Positron emission tomography of sodium glucose cotransport activity in high grade astrocytomas.

A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects. Immunocytochemistry was carried out on Grade IV astrocytomas to determine the cellular location of SGLT proteins within the tumors. Me-4FDG retention was pronounced in astrocytomas in dramatic contrast to the lack of uptake into the normal brain, resulting in a high signal-to-noise ratio. Macroscopically, the distribution of Me-4FDG within the tumors overlapped with that of 2-FDG uptake and tumor definition using contrast-enhanced MRI images. Microscopically, the SGLT2 protein was found to be expressed in neoplastic glioblastoma cells and endothelial cells of the proliferating microvasculature. This preliminary study shows that Me-4FDG is a highly sensitive probe for visualization of high-grade astrocytomas by PET. The distribution of Me-4FDG within tumors overlapped that for 2-FDG, but the absence of background brain Me-4FDG resulted in superior imaging sensitivity. Furthermore, the presence of SGLT2 protein in astrocytoma cells and the proliferating microvasculature may offer a novel therapy using the SGLT2 inhibitors already approved by the FDA to treat type 2 diabetes mellitus

Age-Associated Changes in Hearts of Male Fischer 344/Brown Norway F1 Rats

Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other recordings from parasternal long- and short-axis views were obtained using a Phillips 5500 ECHO system with a 12 megahertz transducer. Hearts and aortas from sacrificed rats were evaluated grossly and microscopically. The ECHO studies revealed persistent cardiac arrhythmias (chiefly PVCs) in 72% (13/18) of 36-mo rats, 10% (1/10) of 30-mo rats, and none in 6-mo rats (0/16). Gross and microscopic studies showed left ventricular (LV) dilatation, borderline to mild hypertrophy, and areas of fibrosis that were common in 36-mo rats, less evident in 30-mo rats, and absent in 6-mo rats. Aging was associated with mild to moderate decreases of LV diastolic and systolic function. Thus, male F344/BN F1 rats demonstrated progressive age-related (a) decline in cardiac function (diastolic and systolic indices), (b) LV structural changes (chamber dimensions, volumes, and wall thicknesses), and (c) persistent arrhythmias. These changes are consistent with those in humans. The noninvasive ECHO technique offers a means to monitor serial age-related cardiac failure and therapeutic responses in the same rats over designated time intervals

Pluralism about Knowledge

In this paper I consider the prospects for pluralism about knowledge, that is, the view that there is a plurality of knowledge relations. After a brief overview of some views that entail a sort of pluralism about knowledge, I focus on a particular kind of knowledge pluralism I call standards pluralism. Put roughly, standards pluralism is the view that one never knows anything simpliciter. Rather, one knows by this-or-that epistemic standard. Because there is a plurality of epistemic standards, there is a plurality of knowledge relations. In §1 I argue that one can construct an impressive case for standards pluralism. In §2 I clarify the relationship between standards pluralism, epistemic contextualism and epistemic relativism. In §3 I argue that standards pluralism faces a serious objection. The gist of the objection is that standards pluralism is incompatible with plausible claims about the normative role of knowledge. In §4 I finish by sketching the form that a standards pluralist response to this objection might take

Acetaminophen Protects Against Iron-Induced Cardiac Damage in Gerbils

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and drug treatments. Liver and cardiac iron contents were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Iron-overloaded controls had 232-fold and 16-fold increases in liver and cardiac iron content, respectively, compared to saline controls. In iron-overloaded controls, echocardiography showed cardiac hypertrophy, right and left ventricular distension, significant reduction in left ventricular ejection fraction (−22%), and fractional shortening (−31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally effective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also significantly reduced excess hepatic iron content, although acetaminophen was less effective than deferoxamine. The results suggest that acetaminophen may be useful for treatment of iron-induced pathology

Cryogenic Optical Performance of a Lightweighted Mirror Assembly for Future Space Astronomical Telescopes: Correlating Optical Test Results and Thermal Optical Model

A 43cm diameter stacked core mirror demonstrator was interferometrically tested at room temperature down to 250 degrees Kelvin for thermal deformation. The 2.5m radius of curvature spherical mirror assembly was constructed by low temperature fusing three abrasive waterjet core sections between two CNC pocket milled face sheets. The 93% lightweighted Corning ULE mirror assembly represents the current state of the art for future UV, optical, near IR space telescopes. During the multiple thermal test cycles, test results of interferometric test, thermal IR images of the front face were recorded in order to validate thermal optical model

Cryogenic Optical Performance of a Light-weight Mirror Assembly for Future Space Astronomical Telescopes: Optical Test Results and Thermal Optical Model

A 40 cm diameter mirror assembly was interferometrically tested at room temperature down to 250 degrees Kelvin for thermal deformation. The 2.5 m radius of curvature spherical mirror assembly was constructed by low temperature fusing three abrasive waterjet core sections between two face sheets. The 93% lightweighted Corning ULE mirror assembly represents the current state of the art for future UV, optical, near IR space telescopes. During the multiple thermal test cycles, test results of interferometric test, thermal IR images of the front face were recorded in order to validate thermal optical model

The First Flight of the Marshall Grazing Incidence X-ray Spectrometer (MaGIXS)

The Marshall Grazing Incidence X-ray Spectrometer (MaGIXS) sounding rocket experiment launched on July 30, 2021 from the White Sands Missile Range in New Mexico. MaGIXS is a unique solar observing telescope developed to capture X-ray spectral images, in the 6 - 24 Angstrom wavelength range, of coronal active regions. Its novel design takes advantage of recent technological advances related to fabricating and optimizing X-ray optical systems as well as breakthroughs in inversion methodologies necessary to create spectrally pure maps from overlapping spectral images. MaGIXS is the first instrument of its kind to provide spatially resolved soft X-ray spectra across a wide field of view. The plasma diagnostics available in this spectral regime make this instrument a powerful tool for probing solar coronal heating. This paper presents details from the first MaGIXS flight, the captured observations, the data processing and inversion techniques, and the first science results.Comment: 20 pages, 18 figure

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London