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1.
Gastro Hep Adv ; 2(5): 666-675, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469521

RESUMO

Background and Aims: Necrotizing enterocolitis (NEC) is a life-threatening disease and the most common gastrointestinal emergency in premature infants. Accurate early diagnosis is challenging. Modified Bell's staging is routinely used to guide diagnosis, but early diagnostic signs are nonspecific, potentially leading to unobserved disease progression, which is problematic given the often rapid deterioration observed. We investigated fecal cytokine levels, coupled with gut microbiota profiles, as a noninvasive method to discover specific NEC-associated signatures that can be applied as potential diagnostic markers. Methods: Premature babies born below 32 weeks of gestation were admitted to the 2-site neonatal intensive care unit (NICU) of Imperial College hospitals (St. Mary's or Queen Charlotte's & Chelsea) between January 2011 and December 2012. During the NICU stay, expert neonatologists grouped individuals by modified Bell's staging (healthy, NEC1, NEC2/3) and fecal samples from diapers were collected consecutively. Microbiota profiles were assessed by 16S rRNA gene amplicon sequencing and cytokine concentrations were measured by V-Plex multiplex assays. Results: Early evaluation of microbiota profiles revealed only minor differences. However, at later time points, significant changes in microbiota composition were observed for Bacillota (adj. P = .0396), with Enterococcus being the least abundant in Bell stage 2/3 NEC. Evaluation of fecal cytokine levels revealed significantly higher concentrations of IL-1α (P = .045), IL-5 (P = .0074), and IL-10 (P = .032) in Bell stage 1 NEC compared to healthy individuals. Conclusion: Differences in certain fecal cytokine profiles in patients with NEC indicate their potential use as diagnostic biomarkers to facilitate earlier diagnosis. Additionally, associations between microbial and cytokine profiles contribute to improving knowledge about NEC pathogenesis.

2.
Nat Microbiol ; 8(6): 1160-1175, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37231089

RESUMO

Clostridium perfringens is an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link between C. perfringens and the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundant C. perfringens termed C. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272 C. perfringens isolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O, pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typical pfoA-encoding virulent lineages. We determined that infant-associated pfoA+ strains caused significantly more cellular damage than pfoA- strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance of pfoA+ C. perfringens as a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies.


Assuntos
Clostridium perfringens , Doenças do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Animais , Camundongos , Clostridium perfringens/genética , Recém-Nascido Prematuro , Estudos Retrospectivos , Virulência/genética , Genômica
3.
Rev Sci Instrum ; 94(1): 013104, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36725556

RESUMO

An x-ray Fresnel diffractive radiography platform was designed for use at the National Ignition Facility. It will enable measurements of micron-scale changes in the density gradients across an interface between isochorically heated warm dense matter materials, the evolution of which is driven primarily through thermal conductivity and mutual diffusion. We use 4.75 keV Ti K-shell x-ray emission to heat a 1000 µm diameter plastic cylinder, with a central 30 µm diameter channel filled with liquid D2, up to 8 eV. This leads to a cylindrical implosion of the liquid D2 column, compressing it to ∼2.3 g/cm3. After pressure equilibration, the location of the D2/plastic interface remains steady for several nanoseconds, which enables us to track density gradient changes across the material interface with high precision. For radiography, we use Cu He-α x rays at 8.3 keV. Using a slit aperture of only 1 µm width increases the spatial coherence of the source, giving rise to significant diffraction features in the radiography signal, in addition to the refraction enhancement, which further increases its sensitivity to density scale length changes at the D2/plastic interface.

4.
Gut Pathog ; 15(1): 3, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647112

RESUMO

BACKGROUND: The gastrointestinal (GI) microbiota has been linked to health consequences throughout life, from early life illnesses (e.g. sepsis and necrotising enterocolitis) to lifelong chronic conditions such as obesity and inflammatory bowel disease. It has also been observed that events in early life can lead to shifts in the microbiota, with some of these changes having been documented to persist into adulthood. A particularly extreme example of a divergent early GI microbiota occurs in premature neonates, who display a very different GI community to term infants. Certain characteristic patterns have been associated with negative health outcomes during the neonatal period, and these patterns may prove to have continual damaging effects if not resolved. RESULTS: In this study we compared a set of premature infants with a paired set of term infants (n = 37 pairs) at 6 weeks of age and at 2 years of age. In the samples taken at 6 weeks of age we found microbial communities differing in both diversity and specific bacterial groups between the two infant cohorts. We identified clinical factors associated with over-abundance of potentially pathogenic organisms (e.g. Enterobacteriaceae) and reduced abundances of some beneficial organisms (e.g. Bifidobacterium). We contrasted these findings with samples taken at 2 years of age, which indicated that despite a very different initial gut microbiota, the two infant groups converged to a similar, more adult-like state. We identified clinical factors, including both prematurity and delivery method, which remain associated with components of the gut microbiota. Both clinical factors and microbial characteristics are compared to the occurrence of childhood wheeze and eczema, revealing associations between components of the GI microbiota and the development of these allergic conditions. CONCLUSIONS: The faecal microbiota differs greatly between infants born at term and those born prematurely during early life, yet it converges over time. Despite this, early clinical factors remain significantly associated with the abundance of some bacterial groups at 2 years of age. Given the associations made between health conditions and the microbiota, factors that alter the makeup of the gut microbiota, and potentially its trajectory through life, could have important lifelong consequences.

5.
Phys Rev Lett ; 129(19): 195002, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36399755

RESUMO

The application of an external 26 Tesla axial magnetic field to a D_{2} gas-filled capsule indirectly driven on the National Ignition Facility is observed to increase the ion temperature by 40% and the neutron yield by a factor of 3.2 in a hot spot with areal density and temperature approaching what is required for fusion ignition [1]. The improvements are determined from energy spectral measurements of the 2.45 MeV neutrons from the D(d,n)^{3}He reaction, and the compressed central core B field is estimated to be ∼4.9 kT using the 14.1 MeV secondary neutrons from the D(T,n)^{4}He reactions. The experiments use a 30 kV pulsed-power system to deliver a ∼3 µs current pulse to a solenoidal coil wrapped around a novel high-electrical-resistivity AuTa_{4} hohlraum. Radiation magnetohydrodynamic simulations are consistent with the experiment.

6.
BMC Pediatr ; 22(1): 166, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361147

RESUMO

BACKGROUND: Respiratory virus infection is common in early childhood, and children may be symptomatic or symptom-free. Little is known regarding the association between symptomatic/asymptomatic infection and particular clinical factors such as breastfeeding as well as the consequences of such infection. METHOD: We followed an unselected cohort of term neonates to two years of age (220 infants at recruitment, 159 who remained in the study to 24 months), taking oral swabs at birth and oropharyngeal swabs at intervals subsequently (at 1.5, 6, 9, 12, 18 and 24 months and in a subset at 3 and 4.5 months) while recording extensive metadata including the presence of respiratory symptoms and breastfeeding status. After 2 years medical notes from the general practitioner were inspected to ascertain whether doctor-diagnosed wheeze had occurred by this timepoint. Multiplex PCR was used to detect a range of respiratory viruses: influenza (A&B), parainfluenza (1-4), bocavirus, human metapneumovirus, rhinovirus, coronavirus (OC43, 229E, NL63, HKU1), adenovirus, respiratory syncytial virus (RSV), and polyomavirus (KI, WU). Logistic regression and generalised estimating equations were used to identify associations between clinical factors and virus detection. RESULTS: Overall respiratory viral incidence increased with age. Rhinovirus was the virus most frequently detected. The detection of a respiratory virus was positively associated with respiratory symptoms, male sex, season, childcare and living with another child. We did not observe breastfeeding (whether assessed as the number of completed months of breastfeeding or current feed status) to be associated with the detection of a respiratory virus. There was no association between early viral infection and doctor-diagnosed wheeze by age 2 years. CONCLUSION: Asymptomatic and symptomatic viral infection is common in the first 2 years of life with rhinovirus infection being the most common. Whilst there was no association between early respiratory viral infection and doctor-diagnosed wheeze, we have not ruled out an association of early viral infections with later asthma, and long-term follow-up of the cohort continues.


Assuntos
Coronavirus , Infecções Respiratórias , Viroses , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Lactente , Recém-Nascido , Estilo de Vida , Masculino , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Viroses/diagnóstico
7.
BMC Microbiol ; 21(1): 225, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362295

RESUMO

BACKGROUND: Necrotising enterocolitis (NEC) is a devastating bowel disease, primarily affecting premature infants, with a poorly understood aetiology. Prior studies have found associations in different cases with an overabundance of particular elements of the faecal microbiota (in particular Enterobacteriaceae or Clostridium perfringens), but there has been no explanation for the different results found in different cohorts. Immunological studies have indicated that stimulation of the TLR4 receptor is involved in development of NEC, with TLR4 signalling being antagonised by the activated TLR9 receptor. We speculated that differential stimulation of these two components of the signalling pathway by different microbiota might explain the dichotomous findings of microbiota-centered NEC studies. Here we used shotgun metagenomic sequencing and qPCR to characterise the faecal microbiota community of infants prior to NEC onset and in a set of matched controls. Bayesian regression was used to segregate cases from control samples using both microbial and clinical data. RESULTS: We found that the infants suffering from NEC fell into two groups based on their microbiota; one with low levels of CpG DNA in bacterial genomes and the other with high abundances of organisms expressing LPS. The identification of these characteristic communities was reproduced using an external metagenomic validation dataset. We propose that these two patterns represent the stimulation of a common pathway at extremes; the LPS-enriched microbiome suggesting overstimulation of TLR4, whilst a microbial community with low levels of CpG DNA suggests reduction of the counterbalance to TLR4 overstimulation. CONCLUSIONS: The identified microbial community patterns support the concept of NEC resulting from TLR-mediated pathways. Identification of these signals suggests characteristics of the gastrointestinal microbial community to be avoided to prevent NEC. Potential pre- or pro-biotic treatments may be designed to optimise TLR signalling.


Assuntos
Enterocolite Necrosante/microbiologia , Células Epiteliais/imunologia , Microbioma Gastrointestinal/genética , Doenças do Prematuro/microbiologia , Receptor 4 Toll-Like/imunologia , Teorema de Bayes , DNA Bacteriano/genética , Enterocolite Necrosante/imunologia , Células Epiteliais/microbiologia , Fezes/microbiologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/imunologia , Metagenômica , RNA Ribossômico 16S/genética , Receptor 4 Toll-Like/genética
8.
Phys Rev Lett ; 125(15): 155003, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33095614

RESUMO

The implosion efficiency in inertial confinement fusion depends on the degree of stagnated fuel compression, density uniformity, sphericity, and minimum residual kinetic energy achieved. Compton scattering-mediated 50-200 keV x-ray radiographs of indirect-drive cryogenic implosions at the National Ignition Facility capture the dynamic evolution of the fuel as it goes through peak compression, revealing low-mode 3D nonuniformities and thicker fuel with lower peak density than simulated. By differencing two radiographs taken at different times during the same implosion, we also measure the residual kinetic energy not transferred to the hot spot and quantify its impact on the implosion performance.

9.
Cell Rep Med ; 1(5): 100077, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32904427

RESUMO

Supplementation with members of the early-life microbiota as "probiotics" is increasingly used in attempts to beneficially manipulate the preterm infant gut microbiota. We performed a large observational longitudinal study comprising two preterm groups: 101 infants orally supplemented with Bifidobacterium and Lactobacillus (Bif/Lacto) and 133 infants non-supplemented (control) matched by age, sex, and delivery method. 16S rRNA gene profiling on fecal samples (n = 592) showed a predominance of Bifidobacterium and a lower abundance of pathobionts in the Bif/Lacto group. Metabolomic analysis showed higher fecal acetate and lactate and a lower fecal pH in the Bif/Lacto group compared to the control group. Fecal acetate positively correlated with relative abundance of Bifidobacterium, consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides into acetate. This study demonstrates that microbiota supplementation is associated with a Bifidobacterium-dominated preterm microbiota and gastrointestinal environment more closely resembling that of full-term infants.


Assuntos
Bifidobacterium/fisiologia , Microbioma Gastrointestinal/fisiologia , Recém-Nascido Prematuro/metabolismo , Recém-Nascido Prematuro/fisiologia , Lactobacillus/fisiologia , Metaboloma/fisiologia , Bifidobacterium/genética , Aleitamento Materno/métodos , Suplementos Nutricionais/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Lactente , Recém-Nascido , Lactobacillus/genética , Estudos Longitudinais , Leite Humano/microbiologia , Probióticos/administração & dosagem , RNA Ribossômico 16S/genética
10.
BMC Pediatr ; 20(1): 75, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070310

RESUMO

BACKGROUND: Clostridium perfringens forms part of the human gut microbiota and has been associated with life-threatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains. METHODS: C. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis. RESULTS: 29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis, whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B, netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC. CONCLUSIONS: Approximately a third of preterm infants are colonised 3 weeks after birth with toxin gene-carrying C. perfringens. We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens. Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC. TRIAL REGISTRATION: clinicaltrials.gov NCT01102738, registered 13th April 2010.


Assuntos
Infecções por Clostridium , Clostridium perfringens , Microbioma Gastrointestinal , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Clostridium perfringens/patogenicidade , Enterotoxinas , Fezes , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Gravidez
11.
Sci Adv ; 6(6): eaay8967, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32076652

RESUMO

The Earth's atmosphere contains a multitude of emitted (primary) and chemically formed (secondary) gases and particles that degrade air quality and modulate the climate. Reactive organic carbon (ROC) species are the fuel of the chemistry of the atmosphere, dominating short-lived emissions, reactivity, and the secondary production of key species such as ozone, particulate matter, and carbon dioxide. Despite the central importance of ROC, the diversity and complexity of this class of species has been a longstanding obstacle to developing a comprehensive understanding of how the composition of our atmosphere, and the associated environmental implications, will evolve. Here, we characterize the role of ROC in atmospheric chemistry and the challenges inherent in measuring and modeling ROC, and highlight recent progress toward achieving mass closure for the complete description of atmospheric ROC.

12.
J Matern Fetal Neonatal Med ; 33(3): 398-403, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29945481

RESUMO

Background and aims: The etiology of necrotizing enterocolitis (NEC) is unclear and postulated as being multifactorial. It has been suggested that one causative factor is the transfusion of packed red blood cells (PRBCs) leading to the disease entity commonly referred to as transfusion-associated NEC (TANEC). TANEC has been reported in North America but its incidence has not been formally investigated in the UK. Our aims were to identify the incidence of NEC and TANEC in tertiary-level UK neonatal units and to describe characteristics of TANEC cases.Materials and methods: Using strict case definitions for NEC and TANEC, we undertook a retrospective review to estimate the incidence of TANEC cases occurring in four UK tertiary-level centers during a 38-month period.Results: Of 8007 consecutive neonatal admissions of all gestations to the four centers, 68 babies went on to develop NEC and all affected infants were of very low birth weight (VLBW); 34 of these had previously received a transfusion of PRBCs but did not fit the diagnostic criteria for TANEC, whereas 15 (22%) of the 68 babies with NEC qualified as TANEC cases. UK cases occurred at an earlier postnatal age than cases reported in multiple large North American series and were of a lower birth weight.Conclusions: We have confirmed the presence of TANEC in the UK VLBW neonatal population. Its incidence lies within the wide range described in previous reports of this phenomenon globally, though with some local variation in characteristics. Further work is needed to clarify causation, pathophysiology, and possible mechanisms of prevention of TANEC.


Assuntos
Enterocolite Necrosante/etiologia , Reação Transfusional/complicações , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Estudos Retrospectivos
13.
Toxins (Basel) ; 11(9)2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546794

RESUMO

Clostridium perfringens toxinotype D, toxinotype E, and gastroenteritis-linked BEC/CPILE-positive strains have never been reported in healthy children. We isolated, whole-genome sequenced and bioinformatically characterised three C. perfringens isolates-type D (IQ1), type E (IQ2) and BEC/CPILE-positive (IQ3), recovered from the stools of three healthy two-year-olds, which were further compared to 128 C. perfringens genomes available from NCBI. The analysis uncovered a previously under-described putative toxin gene alv (alveolysin) encoded by isolates IQ2 and IQ3, which appeared to be a clade-specific trait associated with strains from domestic animals. A plasmid analysis indicated that the iota-toxin was encoded on a near-intact previously described plasmid pCPPB-1 in type E strain IQ2. The BEC genes becA and becB were carried on a near-identical pCPOS-1 plasmid previously associated with Japanese gastroenteritis outbreaks. Furthermore, a close phylogenetic relatedness was inferred between the French C. perfringens type E isolates cp515.17 and newly sequenced IQ2, suggesting geographical links. This study describes novel C. perfringens isolates from healthy individuals which encode important toxin genes, indicating the potential spread of these veterinary and clinically important strains and mobile genetic elements, and highlights areas for future research.


Assuntos
Clostridium perfringens/genética , Fezes/microbiologia , Toxinas Bacterianas/genética , Sequência de Bases , Pré-Escolar , Infecções por Clostridium/microbiologia , Clostridium perfringens/isolamento & purificação , Genômica , Humanos , Filogenia , Polimorfismo de Nucleotídeo Único
14.
Int J Legal Med ; 133(6): 1889-1894, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31263946

RESUMO

The aim of this study is to assess the added value of post-mortem computed tomography (PMCT) in fatal shooting incidents compared with autopsy findings. For this study, the analysis was restricted to the following four features: location of the entrance and exit wounds, internal injuries, location of projectiles or metal fragments and course of the trajectories. These features were selected because they provide essential information on the cause and manner of death. All data were retrospectively collected from medical forensic examinations of fatal shooting incidents in the Netherlands that occurred in 2010-2014. Twenty-one fatal shooting victims were included in this study, with a total of 100 trajectories. For all 100 trajectories, the forensic radiologist and pathologist came to a consensus on which examination had the highest diagnostic value for each of the four features. PMCT provides superior information on the presence of metal fragments, internal injuries and the course of trajectories. PMCT provides limited information on the discrimination of entrance and exit wounds. In conclusion, PMCT provides additional relevant information in over 60% of forensic medical examinations of deceased victims of shooting incidents. We therefore recommend adding PMCT as a standard examination in these cases.


Assuntos
Tomografia Computadorizada por Raios X , Ferimentos por Arma de Fogo/diagnóstico por imagem , Ferimentos por Arma de Fogo/patologia , Autopsia , Patologia Legal , Humanos , Países Baixos , Estudos Retrospectivos
15.
EBioMedicine ; 46: 486-498, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31353293

RESUMO

BACKGROUND: A critical window in infancy has been proposed, during which the microbiota may affect subsequent health. The longitudinal development of the oropharyngeal microbiota is under-studied and may be associated with early-life wheeze. We aimed to investigate the temporal association of the development of the oropharyngeal microbiota with early-life wheeze. METHODS: A population-based birth cohort based in London, UK was followed for 24 months. We collected oropharyngeal swabs at six time-points. Microbiota was determined using sequencing of the V3-V5 region of the 16S rRNA-encoding gene. Medical records were reviewed for the outcome of doctor diagnosed wheeze. We used a time-varying model to investigate the temporal association between the development of microbiota and doctor-diagnosed wheeze. FINDINGS: 159 participants completed the study to 24 months and for 98 there was complete sequencing data at all timepoints and outcome data. Of these, 26 had doctor-diagnosed wheeze. We observed significant increase in the abundance of Neisseria between 9 and 24 months in children who developed wheeze (p = 0∙003), while in those without wheezing there was a significant increment in the abundance of Granulicatella (p = 0∙012) between 9 and 12 months, and of Prevotella (p = 0∙018) after 18 months. INTERPRETATION: A temporal association between the respiratory commensal Granulicatella and also Prevotella with wheeze (negative), and between Neisseria and wheeze (positive) was identified in infants prior to one year of age. This adds to evidence for the proposed role of the microbiota in the development of wheeze. FUND: Research funding from the Winnicott Foundation, Meningitis Now and Micropathology Ltd.


Assuntos
Microbiota , Orofaringe/microbiologia , Sons Respiratórios/etiologia , Fatores Etários , Biodiversidade , Estudos de Coortes , Feminino , Humanos , Masculino , Metagenoma , Metagenômica/métodos , Vigilância da População , Reino Unido/epidemiologia
16.
Int J Legal Med ; 133(6): 1869-1877, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30911839

RESUMO

PURPOSE: Forensic investigations could benefit from non-invasive in situ characterization of bullets. Therefore, the use of CT imaging was explored for the analysis of bullet geometry and composition. Bullet visualization with CT is challenging as the metal constituents suffer from excessive X-ray attenuation due to their high atomic number, density, and geometry. METHODS: A metal reference phantom was developed containing small discs of various common metals (aluminum, iron, stainless steel, copper, brass, tungsten, and lead). CT images were acquired with 70-150 kVp and 200-400 mAs and were reconstructed using an extended Hounsfield unit (HU) scale (- 10,240 to + 30,710). For each material, the mean CT number (HU) was measured to construct a metal database. Different bullets (n = 11) were scanned in a soft tissue-mimicking phantom. Bullet size and shape were measured, and composition was evaluated by comparison with the metal database. Also, the effect of bullet orientation within the CT scanner was evaluated. RESULTS: In the reference phantom, metals were classified into three groups according to their atomic number (Z): low (Z ≤ 13; HU < 3000), medium (Z = 25-30; HU = 13,000-20,000), and high (Z ≥ 74; HU > 30,000). External bullet contours could be accurately delineated. Internal interfaces between jacket and core could not be identified. Cross-sectional spatial profile plots of the CT number along bullets' short axis revealed beam hardening and photon starvation effects that depended on bullet size, shape, and orientation within the CT scanner. Therefore, the CT numbers of bullets were unreliable and could not be used for material characterization by comparison with the reference phantom. CONCLUSION: CT-based characterization of bullets was feasible in terms of size and shape but not composition.


Assuntos
Balística Forense , Metais , Imagens de Fantasmas , Tomografia Computadorizada por Raios X , Armas de Fogo , Humanos
17.
Microbiome ; 7(1): 40, 2019 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-30878035

RESUMO

BACKGROUND: The growth in publically available microbiome data in recent years has yielded an invaluable resource for genomic research, allowing for the design of new studies, augmentation of novel datasets and reanalysis of published works. This vast amount of microbiome data, as well as the widespread proliferation of microbiome research and the looming era of clinical metagenomics, means there is an urgent need to develop analytics that can process huge amounts of data in a short amount of time. To address this need, we propose a new method for tyrhe compact representation of microbiome sequencing data using similarity-preserving sketches of streaming k-mer spectra. These sketches allow for dissimilarity estimation, rapid microbiome catalogue searching and classification of microbiome samples in near real time. RESULTS: We apply streaming histogram sketching to microbiome samples as a form of dimensionality reduction, creating a compressed 'histosketch' that can efficiently represent microbiome k-mer spectra. Using public microbiome datasets, we show that histosketches can be clustered by sample type using the pairwise Jaccard similarity estimation, consequently allowing for rapid microbiome similarity searches via a locality sensitive hashing indexing scheme. Furthermore, we use a 'real life' example to show that histosketches can train machine learning classifiers to accurately label microbiome samples. Specifically, using a collection of 108 novel microbiome samples from a cohort of premature neonates, we trained and tested a random forest classifier that could accurately predict whether the neonate had received antibiotic treatment (97% accuracy, 96% precision) and could subsequently be used to classify microbiome data streams in less than 3 s. CONCLUSIONS: Our method offers a new approach to rapidly process microbiome data streams, allowing samples to be rapidly clustered, indexed and classified. We also provide our implementation, Histosketching Using Little K-mers (HULK), which can histosketch a typical 2 GB microbiome in 50 s on a standard laptop using four cores, with the sketch occupying 3000 bytes of disk space. ( https://github.com/will-rowe/hulk ).


Assuntos
Bactérias/classificação , Microbioma Gastrointestinal , Metagenômica/métodos , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Estudos de Coortes , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Aprendizado de Máquina , Análise de Sequência de DNA , Software
18.
Rev Sci Instrum ; 89(10): 10K111, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30399855

RESUMO

Achieving a symmetric implosion in National Ignition Facility indirect drive targets requires understanding and control of dynamic changes to the laser power transport in the hohlraum. We developed a new experimental platform to simultaneously visualize wall-plasma motion and dynamic laser power transport in the hohlraum and are using it to investigate correlations of these measurements with the imploded capsule symmetry. In a series of experiments where we made one single parameter variation, we show the value of this new platform in developing an understanding of laser transport and implosion symmetry. This platform also provides a new way to evaluate dynamic performance of advanced hohlraum designs.

19.
Rev Sci Instrum ; 89(10): 10G108, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30399872

RESUMO

In the quest for reaching ignition of deuterium-tritium (DT) fuel capsule implosions, experiments on the National Ignition Facility (NIF) have shown lower final fuel areal densities than simulated. Possible explanations for reduced compression are higher preheat that can increase the ablator-DT ice density jump and induce mix at that interface or reverberating shocks. We are hence developing x-ray Refraction Enhanced Radiography (RER) to infer the inflight density profiles in layered fuel capsule implosions. We use a 5 µm slit backlit by a Ni 7.8 keV He-α NIF laser driven x-ray source positioned at 20 mm from the capsule to cast refracted images of the inflight capsule onto a streak camera in a high magnification (M ∼ 60×) setup. Our first experiments have validated our setup that recorded a streaked x-ray fringe pattern from an undriven high density carbon (HDC) capsule consistent with ray tracing calculations at the required ∼6 µm and 25 ps resolution. Streaked RER was then applied to inflight layered HDC capsule implosions using a hydrogen-tritium fuel mix rather than DT to reduce neutron yields and associated backgrounds. The first RER of an imploding capsule revealed strong features associated with the ablation front and ice-ablator interface that are not visible in standard absorption radiographs.

20.
Nat Commun ; 9(1): 4615, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-30397206

RESUMO

Circuit quantum electrodynamics has proven to be a powerful tool to probe mesoscopic effects in hybrid systems and is used in several quantum computing (QC) proposals that require a transmon qubit able to operate in strong magnetic fields. To address this we integrate monolayer graphene Josephson junctions into microwave frequency superconducting circuits to create graphene based transmons. Using dispersive microwave spectroscopy we resolve graphene's characteristic band dispersion and observe coherent electronic interference effects confirming the ballistic nature of our graphene Josephson junctions. We show that the monoatomic thickness of graphene renders the device insensitive to an applied magnetic field, allowing us to perform energy level spectroscopy of the circuit in a parallel magnetic field of 1 T, an order of magnitude higher than previous studies. These results establish graphene based superconducting circuits as a promising platform for QC and the study of mesoscopic quantum effects that appear in strong magnetic fields.

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