a child having a respiratory health condition. CONCLUSIONS: Findings demonstrate the utility of the expanded six-group cohort framework for examining intergenerational patterns in health conditions among immigrant groups.

The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9.

The t(7;11)(p15;p15) translocation is a recurrent chromosomal abnormality associated primarily with acute myeloid leukaemia (FAB M2 and M4). We present here the molecular definition of this translocation. On chromosome 7 positional cloning revealed the consistent rearrangement of the HOXA9 gene, which encodes a class I homeodomain protein potentially involved in myeloid differentiation. On chromosome 11 the translocation targets the human homologue of NUP98, a member of the GLFG nucleoporin family. Chimaeric messages spliced over the breakpoint fuse the GLFG repeat domains of NUP98 in-frame to the HOXA9 homeobox. The predicted NUP98-HOXA9 fusion protein may promote leukaemogenesis through inhibition of HOXA9-mediated terminal differentiation and/or aberrant nucleocytoplasmic transport.

Laser-direct-drive fusion target design with a high-Z gradient-density pusher shell.

Laser-direct-drive fusion target designs with solid deuterium-tritium (DT) fuel, a high-Z gradient-density pusher shell (GDPS), and a Au-coated foam layer have been investigated through both 1D and 2D radiation-hydrodynamic simulations. Compared with conventional low-Z ablators and DT-push-on-DT targets, these GDPS targets possess certain advantages of being instability-resistant implosions that can be high adiabat (α≥8) and low hot-spot and pusher-shell convergence (CR_{hs}≈22 and CR_{PS}≈17), and have a low implosion velocity (v_{imp}<3×10^{7}cm/s). Using symmetric drive with laser energies of 1.9 to 2.5MJ, 1D lilac simulations of these GDPS implosions can result in neutron yields corresponding to ≳50-MJ energy, even with reduced laser absorption due to the cross-beam energy transfer (CBET) effect. Two-dimensional draco simulations show that these GDPS targets can still ignite and deliver neutron yields from 4 to ∼10MJ even if CBET is present, while traditional DT-push-on-DT targets normally fail due to the CBET-induced reduction of ablation pressure. If CBET is mitigated, these GDPS targets are expected to produce neutron yields of >20MJ at a driven laser energy of ∼2MJ. The key factors behind the robust ignition and moderate energy gain of such GDPS implosions are as follows: (1) The high initial density of the high-Z pusher shell can be placed at a very high adiabat while the DT fuel is maintained at a relatively low-entropy state; therefore, such implosions can still provide enough compression ρR>1g/cm^{2} for sufficient confinement; (2) the high-Z layer significantly reduces heat-conduction loss from the hot spot since thermal conductivity scales as ∼1/Z; and (3) possible radiation trapping may offer an additional advantage for reducing energy loss from such high-Z targets.

Manipulation of ultracold Rb atoms using a single linearly chirped laser pulse.

At ultracold temperatures, atoms are free from thermal motion, which makes them ideal objects of investigations aiming to advance high-precision spectroscopy, metrology, quantum computation, producing Bose condensates, etc. The quantum state of ultracold atoms may be created and manipulated by making use of quantum control methods employing low-intensity pulses. We theoretically investigate population dynamics of ultracold Rb vapor induced by nanosecond linearly chirped pulses having kW/cm2 beam intensity and show a possibility of controllable population transfer between hyperfine (HpF) levels of 5(2)/S(1/2) state through Raman transitions. Satisfying the one-photon resonance condition with the lowest of the HpF states of 5(2)/P(1/2) or 5(2)/P(3/2) state allows us to enter the adiabatic region of population transfer at very low field intensities, such that corresponding Rabi frequencies are less than or equal to the HpF splitting. This methodology provides a robust way to create a specifically designed superposition state in Rb in the basis of HpF levels and perform state manipulation controllable on the picosecond-to-nanosecond time scale.

Automatic surgical phase recognition in laparoscopic inguinal hernia repair with artificial intelligence.

BACKGROUND: Because of the complexity of the intra-abdominal anatomy in the posterior approach, a longer learning curve has been observed in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair. Consequently, automatic tools using artificial intelligence (AI) to monitor TAPP procedures and assess learning curves are required. The primary objective of this study was to establish a deep learning-based automated surgical phase recognition system for TAPP. A secondary objective was to investigate the relationship between surgical skills and phase duration. METHODS: This study enrolled 119 patients who underwent the TAPP procedure. The surgical videos were annotated (delineated in time) and split into seven surgical phases (preparation, peritoneal flap incision, peritoneal flap dissection, hernia dissection, mesh deployment, mesh fixation, peritoneal flap closure, and additional closure). An AI model was trained to automatically recognize surgical phases from videos. The relationship between phase duration and surgical skills were also evaluated. RESULTS: A fourfold cross-validation was used to assess the performance of the AI model. The accuracy was 88.81 and 85.82%, in unilateral and bilateral cases, respectively. In unilateral hernia cases, the duration of peritoneal incision (p = 0.003) and hernia dissection (p = 0.014) detected via AI were significantly shorter for experts than for trainees. CONCLUSION: An automated surgical phase recognition system was established for TAPP using deep learning with a high accuracy. Our AI-based system can be useful for the automatic monitoring of surgery progress, improving OR efficiency, evaluating surgical skills and video-based surgical education. Specific phase durations detected via the AI model were significantly associated with the surgeons' learning curve.

Molecular ecology meets remote sensing: environmental drivers to population structure of humpback dolphins in the Western Indian Ocean.

Genetic analyses of population structure can be placed in explicit environmental contexts if appropriate environmental data are available. Here, we use high-coverage and high-resolution oceanographic and genetic sequence data to assess population structure patterns and their potential environmental influences for humpback dolphins in the Western Indian Ocean. We analyzed mitochondrial DNA data from 94 dolphins from the coasts of South Africa, Mozambique, Tanzania and Oman, employing frequency-based and maximum-likelihood algorithms to assess population structure and migration patterns. The genetic data were combined with 13 years of remote sensing oceanographic data of variables known to influence cetacean dispersal and population structure. Our analyses show strong and highly significant genetic structure between all putative populations, except for those in South Africa and Mozambique. Interestingly, the oceanographic data display marked environmental heterogeneity between all sampling areas and a degree of overlap between South Africa and Mozambique. Our combined analyses therefore suggest the occurrence of genetically isolated populations of humpback dolphins in areas that are environmentally distinct. This study highlights the utility of molecular tools in combination with high-resolution and high-coverage environmental data to address questions not only pertaining to genetic population structure, but also to relevant ecological processes in marine species.

Augmented Reality Guided Laparoscopic Surgery of the Uterus.

A major research area in Computer Assisted Intervention (CAI) is to aid laparoscopic surgery teams with Augmented Reality (AR) guidance. This involves registering data from other modalities such as MR and fusing it with the laparoscopic video in real-time, to reveal the location of hidden critical structures. We present the first system for AR guided laparoscopic surgery of the uterus. This works with pre-operative MR or CT data and monocular laparoscopes, without requiring any additional interventional hardware such as optical trackers. We present novel and robust solutions to two main sub-problems: the initial registration, which is solved using a short exploratory video, and update registration, which is solved with real-time tracking-by-detection. These problems are challenging for the uterus because it is a weakly-textured, highly mobile organ that moves independently of surrounding structures. In the broader context, our system is the first that has successfully performed markerless real-time registration and AR of a mobile human organ with monocular laparoscopes in the OR.

How decision-making about euthanasia for animals is taught to Australasian veterinary students.

This study set out to explore how euthanasia decision-making for animals was taught to students in eight Australasian veterinary schools. A questionnaire-style interview guide was used by a representative at each university to interview educators. Educators were interviewed about their teaching of euthanasia decision-making for four categories of animals: livestock, equine, companion and avian/wildlife. Using thematic analysis, the terms provided by participants to describe how (mode of teaching) and what (specific content) they taught to students were categorised. Information about content was categorised into human-centred factors that influence decision-making, and animal-based indicators used to directly inform decision-making. All eight representatives reported some teaching relevant to euthanasia decision-making at their university for livestock, companion animal and avian/wildlife. One representative reported no such teaching for equid animals at their university. Observation of a euthanasia case was rarely reported as a teaching method. Five universities reported multiple modes of teaching relevant information, while two universities made use of modalities that could be described as opportunistic teaching (e.g., 'Discussion of clinical cases'). Factors taught at most universities included financial considerations, and that it is the owner's decision to make, while animal-based indicators taught included QoL/animal welfare, prognosis and behaviour change. Overall, most universities used a variety of methods to cover relevant material, usually including lectures and several other approaches for all animal types. However, because two universities relied on presentation of clinical cases, not all students at these veterinary schools will be exposed to make, or assist in making, euthanasia decisions.

NF-kappa B and I kappa B alpha: an inducible regulatory system in endothelial activation.

Structural analysis of the promoters of several endothelial genes induced at sites of inflammatory or immune responses reveals binding sites for the transcription factor nuclear factor kappa B (NF-kappa B). Endothelial cells express transcripts encoding the p50/p105 and p65 components of NF-kappa B and the rel-related proto-oncogene c-rel; steady state levels of these transcripts are transiently increased by tumor necrosis factor alpha (TNF-alpha). Western blotting revealed that stimulation of endothelial cells with TNF-alpha resulted in nuclear accumulation of the p50 and p65 components of NF-kappa B. Ultraviolet crosslinking and immunoprecipitation demonstrated binding of the p50 and p65 components of NF-kappa B to the E-selectin kappa B site. Endothelial cells express an inhibitor of NF-kappa B activation, I kappa B-alpha (MAD-3). Protein levels of this inhibitor fall rapidly after TNF-alpha stimulation. In parallel, p50 and p65 accumulate in the nucleus and RNA transcript levels for I kappa B-alpha are dramatically upregulated. Recombinant p65 stimulates expression of E-selectin promoter-reporter constructs. I kappa B-alpha inhibits p65 or TNF-alpha-stimulated E-selectin promoter-reporter gene expression in transfected endothelial cells. The NF-kappa B and I kappa B-alpha system may be an inducible regulatory mechanism in endothelial activation.