Mapping lumbar efferent and afferent spinal circuitries via paddle array in a porcine model.

BACKGROUND: Preclinical models are essential for identifying changes occurring after neurologic injury and assessing therapeutic interventions. Yucatan miniature pigs (minipigs) have brain and spinal cord dimensions like humans and are useful for laboratory-to-clinic studies. Yet, little work has been done to map spinal sensorimotor distributions and identify similarities and differences between the porcine and human spinal cords. NEW METHODS: To characterize efferent and afferent signaling, we implanted a conventional 32-contact, four-column array into the dorsal epidural space over the lumbosacral spinal cord, spanning the L5-L6 vertebrae, in two Yucatan minipigs. Spinally evoked motor potentials were recorded bilaterally in four hindlimb muscles during stimulation delivered from different array locations. Then, cord dorsum potentials were recorded via the array by stimulating the left and right tibial nerves. RESULTS: Utilizing epidural spinal stimulation, we achieved selective left, right, proximal, and distal activation in the hindlimb muscles. We then determined the selectivity of each muscle as a function of stimulation location which relates to the distribution of the lumbar motor pools. COMPARISON WITH EXISTING METHODS: Mapping motoneuron distribution to hindlimb muscles and recording responses to peripheral nerve stimulation in the dorsal epidural space reveals insights into ascending and descending signal propagation in the lumbar spinal cord. Clinical-grade arrays have not been utilized in a porcine model. CONCLUSIONS: These results indicate that efferent and afferent spinal sensorimotor networks are spatially distinct, provide information about the organization of motor pools in the lumbar enlargement, and demonstrate the feasibility of using clinical-grade devices in large animal research.

Post-transfusion purpura after cardiac surgery associated with veno-arterial extracorporeal membrane oxygenation.

We report the case of a woman who developed post-transfusion purpura following complicated cardiac surgery requiring multiple blood product transfusions and extracorporeal life support. This case highlights the challenges of managing thrombocytopenia in patients supported with prolonged mechanical cardiovascular and renal support with ongoing blood product transfusion requirements. The differential diagnoses are broad, varied and may overlap. Whilst post-transfusion purpura is very rare, clinical signs may prompt consideration and further specific diagnostic testing. Once confirmed, management is then specific, with some aspects which are at direct variance with standard intensive care and extracorporeal life support guidelines for the management of non-specific thrombocytopenia. Consideration of the diagnosis of post-transfusion purpura early in the clinical course could help anticipate and prevent a vicious cycle of bleeding, transfusion and autoimmune-mediated platelet disruption, and may improve clinical outcomes.

Distinct spatial landscapes in clear-cell renal cell carcinoma as revealed by whole transcriptome analysis.

Background: Clear-cell renal cell carcinoma (ccRCC) is the most common and aggressive form of renal cancer and a paradigm of inter- and intratumor heterogeneity. We carried out an exploratory digital spatial profiling of the tumor interior and periphery of two ccRCC tumor specimens and mapped spatially the molecular and cellular composition of their tumor microenvironment and ecosystem. Materials and methods: Digital spatial profiling of the whole transcriptome of 19 regions of interest (ROIs) was carried out from two selected highly immunogenic stage pT3a/grade 3 (G3) and stage pT3a/grade 4 (G4) ccRCC. A total of 9-10 ROIs were selected from distinct areas from each tumor, including tumor interior and tumor periphery, and differences in gene expression were analyzed by RNA sequencing, pathway enrichment analysis, and cell deconvolution. Results: The distinct areas from the two locally advanced tumors displayed unique gene expression spatial patterns defining distinct biological pathways. Dimensional reduction analysis showed that the G3 ccRCC, compared to the G4 ccRCC, correlated with more variability between regions from the tumor interior and tumor periphery. Cell deconvolution analysis illustrated higher abundance of immune cells, including macrophages, myeloid dendritic cells, and CD4 T cells, and lower abundance of regulatory T cells in the tumor periphery compared to the tumor interior. Conclusions: Transcriptome spatial profiling revealed high inter- and intratumor heterogeneity in the analyzed tumors and provided information with potential clinical utility. This included the finding of less intratumor heterogeneity and more tumor-infiltrated T cells in the ccRCC tumor specimen with a higher grade.

Attosecond-Angstrom free-electron-laser towards the cold beam limit.

Electron beam quality is paramount for X-ray pulse production in free-electron-lasers (FELs). State-of-the-art linear accelerators (linacs) can deliver multi-GeV electron beams with sufficient quality for hard X-ray-FELs, albeit requiring km-scale setups, whereas plasma-based accelerators can produce multi-GeV electron beams on metre-scale distances, and begin to reach beam qualities sufficient for EUV FELs. Here we show, that electron beams from plasma photocathodes many orders of magnitude brighter than state-of-the-art can be generated in plasma wakefield accelerators (PWFAs), and then extracted, captured, transported and injected into undulators without significant quality loss. These ultrabright, sub-femtosecond electron beams can drive hard X-FELs near the cold beam limit to generate coherent X-ray pulses of attosecond-Angstrom class, reaching saturation after only 10 metres of undulator. This plasma-X-FEL opens pathways for advanced photon science capabilities, such as unperturbed observation of electronic motion inside atoms at their natural time and length scale, and towards higher photon energies.

Stable Positron Acceleration in Thin, Warm, Hollow Plasma Channels.

Hollow plasma channels are attractive for lepton acceleration because they provide intrinsic emittance preservation regimes. However, beam breakup instabilities dominate the dynamics. Here, we show that thin, warm hollow channels can sustain large-amplitude plasma waves ready for high-quality positron acceleration. We verify that the combination of warm electrons and thin hollow channels enables positron focusing structures. Such focusing wakefields unlock beam breakup damping mechanisms. We demonstrate that such channels emerge self-consistently during the long-term plasma dynamics in the blowout's regime aftermath, allowing for experimental demonstration.

Accurate and confident prediction of electron beam longitudinal properties using spectral virtual diagnostics.

Longitudinal phase space (LPS) provides a critical information about electron beam dynamics for various scientific applications. For example, it can give insight into the high-brightness X-ray radiation from a free electron laser. Existing diagnostics are invasive, and often times cannot operate at the required resolution. In this work we present a machine learning-based Virtual Diagnostic (VD) tool to accurately predict the LPS for every shot using spectral information collected non-destructively from the radiation of relativistic electron beam. We demonstrate the tool's accuracy for three different case studies with experimental or simulated data. For each case, we introduce a method to increase the confidence in the VD tool. We anticipate that spectral VD would improve the setup and understanding of experimental configurations at DOE's user facilities as well as data sorting and analysis. The spectral VD can provide confident knowledge of the longitudinal bunch properties at the next generation of high-repetition rate linear accelerators while reducing the load on data storage, readout and streaming requirements.

Personalised nutrition for older adults: design challenges, SME barriers, and options and competencies for innovation.

Personalised nutrition (PN) products and services have the potential to enhance the health and quality of life of older adults. However, PN innovation is challenging and requires specific competencies and supportive collaborations. This paper reports findings from a Collective Intelligence Scenario-Based Design session conducted with PN experts as part of the Horizon 2020 project INCluSilver, which aims to support the development of products, services, and systems that improve the health and quality of life of older adults through innovation in PN. Experts identified challenges to the design of PN products and services and barriers that small and medium enterprises (SMEs) face when innovating PN products and services for older adults. Options to address these barriers were generated and specific SME competencies supporting PN innovation were identified. This study provides a useful framework for understanding the challenges, opportunities, and key competencies needed to innovate PN products and services for older adults.

Dissipation of electron-beam-driven plasma wakes.

Metre-scale plasma wakefield accelerators have imparted energy gain approaching 10 gigaelectronvolts to single nano-Coulomb electron bunches. To reach useful average currents, however, the enormous energy density that the driver deposits into the wake must be removed efficiently between shots. Yet mechanisms by which wakes dissipate their energy into surrounding plasma remain poorly understood. Here, we report picosecond-time-resolved, grazing-angle optical shadowgraphic measurements and large-scale particle-in-cell simulations of ion channels emerging from broken wakes that electron bunches from the SLAC linac generate in tenuous lithium plasma. Measurements show the channel boundary expands radially at 1 million metres-per-second for over a nanosecond. Simulations show that ions and electrons that the original wake propels outward, carrying 90 percent of its energy, drive this expansion by impact-ionizing surrounding neutral lithium. The results provide a basis for understanding global thermodynamics of multi-GeV plasma accelerators, which underlie their viability for applications demanding high average beam current.

Influenza vaccine uptake and attitudes of healthcare workers in Ireland.

BACKGROUND: Influenza vaccination uptake by Irish healthcare workers remains sub-optimal despite local initiatives to increase it. AIMS: To investigate hospital workers' attitudes to influenza vaccination and how this influenced their decisions about vaccination. METHODS: A questionnaire survey of Irish hospital workers, measuring uptake of and attitudes to influenza vaccination. RESULTS: There were 747 responders, of whom 361 (48%) reported having received influenza vaccination. Attitudes predicting vaccination uptake included a belief that vaccination would protect family members (P < 0.0005, CI 1.191-1.739), a perception of susceptibility to 'flu (P < 0.0005, CI 1.182-1.685), a belief that all healthcare workers should be vaccinated (P < 0.005, CI 1.153-1.783), perceived ease of getting 'flu vaccination at work (P < 0.0005, CI 1.851-2.842) and encouragement by line managers (P < 0.05, CI 1.018-1.400). Attitudes negatively associated with vaccination uptake included fear of needles (P < 0.05, CI 0.663-0.985) and a belief that vaccination would cause illness (P < 0.0005, CI 0.436-0.647). Medical staff were significantly more likely to be vaccinated. Healthcare students were least likely to be vaccinated (P < 0.0005). CONCLUSION: Addressing specific barriers to influenza vaccination in healthcare workers may improve uptake.

Conductivity Induced by High-Field Terahertz Waves in Dielectric Material.

An intense, subpicosecond, relativistic electron beam traversing a dielectric-lined waveguide generates very large amplitude electric fields at terahertz (THz) frequencies through the wakefield mechanism. In recent work employing this technique to accelerate charged particles, the generation of high-power, narrow-band THz radiation was demonstrated. The radiated waves contain fields with measured amplitude exceeding 2 GV/m, orders of magnitude greater than those available by other THz generation techniques at a narrow bandwidth. For fields approaching the GV/m level, a strong damping has been observed in SiO_{2}. This wave attenuation with an onset near 850 MV/m is consistent with changes to the conductivity of the dielectric lining and is characterized by a distinctive latching mechanism that is reversible on longer timescales. We describe the detailed measurements that serve to clarify the underlying physical mechanisms leading to strong field-induced damping of THz radiation (hω=1.59 meV, f=0.38 THz) in SiO_{2}, a bulk, wide band-gap (8.9 eV) dielectric.

Directions in plasma wakefield acceleration.

This introductory article is a synopsis of the status and prospects of particle-beam-driven plasma wakefield acceleration (PWFA). Conceptual and experimental breakthroughs obtained over the last years have initiated a rapid growth of the research field, and increased maturity of underlying technology allows an increasing number of research groups to engage in experimental R&D. We briefly describe the fundamental mechanisms of PWFA, from which its chief attractions arise. Most importantly, this is the capability of extremely rapid acceleration of electrons and positrons at gradients many orders of magnitude larger than in conventional accelerators. This allows the size of accelerator units to be shrunk from the kilometre to metre scale, and possibly the quality of accelerated electron beam output to be improved by orders of magnitude. In turn, such compact and high-quality accelerators are potentially transformative for applications across natural, material and life sciences. This overview provides contextual background for the manuscripts of this issue, resulting from a Theo Murphy meeting held in the summer of 2018. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Producing multi-coloured bunches through beam-induced ionization injection in plasma wakefield accelerator.

This paper discusses the properties of electron beams formed in plasma wakefield accelerators through ionization injection. In particular, the potential for generating a beam composed of co-located multi-colour beamlets is demonstrated in the case where the ionization is initiated by the evolving charge field of the drive beam itself. The physics of the processes of ionization and injection are explored through OSIRIS simulations. Experimental evidence showing similar features are presented from the data obtained in the E217 experiment at the FACET facility of the SLAC National Laboratory. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Betatron radiation and emittance growth in plasma wakefield accelerators.

Beam-driven plasma wakefield acceleration (PWFA) has demonstrated significant progress during the past two decades of research. The new Facility for Advanced Accelerator Experimental Tests (FACET) II, currently under construction, will provide 10 GeV electron beams with unprecedented parameters for the next generation of PWFA experiments. In the context of the FACET II facility, we present simulation results on expected betatron radiation and its potential application to diagnose emittance preservation and hosing instability in the upcoming PWFA experiments. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Prospect of Studying Nonperturbative QED with Beam-Beam Collisions.

We demonstrate the experimental feasibility of probing the fully nonperturbative regime of quantum electrodynamics with a 100 GeV-class particle collider. By using tightly compressed and focused electron beams, beamstrahlung radiation losses can be mitigated, allowing the particles to experience extreme electromagnetic fields. Three-dimensional particle-in-cell simulations confirm the viability of this approach. The experimental forefront envisaged has the potential to establish a novel research field and to stimulate the development of a new theoretical methodology for this yet unexplored regime of strong-field quantum electrodynamics.

Biomechanical properties of female dolphin reproductive tissue.

Whales, dolphins, and porpoises have unusual vaginal folds of unknown function(s) that are hypothesized to play an important role in sexual selection. The potential function of vaginal folds was assessed by testing the mechanical properties of common bottlenose dolphin (Tursiops truncatus) reproductive tract tissues in 6 different regions and across age classes in post-mortem specimens. We assessed the regional (local) and overall effective elastic modulus of tissues using indentation and tensile tests, respectively. We explore the non-linear mechanical response of biological tissues, which are not often quantified. Indentation tests demonstrated that sexual maturity state, tissue region, force history, and force magnitude values significantly affected the measured effective elastic modulus. Tissue was stiffest in the vaginal fold region and overall stiffer in sexually immature compared to mature animals, likely reflecting biomechanical adaptations associated with copulation and parturition. Tensile tests showed that only tissue region significantly affected the effective modulus. Our data support the hypothesis that vaginal folds function as mechanical barriers to the penis and may provide females with mechanisms to reduce copulatory forces on other reproductive tissue. STATEMENT OF SIGNIFICANCE: Cetaceans have unusual folds of vaginal wall tissue that appear to evolve under sexual selection mechanisms and present physical barriers to the penis during copulation. We explore the biomaterial properties of vaginal fold tissue, how it varies from other reproductive tract tissues, and ontogenetic patterns. We demonstrate that vaginal folds can withstand higher mechanical forces and respond in a manner conducive to dissipating copulatory forces to other reproductive tissues. This study yields exciting insights on how female genital tissue may function during copulation, and is the first to do so in any vertebrate species. Additionally, we provide an example for testing biological tissues, non-linear properties, and materials with uneven surface structure and uneven thickness.

The influence of childhood intelligence, social class, education and social mobility on memory and memory decline in late life.

In an observational longitudinal study of a sub-sample of the Aberdeen 1936 birth cohort, from age 62 to 77 years, we investigated childhood intelligence, social class, education, life-course social mobility, memory test performance and memory decline in late life. We examined 388 local residents who had attended school in Aberdeen in 1947 and measured Auditory-Verbal Learning Test (AVLT) at recruitment age about 64 years and up to five times until age about 77 years. Better performance at age about 64 on AVLT was predicted by early socioeconomic status (SES), social mobility and childhood intelligence. The trajectory of AVLT decline was steeper in those who had received less education. This relationship was independent of childhood ability, sex, SES in childhood and social mobility. The protection of memory by education suggests that education supports resilience to age-related cognitive impairment. Upward social mobility does not enhance this effect, suggesting that resilience to age-related decline may be established in early life.

Measurement of Transverse Wakefields Induced by a Misaligned Positron Bunch in a Hollow Channel Plasma Accelerator.

Hollow channel plasma wakefield acceleration is a proposed method to provide high acceleration gradients for electrons and positrons alike: a key to future lepton colliders. However, beams which are misaligned from the channel axis induce strong transverse wakefields, deflecting beams and reducing the collider luminosity. This undesirable consequence sets a tight constraint on the alignment accuracy of the beam propagating through the channel. Direct measurements of beam misalignment-induced transverse wakefields are therefore essential for designing mitigation strategies. We present the first quantitative measurements of transverse wakefields in a hollow plasma channel, induced by an off-axis 20 GeV positron bunch, and measured with another 20 GeV lower charge trailing positron probe bunch. The measurements are largely consistent with theory.

Efficacy of an exercise intervention among children with comorbid asthma and obesity.

OBJECTIVES: Children with comorbid asthma and obesity present with more severe and harder-to-control disease than asthmatic children at healthy weight. Weight loss has been shown to improve asthma symptoms, yet physical activity may be difficult due to exercise-induced bronchospasm. Children with asthma have lower exercise rates than non-asthmatics. The objective of this study was to retrospectively evaluate attrition rates and program outcome measures (Body Mass Index [BMI] and maximum oxygen consumption [VO2max]) among asthmatic and non-asthmatic participants. STUDY DESIGN: Clinical data were collected from the Healthy Hearts Program, a 12-week nutrition and activity intervention program for children who are overweight, obese, or at risk for heart disease and other conditions, and used for the study. METHODS: Intervention data and demographics were obtained from medical records at the Children's Heart Center Nevada. Descriptive statistics, paired t-tests, Cox regression analysis, and analysis of covariance were conducted. RESULTS: The mean age of this population (N = 232) was 11 years; 54% were male, 64% were Hispanic, and 37% had asthma. Median time in the program was 9 weeks, and 58% of the population completed the program. Unadjusted analyses showed significant BMI decreases in asthmatic (P = 0.002) and non-asthmatic (P = 0.001) participants and increases in cardiorespiratory function for asthmatic males and females (P = 0.003, P = 0.004) and non-asthmatic males and females (P < 0.001 for both). Asthmatic and non-asthmatic children both had improved exercise intensity (P = 0.033, P < 0.001). CONCLUSIONS: This program is both beneficial and practical for obese children with asthma for losing weight and improving cardiorespiratory function.

Acceleration of a trailing positron bunch in a plasma wakefield accelerator.

High gradients of energy gain and high energy efficiency are necessary parameters for compact, cost-efficient and high-energy particle colliders. Plasma Wakefield Accelerators (PWFA) offer both, making them attractive candidates for next-generation colliders. In these devices, a charge-density plasma wave is excited by an ultra-relativistic bunch of charged particles (the drive bunch). The energy in the wave can be extracted by a second bunch (the trailing bunch), as this bunch propagates in the wake of the drive bunch. While a trailing electron bunch was accelerated in a plasma with more than a gigaelectronvolt of energy gain, accelerating a trailing positron bunch in a plasma is much more challenging as the plasma response can be asymmetric for positrons and electrons. We report the demonstration of the energy gain by a distinct trailing positron bunch in a plasma wakefield accelerator, spanning nonlinear to quasi-linear regimes, and unveil the beam loading process underlying the accelerator energy efficiency. A positron bunch is used to drive the plasma wake in the experiment, though the quasi-linear wake structure could as easily be formed by an electron bunch or a laser driver. The results thus mark the first acceleration of a distinct positron bunch in plasma-based particle accelerators.

Observation of Quasichanneling Oscillations.

We report on the first experimental observations of quasichanneling oscillations, recently seen in simulations and described theoretically. Although above-barrier particles penetrating a single crystal are generally seen as behaving almost as in an amorphous substance, distinct oscillation peaks nevertheless appear for particles in that category. The quasichanneling oscillations were observed at SLAC National Accelerator Laboratory by aiming 20.35 GeV positrons and electrons at a thin silicon crystal bent to a radius of R=0.15 m, exploiting the quasimosaic effect. For electrons, two relatively faint quasichanneling peaks were observed, while for positrons, seven quasichanneling peaks were clearly identified.