Measurement of the decay of laser-driven linear plasma wakefields.

We present measurements of the temporal decay rate of one-dimensional (1D), linear Langmuir waves excited by an ultrashort laser pulse. Langmuir waves with relative amplitudes of approximately 6% were driven by 1.7J, 50fs laser pulses in hydrogen and deuterium plasmas of density n_{e0}=8.4×10^{17}cm^{-3}. The wakefield lifetimes were measured to be τ_{wf}^{H_{2}}=(9±2) ps and τ_{wf}^{D_{2}}=(16±8) ps, respectively, for hydrogen and deuterium. The experimental results were found to be in good agreement with 2D particle-in-cell simulations. In addition to being of fundamental interest, these results are particularly relevant to the development of laser wakefield accelerators and wakefield acceleration schemes using multiple pulses, such as multipulse laser wakefield accelerators.

Observation of Monoenergetic Electrons from Two-Pulse Ionization Injection in Quasilinear Laser Wakefields.

The generation of low emittance electron beams from laser-driven wakefields is crucial for the development of compact x-ray sources. Here, we show new results for the injection and acceleration of quasimonoenergetic electron beams in low amplitude wakefields experimentally and using simulations. This is achieved by using two laser pulses decoupling the wakefield generation from the electron trapping via ionization injection. The injection duration, which affects the beam charge and energy spread, is found to be tunable by adjusting the relative pulse delay. By changing the polarization of the injector pulse, reducing the ionization volume, the electron spectra of the accelerated electron bunches are improved.

Modelling Representative Population Mobility for COVID-19 Spatial Transmission in South Africa.

The COVID-19 pandemic starting in the first half of 2020 has changed the lives of everyone across the world. Reduced mobility was essential due to it being the largest impact possible against the spread of the little understood SARS-CoV-2 virus. To understand the spread, a comprehension of human mobility patterns is needed. The use of mobility data in modelling is thus essential to capture the intrinsic spread through the population. It is necessary to determine to what extent mobility data sources convey the same message of mobility within a region. This paper compares different mobility data sources by constructing spatial weight matrices at a variety of spatial resolutions and further compares the results through hierarchical clustering. We consider four methods for constructing spatial weight matrices representing mobility between spatial units, taking into account distance between spatial units as well as spatial covariates. This provides insight for the user into which data provides what type of information and in what situations a particular data source is most useful.

Meter-scale conditioned hydrodynamic optical-field-ionized plasma channels.

We demonstrate through experiments and numerical simulations that low-density, low-loss, meter-scale plasma channels can be generated by employing a conditioning laser pulse to ionize the neutral gas collar surrounding a hydrodynamic optical-field-ionized (HOFI) plasma channel. We use particle-in-cell simulations to show that the leading edge of the conditioning pulse ionizes the neutral gas collar to generate a deep, low-loss plasma channel which guides the bulk of the conditioning pulse itself as well as any subsequently injected pulses. In proof-of-principle experiments, we generate conditioned HOFI (CHOFI) waveguides with axial electron densities of n_{e0}≈1×10^{17}cm^{-3} and a matched spot size of 26µm. The power attenuation length of these CHOFI channels was calculated to be L_{att}=(21±3)m, more than two orders of magnitude longer than achieved by HOFI channels. Hydrodynamic and particle-in-cell simulations demonstrate that meter-scale CHOFI waveguides with attenuation lengths exceeding 1 m could be generated with a total laser pulse energy of only 1.2 J per meter of channel. The properties of CHOFI channels are ideally suited to many applications in high-intensity light-matter interactions, including multi-GeV plasma accelerator stages operating at high pulse repetition rates.

Erratum: Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study.

[This corrects the article DOI: 10.1093/eep/dvz023.][This corrects the article DOI: 10.1093/eep/dvz023.].

Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study.

Epidemiological studies suggest that father's smoking might influence their future children's health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. To investigate a potential association between fathers' smoking exposures and offspring DNA methylation using epigenome-wide association studies. We used data from 195 males and females (11-54 years) participating in two population-based cohorts. DNA methylation was quantified in whole blood using Illumina Infinium MethylationEPIC Beadchip. Comb-p was used to analyse differentially methylated regions (DMRs). Robust multivariate linear models, adjusted for personal/maternal smoking and cell-type proportion, were used to analyse offspring differentially associated probes (DMPs) related to paternal smoking. In sensitivity analyses, we adjusted for socio-economic position and clustering by family. Adjustment for inflation was based on estimation of the empirical null distribution in BACON. Enrichment and pathway analyses were performed on genes annotated to cytosine-phosphate-guanine (CpG) sites using the gometh function in missMethyl. We identified six significant DMRs (Sidak-corrected P values: 0.0006-0.0173), associated with paternal smoking, annotated to genes involved in innate and adaptive immunity, fatty acid synthesis, development and function of neuronal systems and cellular processes. DMP analysis identified 33 CpGs [false discovery rate (FDR) < 0.05]. Following adjustment for genomic control (λ = 1.462), no DMPs remained epigenome-wide significant (FDR < 0.05). This hypothesis-generating study found that fathers' smoking was associated with differential methylation in their adolescent and adult offspring. Future studies are needed to explore the intriguing hypothesis that fathers' exposures might persistently modify their future offspring's epigenome.

Mutation of the ATPase Domain of MutS Homolog-5 (MSH5) Reveals a Requirement for a Functional MutSγ Complex for All Crossovers in Mammalian Meiosis.

During meiosis, induction of DNA double strand breaks (DSB) leads to recombination between homologous chromosomes, resulting in crossovers (CO) and non-crossovers (NCO). In the mouse, only 10% of DSBs resolve as COs, mostly through a class I pathway dependent on MutSγ (MSH4/ MSH5) and MutLγ (MLH1/MLH3), the latter representing the ultimate marker of these CO events. A second Class II CO pathway accounts for only a few COs, but is not thought to involve MutSγ/ MutLγ, and is instead dependent on MUS81-EME1. For class I events, loading of MutLγ is thought to be dependent on MutSγ, however MutSγ loads very early in prophase I at a frequency that far exceeds the final number of class I COs. Moreover, loss of MutSγ in mouse results in apoptosis before CO formation, preventing the analysis of its CO function. We generated a mutation in the ATP binding domain of Msh5 (Msh5GA ). While this mutation was not expected to affect MutSγ complex formation, MutSγ foci do not accumulate during prophase I. However, most spermatocytes from Msh5GA/GA mice progress to late pachynema and beyond, considerably further than meiosis in Msh5-/- animals. At pachynema, Msh5GA/GA spermatocytes show persistent DSBs, incomplete homolog pairing, and fail to accumulate MutLγ. Unexpectedly, Msh5GA/GA diakinesis-staged spermatocytes have no chiasmata at all from any CO pathway, indicating that a functional MutSγ complex is critical for all CO events regardless of their mechanism of generation.

Different definitions of atopic dermatitis: impact on prevalence estimates and associated risk factors.

BACKGROUND: There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD), and no uniform clinical definition. OBJECTIVES: To investigate to what extent operational definitions of AD cause fluctuation in the prevalence estimates and the associated risk factors. METHODS: We first reviewed the operational definitions of AD used in the literature. We then tested the impact of the choice of the most common definitions of 'cases' and 'controls' on AD prevalence estimates and associated risk factors (including filaggrin mutations) among children aged 5 years in two population-based birth cohorts: the Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford. Model performance was measured by the percentage of children within an area of clinical indecision (defined as having a posterior probability of AD between 25% and 60%). RESULTS: We identified 59 different definitions of AD across 45 reviewed studies. Of those, we chose four common 'case' definitions and two definitions of 'controls'. The prevalence estimates using different case definitions ranged between 22% and 33% in MAAS, and between 12% and 22% in Ashford. The area of clinical indecision ranged from 32% to 44% in MAAS and from 9% to 29% in Ashford. Depending on the case definition used, the associations with filaggrin mutations varied, with odds ratios (95% confidence intervals) ranging from 1·8 (1·1-2·9) to 2·2 (1·3-3·7) in MAAS and 1·7 (0·8-3·7) to 2·3 (1·2-4·5) in Ashford. Associations with filaggrin mutations also differed when using the same 'case' definition but different definitions of 'controls'. CONCLUSIONS: Use of different definitions of AD results in substantial differences in prevalence estimates, the performance of prediction models and association with risk factors. What's already known about this topic? There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD) and no uniform clinical definition. This results in different definitions utilized in AD studies, raising concerns on the generalizability of the results and comparability across different studies. What does this study add? This study has shown that different definitions of 'cases' and 'controls' have major impacts upon prevalence estimates and associations with risk factors, including genetics, in two population-based birth cohorts. These findings suggest the importance of developing a consensus on AD definitions of both 'controls' and 'cases' to minimize biases in studies.

Observation of Laser Power Amplification in a Self-Injecting Laser Wakefield Accelerator.

We report on the depletion and power amplification of the driving laser pulse in a strongly driven laser wakefield accelerator. Simultaneous measurement of the transmitted pulse energy and temporal shape indicate an increase in peak power from 187±11 TW to a maximum of 318±12 TW after 13 mm of propagation in a plasma density of 0.9×10^{18} cm^{-3}. The power amplification is correlated with the injection and acceleration of electrons in the nonlinear wakefield. This process is modeled by including a localized redshift and subsequent group delay dispersion at the laser pulse front.

Hydrodynamic optical-field-ionized plasma channels.

We present experiments and numerical simulations which demonstrate that fully ionized, low-density plasma channels could be formed by hydrodynamic expansion of plasma columns produced by optical field ionization. Simulations of the hydrodynamic expansion of plasma columns formed in hydrogen by an axicon lens show the generation of 200 mm long plasma channels with axial densities of order n_{e}(0)=1×10^{17}cm^{-3} and lowest-order modes of spot size W_{M}≈40µm. These simulations show that the laser energy required to generate the channels is modest: of order 1 mJ per centimeter of channel. The simulations are confirmed by experiments with a spherical lens which show the formation of short plasma channels with 1.5×10^{17}cm^{-3}≲n_{e}(0)≲1×10^{18}cm^{-3} and 61µm≳W_{M}≳33µm. Low-density plasma channels of this type would appear to be well suited as multi-GeV laser-plasma accelerator stages capable of long-term operation at high pulse repetition rates.

Acquisition, remission, and persistence of eczema, asthma, and rhinitis in children.

BACKGROUND: Allergic sensitization is associated with eczema, asthma, and rhinitis. However, it is unknown whether and how allergic sensitization is associated over time with acquisition, remission, and persistence of these diseases and their comorbidity. OBJECTIVE: To gain a better understanding of factors including allergic sensitization transitions that influence the temporal pattern of asthma, eczema, and rhinitis and their comorbidity during childhood. METHODS: In the Isle of Wight birth cohort, information on allergic sensitization to common allergens was collected at ages 4, 10, and 18 years along with asthma, rhinitis, and eczema status determined by clinical diagnosis. Logistic regressions were used to estimate subsequent and concurrent odds ratios of diseases transition with allergic sensitization transition status as the main independent variable. Two transition periods were considered, 4 to 10 years of age and 10 to 18 years of age. RESULTS: The odds of new diagnosis of allergic disease (no-yes) was increased among subjects with acquired or persistent allergic sensitization to common allergens compared to subjects with no sensitization (acquisition of sensitization odds ratio [OR]=3.22, P < .0001; persistence of sensitization, OR=6.33, P < .0001). The odds of remission of allergic diseases (yes-no) was lower among subjects with acquired or sustained allergic sensitization (acquisition, OR=0.18, P = .0001; persistence, OR=0.085, P < .0001), compared to subjects not sensitized. Subjects with acquired or persistent allergic sensitization were also had higher odds for persistence of disease (yes-yes) than subjects not sensitized (acquisition, OR=5.49, P = .0001; persistence, OR=11.79, P < .0001). CONCLUSION: Transition of allergic sensitizations to common allergens is a prognostic factor for subsequent or concurrent transition of eczema, asthma, and rhinitis. Prevention or reduction in allergic sensitization has a potential to lead to remission of these conditions.

Maternal and fetal genetic contribution to gestational weight gain.

BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Zoonotic helminth exposure and risk of allergic diseases: A study of two generations in Norway.

BACKGROUND: Animal and human studies indicate that definitive host helminth infections may confer protection from allergies. However, zoonotic helminths, such as Toxocara species (spp.), have been associated with increased allergies. OBJECTIVE: We describe the prevalence of Toxocara spp. and Ascaris spp. seropositivity and associations with allergic diseases and sensitization, in 2 generations in Bergen, Norway. METHODS: Serum levels of total IgG4, anti-Toxocara spp. IgG4 and Ascaris spp. IgG4 were established by ELISA in 2 cohorts: parents born 1945-1972 (n = 171) and their offspring born 1969-2003 (n = 264). Allergic outcomes and covariates were recorded through interviews and clinical examinations including serum IgEs and skin prick tests. RESULTS: Anti-Ascaris spp. IgG4 was detected in 29.2% of parents and 10.3% of offspring, and anti-Toxocara spp. IgG4 in 17.5% and 8.0% of parents and offspring, respectively. Among offspring, anti-Toxocara spp. IgG4 was associated with pet keeping before age 15 (OR = 6.15; 95% CI = 1.37-27.5) and increasing BMI (1.16[1.06-1.25] per kg/m2 ). Toxocara spp. seropositivity was associated with wheeze (2.97[1.45- 7.76]), hayfever (4.03[1.63-9.95]), eczema (2.89[1.08-7.76]) and cat sensitization (5.65[1.92-16.6]) among offspring, but was not associated with allergic outcomes among parents. Adjustment for childhood or current pet keeping did not alter associations with allergies. Parental Toxocara spp. seropositivity was associated with increased offspring allergies following a sex-specific pattern. CONCLUSIONS & CLINICAL RELEVANCE: Zoonotic helminth exposure in Norway was less frequent in offspring than parents; however, Toxocara spp. seropositivity was associated with increased risk of allergic manifestations in the offspring generation, but not among parents. Changes in response to helminth exposure may provide insights into the increase in allergy incidence in affluent countries.

NIMA-related kinase 1 (NEK1) regulates meiosis I spindle assembly by altering the balance between α-Adducin and Myosin X.

NIMA-related kinase 1 (NEK1) is a serine/threonine and tyrosine kinase that is highly expressed in mammalian germ cells. Mutations in Nek1 induce anemia, polycystic kidney and infertility. In this study we evaluated the role of NEK1 in meiotic spindle formation in both male and female gametes. Our results show that the lack of NEK1 provokes an abnormal organization of the meiosis I spindle characterized by elongated and/or multipolar spindles, and abnormal chromosome congression. The aberrant spindle structure is concomitant with the disruption in localization and protein levels of myosin X (MYO10) and α-adducin (ADD1), both of which are implicated in the regulation of spindle formation during mitosis. Interaction of ADD1 with MYO10 is dependent on phosphorylation, whereby phosphorylation of ADD1 enables its binding to MYO10 on mitotic spindles. Reduction in ADD1 protein in NEK1 mutant mice is associated with hyperphosphorylation of ADD1, thereby preventing the interaction with MYO10 during meiotic spindle formation. Our results reveal a novel regulatory role for NEK1 in the regulation of spindle architecture and function during meiosis.

Brilliant X-rays using a Two-Stage Plasma Insertion Device.

Particle accelerators have made an enormous impact in all fields of natural sciences, from elementary particle physics, to the imaging of proteins and the development of new pharmaceuticals. Modern light sources have advanced many fields by providing extraordinarily bright, short X-ray pulses. Here we present a novel numerical study, demonstrating that existing third generation light sources can significantly enhance the brightness and photon energy of their X-ray pulses by undulating their beams within plasma wakefields. This study shows that a three order of magnitude increase in X-ray brightness and over an order of magnitude increase in X-ray photon energy is achieved by passing a 3 GeV electron beam through a two-stage plasma insertion device. The production mechanism micro-bunches the electron beam and ensures the pulses are radially polarised on creation. We also demonstrate that the micro-bunched electron beam is itself an effective wakefield driver that can potentially accelerate a witness electron beam up to 6 GeV.

Expression of the filaggrin gene in umbilical cord blood predicts eczema risk in infancy: A birth cohort study.

BACKGROUND: Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking. OBJECTIVE: This study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy. METHODS: Infants enrolled in a birth cohort study (n=94) were assessed for eczema at ages 3, 6, and 12 months. Five probes measuring FLG transcripts expression in UCB were available from genomewide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression. RESULTS: Increased level of FLG expression measured by probe A_24_P51322 was associated with reduced risk of eczema during the first year of life (RR=0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense transcripts measured by probe A_21_P0014075 was associated with increased risk of eczema (RR=2.02, 95% CI: 1.10-3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3 months of age was high (AUC: 0.91, 95% CI: 0.84-0.98). CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention.

The interacting roles of climate, soils, and plant production on soil microbial communities at a continental scale.

Soil microbial communities control critical ecosystem processes such as decomposition, nutrient cycling, and soil organic matter formation. Continental scale patterns in the composition and functioning of microbial communities are related to climatic, biotic, and edaphic factors such as temperature and precipitation, plant community composition, and soil carbon, nitrogen, and pH. Although these relationships have been well explored individually, the examination of the factors that may act directly on microbial communities vs. those that may act indirectly through other ecosystem properties has not been well developed. To further such understanding, we utilized structural equation modeling (SEM) to evaluate a set of hypotheses about the direct and indirect effects of climatic, biotic, and edaphic variables on microbial communities across the continental United States. The primary goals of this work were to test our current understanding of the interactions among climate, soils, and plants in affecting microbial community composition, and to examine whether variation in the composition of the microbial community affects potential rates of soil enzymatic activities. A model of interacting factors created through SEM shows several expected patterns. Distal factors such as climate had indirect effects on microbial communities by influencing plant productivity, soil mineralogy, and soil pH, but factors related to soil organic matter chemistry had the most direct influence on community composition. We observed that both plant productivity and soil mineral composition were important indirect influences on community composition at the continental scale, both interacting to affect organic matter content and microbial biomass and ultimately community composition. Although soil hydrolytic enzymes were related to the moisture regime and soil carbon, oxidative enzymes were also affected by community composition, reflected in the abundance of soil fungi. These results highlight that soil microbial communities can be modeled within the context of multiple interacting ecosystem properties acting both directly and indirectly on their composition and function, and this provides a rich and informative context with which to examine communities. This work also highlights that variation in climate, microbial biomass, and microbial community composition can affect maximum rates of soil enzyme activities, potentially influencing rates of decomposition and nutrient mineralization in soils.

Dense plasma heating by crossing relativistic electron beams.

Here we investigate, using relativistic fluid theory and Vlasov-Maxwell simulations, the local heating of a dense plasma by two crossing electron beams. Heating occurs as an instability of the electron beams drives Langmuir waves, which couple nonlinearly into damped ion-acoustic waves. Simulations show a factor 2.8 increase in electron kinetic energy with a coupling efficiency of 18%. Our results support applications to the production of warm dense matter and as a driver for inertial fusion plasmas.

Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients.

RATIONALE: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studies have identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking. OBJECTIVES: We aimed to comprehensively determine the uPAR expression profile in asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features. METHODS: uPAR levels were determined in control (n = 9) and asthmatic (n = 27) bronchial biopsies using immunohistochemistry, with a semi-quantitative score defining intensity in multiple cell types. Soluble-cleaved (sc) uPAR levels were determined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts. MEASUREMENTS AND MAIN RESULTS: In bronchial tissue, uPAR was elevated in inflammatory cells in the lamina propria (P = 0.0019), bronchial epithelial (P = 0.0002) and airway smooth muscle cells (P = 0.0352) of patients with asthma, with uPAR levels correlated between the cell types. No correlation with disease severity or asthma clinical features was identified. scuPAR serum levels were elevated in patients with asthma (1.5-fold; P = 0.0008), and we identified an association between high uPAR serum levels and severe, nonatopic disease. CONCLUSIONS: This study provides novel data that elevated airway and blood uPAR is a feature of asthma and that blood uPAR is particularly related to severe, nonatopic asthma. The findings warrant further investigation and may provide a therapeutic opportunity for this refractory population.

Mitigation of hard x-ray background in backlit pinhole imagers.

Experiments were performed to mitigate the hard x-ray background commonly observed in backlit pinhole imagers. The material of the scaffold holding the primary backlighter foil was varied to reduce the laser-plasma instabilities responsible for hot electrons and resulting hard x-ray background. Radiographic measurements with image plates showed a factor of >25 decrease in x-rays between 30 and 67 keV when going from a plastic to Al or V scaffold. A potential design using V scaffold offers a signal-to-background ratio of 6:1, a factor of 2 greater than using the bare plastic scaffold.