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1.
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.

2.
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
3.
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
4.
Proc Natl Acad Sci U S A ; 115(2): 290-295, 2018 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-29279369

RESUMO

Exposure to atmospheric particulate matter (PM) exacerbates respiratory and cardiovascular conditions and is a leading source of premature mortality globally. Organic aerosol contributes a significant fraction of PM in the United States. Here, using surface observations between 1990 and 2012, we show that organic carbon has declined dramatically across the entire United States by 25-50%; accounting for more than 30% of the US-wide decline in PM. The decline is in contrast with the increasing organic aerosol due to wildfires and no clear trend in biogenic emissions. By developing a carbonaceous emissions database for the United States, we show that at least two-thirds of the decline in organic aerosol can be explained by changes in anthropogenic emissions, primarily from vehicle emissions and residential fuel burning. We estimate that the decrease in anthropogenic organic aerosol is responsible for averting 180,000 (117,000-389,000) premature deaths between 1990 and 2012. The unexpected decrease in organic aerosol, likely a consequence of the implementation of Clean Air Act Amendments, results in 84,000 (30,000-164,000) more lives saved than anticipated by the EPA between 2000 and 2010.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Material Particulado/análise , Aerossóis/química , Carbono/química , Monitoramento Ambiental/legislação & jurisprudência , Monitoramento Ambiental/métodos , Combustíveis Fósseis/análise , Geografia , Estados Unidos , United States Environmental Protection Agency/legislação & jurisprudência , Emissões de Veículos/prevenção & controle
5.
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.

6.
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
7.
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
8.
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
9.
J Allergy Clin Immunol ; 141(4): 1334-1342.e5, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28866384

RESUMO

BACKGROUND: Development of the gut microbiota in infancy is important in maturation of the immune system. Deviations in colonization patterns have been associated with allergic manifestations such as eczema, but exact microbiome dysfunctions underlying allergies remain unclear. We studied the gut microbiota of 138 infants at increased risk of allergy, participating in a clinical trial investigating the effectiveness of a partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides on the prevention of eczema. OBJECTIVE: The effects of interventions and breast-feeding on fecal microbiota were investigated. Additionally, we aimed to identify microbial patterns associated with the onset of eczema. METHODS: Bacterial taxonomic compositions in the first 26 weeks of life were analyzed by using 16S rRNA gene sequencing. Additionally, fecal pH and microbial metabolite levels were measured. RESULTS: Fecal microbial composition, metabolites, and pH of infants receiving partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides was closer to that of breast-fed infants than that of infants receiving standard cow's milk formula. Infants with eczema by 18 months showed discordant development of bacterial genera of Enterobacteriaceae and Parabacteroides species in the first 26 weeks, as well as decreased acquisition of lactate-utilizing bacteria producing butyrate, namely Eubacterium and Anaerostipes species, supported by increased lactate and decreased butyrate levels. CONCLUSIONS: We showed that a partially hydrolyzed protein infant formula with specific prebiotics modulated the gut microbiota closer to that of breast-fed infants. Additionally, we identified a potential link between microbial activity and onset of eczema, which might reflect a suboptimal implementation of gut microbiota at specific developmental stages in infants at high risk for allergy.


Assuntos
Aleitamento Materno , Eczema/prevenção & controle , Microbioma Gastrointestinal , Fórmulas Infantis/química , Prebióticos , Método Duplo-Cego , Eczema/microbiologia , Fezes/microbiologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Resultado do Tratamento
10.
Emerg Infect Dis ; 24(3): 443-452, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29460728

RESUMO

Encapsulated Haemophilus influenzae strains belong to type-specific genetic lineages. Reliable capsule typing requires PCR, but a more efficient method would be useful. We evaluated capsule typing by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Isolates of all capsule types (a-f and nontypeable; n = 258) and isogenic capsule transformants (types a-d) were investigated. Principal component and biomarker analyses of mass spectra showed clustering, and mass peaks correlated with capsule type-specific genetic lineages. We used 31 selected isolates to construct a capsule typing database. Validation with the remaining isolates (n = 227) showed 100% sensitivity and 92.2% specificity for encapsulated strains (a-f; n = 61). Blinded validation of a supplemented database (n = 50) using clinical isolates (n = 126) showed 100% sensitivity and 100% specificity for encapsulated strains (b, e, and f; n = 28). MALDI-TOF mass spectrometry is an accurate method for capsule typing of H. influenzae.


Assuntos
Cápsulas Bacterianas , Técnicas de Tipagem Bacteriana , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/classificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Cápsulas Bacterianas/genética , Evolução Molecular , Ligação Genética , Haemophilus influenzae/genética , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
11.
Phys Rev Lett ; 121(9): 095002, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30230893

RESUMO

We report on the first multilocation electron temperature (T_{e}) and flow measurements in an ignition hohlraum at the National Ignition Facility using the novel technique of mid-Z spectroscopic tracer "dots." The measurements define a low resolution "map" of hohlraum plasma conditions and provide a basis for the first multilocation tests of particle and energy transport physics in a laser-driven x-ray cavity. The data set is consistent with classical heat flow near the capsule but reduced heat flow near the laser entrance hole. We evaluate the role of kinetic effects, self-generated magnetic fields, and instabilities in causing spatially dependent heat transport in the hohlraum.

12.
Infect Immun ; 85(5)2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28264906

RESUMO

Neisseria meningitidis is a commensal microbe that colonizes the human nasopharynx but occasionally invades the bloodstream to cause life-threatening infection. N. meningitidis MC58 NMB0419 encodes a Sel1-like repeat (SLR)-containing protein, previously implicated in invasion of epithelial cells. A gene-regulatory function was revealed in Escherichia coli expressing plasmid-borne NMB0419 and showing significantly increased epithelial adherence compared to the wild type, due to increased expression of mannose-sensitive type 1 pili. While a meningococcal NMB0419 mutant did not have altered epithelial adherence, in a transcriptome-wide comparison of the wild type and an NMB0419 mutant, a large proportion of genes differentially regulated in the mutant were involved in iron acquisition and metabolism. Fifty-one percent and 38% of genes, respectively, up- and downregulated in the NMB0419 mutant had previously been identified as being induced and repressed by meningococcal Fur. An in vitro growth defect of the NMB0419 mutant under iron restriction was consistent with the downregulation of tbpAB and hmbR, while an intraepithelial replication defect was consistent with the downregulation of tonB, exbB, and exbD, based on a known phenotype of a meningococcal tonB mutant. Disruption of the N-terminal NMB0419 signal peptide, predicted to export the protein beyond the cytoplasmic membrane, resulted in loss of functional traits in N. meningitidis and E. coli Our study indicates that the expression of NMB0419 is associated with transcriptional changes counterbalancing the regulatory function of Fur, offering a new perspective on regulatory mechanisms involved in meningococcal interaction with epithelial cells, and suggests new insights into the roles of SLR-containing genes in other bacteria.


Assuntos
Proteínas de Bactérias/metabolismo , Células Epiteliais/microbiologia , Neisseria meningitidis/crescimento & desenvolvimento , Neisseria meningitidis/genética , Regulon , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Aderência Bacteriana , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Técnicas de Inativação de Genes , Ferro/metabolismo , Plasmídeos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Fatores de Transcrição/genética
13.
Faraday Discuss ; 200: 579-598, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28574567

RESUMO

Organic compounds in the atmosphere vary widely in their molecular composition and chemical properties, so no single instrument can reasonably measure the entire range of ambient compounds. Over the past decade, a new generation of in situ, field-deployable mass spectrometers has dramatically improved our ability to detect, identify, and quantify these organic compounds, but no systematic approach has been developed to assess the extent to which currently available tools capture the entire space of chemical identity and properties that is expected in the atmosphere. Reduced-parameter frameworks that have been developed to describe atmospheric mixtures are exploited here to characterize the range of chemical properties accessed by a suite of instruments. Multiple chemical spaces (e.g. oxidation state of carbon vs. volatility, and oxygen number vs. carbon number) were populated with ions measured by several mass spectrometers, with gas- and particle-phase α-pinene oxidation products serving as the test mixture of organic compounds. Few gaps are observed in the coverage of the parameter spaces by the instruments employed in this work, though the full extent to which comprehensive measurement was achieved is difficult to assess due to uncertainty in the composition of the mixture. Overlaps between individual ions and regions in parameter space were identified, both between gas- and particle-phase measurements, and within each phase. These overlaps were conservatively found to account for little (<10%) of the measured mass. However, challenges in identifying overlaps and in accurately converting molecular formulas into chemical properties (such as volatility or reactivity) highlight a continued need to incorporate structural information into atmospheric measurements.

14.
J Pediatr Gastroenterol Nutr ; 64(2): 230-237, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27070657

RESUMO

OBJECTIVES: Inflammatory bowel disease states are associated with gastrointestinal dysbiosis. Mucosal biopsy sampling, retrieving the bacterial community that most directly interacts with the host, is an invasive procedure that, we hypothesis, may be sufficiently approximated by other sampling methods. We investigate the relatedness of samples obtained by different methods and the effects of bowel preparation on the gastrointestinal community in a paediatric population. METHODS: We recruited a cohort of patients undergoing colonoscopy, collecting serial samples via differing methods (rectal swabs, biopsies, and faecal matter/luminal contents) prebowel preparation, during colonoscopy and after colonoscopy. Next-generation sequencing was used to determine the structure of the microbial community. RESULTS: The microbial community in luminal contents collected during colonoscopy was found to be more similar to that of mucosal biopsies than rectal swabs. Community traits of the mucosal biopsies could be used to segregate patients with inflammatory bowel disease from other patients, and the similarity of the communities in the luminal contents was sufficient for the segregation to be reproduced. Microbial communities sampled by rectal swabs and prebowel preparation faeces were less similar to mucosal biopsies. Bowel preparation was found to have no significant long-term effects on the microbial community, despite the transient effects evident during colonoscopy. CONCLUSIONS: A clinically relevant description of the mucosal microbial community can be obtained via the noninvasive collection of luminal contents after bowel cleansing. Bowel preparation in a paediatric population results in no consistent sustained alterations to the gastrointestinal microbiota.


Assuntos
Catárticos/farmacologia , Colo/microbiologia , Colonoscopia , Fezes/microbiologia , Microbioma Gastrointestinal , Mucosa Intestinal/microbiologia , Laxantes/farmacologia , Adolescente , Biópsia , Catárticos/administração & dosagem , Criança , Pré-Escolar , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Laxantes/administração & dosagem , Masculino
15.
Psychol Med ; 46(14): 3025-3039, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27523311

RESUMO

BACKGROUND: Very preterm birth (VPT; <32 weeks of gestation) has been associated with impairments in emotion regulation, social competence and communicative skills. However, the neuroanatomical mechanisms underlying such impairments have not been systematically studied. Here we investigated the functional integrity of the amygdala connectivity network in relation to the ability to recognize emotions from facial expressions in VPT adults. METHOD: Thirty-six VPT-born adults and 38 age-matched controls were scanned at rest in a 3-T MRI scanner. Resting-state functional connectivity (rs-fc) was assessed with SPM8. A seed-based analysis focusing on three amygdalar subregions (centro-medial/latero-basal/superficial) was performed. Participants' ability to recognize emotions was assessed using dynamic stimuli of human faces expressing six emotions at different intensities with the Emotion Recognition Task (ERT). RESULTS: VPT individuals compared to controls showed reduced rs-fc between the superficial subregion of the left amygdala, and the right posterior cingulate cortex (p = 0.017) and the left precuneus (p = 0.002). The VPT group further showed elevated rs-fc between the left superficial amygdala and the superior temporal sulcus (p = 0.008). Performance on the ERT showed that the VPT group was less able than controls to recognize anger at low levels of intensity. Anger scores were significantly associated with rs-fc between the superficial amygdala and the posterior cingulate cortex in controls but not in VPT individuals. CONCLUSIONS: These findings suggest that alterations in rs-fc between the amygdala, parietal and temporal cortices could represent the mechanism linking VPT birth and deficits in emotion processing.


Assuntos
Tonsila do Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Emoções/fisiologia , Expressão Facial , Lactente Extremamente Prematuro/fisiologia , Percepção Social , Adulto , Tonsila do Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino
16.
Int J Legal Med ; 130(2): 457-62, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26518298

RESUMO

PURPOSE: Multi-detector computed tomography (MDCT) has proven to be of value for the reconstruction of trajectories of projectiles and the assessment of the injuries in deceased gunshot victim. For the depiction of soft tissue injury, MRI is superior to MDCT and MRI may be of value to assess trajectories. In a clinical setting, there are guidelines for the application of MRI in patients with projectiles or projectile fragments and with precautions MRI is safe for these patients. However, this has not been studied for the postmortem application of MRI from a forensic point of view. SUBJECTS AND METHOD: To assess the behaviour of projectiles, two ferromagnetic and one non-ferromagnetic projectile were exposed to the magnetic field of a 1.5- and 3-T MRI. Projectiles were placed in six phantoms with the characteristics of human muscle tissue, with and without a simulated trajectory in the gel. Before and after exposure to the magnetic field, the gelatine phantoms were imaged with MDCT to assess the position of the projectiles. RESULTS: The ferromagnetic projectiles rotate to a position where their long axis is parallel to the z-axis of the magnetic field and five out of the six projectiles moved through, either through the simulated trajectory or through a new trajectory. This was observed in both the 1.5- and 3-T systems. CONCLUSION: Ferromagnetic projectiles can rotate and migrate in a gelatine phantom. It is very likely that these projectiles will also migrate in a human body in a MRI system. Therefore, from a forensic point of view, postmortem MR will make a reconstruction of the trajectories in the body and of the reconstruction of the incident as a whole less reliable.


Assuntos
Balística Forense/métodos , Imageamento por Ressonância Magnética , Ferimentos por Arma de Fogo/diagnóstico por imagem , Gelatina , Humanos , Modelos Biológicos , Tomografia Computadorizada Multidetectores , Imagens de Fantasmas
17.
J Bacteriol ; 197(24): 3834-47, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26459556

RESUMO

UNLABELLED: Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. IMPORTANCE: By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats.


Assuntos
Complexo Antígeno-Anticorpo/ultraestrutura , Brucella abortus/imunologia , Neisseria meningitidis/imunologia , Superóxido Dismutase/imunologia , Superóxido Dismutase/ultraestrutura , Animais , Anticorpos/administração & dosagem , Anticorpos/imunologia , Sítios de Ligação de Anticorpos , Vacina contra Brucelose/imunologia , Brucella abortus/patogenicidade , Brucelose/imunologia , Brucelose/prevenção & controle , Cristalografia por Raios X , Modelos Animais de Doenças , Imunização Passiva/métodos , Meningite Meningocócica/imunologia , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/imunologia , Camundongos , Neisseria meningitidis/patogenicidade , Superóxido Dismutase/genética , Fatores de Virulência/imunologia
18.
Clin Infect Dis ; 60(3): 389-97, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25344536

RESUMO

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel disease of premature infants speculatively associated with infection. Suspected NEC can be indistinguishable from sepsis, and in established cases an infant may die within hours of diagnosis. Present treatment is supportive. A means of presymptomatic diagnosis is urgently needed. We aimed to identify microbial signatures in the gastrointestinal microbiota preceding NEC diagnosis in premature infants. METHODS: Fecal samples and clinical data were collected from a 2-year cohort of 369 premature neonates. Next-generation sequencing of 16S ribosomal RNA gene regions was used to characterize the microbiota of prediagnosis fecal samples from 12 neonates with NEC, 8 with suspected NEC, and 44 controls. Logistic regression was used to determine clinical characteristics and operational taxonomic units (OTUs) discriminating cases from controls. Samples were cultured and isolates identified using matrix-assisted laser desorption/ionization-time of flight. Clostridial isolates were typed and toxin genes detected. RESULTS: A clostridial OTU was overabundant in prediagnosis samples from infants with established NEC (P = .006). Culture confirmed the presence of Clostridium perfringens type A. Fluorescent amplified fragment-length polymorphism typing established that no isolates were identical. Prediagnosis samples from NEC infants not carrying profuse C. perfringens revealed an overabundance of a Klebsiella OTU (P = .049). Prolonged continuous positive airway pressure (CPAP) therapy with supplemental oxygen was also associated with increased NEC risk. CONCLUSIONS: Two fecal microbiota signatures (Clostridium and Klebsiella OTUs) and need for prolonged CPAP oxygen signal increased risk of NEC in presymptomatic infants. These biomarkers will assist development of a screening tool to allow very early diagnosis of NEC. Clinical Trials Registration. NCT01102738.


Assuntos
Disbiose , Enterocolite Necrosante/microbiologia , Doenças do Prematuro/microbiologia , Clostridium perfringens/genética , Clostridium perfringens/isolamento & purificação , Pressão Positiva Contínua nas Vias Aéreas , Enterocolite Necrosante/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/terapia , Klebsiella/genética , Klebsiella/isolamento & purificação , Masculino , Gravidez , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
19.
Phys Rev Lett ; 114(17): 175001, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25978240

RESUMO

Recent experiments on the National Ignition Facility [M. J. Edwards et al., Phys. Plasmas 20, 070501 (2013)] demonstrate that utilizing a near-vacuum hohlraum (low pressure gas-filled) is a viable option for high convergence cryogenic deuterium-tritium (DT) layered capsule implosions. This is made possible by using a dense ablator (high-density carbon), which shortens the drive duration needed to achieve high convergence: a measured 40% higher hohlraum efficiency than typical gas-filled hohlraums, which requires less laser energy going into the hohlraum, and an observed better symmetry control than anticipated by standard hydrodynamics simulations. The first series of near-vacuum hohlraum experiments culminated in a 6.8 ns, 1.2 MJ laser pulse driving a 2-shock, high adiabat (α∼3.5) cryogenic DT layered high density carbon capsule. This resulted in one of the best performances so far on the NIF relative to laser energy, with a measured primary neutron yield of 1.8×10(15) neutrons, with 20% calculated alpha heating at convergence ∼27×.

20.
PLoS Comput Biol ; 10(6): e1003646, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24945836

RESUMO

Estimation of immunological and microbiological diversity is vital to our understanding of infection and the immune response. For instance, what is the diversity of the T cell repertoire? These questions are partially addressed by high-throughput sequencing techniques that enable identification of immunological and microbiological "species" in a sample. Estimators of the number of unseen species are needed to estimate population diversity from sample diversity. Here we test five widely used non-parametric estimators, and develop and validate a novel method, DivE, to estimate species richness and distribution. We used three independent datasets: (i) viral populations from subjects infected with human T-lymphotropic virus type 1; (ii) T cell antigen receptor clonotype repertoires; and (iii) microbial data from infant faecal samples. When applied to datasets with rarefaction curves that did not plateau, existing estimators systematically increased with sample size. In contrast, DivE consistently and accurately estimated diversity for all datasets. We identify conditions that limit the application of DivE. We also show that DivE can be used to accurately estimate the underlying population frequency distribution. We have developed a novel method that is significantly more accurate than commonly used biodiversity estimators in microbiological and immunological populations.


Assuntos
Algoritmos , Variação Genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Receptores de Antígenos de Linfócitos T/genética , Biologia Computacional , Bases de Dados Genéticas/estatística & dados numéricos , Fezes/microbiologia , Infecções por HTLV-I/virologia , Humanos , Lactente , Microbiota/genética , Modelos Genéticos , Água do Mar/microbiologia , Estatísticas não Paramétricas
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