Fit for Duty: Lessons Learned from Outpatient and Homebound Hematopoietic Cell Transplantation to Prepare Family Caregivers for Home-Based Care.

In the past decade, the demand for home-based care has been amplified by the Coronavirus disease 2019 pandemic. Home-based care has significant benefits for patients, their families, and healthcare systems, but it relies on the often-invisible workforce of family and friend caregivers who shoulder essential health care responsibilities, frequently with inadequate training and support. Hematopoietic cell transplantation (HCT), a potentially curative but intensive treatment for many patients with blood disorders, is being increasingly offered in home-based care settings and necessitates the involvement of family caregivers for significant patient care responsibilities. However, guidelines for supporting and preparing HCT caregivers to effectively care for their loved ones at home have not yet been established. Here, informed by the literature and our collective experience as clinicians and researchers who care for diverse patients with hematologic malignancies undergoing HCT, we provide considerations and recommendations to better support and prepare family caregivers in home-based HCT and, by extension, family caregivers supporting patients with other serious illnesses at home. We suggest tangible ways to screen family caregivers for distress and care delivery challenges, educate and train them to prepare for their caregiving role, and create an infrastructure of support for family caregivers within this emerging care delivery model.

An Investigation of Micro-CT Analysis of Bone as a New Diagnostic Method for Paleopathological Cases of Osteomalacia.

OBJECTIVE: This paper looks to broaden the methodological possibilities for diagnosing osteomalacia in archaeological bone using micro-CT analysis. Increasing the identification of osteomalacia in paleopathology will provide support for important interpretive frameworks. MATERIALS: Nine embedded and two unembedded rib fragments were sourced from St. Martin's Birmingham and Ancaster, UK, and Lisieux Michelet, France. Of the 11 samples, nine were previously confirmed as osteomalacic, and presented with varying levels of diagenesis and two were non-osteomalacic controls, one of which exhibits diagenetic change. METHODS: Micro-CT, backscattered scanning electron microscopy, and light microscopy were employed. Micro-CT images were evaluated for osteomalacic features using corresponding microscopic images. RESULTS: Micro-CT images from osteomalacic samples demonstrated the presence of defective mineralization adjacent to cement lines, areas of incomplete mineralization, and resorptive bays/borders, three key diagnostic features of osteomalacia. Diagenetic change was also detectable in micro-CT images, but did not prevent the diagnosis of osteomalacia. CONCLUSIONS: Micro-CT analysis is a non-destructive method capable of providing microstructural images of osteomalacic features in embedded and unembedded samples. When enough of these features are present, micro-CT images are capable of confirming a diagnosis of osteomalacia. SIGNIFICANCE: Vitamin D deficiency has important health consequences which operate throughout the life course. Increasing the ability to detect cases of vitamin D deficiency provides researchers with a greater understanding of health and disease in past communities. LIMITATIONS: Only adult rib samples were used. SUGGESTIONS FOR FURTHER RESEARCH: Paleopathologists should look to test the utility of micro-CT analysis in diagnosing active rickets in subadult individuals.

Organic dust-induced lung injury and repair: Bi-directional regulation by TNFα and IL-10.

Exposure to organic dust increases chronic airway inflammatory disorders. Effective treatment strategies are lacking. It has been reported that hog barn dust extracts (HDE) induce TNFα through protein kinase C (PKC) activation and that lung inflammation is enhanced in scavenger receptor A (SRA/CD204) knockout (KO) mice following HDE. Because interleukin (IL)-10 production can limit excessive inflammation, it was hypothesized here that HDE-induced IL-10 would require CD204 to effect inflammatory responses. C57BL/6 wild-type (WT), SRA KO, and IL-10 KO mice were intranasally challenged daily for 8 days with HDE and subsequently rested for 3 days with/without recombinant IL-10 (rIL-10) treatment. Primary peritoneal macrophages (PM) and murine alveolar macrophages (MH-S cells) were treated in vitro with HDE, SRA ligand (fucoidan), rIL-10, and/or PKC isoform inhibitors. HDE induced in vivo lung IL-10 in WT, but not SRA KO mice, and similar trends were demonstrated in isolated PM from same treated mice. Lung lymphocyte aggregates and neutrophils were elevated in in vivo HDE-treated SRA and IL-10 KO mice after a 3-d recovery, and treatment during recovery with rIL-10 abrogated these responses. In vitro rIL-10 treatment reduced HDE-stimulated TNFα release in MH-S and WT PM. In SRA KO macrophages, there was reduced IL-10 and PKC zeta (ζ) activity and increased TNFα following in vitro HDE stimulation. Similarly, blocking SRA (24 hr fucoidan pre-treatment) resulted in enhanced HDE-stimulated macrophage TNFα and decreased IL-10 and PKCζ activation. PKCζ inhibitors blocked HDE-stimulated IL-10, but not TNFα. Collectively, HDE stimulates IL-10 by an SRA- and PKCζ-dependent mechanism to regulate TNFα. Enhancing resolution of dust-mediated lung inflammation through targeting IL-10 and/or SRA may represent new approaches to therapeutic interventions.

Data showing regional differences in rat brain monoaminergic function.

Chemical neurotransmitters (such as dopamine) modulate cognitive function via ascending projections to various cortical and sub-cortical brain regions. This report describes and links to a relatively large dataset (up to N = 112) compiled from control (untreated) brain samples taken during a series of experimental in vivo studies. The dataset is freely available, to explore the normal interrelationships between levels of neurotransmitter (e.g., dopamine, serotonin), across brain regions implicated in both normal reward and drug addiction, as well as in disorders such as schizophrenia (e.g., nucleus accumbens, prefrontal cortex). Most experimental studies run with a relatively small control group, so there is a lack of baseline data on the expected levels of neurotransmitters and their metabolites in different brain regions. Accordingly, the available dataset has been compiled from a number of studies run in the same laboratory, and using closely similar behavioural procedures, sampling selected brain regions of a priori interest. These collated data can be used to explore differences in the distribution of the monoamines and their metabolites, patterns of neurotransmitter intercorrelations, both between and within different brain structures and including some consideration of laterality effects.

Eyeing the past: synchrotron µ-XANES and XRF imaging of tarnish distribution on 19th century daguerreotypes.

Louis-Jacques-Mandé Daguerre introduced the first successful photographic process, the daguerreotype, in 1839. Tarnished regions on daguerreotypes supplied by the National Gallery of Canada were examined using scanning electron microscopy energy-dispersive X-ray spectroscopy and synchrotron-radiation analysis. Synchrotron X-ray fluorescence imaging visualized the distribution of sulfur and chlorine, two primary tarnish contributors, and showed that they were associated with the distribution of image particles on the surface. X-ray absorption near-edge structure spectroscopy determined the tarnish to be primarily composed of AgCl and Ag2S. Au2S, Au2SO4, HAuCl4 and HgSO4 were also observed to be minor contributors. Environmental contamination may be a source of these degradation compounds. Implications of these findings will be discussed.

Molecular imaging with neural training of identification algorithm (neural network localization identification).

Superresolution localization microscopy strongly relies on robust identification algorithms for accurate reconstruction of the biological systems it is used to measure. The fields of machine learning and computer vision have provided promising solutions for automated object identification, but usually rely on well represented training sets to learn object features. However, using a static training set can result in the learned identification algorithm making mistakes on data that is not well represented by the training set. Here, we present a method for training an artificial neural network without providing a training set in advance. This method uses the data to be analyzed, and the fitting algorithm to train an artificial neural network tailored to that data set. We show that the same artificial neural network can learn to identify at least two types of molecular emissions: the regular point spread functions (PSFs), and the astigmatism PSF. Simulations indicate that this method can be extremely reliable in extracting molecular emission signatures. Additionally, we implemented the artificial neural network calculation to be performed on a graphics processing unit (GPU) for massively parallelized calculation which drastically reduces the time required for the identification process. By implementing the neural identification on a GPU, we allow this method of identification to be used in a real time analysis algorithm. RESEARCH HIGHLIGHTS: Here, we present a machine learning algorithm for identifying point-spread functions without the need for an a priori training set. We show that this method can detect over 90% of molecules with less than 1% false positive identification in simulations. We further show that because this algorithm does not make assumptions of about the shape of molecular emission, it is compatible with models beyond the symmetric 2D Gaussian.

The origins of individual differences in how learning is expressed in rats: A general-process perspective.

Laboratory rats can exhibit marked, qualitative individual differences in the form of acquired behaviors. For example, when exposed to a signal-reinforcer relationship some rats show marked and consistent changes in sign-tracking (interacting with the signal; e.g., a lever) and others show marked and consistent changes in goal-tracking (interacting with the location of the predicted reinforcer; e.g., the food well). Here, stable individual differences in rats' sign-tracking and goal-tracking emerged over the course of training, but these differences did not generalize across different signal-reinforcer relationships (Experiment 1). This selectivity suggests that individual differences in sign- and goal-tracking reflect differences in the value placed on individual reinforcers. Two findings provide direct support for this interpretation: the palatability of a reinforcer (as measured by an analysis of lick-cluster size) was positively correlated with goal-tracking (and negatively correlated with sign-tracking); and sating rats with a reinforcer affected goal-tracking but not sign-tracking (Experiment 2). These results indicate that the observed individual differences in sign- and goal-tracking behavior arise from the interaction between the palatability or value of the reinforcer and processes of association as opposed to dispositional differences (e.g., in sensory processes, "temperament," or response repertoire). (PsycINFO Database Record

Cortical and corticospinal output modulations during reaching movements with varying directions and magnitudes of interaction torques.

The neural command required to coordinate a multi-joint movement is inherently complex. During multi-joint movement of the limb, the force created from movement at one joint may create a torque at a second joint known as an interaction torque. Interaction torques may be assistive or resistive thereby aiding or opposing the motion of the second joint, respectively. For movement to be effectively controlled, the central nervous system should modulate neural output to the muscles to appropriately account for interaction torques. The present study examined the neural output from the primary motor cortex before and during reaching movements that required different combinations of assistive and resistive interaction torques occurring at the shoulder and elbow joints. Using transcranial magnetic stimulation to probe neural output from the primary motor cortex, results indicate that corticospinal output controlling the upper arm is related to resistive interaction torques occurring at the shoulder joint. Further, cortical output to bi-articular muscles is associated with interaction torque and this may be driven by the fact that these muscles are in an advantageous position to control torques produced between inter-connection segments. Humans have a tendency to avoid reaching movements that involve resistive interaction torques and this may be driven by the requirement of increased neural output associated with these movements.

A combined theoretical and experimental investigation of uranium dioxide under high static pressure.

We have investigated the behavior of uranium dioxide (UO2) under high static pressure using a combination of experimental and theoretical techniques. We have made Raman spectroscopic measurements up to 87 GPa, electrical transport measurements up to 50 GPa from 10 K to room temperature, and optical transmission measurements up to 28 GPa. We have also carried out theoretical calculations within the GGA + U framework. We find that Raman frequencies match to a large extent, theoretical predictions for the cotunnite (Pnma) structure above 30 GPa, but at higher pressures some behavior is not captured theoretically. The Raman measurements also imply that the low-pressure fluorite phase coexists with the cotunnite phase up to high pressures, consistent with earlier reports. Electrical transport measurements show that the resistivity decreases by more than six orders of magnitude with increasing pressure up to 50 GPa but that the material never adopts archetypal metallic behavior. Optical transmission spectra show that while UO2 becomes increasingly opaque with increasing pressure, a likely direct optical band gap of more than 1 eV exists up to at least 28 GPa. Together with the electrical transport measurements, we conclude that the high pressure electrical conductivity of UO2 is mediated by variable-range hopping.

The effect of retrosplenial cortex lesions in rats on incidental and active spatial learning.

The study examined the importance of the retrosplenial cortex for the incidental learning of the spatial arrangement of distinctive features within a scene. In a modified Morris water-maze, rats spontaneously learnt the location of an escape platform prior to swimming to that location. For this, rats were repeatedly placed on a submerged platform in one corner of either a rectangular (Experiment 1) or square (Experiments 2, 3) pool with walls of different appearance. The rats were then released in the center of the pool for their first test trial. In Experiment 1, the correct corner and its diagonally opposite partner (also correct) were specified by the geometric properties of the pool. Rats with retrosplenial lesions took longer to first reach a correct corner, subsequently showing an attenuated preference for the correct corners. A reduced preference for the correct corner was also found in Experiment 2, when platform location was determined by the juxtaposition of highly salient visual cues (black vs. white walls). In Experiment 3, less salient visual cues (striped vs. white walls) led to a robust lesion impairment, as the retrosplenial lesioned rats showed no preference for the correct corner. When subsequently trained actively to swim to the correct corner over successive trials, retrosplenial lesions spared performance on all three discriminations. The findings not only reveal the importance of the retrosplenial cortex for processing various classes of visuospatial information but also highlight a broader role in the incidental learning of the features of a spatial array, consistent with the translation of scene information.

Ro 04-6790-induced cognitive enhancement: no effect in trace conditioning and novel object recognition procedures in adult male Wistar rats.

The evidence for cognitively enhancing effects of 5-hydroxytryptamine6 (5-HT6) receptor antagonists such as Ro 04-6790 is inconsistent and seems to depend on the behavioral test variant in use. Trace conditioning holds promise as a behavioral assay for hippocampus-dependent working memory function. Accordingly, Experiment 1 assessed the effect of Ro 04-6790 (5 and 10mg/kg i.p.) on associating a noise conditioned stimulus paired with foot shock (unconditioned stimulus) at a 3 or 30s trace interval in adult male Wistar rats. Contextual conditioning was measured as suppression to the contextual cues provided by the experimental chambers and as suppression to a temporally extended light background stimulus which provided an experimental context. Experiment 2 assessed the effect of Ro 04-6790 (5 and 10mg/kg i.p.) on recognition memory as tested by the exploration of novel relative to familiar objects in an open arena. In Experiment 1, Ro 04-6790 (5 and 10mg/kg) was without effect on trace and contextual conditioning. In Experiment 2, there was no indication of the expected improvement under Ro 04-6790 at the same doses previously found to enhance recognition memory as measured in tests of novel object exploration. Thus, there was no evidence that treatment with the 5-HT6 receptor antagonist Ro 04-6790 acted as a cognitive enhancer in either trace conditioning or object recognition procedures. We cannot exclude the possibility that the experimental procedures used in the present study would have been sensitive to the cognitive enhancing effects of Ro 04-6790 in a different dose range, behavioral test variant, or in a different strain of rat. Nonetheless the drug treatment was not ineffective in that object exploration was reduced under 10mg/kg Ro 04-6790.

A technique for verifying the input response function of neutron time-of-flight scintillation detectors using cosmic rays.

An accurate interpretation of DD or DT fusion neutron time-of-flight (nTOF) signals from current mode detectors employed at the Z-facility at Sandia National Laboratories requires that the instrument response functions (IRF's) be deconvolved from the measured nTOF signals. A calibration facility that produces detectable sub-ns radiation pulses is typically used to measure the IRF of such detectors. This work, however, reports on a simple method that utilizes cosmic radiation to measure the IRF of nTOF detectors, operated in pulse-counting mode. The characterizing metrics reported here are the throughput delay and full-width-at-half-maximum. This simple approach yields consistent IRF results with the same detectors calibrated in 2007 at a LINAC bremsstrahlung accelerator (Idaho State University). In particular, the IRF metrics from these two approaches and their dependence on the photomultipliers bias agree to within a few per cent. This information may thus be used to verify if the IRF for a given nTOF detector employed at Z has changed since its original current-mode calibration and warrants re-measurement.

Predicting the sensitivity of the beryllium/scintillator layer neutron detector using Monte Carlo and experimental response functions.

A methodology for obtaining empirical curves relating absolute measured scintillation light output to beta energy deposited is presented. Output signals were measured from thin plastic scintillator using NIST traceable beta and gamma sources and MCNP5 was used to model the energy deposition from each source. Combining the experimental and calculated results gives the desired empirical relationships. To validate, the sensitivity of a beryllium/scintillator-layer neutron activation detector was predicted and then exposed to a known neutron fluence from a Deuterium-Deuterium fusion plasma (DD). The predicted and the measured sensitivity were in statistical agreement.

Fusion-neutron-yield, activation measurements at the Z accelerator: design, analysis, and sensitivity.

We present a general methodology to determine the diagnostic sensitivity that is directly applicable to neutron-activation diagnostics fielded on a wide variety of neutron-producing experiments, which include inertial-confinement fusion (ICF), dense plasma focus, and ion beam-driven concepts. This approach includes a combination of several effects: (1) non-isotropic neutron emission; (2) the 1/r(2) decrease in neutron fluence in the activation material; (3) the spatially distributed neutron scattering, attenuation, and energy losses due to the fielding environment and activation material itself; and (4) temporally varying neutron emission. As an example, we describe the copper-activation diagnostic used to measure secondary deuterium-tritium fusion-neutron yields on ICF experiments conducted on the pulsed-power Z Accelerator at Sandia National Laboratories. Using this methodology along with results from absolute calibrations and Monte Carlo simulations, we find that for the diagnostic configuration on Z, the diagnostic sensitivity is 0.037% ± 17% counts/neutron per cm(2) and is ∼ 40% less sensitive than it would be in an ideal geometry due to neutron attenuation, scattering, and energy-loss effects.

Localization microscopy: mapping cellular dynamics with single molecules.

Resolution describes the smallest details within a sample that can be recovered by a microscope lens system. For optical microscopes detecting visible light, diffraction limits the resolution to ∼200-250 nm. In contrast, localization measures the position of an isolated object using its image. Single fluorescent molecules can be localized with an uncertainty of a few tens of nanometres, and in some cases less than one nanometre. Superresolution fluorescence localization microscopy (SRFLM) images and localizes fluorescent molecules in a sample. By controlling the visibility of the fluorescent molecules with light, it is possible to cause a sparse subset of the tags to fluoresce and be spatially separated from each other. A movie is acquired with a camera, capturing images of many sets of visible fluorescent tags over a period of time. The movie is then analysed by a computer whereby all of the single molecules are independently measured, and their positions are recorded. When the coordinates of a sufficient number of molecules are collected, an image can be rendered by plotting the coordinates of the localized molecules. The spatial resolution of these rendered images can be better than 20 nm, roughly an order of magnitude better than the diffraction limited resolution. The invention of SRFLM has led to an explosion of related techniques. Through the use of specialized optics, the fluorescent signal can be split into multiple detection channels. These channels can capture additional information such as colour (emission wavelength), orientation and three-dimensional position of the detected molecules. Measurement of the colour of the detected fluorescence can allow researchers to distinguish multiple types of fluorescent tags and to study the interaction between multiple molecules of interest. Three-dimensional imaging and determination of molecular orientations offer insight into structural organization of the sample. SRFLM is compatible with living samples and has helped to illuminate many dynamic biological processes, such as the trajectories of molecules within living cells. This review discusses the concept and process of SRFLM imaging and investigates recent advances in SRFLM functionality. Since its announcement in 2006, SRFLM has been quickly adopted and modified by many researchers to help investigate questions whose answers lie below the diffraction limit. The versatility of the SRFLM technique has great promise for improving our understanding of cell biology at the molecular level.

The rat retrosplenial cortex is required when visual cues are used flexibly to determine location.

The present study examined the consequences of retrosplenial cortex lesions in rats on two novel spatial tasks. In the first experiment, rats discriminated opposing room views from the same general location, along with their opposing directions of travel ('Perspective' task). Rats were trained with food rewards using a go/no-go design. Extensive retrosplenial cortex lesions involving both the granular and dysgranular areas impaired acquisition of this discrimination, which relied on distal visual cues. The same rats were then trained on a non-spatial go/no-go discrimination between different digging media. No lesion effect was apparent. In the final experiment, rats discriminated between two locations within a room ('Location' task) such that direction of travel at each location would be of less help in solving the problem. Both extensive retrosplenial lesions and selective dysgranular retrosplenial lesions impaired this Location task. These results highlight the importance of the retrosplenial cortex (areas 29 and 30), including the dysgranular cortex (area 30), for the effective use of distal visual cues to solve spatial problems. The findings, which help to explain the bias away from visual allocentric solutions that is shown by rats with retrosplenial cortex lesions when performing spatial tasks, also support the notion that the region assists the integration of different categories of visuospatial information.

Cardiac magnetic resonance, transthoracic and transoesophageal echocardiography: a comparison of in vivo assessment of ventricular function in rats.

In vivo assessment of ventricular function in rodents has largely been restricted to transthoracic echocardiography (TTE). However 1.5 T cardiac magnetic resonance (CMR) and transoesophageal echocardiography (TOE) have emerged as possible alternatives. Yet, to date, no study has systematically assessed these three imaging modalities in determining ejection fraction (EF) in rats. Twenty rats underwent imaging four weeks after surgically-induced myocardial infarction. CMR was performed on a 1.5 T scanner, TTE was conducted using a 9.2 MHz transducer and TOE was performed with a 10 MHz intracardiac echo catheter. Correlation between the three techniques for EF determination and analysis reproducibility was assessed. Moderate-strong correlation was observed between the three modalities; the greatest between CMR and TOE (intraclass correlation coefficient (ICC) = 0.89), followed by TOE and TTE (ICC = 0.70) and CMR and TTE (ICC = 0.63). Intra- and inter-observer variations were excellent with CMR (ICC = 0.99 and 0.98 respectively), very good with TTE (0.90 and 0.89) and TOE (0.87 and 0.84). Each modality is a viable option for evaluating ventricular function in rats, however the high image quality and excellent reproducibility of CMR offers distinct advantages even at 1.5 T with conventional coils and software.

Radiological evaluation of the evisceration tradition in ancient Egyptian mummies.

Descriptions of the preparation of ancient Egyptian mummies that appear in both scientific and popular literature are derived largely from accounts by the Greek historians Herodotus and Diodorus Siculus. Our reliance on these normative descriptions obscures the wide range of techniques practised, and so stifles the study of geographic, chronological, and social variations in the practice. Using published descriptions in the literature for 150 mummies and 3D reconstructions from computed tomography data for 7 mummies, this study compares empirical data with classical descriptions of evisceration, organ treatment, and body cavity treatment. Techniques for accessing the body cavity, removal and treatment of the organs, and treatment of the eviscerated body cavity vary with time period, sex, and status, and are discussed in relation to their treatment in the literature and their radiological appearance. The Herodotean and Diodorean stereotypes, including the restriction of transabdominal evisceration to the elite and cedar oil enema evisceration to commoners, are falsified by the data. The transperineal forms are present only in elites, and chemical evisceration is not apparent at all. Additionally, the dogmatic contention that the heart was universally retained in situ, or replaced if accidentally removed, is also greatly exaggerated.

Paradoxical effects of low dose MDMA on latent inhibition in the rat.

The cognitive effects of MDMA ('Ecstasy') are controversial, particularly in the case of acute administration of low doses. Latent inhibition (LI) refers to the reduction in conditioning to a stimulus that has received non-reinforced pre-exposure, an effect typically abolished by amphetamines and enhanced by antipsychotics. LI enhancement has also been shown using the 5-HT reuptake blocker sertraline. In the present study, the effects of MDMA (6 mg/kg, known to increase 5-HT release) were tested using 10 and 40 pre-exposures to produce weak and strong LI in controls, respectively. MDMA (injected twice, prior to pre-exposure and conditioning) significantly enhanced LI in that the effect was clearly demonstrated after only 10 pre-exposures, when it was absent in the saline controls. On its own such a profile of action would be consistent with a procognitive effect of MDMA mediated by increased availability of 5-HT. However, paradoxically the same MDMA treatment reduced LI in the 40 pre-exposures condition. This component of action is likely attributable to MDMA's actions on catecholaminergic systems and is consistent with other evidence of its adverse effects. Moreover, there were small but significant reductions in 5-HT in medial prefrontal cortex (mPFC) and amygdala assayed 7 days post MDMA administration (2 × 6 mg/kg, 24 h apart).

Measuring the absolute deuterium-tritium neutron yield using the magnetic recoil spectrometer at OMEGA and the NIF.

A magnetic recoil spectrometer (MRS) has been installed and extensively used on OMEGA and the National Ignition Facility (NIF) for measurements of the absolute neutron spectrum from inertial confinement fusion implosions. From the neutron spectrum measured with the MRS, many critical implosion parameters are determined including the primary DT neutron yield, the ion temperature, and the down-scattered neutron yield. As the MRS detection efficiency is determined from first principles, the absolute DT neutron yield is obtained without cross-calibration to other techniques. The MRS primary DT neutron measurements at OMEGA and the NIF are shown to be in excellent agreement with previously established yield diagnostics on OMEGA, and with the newly commissioned nuclear activation diagnostics on the NIF.