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1.
Opt Express ; 30(21): 38405-38422, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36258406

RESUMEN

Inertial confinement fusion (ICF) holds increasing promise as a potential source of abundant, clean energy, but has been impeded by defects such as micro-voids in the ablator layer of the fuel capsules. It is critical to understand how these micro-voids interact with the laser-driven shock waves that compress the fuel pellet. At the Matter in Extreme Conditions (MEC) instrument at the Linac Coherent Light Source (LCLS), we utilized an x-ray pulse train with ns separation, an x-ray microscope, and an ultrafast x-ray imaging (UXI) detector to image shock wave interactions with micro-voids. To minimize the high- and low-frequency variations of the captured images, we incorporated principal component analysis (PCA) and image alignment for flat-field correction. After applying these techniques we generated phase and attenuation maps from a 2D hydrodynamic radiation code (xRAGE), which were used to simulate XPCI images that we qualitatively compare with experimental images, providing a one-to-one comparison for benchmarking material performance. Moreover, we implement a transport-of-intensity (TIE) based method to obtain the average projected mass density (areal density) of our experimental images, yielding insight into how defect-bearing ablator materials alter microstructural feature evolution, material compression, and shock wave propagation on ICF-relevant time scales.

2.
J Synchrotron Radiat ; 27(Pt 3): 608-615, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32381760

RESUMEN

The ePix10ka2M (ePix10k) is a new large area detector specifically developed for X-ray free-electron laser (XFEL) applications. The hybrid pixel detector was developed at SLAC to provide a hard X-ray area detector with a high dynamic range, running at the 120 Hz repetition rate of the Linac Coherent Light Source (LCLS). The ePix10k consists of 16 modules, each with 352 × 384 pixels of 100 µm × 100 µm distributed on four ASICs, resulting in a 2.16 megapixel detector, with a 16.5 cm × 16.5 cm active area and ∼80% coverage. The high dynamic range is achieved with three distinct gain settings (low, medium, high) as well as two auto-ranging modes (high-to-low and medium-to-low). Here the three fixed gain modes are evaluated. The resulting dynamic range (from single photon counting to 10000 photons pixel-1 pulse-1 at 8 keV) makes it suitable for a large number of different XFEL experiments. The ePix10k replaces the large CSPAD in operation since 2011. The dimensions of the two detectors are similar, making the upgrade from CSPAD to ePix10k straightforward for most setups, with the ePix10k improving on experimental performance. The SLAC-developed ePix cameras all utilize a similar platform, are tailored to target different experimental conditions and are designed to provide an upgrade path for future high-repetition-rate XFELs. Here the first measurements on this new ePix10k detector are presented and the performance under typical XFEL conditions evaluated during an LCLS X-ray diffuse scattering experiment measuring the 9.5 keV X-ray photons scattered from a thin liquid jet.

3.
J Synchrotron Radiat ; 26(Pt 2): 346-357, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30855242

RESUMEN

The Macromolecular Femtosecond Crystallography (MFX) instrument at the Linac Coherent Light Source (LCLS) is the seventh and newest instrument at the world's first hard X-ray free-electron laser. It was designed with a primary focus on structural biology, employing the ultrafast pulses of X-rays from LCLS at atmospheric conditions to overcome radiation damage limitations in biological measurements. It is also capable of performing various time-resolved measurements. The MFX design consists of a versatile base system capable of supporting multiple methods, techniques and experimental endstations. The primary techniques supported are forward scattering and crystallography, with capabilities for various spectroscopic methods and time-resolved measurements. The location of the MFX instrument allows for utilization of multiplexing methods, increasing user access to LCLS by running multiple experiments simultaneously.

4.
J Surg Oncol ; 117(6): 1260-1266, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29205349

RESUMEN

BACKGROUND: Soluble signaling molecules may play an important role in malignant pathogenesis. We hypothesize that perioperative cytokine levels are associated with outcomes in patients with pancreatic adenocarcinoma (PDAC) undergoing surgical resection. METHODS: One hundered and eighteen patients with benign or malignant pancreatic disease were enrolled in a prospective study through a protocol for banking biologic samples. Peripheral blood was drawn at time of operation, and a multiplex cytokine assay was performed. Statistical analysis was via χ2 and Kaplan Meier methods. RESULTS: Of 118 patients enrolled, 85 (72%) had a diagnosis of PDAC, and 60 (70%) ultimately underwent partial pancreatectomy. Cytokine levels were not associated with postoperative complications in this initial cohort. A plasma level of monocyte chemoattractant protein-1 (MCP-1) pg/mL ≤118 was associated with better overall survival (OS) (median survival 21 months vs 12.8 months, P = 0.023), as was non-detectable interleukin-8 (IL-8) (19 months) versus detectable IL-8 (12.8 months, P = 0.05). Patients with both MCP-1 >118 pg/mL and detectable IL-8 had a median survival of 10.6 months (P = 0.028). CONCLUSIONS: MCP-1 and IL-8 cytokine levels are associated with decreased survival following pancreatectomy for PDAC, and may be useful biomarkers. Measurement of these cytokine levels at different time points in future investigations will be important to validate these findings.


Asunto(s)
Adenocarcinoma/mortalidad , Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/mortalidad , Quimiocina CCL2/sangre , Interleucina-8/sangre , Pancreatectomía/mortalidad , Neoplasias Pancreáticas/mortalidad , Adenocarcinoma/sangre , Adenocarcinoma/cirugía , Anciano , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/cirugía , Atención Perioperativa , Complicaciones Posoperatorias , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Neoplasias Pancreáticas
5.
J Synchrotron Radiat ; 23(Pt 5): 1171-9, 2016 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27577772

RESUMEN

A prototype ePix100 detector was used in small-angle scattering geometry to capture speckle patterns from a static sample using the Linac Coherent Light Source (LCLS) hard X-ray free-electron laser at 8.34 keV. The average number of detected photons per pixel per pulse was varied over three orders of magnitude from about 23 down to 0.01 to test the detector performance. At high average photon count rates, the speckle contrast was evaluated by analyzing the probability distribution of the pixel counts at a constant scattering vector for single frames. For very low average photon counts of less than 0.2 per pixel, the `droplet algorithm' was first applied to the patterns for correcting the effect of charge sharing, and then the pixel count statistics of multiple frames were analyzed collectively to extract the speckle contrast. Results obtained using both methods agree within the uncertainty intervals, providing strong experimental evidence for the validity of the statistical analysis. More importantly it confirms the suitability of the ePix100 detector for X-ray coherent scattering experiments, especially at very low count rates with performances surpassing those of previously available LCLS detectors.

6.
J Synchrotron Radiat ; 22(3): 577-83, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25931071

RESUMEN

Free-electron lasers (FELs) present new challenges for camera development compared with conventional light sources. At SLAC a variety of technologies are being used to match the demands of the Linac Coherent Light Source (LCLS) and to support a wide range of scientific applications. In this paper an overview of X-ray detector design requirements at FELs is presented and the various cameras in use at SLAC are described for the benefit of users planning experiments or analysts looking at data. Features and operation of the CSPAD camera, which is currently deployed at LCLS, are discussed, and the ePix family, a new generation of cameras under development at SLAC, is introduced.

7.
Ann Rheum Dis ; 74(6): 1171-7, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25667206

RESUMEN

OBJECTIVES: To evaluate the efficacy of rituximab (RTX) in IgG4-related disease (IgG4-RD) in an open-label pilot trial. METHODS: We treated 30 IgG4-RD patients with two doses of RTX (1000 mg each). The participants were either treated with RTX alone (n = 26; 87%) or required to discontinue baseline glucocorticoids (GC) within 2 months (n = 4; 13%). Disease activity was measured by the IgG4-RD Responder Index (IgG4-RD RI) and physician's global assessment (PGA). Disease response was defined as the improvement of the IgG4-RD RI by two points. The primary outcome, measured at 6 months, was defined as: (1) decline of the IgG4-RD RI ≥2 points compared with baseline; (2) no disease flares before month 6; and (3) no GC use between months 2 and 6. Complete remission was defined as an IgG4-RD RI score of 0 with no GC use. RESULTS: Disease responses occurred in 97% of participants. The baseline IgG4-RD RI and PGA values, 11±7 and 63±22 mm, respectively, declined to 1±2 and 11±16 mm at 6 months (both p<0.00001). The primary outcome was achieved by 23 participants (77%). Fourteen (47%) were in complete remission at 6 months, and 12 (40%) remained in complete remission at 12  months. Among the 19 with elevated baseline serum IgG4, IgG4 concentrations declined from a mean of 911 mg/dL (range 138-4780 mg/dL) to 422 mg/dL (range 56-2410 mg/dL) at month 6 (p<0.05). However, only 8 (42%) of the 19 achieved normal values. CONCLUSIONS: RTX appears to be an effective treatment for IgG4-RD, even without concomitant GC therapy. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT01584388.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antirreumáticos/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Inmunoglobulina G/inmunología , Anciano , Enfermedades Autoinmunes/inmunología , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Inducción de Remisión , Rituximab , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
8.
Proc Natl Acad Sci U S A ; 109(47): 19103-7, 2012 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-23129631

RESUMEN

The ultrabright femtosecond X-ray pulses provided by X-ray free-electron lasers open capabilities for studying the structure and dynamics of a wide variety of systems beyond what is possible with synchrotron sources. Recently, this "probe-before-destroy" approach has been demonstrated for atomic structure determination by serial X-ray diffraction of microcrystals. There has been the question whether a similar approach can be extended to probe the local electronic structure by X-ray spectroscopy. To address this, we have carried out femtosecond X-ray emission spectroscopy (XES) at the Linac Coherent Light Source using redox-active Mn complexes. XES probes the charge and spin states as well as the ligand environment, critical for understanding the functional role of redox-active metal sites. Kß(1,3) XES spectra of Mn(II) and Mn(2)(III,IV) complexes at room temperature were collected using a wavelength dispersive spectrometer and femtosecond X-ray pulses with an individual dose of up to >100 MGy. The spectra were found in agreement with undamaged spectra collected at low dose using synchrotron radiation. Our results demonstrate that the intact electronic structure of redox active transition metal compounds in different oxidation states can be characterized with this shot-by-shot method. This opens the door for studying the chemical dynamics of metal catalytic sites by following reactions under functional conditions. The technique can be combined with X-ray diffraction to simultaneously obtain the geometric structure of the overall protein and the local chemistry of active metal sites and is expected to prove valuable for understanding the mechanism of important metalloproteins, such as photosystem II.

9.
Pancreas ; 51(1): 94-99, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35195601

RESUMEN

OBJECTIVES: The aim of this project was to assess malnutrition risk in a well-defined cohort of pancreatic diseases. METHODS: We performed a retrospective, cross-sectional study of 401 subjects with available malnutrition screening tool scores who received care at a single outpatient pancreas clinic during a 6-month study period. Univariate analyses were performed to compare demographic, anthropometric, symptoms/diseases, and risk for malnutrition characteristics across 3 strata of diseases: acute pancreatitis (n = 141), chronic pancreatitis (n = 193), and other pancreatic diagnoses (n = 67). RESULTS: A total of 18% of subjects were identified as at risk for malnutrition, including 25% who reported involuntary weight loss and/or decreased appetite. Subjects categorized as at risk for malnutrition were more likely to have gastrointestinal symptoms. Although the nutrition consultation rates were higher in subjects at risk for malnutrition (P = 0.03), 66% did not receive a clearly indicated dietary evaluation or management recommendations. One fifth of all patients in an ambulatory pancreas clinic are identified as at risk for malnutrition using a simple, validated tool. CONCLUSIONS: The majority of patients at increased risk for nutritional complications did not receive nutritional recommendations.


Asunto(s)
Instituciones de Atención Ambulatoria , Desnutrición/diagnóstico , Desnutrición/etiología , Tamizaje Masivo/instrumentación , Páncreas , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Estudios Retrospectivos , Medición de Riesgo
10.
Front Physiol ; 13: 866945, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35721529

RESUMEN

Objectives: CT scans are commonly performed in patients with chronic pancreatitis (CP). Osteopathy and fractures are recognized in CP but no osteoporosis screening guidelines are recommended. "Opportunistic" CT scan-derived bone density thresholds are assessed for identifying osteoporosis in CP. Methods: Retrospective pilot cohort study. CP subjects who had CT scans and dual-energy x-ray absorptiometry (DXA) within 1 year were included. CT-derived bone density was measured at the L1 level. Pearson's correlation was performed between age and CT-derived bone density in Hounsfield unit (HU). Univariate analysis using HU to identify osteoporosis was performed at various thresholds of bone density. The discriminatory ability of the model was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC). Several HU thresholds were tested. Results: Twenty-seven CP subjects were included, of whom 11 had normal bone density, 12 osteopenia, and four osteoporosis on DXA. The mean age was 59.9 years (SD 13.0). There was a negative correlation of age with HU (r = -0.519, p = 0.006). CT-derived bone density predicted DXA-based osteoporosis in the univariable analysis (Odds Ratio (OR) = 0.97 95% Confidence Interval (CI) 0.94-1.00, p = 0.03). HU thresholds were tested. A threshold of 106 HU maximized the accuracy (AUC of 0.870). Conclusions: CT scan may be repurposed for "opportunistic" screening to rule out osteoporosis in CP. A larger study is warranted to confirm these results.

11.
Rev Sci Instrum ; 93(10): 103502, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36319339

RESUMEN

Mesoscale imperfections, such as pores and voids, can strongly modify the properties and the mechanical response of materials under extreme conditions. Tracking the material response and microstructure evolution during void collapse is crucial for understanding its performance. In particular, imperfections in the ablator materials, such as voids, can limit the efficiency of the fusion reaction and ultimately hinder ignition. To characterize how voids influence the response of materials during dynamic loading and seed hydrodynamic instabilities, we have developed a tailored fabrication procedure for designer targets with voids at specific locations. Our procedure uses SU-8 as a proxy for the ablator materials and hollow silica microspheres as a proxy for voids and pores. By using photolithography to design the targets' geometry, we demonstrate precise and highly reproducible placement of a single void within the sample, which is key for a detailed understanding of its behavior under shock compression. This fabrication technique will benefit high-repetition rate experiments at x-ray and laser facilities. Insight from shock compression experiments will provide benchmarks for the next generation of microphysics modeling.

12.
Proc Natl Acad Sci U S A ; 105(45): 17408-13, 2008 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-18988734

RESUMEN

The plant cytotoxin ricin enters target mammalian cells by receptor-mediated endocytosis and undergoes retrograde transport to the endoplasmic reticulum (ER). Here, its catalytic A chain (RTA) is reductively separated from the cell-binding B chain, and free RTA enters the cytosol where it inactivates ribosomes. Cytosolic entry requires unfolding of RTA and dislocation across the ER membrane such that it arrives in the cytosol in a vulnerable, nonnative conformation. Clearly, for such a dislocated toxin to become active, it must avoid degradation and fold to a catalytic conformation. Here, we show that, in vitro, Hsc70 prevents aggregation of heat-treated RTA, and that RTA catalytic activity is recovered after chaperone treatment. A combination of pharmacological inhibition and cochaperone expression reveals that, in vivo, cytosolic RTA is scrutinized sequentially by the Hsc70 and Hsp90 cytosolic chaperone machineries, and that its eventual fate is determined by the balance of activities of cochaperones that regulate Hsc70 and Hsp90 functions. Cytotoxic activity follows Hsc70-mediated escape of RTA from an otherwise destructive pathway facilitated by Hsp90. We demonstrate a role for cytosolic chaperones, proteins typically associated with folding nascent proteins, assembling multimolecular protein complexes and degrading cytosolic and stalled, cotranslocational clients, in a toxin triage, in which both toxin folding and degradation are initiated from chaperone-bound states.


Asunto(s)
Citosol/metabolismo , Retículo Endoplásmico/metabolismo , Proteínas del Choque Térmico HSC70/metabolismo , Chaperonas Moleculares/metabolismo , Ricina/metabolismo , Electroforesis en Gel de Poliacrilamida , Proteínas HSP90 de Choque Térmico/metabolismo , Células HeLa , Humanos , Conformación Proteica , Ribosomas/metabolismo , Ricina/toxicidad , Ubiquitinación
13.
Pancreas ; 50(9): 1298-1304, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34860815

RESUMEN

OBJECTIVES: Abdominal pain is the primary symptom of chronic pancreatitis (CP), but pain is difficult to assess, and objective methods for pain assessment are lacking. The characterization of the sensory component of pain as a surrogate for nociception can be achieved by sensory testing using standardized stimuli. Herein, we describe the rationale for and development of an international consortium to better understand and characterize CP pain. METHODS: A collaboration was initially formed between the University of Aalborg, Johns Hopkins University, and the University of Pittsburgh. This group refined the protocol for pancreatic quantitative sensory testing (P-QST) and then expanded the collaboration with plans for incorporating P-QST into prospective studies. RESULTS: The collaboration has successfully developed a P-QST nomogram. Chronic pancreatitis patients identified with P-QST as having widespread hyperalgesia had higher pain intensity scores, higher prevalence of constant pain, and decreased quality of life. Psychiatric comorbidities were independent of pain phenotypes. Multiple studies are underway to validate these findings and evaluate their utility in clinical trials. CONCLUSIONS: Development of the P-QST Consortium will facilitate collaborative efforts to use P-QST as a means for evaluation and characterization of pain in CP patients, and optimize methods to guide individualized pain management approaches.


Asunto(s)
Dolor Abdominal/diagnóstico , Dimensión del Dolor/métodos , Dolor/diagnóstico , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/fisiopatología , Dolor Abdominal/fisiopatología , Adulto , Femenino , Humanos , Masculino , Nomogramas , Dolor/fisiopatología , Manejo del Dolor/métodos , Páncreas/fisiopatología , Pancreatitis Crónica/terapia , Estudios Prospectivos , Calidad de Vida , Reproducibilidad de los Resultados , Centros de Atención Terciaria/estadística & datos numéricos
14.
J Diabetes Res ; 2020: 9282310, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33426086

RESUMEN

Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.


Asunto(s)
Glucemia/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/trasplante , Insulina/uso terapéutico , Trasplante de Islotes Pancreáticos , Pancreatectomía , Pancreatitis Crónica/cirugía , Adulto , Biomarcadores/sangre , Glucemia/metabolismo , Femenino , Humanos , Células Secretoras de Insulina/metabolismo , Trasplante de Islotes Pancreáticos/efectos adversos , Masculino , Persona de Mediana Edad , Ohio , Pancreatectomía/efectos adversos , Pancreatitis Crónica/diagnóstico , Estudios Retrospectivos , Factores de Tiempo , Trasplante Autólogo , Resultado del Tratamiento , Adulto Joven
15.
Crit Care Resusc ; 21(2): 126-131, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31142243

RESUMEN

BACKGROUND: In Australia and New Zealand, the numbers of intensive care medicine trainees have increased significantly over the past 15 years. This has implications for supervision, clinical and procedural experience, and availability of rotations. The College of Intensive Care Medicine of Australia and New Zealand (CICM) decided to estimate the current training resources using several domains. METHODS: An online survey was sent to all CICM trainees (n = 528) and all directors of intensive care units (ICUs) (n = 106), using the SurveyMonkey tool. RESULTS: The overall response rate for the survey was 44% (trainees, 38%; directors, 72%). Most trainees had a 1:1 day-night roster system. Experience among trainees with common ICU procedures appeared limited. Fifty-six per cent of trainees reported spending more than 20% of their time attending medical emergency team calls. Difficulty accessing anaesthesia, medicine, paediatric and rural terms were reported by 35%, 26% 46% and 40% of trainees, respectively. Thirty-seven percent of trainees reported having to wait at least 1 year and 10% waited up to 2 years over and above their required training time to secure an anaesthesia term. Owing to gaps in experience in certain modules, one-third of final-year trainees felt underprepared to take on a role as a specialist, an observation shared by 15% of directors. CONCLUSION: This report has provided an assessment of the available resources within Australia and New Zealand for training doctors in intensive care medicine, and has identified significant limitations and concerns among trainees and ICU directors regarding the capacity to train. The findings call for a review of the training program, including a determination of optimal numbers of training positions.


Asunto(s)
Acreditación , Cuidados Críticos , Educación de Postgrado en Medicina/normas , Unidades de Cuidados Intensivos , Internado y Residencia , Ejecutivos Médicos , Australia , Niño , Educación de Postgrado en Medicina/organización & administración , Humanos , Internado y Residencia/organización & administración , Nueva Zelanda , Evaluación de Programas y Proyectos de Salud , Encuestas y Cuestionarios , Enseñanza/organización & administración
16.
Sci Adv ; 5(5): eaav8801, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31058226

RESUMEN

The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution.

17.
Public Underst Sci ; 27(7): 807-823, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30058947

RESUMEN

Scholars have recently suggested that communicating levels of scientific consensus (e.g. the percentage of scientists who agree about human-caused climate change) can shift public opinion toward the dominant scientific opinion. Initial research suggested that consensus communication effectively reduces public skepticism. However, other research failed to find a persuasive effect for those with conflicting prior beliefs. This study enters this contested space by experimentally testing how different levels of consensus shape perceptions of scientific certainty. We further examine how perceptions of certainty influence personal agreement and policy support. Findings indicate that communicating higher levels of consensus increases perceptions of scientific certainty, which is associated with greater personal agreement and policy support for non-political issues. We find some suggestive evidence that this mediated effect is moderated by participants' overall trust in science, such that those with low trust in science fail to perceive higher agreement as indicative of greater scientific certainty.

18.
Nat Commun ; 9(1): 1917, 2018 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-29765052

RESUMEN

The dynamics of liquid water feature a variety of time scales, ranging from extremely fast ballistic-like thermal motion, to slower molecular diffusion and hydrogen-bond rearrangements. Here, we utilize coherent X-ray pulses to investigate the sub-100 fs equilibrium dynamics of water from ambient conditions down to supercooled temperatures. This novel approach utilizes the inherent capability of X-ray speckle visibility spectroscopy to measure equilibrium intermolecular dynamics with lengthscale selectivity, by measuring oxygen motion in momentum space. The observed decay of the speckle contrast at the first diffraction peak, which reflects tetrahedral coordination, is attributed to motion on a molecular scale within the first 120 fs. Through comparison with molecular dynamics simulations, we conclude that the slowing down upon cooling from 328 K down to 253 K is not due to simple thermal ballistic-like motion, but that cage effects play an important role even on timescales over 25 fs due to hydrogen-bonding.

19.
J Hum Lact ; 23(1): 52-9, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17293551

RESUMEN

Nipple position is believed to influence breastfeeding success. To investigate this belief, submental ultrasound images were obtained during breastfeeding of normal term infants. This study measured nipple to hard-soft palate distance (NHSPD) in 18 mother-infant pairs during the first and fourth weeks of life. Median NHSPD was 5 mm (interquartile: 4, 6 mm). There were no significant differences in median NHSPD between first, second, and fifth minutes of feeding (P = .675) or between week 1 and week 4 (P = .320). The nipple was not stationary during feeding, with mean nipple movement of 4.0 -/+ 1.3 mm. Further research is required with more infants to confirm the boundaries of normality for ultrasound measurements of nipple position during successful breastfeeding.


Asunto(s)
Lactancia/fisiología , Pezones/diagnóstico por imagen , Pezones/fisiología , Conducta en la Lactancia , Adulto , Lactancia Materna , Femenino , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Masculino , Factores de Tiempo , Ultrasonografía
20.
Patient Prefer Adherence ; 11: 661-669, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28405158

RESUMEN

OBJECTIVE: The objective of this study was to describe patient experience with intravenous (IV) biologics for ankylosing spondylitis, Crohn's disease, psoriatic arthritis, psoriasis, rheumatoid arthritis, or ulcerative colitis. METHODS: Semi-structured telephone interviews were conducted in 405 patients with these autoimmune diseases who were receiving an IV biologic to treat their disease. RESULTS: On a 7-point scale (1= not at all satisfied; 7= very satisfied), mean satisfaction with IV medication was rated 6.1; 77% of patients rated satisfaction as 6 or 7. The most frequently perceived benefits of IV therapy were related to supervision provided by health care professionals. Most patients (82%, n=332) preferred their IV medication to subcutaneous injection. The three most common reasons for preferring IV were not wanting to self-inject (43%), less frequent dosing (34%), and preference for administration by a health care professional (24%). African-American/black patients had a stronger preference for IV administration than Caucasian/white patients (97% vs 80%, P<0.05) and a greater dislike of needles/self-injection (71% vs 40%, P<0.05). Hospital outpatient departments were not rated as well as physician in-office infusion. Only half (49%) of the patients reported that both they and their physician equally influenced the choice to switch from subcutaneous to IV therapy, and only 30% were given a choice of infusion center. CONCLUSION: Users of IV biologics are highly satisfied with their medications and perceive the opportunity for health care provider interaction at their infusion facilities as an advantage of their regimen. These findings support continued need for IV therapeutic options and shared decision-making between patients and physicians while selecting biologic treatments.

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