Summary Background Public objection to autopsy has led to a search for minimally invasive alternatives. Imaging has potential, but its accuracy is unknown. We aimed to identify the accuracy of ...post-mortem CT and MRI compared with full autopsy in a large series of adult deaths. Methods This study was undertaken at two UK centres in Manchester and Oxford between April, 2006, and November, 2008. We used whole-body CT and MRI followed by full autopsy to investigate a series of adult deaths that were reported to the coroner. CT and MRI scans were reported independently, each by two radiologists who were masked to the autopsy findings. All four radiologists then produced a consensus report based on both techniques, recorded their confidence in cause of death, and identified whether autopsy was needed. Findings We assessed 182 unselected cases. The major discrepancy rate between cause of death identified by radiology and autopsy was 32% (95% CI 26–40) for CT, 43% (36–50) for MRI, and 30% (24–37) for the consensus radiology report; 10% (3–17) lower for CT than for MRI. Radiologists indicated that autopsy was not needed in 62 (34%; 95% CI 28–41) of 182 cases for CT reports, 76 (42%; 35–49) of 182 cases for MRI reports, and 88 (48%; 41–56) of 182 cases for consensus reports. Of these cases, the major discrepancy rate compared with autopsy was 16% (95% CI 9–27), 21% (13–32), and 16% (10–25), respectively, which is significantly lower (p<0·0001) than for cases with no definite cause of death. The most common imaging errors in identification of cause of death were ischaemic heart disease (n=27), pulmonary embolism (11), pneumonia (13), and intra-abdominal lesions (16). Interpretation We found that, compared with traditional autopsy, CT was a more accurate imaging technique than MRI for providing a cause of death. The error rate when radiologists provided a confident cause of death was similar to that for clinical death certificates, and could therefore be acceptable for medicolegal purposes. However, common causes of sudden death are frequently missed on CT and MRI, and, unless these weaknesses are addressed, systematic errors in mortality statistics would result if imaging were to replace conventional autopsy. Funding Policy Research Programme, Department of Health, UK.
The study of mouse lung mechanics provides essential insights into the physiological mechanisms of pulmonary disease. Consequently, investigators assemble custom systems comprising ...infusion-withdrawal syringe pumps and analog pressure sensors to investigate the lung function of these animals. But these systems are expensive and require ongoing regulation, making them challenging to use. Here I introduce LungElast, an open-source, inexpensive, and self-contained instrument that can experimentally determine lung elasticity and volumes even in immature mice. It is assembled using custom 3D printed parts and readily available or easily constructed components. In this device, a microprocessor-controlled stepper motor automatically regulates lung volume by precisely driving a syringe piston whose position is determined using time-of-flight LIDAR technology. The airway pressures associated with the lung volumes are determined using compact sensor-on-chip technology, retrieved in a digital format, and stored by the microcontroller. The instrument software is modular, which eases device testing, calibration, and use. Data are also provided here that specify the accuracy and precision of the elastometer's sensors and volume delivery and demonstrate its use with lung models and mouse pups. This instrument has excellent potential for research and educational work.
The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical and limbic structures to mediate goal-directed behaviors. Chronic exposure to several ...classes of drugs of abuse disrupts plasticity in this region, allowing drug-associated cues to engender a pathologic motivation for drug seeking. A number of alterations in glutamatergic transmission occur within the nucleus accumbens after withdrawal from chronic drug exposure. These drug-induced neuroadaptations serve as the molecular basis for relapse vulnerability. In this review, we focus on the role that glutamate signal transduction in the nucleus accumbens plays in addiction-related behaviors. First, we explore the nucleus accumbens, including the cell types and neuronal populations present as well as afferent and efferent connections. Next we discuss rodent models of addiction and assess the viability of these models for testing candidate pharmacotherapies for the prevention of relapse. Then we provide a review of the literature describing how synaptic plasticity in the accumbens is altered after exposure to drugs of abuse and withdrawal and also how pharmacological manipulation of glutamate systems in the accumbens can inhibit drug seeking in the laboratory setting. Finally, we examine results from clinical trials in which pharmacotherapies designed to manipulate glutamate systems have been effective in treating relapse in human patients. Further elucidation of how drugs of abuse alter glutamatergic plasticity within the accumbens will be necessary for the development of new therapeutics for the treatment of addiction across all classes of addictive substances.
Placental examination in pregnancies with complications such as pre-eclampsia/toxaemia of pregnancy (PET) or intrauterine growth restriction (IUGR) can provide insight into specific diagnoses, ...recurrence risk and chronicity. Placental findings have clinical significance as they can identify the aetiology of the IUGR (as in inborn errors of metabolism) and predict recurrence (as in maternal floor infarcts). Evaluation of obstetric pathology in such pregnancies should be an integral part of clinical care. This review will highlight the placental findings in IUGR and PET.
Purpose:
Magnetic resonance imaging–guided radiotherapy (MRIgRT) provides superior soft-tissue contrast and real-time imaging compared with standard image-guided RT, which uses x-ray based imaging. ...Several groups are developing integrated MRIgRT machines. Reference dosimetry with these new machines requires accounting for the effects of the magnetic field on the response of the ionization chambers used for dose calibration. Here, the authors propose a formalism for reference dosimetry with integrated MRIgRT devices. The authors also examined the suitability of the
TPR
10
20
and %dd(10)
x
beam quality specifiers in the presence of magnetic fields and calculated detector correction factors to account for the effects of the magnetic field for a range of detectors.
Methods:
The authors used full-head and point-source Monte Carlo models of an MR-linac along with detailed detector models of an Exradin A19, an NE2571, and several PTW Farmer chambers to calculate magnetic field correction factors for six commercial ionization chambers in three chamber configurations. Calculations of ionization chamber response (performed with geant4) were validated with specialized Fano cavity tests. %dd(10)
x
values,
TPR
10
20
values, and Spencer-Attix water-to-air restricted stopping power ratios were also calculated. The results were further validated against measurements made with a preclinical functioning MR-linac.
Results:
The
TPR
10
20
was found to be insensitive to the presence of the magnetic field, whereas the relative change in %dd(10)
x
was 2.4% when a transverse 1.5 T field was applied. The parameters chosen for the ionization chamber calculations passed the Fano cavity test to within ∼0.1%. Magnetic field correction factors varied in magnitude with detector orientation with the smallest corrections found when the chamber was parallel to the magnetic field.
Conclusions:
Reference dosimetry can be performed with integrated MRIgRT devices by using magnetic field correction factors, but care must be taken with the choice of beam quality specifier and chamber orientation. The uncertainties achievable under this formalism should be similar to those of conventional formalisms, although this must be further quantified.
Increasingly, psychologists are extending their research to include online methods of data collection. Psychologists' use of qualitative data obtained or generated online for research purposes poses ...unique challenges because of the "traceability" of quotes, often sensitive content of data and potential impact on both individuals and online communities. In this article, working within a framework that goes beyond "procedural ethics" to examine "ethics in practice," ethical issues associated with conducting qualitative research within online communities are identified. These include tensions over public/private space, authorship versus human research participants, informed consent, anonymity and pseudonymity, covert research, deceptive research identities, reactions to being researched, and the quality of data obtained. Prior to conducting qualitative research in online communities, researchers have an ethical obligation to identify and weigh possible risks and benefits to both the community and community members. Sensitivity to the specific online community and continued ethical consideration throughout the conduct and reporting of the research are required.
Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize liquid biopsies in cancer for early ...detection and treatment stratification, as well as residual disease and recurrence monitoring. Although most efforts have used circulating tumor cells and circulating tumor DNA for this purpose, exosomes and other extracellular vesicles have emerged as a platform with potentially broader and complementary applications. Exosomes/extracellular vesicles are small vesicles released by cells, including cancer cells, into the surrounding biofluids. These exosomes contain tumor-derived materials such as DNA, RNA, protein, lipid, sugar structures, and metabolites. In addition, exosomes carry molecules on their surface that provides clues regarding their origin, making it possible to sort vesicle types and enrich signatures from tissue-specific origins. Exosomes are part of the intercellular communication system and cancer cells frequently use them as biological messengers to benefit their growth. Since exosomes are part of the disease process, they have become of tremendous interest in biomarker research. Exosomes are remarkably stable in biofluids, such as plasma and urine, and can be isolated for clinical evaluation even in the early stages of the disease. Exosome-based biomarkers have quickly become adopted in the clinical arena and the first exosome RNA-based prostate cancer test has already helped >50 000 patients in their decision process and is now included in the National Comprehensive Cancer Network guidelines for early prostate cancer detection. This review will discuss the advantages and challenges of exosome-based liquid biopsies for tumor biomarkers and clinical implementation in the context of circulating tumor DNA and circulating tumor cells.
•Liquid biopsies utilizing exosomes (extracellular vesicles), cell-free DNA (cfDNA), or circulating tumor cells represent three distinct biological entities.•Exosomes carry the RNA transcriptome, protein, and DNA, making them small packages of multi-analyte biomarkers.•Cancer-specific exosomes can be enriched for increased performance.•Combinations of liquid biopsy modalities, such as exosomes + cfDNA, can increase biomarker sensitivity.
Abstract
We study the dependence of satellite star formation rate and morphology on group dynamics for a sample of Sloan Digital Sky Survey groups. We classify the group dynamical state and study ...satellite properties for populations of galaxies at small and large group-centric radii. For galaxies at large radii we find no differences in the star-forming or disc fraction for those in Gaussian groups compared to those in non-Gaussian groups. By comparing the star-forming and disc fractions of infalling galaxies to field galaxies we find evidence for the pre-processing of both star formation rate and morphology. The strength of pre-processing increases with halo mass and is highest for low-mass galaxies infalling on to high-mass haloes. We show that the star formation rate of galaxies at small radii correlates with group dynamical state, with galaxies in non-Gaussian groups showing enhanced star-forming fractions compared to galaxies in Gaussian groups. Similar correlations are not seen for the disc fractions of galaxies at small radii. This seems to suggest that either the mechanisms driving star formation quenching at small halo-centric radii are more efficient in dynamically relaxed groups or that non-Gaussian groups have assembled more recently and therefore satellites of the groups will have been exposed to these transforming mechanisms for less time.
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