Resting-state MRI reveals spontaneous physiological fluctuations in the kidney and tracks diabetic nephropathy in rats.

The kidneys maintain fluid-electrolyte balance and excrete waste in the presence of constant fluctuations in plasma volume and systemic blood pressure. The kidneys perform these functions to control capillary perfusion and glomerular filtration by modulating the mechanisms of autoregulation. An effect of these modulations are spontaneous, natural fluctuations in glomerular perfusion. Numerous other mechanisms can lead to fluctuations in perfusion and flow. The ability to monitor these spontaneous physiological fluctuations in vivo could facilitate the early detection of kidney disease. The goal of this work was to investigate the use of resting-state magnetic resonance imaging (rsMRI) to detect spontaneous physiological fluctuations in the kidney. We performed rsMRI of rat kidneys in vivo over 10 min, applying motion correction to resolve time series in each voxel. We observed spatially variable, spontaneous fluctuations in rsMRI signal between 0 and 0.3 Hz, in frequency bands associated with autoregulatory mechanisms. We further applied rsMRI to investigate changes in these fluctuations in a rat model of diabetic nephropathy. Spectral analysis was performed on time series of rsMRI signals in the kidney cortex and medulla. The power from spectra in specific frequency bands from the cortex correlated with severity of glomerular pathology caused by diabetic nephropathy. Finally, we investigated the feasibility of using rsMRI of the human kidney in two participants, observing the presence of similar, spatially variable fluctuations. This approach may enable a range of preclinical and clinical investigations of kidney function and facilitate the development of new therapies to improve outcomes in patients with kidney disease.NEW & NOTEWORTHY This work demonstrates the development and use of resting-state MRI to detect low-frequency, spontaneous physiological fluctuations in the kidney consistent with previously observed fluctuations in perfusion and potentially due to autoregulatory function. These fluctuations are detectable in rat and human kidneys, and the power of these fluctuations is affected by diabetic nephropathy in rats.

The association of travel burden with prenatal care utilization, what happens after provider-selection.

BACKGROUND: Birthing people in the United States face numerous challenges when accessing adequate prenatal care (PNC), with transportation being a significant obstacle. Nevertheless, previous studies that relied solely on the distance to the nearest provider cannot differentiate the effects of travel burden on provider selection and care utilization. These may exaggerate the degree of inequality in access and fail to capture perceived travel burden. This study investigated whether travel distances to the initially visited provider, to the predominant PNC provider, and perceived travel burden (measured by the travel disadvantage index (TDI)) are associated with PNC utilization. METHODS: A retrospective cohort of people with live births were identified from South Carolina Medicaid claims files in 2015-2018. Travel distances were calculated using Google Maps. The estimated TDI was derived from local pilot survey data. PNC utilization was measured by PNC initiation and frequency. Repeated measure logistic regression test was utilized for categorical variables and one-way repeated measures ANOVA for continuous variables. Unadjusted and adjusted ordinal logistic regressions with repeated measure were utilized to examine the association of travel burdens with PNC usage. RESULTS: For 25,801 pregnancies among those continuously enrolled in Medicaid, birthing people traveled an average of 24.9 and 24.2 miles to their initial and predominant provider, respectively, with an average TDI of -11.4 (SD, 8.5). Of these pregnancies, 60% initiated PNC in the first trimester, with an average of 8 total visits. Compared to the specialties of initial providers, predominant providers were more likely to be OBGYN-related specialists (81.6% vs. 87.9%, p < .001) and midwives (3.5% vs. 4.3%, p < .001). Multiple regression analysis revealed that every doubling of travel distance was associated with less likelihood to initiate timely PNC (OR: 0.95, p < .001) and a lower visit frequency (OR: 0.85, p < .001), and every doubling of TDI was associated with less likelihood to initiate timely PNC (OR: 0.94, p = .04). CONCLUSIONS: Findings suggest that the association between travel burden and PNC utilization was statistically significant but of limited practical significance.

Who is your prenatal care provider? An algorithm to identify the predominant prenatal care provider with claims data.

BACKGROUND: Using claims data to identify a predominant prenatal care (PNC) provider is not always straightforward, but it is essential for assessing access, cost, and outcomes. Previous algorithms applied plurality (providing the most visits) and majority (providing majority of visits) to identify the predominant provider in primary care setting, but they lacked visit sequence information. This study proposes an algorithm that includes both PNC frequency and sequence information to identify the predominant provider and estimates the percentage of identified predominant providers. Additionally, differences in travel distances to the predominant and nearest provider are compared. METHODS: The dataset used for this study consisted of 108,441 live births and 2,155,076 associated South Carolina Medicaid claims from 2015-2018. Analysis focused on patients who were continuously enrolled throughout their pregnancy and had any PNC visit, resulting in 32,609 pregnancies. PNC visits were identified with diagnosis and procedure codes and specialty within the estimated gestational age. To classify PNC providers, seven subgroups were created based on PNC frequency and sequence information. The algorithm was developed by considering both the frequency and sequence information. Percentage of identified predominant providers was reported. Chi-square tests were conducted to assess whether the probability of being identified as a predominant provider for a specific subgroup differed from that of the reference group (who provided majority of all PNC). Paired t-tests were used to examine differences in travel distance. RESULTS: Pregnancies in the sample had an average of 7.86 PNC visits. Fewer than 30% of the sample had an exclusive provider. By applying PNC frequency information, a predominant provider can be identified for 81% of pregnancies. After adding sequential information, a predominant provider can be identified for 92% of pregnancies. Distance was significantly longer for pregnant individuals traveling to the identified predominant provider (an average of 5 miles) than to the nearest provider. CONCLUSIONS: Inclusion of PNC sequential information in the algorithm has increased the proportion of identifiable predominant providers by 11%. Applying this algorithm reveals a longer distance for pregnant individuals travelling to their predominant provider than to the nearest provider.

Geographic Differences in School Success Among Children and Adolescents in the United States.

The purpose of this study was to examine the relationship between rurality and challenges to school success: lack of school engagement, school absenteeism, and repeated grade. Cross-sectional data from the 2020 to 2021 National Survey of Children's Health, children ages 6 to 17 (n = 42,089), was used. Bivariate and multivariable logistic regression models were used to examine the associations between residence rurality and each outcome of interest. In bivariate analysis, rural children were more likely to have school absenteeism and repeat a school grade. In our adjusted models, there were no differences between rurality and the three measures of school success. Rural and urban children may be vulnerable to different risk factors for school failure. Findings from this study may be used by school nurses and policymakers as they design and implement programs in rural schools.

Use of novel structural features to identify urinary biomarkers during acute kidney injury that predict progression to chronic kidney disease.

BACKGROUND: A significant barrier to biomarker development in the field of acute kidney injury (AKI) is the use of kidney function to identify candidates. Progress in imaging technology makes it possible to detect early structural changes prior to a decline in kidney function. Early identification of those who will advance to chronic kidney disease (CKD) would allow for the initiation of interventions to halt progression. The goal of this study was to use a structural phenotype defined by magnetic resonance imaging and histology to advance biomarker discovery during the transition from AKI to CKD. METHODS: Urine was collected and analyzed from adult C57Bl/6 male mice at four days and 12 weeks after folic acid-induced AKI. Mice were euthanized 12 weeks after AKI and structural metrics were obtained from cationic ferritin-enhanced-MRI (CFE-MRI) and histologic assessment. The fraction of proximal tubules, number of atubular glomeruli (ATG), and area of scarring were measured histologically. The correlation between the urinary biomarkers at the AKI or CKD and CFE-MRI derived features was determined, alone or in combination with the histologic features, using principal components. RESULTS: Using principal components derived from structural features, twelve urinary proteins were identified at the time of AKI that predicted structural changes 12 weeks after injury. The raw and normalized urinary concentrations of IGFBP-3 and TNFRII strongly correlated to the structural findings from histology and CFE-MRI. Urinary fractalkine concentration at the time of CKD correlated with structural findings of CKD. CONCLUSIONS: We have used structural features to identify several candidate urinary proteins that predict whole kidney pathologic features during the transition from AKI to CKD, including IGFBP-3, TNFRII, and fractalkine. In future work, these biomarkers must be corroborated in patient cohorts to determine their suitability to predict CKD after AKI.

Estimating Nephron Number from Biopsies: Impact on Clinical Studies.

BACKGROUND: Accumulating evidence supports an association between nephron number and susceptibility to kidney disease. However, it is not yet possible to directly measure nephron number in a clinical setting. Recent clinical studies have used glomerular density from a single biopsy and whole kidney cortical volume from imaging to estimate nephron number and single nephron glomerular filtration rate. However, the accuracy of these estimates from individual subjects is unknown. Furthermore, it is not clear how sample size or biopsy location may influence these estimates. These questions are critical to study design, and to the potential translation of these tools to estimate nephron number in individual subjects. METHODS: We measured the variability in estimated nephron number derived from needle or virtual biopsies and cortical volume in human kidneys declined for transplantation. We performed multiple needle biopsies in the same kidney, and examined the three-dimensional spatial distribution of nephron density by magnetic resonance imaging. We determined the accuracy of a single-kidney biopsy to predict the mean nephron number estimated from multiple biopsies from the same kidney. RESULTS: A single needle biopsy had a 15% chance and virtual biopsy had a 60% chance of being within 20% of the whole-kidney nephron number. Single needle biopsies could be used to detect differences in nephron number between large cohorts of several hundred subjects. CONCLUSIONS: The number of subjects required to accurately detect differences in nephron number between populations can be predicted on the basis of natural intrakidney variability in glomerular density. A single biopsy is insufficient to accurately predict nephron number in individual subjects.

Mapping single-nephron filtration in the isolated, perfused rat kidney using magnetic resonance imaging.

The kidney has an extraordinary ability to maintain glomerular filtration despite natural fluctuations in blood pressure and nephron loss. This is partly due to local coordination between single-nephron filtration and vascular perfusion. An improved understanding of the three-dimensional (3-D) functional coordination between nephrons and the vasculature may provide a new perspective of the heterogeneity of kidney function and could inform targeted therapies and timed interventions to slow or prevent the progression of kidney disease. Here, we developed magnetic resonance imaging (MRI) tools to visualize single-nephron function in 3-D throughout the isolated perfused rat kidney. We used an intravenous slow perfusion of a glomerulus-targeted imaging tracer [cationized ferritin (CF)] to map macromolecular dynamics and to identify glomeruli in 3-D, followed by a bolus of a freely filtered tracer (gadolinium diethylenetriamine penta-acetic acid) to map filtration kinetics. There was a wide intrakidney distribution of CF binding rates and estimated single-nephron glomerular filtration rate (eSNGFR) between nephrons. eSNGFR and CF uptake rates did not vary significantly by distance from the kidney surface. eSNGFR varied from ∼10 to ∼100 nL/min throughout the kidney. Whole single-kidney GFR was similar across all kidneys, despite differences in the distributions eSNGFR of and glomerular number, indicating a robust adaptive regulation of individual nephrons to maintain constant single-kidney GFR in the presence of a natural variation in nephron number. This work provides a framework for future studies of single-nephron function in the whole isolated perfused kidney and experiments of single-nephron function in vivo using MRI.NEW & NOTEWORTHY We report MRI tools to measure and map single-nephron function in the isolated, perfused rat kidney. We used imaging tracers to identify nephrons throughout the kidney and to measure the delivery and filtration of the tracers at the location of the glomeruli. With this technique, we directly measured physiological parameters including estimated single-nephron glomerular filtration rate throughout the kidney. This work provides a foundation for new studies to simultaneously map the function of large numbers of nephrons.

Multicore fibers with 10 and 16 single-mode cores for the visible spectrum.

We report multicore fibers (MCFs) with 10 and 16 linearly distributed cores with single-mode operation in the visible spectrum. The average propagation loss of the cores is 0.06 dB/m at λ = 445 nm and < 0.03 dB/m at wavelengths longer than 488 nm. The low inter-core crosstalk and nearly identical performance of the cores make these MCFs suitable for spatial division multiplexing in the visible spectrum. As a proof-of-concept application, one of the MCFs was coupled to an implantable neural probe to spatially address light-emitting gratings on the probe.

Examining the influence of positive childhood experiences on childhood overweight and obesity using a national sample.

Positive childhood experiences (PCEs) promote healthy social development, improve overall wellness, and help to moderate and prevent exposure to adverse childhood experiences. There has been limited research examining the association between positive childhood experiences and overweight or obesity status in children. The purpose of this study was to examine whether experiencing positive childhood experiences are associated with lower rates of overweight or obesity status in children between 10 and 17 years of age, using cross-sectional data from the 2018-2019 National Survey of Children's Health (n = 28,771), a nationally representative mail and online survey. Frequencies, proportions, and unadjusted associations for each variable were calculated using descriptive statistics and bivariate analyses. To examine the association between overweight or obesity and PCEs, multivariable regression models were used. Compared to children who were underweight or had a healthy weight, children who were overweight or obese were less likely to: participate after school activities (78.1%, p < 0.0001), volunteer in their community, school, or church (45.6%, p < 0.0001), have a mentor they feel comfortable going to for guidance (87.0%, p = 0.02), live in a safe neighborhood (61.3%, p < 0.0001), live in a supportive neighborhood (50.4%, p < 0.0001), and to live with a resilient family (78.3%; p = 0.0099). In adjusted analysis, among children exposed to two or more ACEs, children residing in a supportive neighborhood were less likely to be overweight or obese (aOR 0.87; 0.77-0.98). Our findings suggest that certain PCEs may mitigate overweight and obesity when children have experienced at least some childhood trauma.

Mapping kidney tubule diameter ex vivo by diffusion MRI.

Tubular pathologies are a common feature of kidney disease. Current metrics to assess kidney health, in vivo or in transplant, are generally based on urinary or serum biomarkers and pathological findings from kidney biopsies. Biopsies, usually taken from the kidney cortex, are invasive and prone to sampling error. Tools to directly and noninvasively measure tubular pathology could provide a new approach to assess kidney health. This study used diffusion magnetic resonance imaging (dMRI) as a noninvasive tool to measure the size of the tubular lumen in ex vivo, perfused kidneys. We first used Monte Carlo simulations to demonstrate that dMRI is sensitive to restricted tissue water diffusion at the scale of the kidney tubule. We applied dMRI and biophysical modeling to examine the distribution of tubular diameters in ex vivo, fixed kidneys from mice, rats, and a human donor. The biophysical model to fit the dMRI signal was based on a superposition of freely diffusing water and water diffusing inside infinitely long cylinders of different diameters. Tubular diameters measured by dMRI were within 10% of those measured by histology within the same tissue. Finally, we applied dMRI to investigate kidney pathology in a mouse model of folic-acid-induced acute kidney injury. dMRI detected heterogeneity in the distribution of tubules within the kidney cortex of mice with acute kidney injury compared with control mice. We conclude that dMRI can be used to measure the distribution of tubule diameters in the kidney cortex ex vivo and that dMRI may provide a new noninvasive biomarker of tubular pathology.NEW & NOTEWORTHY Tubular pathologies are a common feature of kidney disease. Current metrics to assess kidney health, in vivo or in transplant, are generally based on urinary or serum biomarkers and pathological findings from kidney biopsies. Diffusion MRI can be used to measure the distribution of tubule diameters in the kidney cortex ex vivo and may provide a new noninvasive biomarker of tubular pathology.

Image analysis techniques to map pyramids, pyramid structure, glomerular distribution, and pathology in the intact human kidney from 3-D MRI.

Kidney pathologies are often highly heterogeneous. To comprehensively understand kidney structure and pathology, it is critical to develop tools to map tissue microstructure in the context of the whole, intact organ. Magnetic resonance imaging (MRI) can provide a unique, three-dimensional view of the kidney and allows for measurements of multiple pathological features. Here, we developed a platform to systematically render and map gross and microstructural features of the human kidney based on three-dimensional MRI. These features include pyramid number and morphology as well as the associated medulla and cortex. In a subset of these kidneys, we also mapped individual glomeruli and glomerular volumes using cationic ferritin-enhanced MRI to report intrarenal heterogeneity in glomerular density and size. Finally, we rendered and measured regions of nephron loss due to pathology and individual glomerular volumes in each pyramidal unit. This work provides new tools to comprehensively evaluate the kidney across scales, with potential applications in anatomic and physiological research, transplant allograft evaluation, biomarker development, biopsy guidance, and therapeutic monitoring. These image rendering and analysis tools could eventually impact the field of transplantation medicine to improve longevity matching of donor allografts and recipients and reduce discard rates through the direct assessment of donor kidneys.NEW & NOTEWORTHY We report the application of cutting-edge image analysis approaches to characterize the pyramidal geometry, glomerular microstructure, and heterogeneity of the whole human kidney imaged using MRI. This work establishes a framework to improve the detection of microstructural pathology to potentially facilitate disease monitoring or transplant evaluation in the individual kidney.

Mapping nephron mass in vivo using positron emission tomography.

Nephron number varies widely in humans. A low nephron endowment at birth or a loss of functioning nephrons is strongly linked to increased susceptibility to chronic kidney disease. In this work, we developed a contrast agent, radiolabeled cationic ferritin (RadioCF), to map functioning glomeruli in vivo in the kidney using positron emission tomography (PET). PET radiotracers can be detected in trace doses (<30 nmol), making them useful for rapid clinical translation. RadioCF is formed from cationic ferritin (CF) and with a radioisotope, Cu-64, incorporated into the ferritin core. We showed that RadioCF binds specifically to kidney glomeruli after intravenous injection in mice, whereas radiolabeled noncationic ferritin (RadioNF) and free Cu-64 do not. We then showed that RadioCF-PET can distinguish kidneys in healthy wild-type (WT) mice from kidneys in mice with oligosyndactylism (Os/+), a model of congenital hypoplasia and low nephron mass. The average standardized uptake value (SUV) measured by PET 90 min after injection was 21% higher in WT mice than in Os/+ mice, consistent with the higher glomerular density in WT mice. The difference in peak SUV from SUV at 90 min correlated with glomerular density in male mice from both WT and Os/+ cohorts (R2 = 0.98). Finally, we used RadioCF-PET to map functioning glomeruli in a donated human kidney. SUV within the kidney correlated with glomerular number (R2= 0.78) measured by CF-enhanced magnetic resonance imaging in the same locations. This work suggests that RadioCF-PET appears to accurately detect nephron mass and has the potential for clinical translation.

Magnetic resonance imaging accurately tracks kidney pathology and heterogeneity in the transition from acute kidney injury to chronic kidney disease.

Acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD). However, there are few tools to detect microstructural changes after AKI. Here, cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) was applied to examine the heterogeneity of kidney pathology in the transition from AKI to CKD. Adult male mice received folic acid followed by cationic ferritin and were euthanized at four days (AKI), four weeks (CKD-4) or 12 weeks (CKD-12). Kidneys were examined by histologic methods and CFE-MRI. In the CKD-4 and CKD-12 groups, glomerular number was reduced and atubular cortical lesions were observed. Apparent glomerular volume was larger in the AKI, CKD-4 and CKD-12 groups compared to controls. Glomerular hypertrophy occurred with ageing. Interglomerular distance and glomerular density were combined with other MRI metrics to distinguish the AKI and CKD groups from controls. Despite significant heterogeneity, the noninvasive (MRI-based) metrics were as accurate as invasive (histological) metrics at distinguishing AKI and CKD from controls. To assess the toxicity of cationic ferritin in a CKD model, CKD-4 mice received cationic ferritin and were examined one week later. The CKD-4 groups with and without cationic ferritin were similar, except the iron content of the kidney, liver, and spleen was greater in the CKD-4 plus cationic ferritin group. Thus, our study demonstrates the accuracy and safety of CFE-MRI to detect whole kidney pathology allowing for the development of novel biomarkers of kidney disease and providing a foundation for future in vivo longitudinal studies in mouse models of AKI and CKD to track nephron fate.

Nephron number and its determinants: a 2020 update.

Studies of human nephron number have been conducted for well over a century and have uncovered a large variability in nephron number. However, the mechanisms influencing nephron endowment and loss, along with the etiology for the wide range among individuals are largely unknown. Advances in imaging technology have allowed investigators to revisit the principles of renal structure and physiology and their roles in the progression of kidney disease. Here, we will review the latest data on the influences impacting nephron number, innovations made over the last 6 years to understand and integrate renal structure and function, and new developments in the tools used to count nephrons in vivo.

Positive Childhood Experiences Promote School Success.

OBJECTIVES: Educational attainment has been demonstrated as a protective factor for the physical and mental health of children into adulthood, yet there has been limited research on the association between positive childhood experiences (PCEs) and school success. The purpose of this study is to examine the associations between PCEs and challenges to school success. METHODS: This cross-sectional study used data of 33,450 children from the 2017-2018 National Survey of Children's Health to examine PCEs and two challenges to school success (school absenteeism and repeated grades), using multivariable logistic regression analysis. RESULTS: The most prevalent types of PCEs were mentor for advice or guidance (89.8%), family resilience (81.1%), and after-school activity participation (79.8%). Children who participated in after-school activities had lower odds of reported school absenteeism (aOR 0.59; 95% CI 0.46-0.76) and repeating a grade (aOR 0.75; 95% CI 0.59-0.97) than their counterparts. Children who shared ideas with their caregiver had lower odds of repeating a grade (aOR 0.78; 95% CI 0.63-0.97) than children who did not share ideas with their caregiver. Children who lived in a supportive neighborhood were less likely to have reported school absenteeism than children who did not live in a supportive neighborhood (aOR 0.77; 95% CI 0.60-0.98). CONCLUSIONS FOR PRACTICE: Participation in after-school activities had optimal associations with both school absenteeism and repeated grade, suggesting its potential protective effect for school success. Promoting PCEs at the school, family, and community levels may help address school absenteeism and grade retention.

Beyond the tubule: pathological variants of LRP2, encoding the megalin receptor, result in glomerular loss and early progressive chronic kidney disease.

Pathogenic variants in the LRP2 gene, encoding the multiligand receptor megalin, cause a rare autosomal recessive syndrome: Donnai-Barrow/Facio-Oculo-Acoustico-Renal (DB/FOAR) syndrome. Because of the rarity of the syndrome, the long-term consequences of the tubulopathy on human renal health have been difficult to ascertain, and the human clinical condition has hitherto been characterized as a benign tubular condition with asymptomatic low-molecular-weight proteinuria. We investigated renal function and morphology in a murine model of DB/FOAR syndrome and in patients with DB/FOAR. We analyzed glomerular filtration rate in mice by FITC-inulin clearance and clinically characterized six families, including nine patients with DB/FOAR and nine family members. Urine samples from patients were analyzed by Western blot analysis and biopsy materials were analyzed by histology. In the mouse model, we used histological methods to assess nephrogenesis and postnatal renal structure and contrast-enhanced magnetic resonance imaging to assess glomerular number. In megalin-deficient mice, we found a lower glomerular filtration rate and an increase in the abundance of injury markers, such as kidney injury molecule-1 and N-acetyl-ß-d-glucosaminidase. Renal injury was validated in patients, who presented with increased urinary kidney injury molecule-1, classical markers of chronic kidney disease, and glomerular proteinuria early in life. Megalin-deficient mice had normal nephrogenesis, but they had 19% fewer nephrons in early adulthood and an increased fraction of nephrons with disconnected glomerulotubular junction. In conclusion, megalin dysfunction, as present in DB/FOAR syndrome, confers an increased risk of progression into chronic kidney disease.

Nephron loss detected by MRI following neonatal acute kidney injury in rabbits.

BACKGROUND: Acute kidney injury affects nearly 30% of preterm neonates in the intensive care unit. We aimed to determine whether nephrotoxin-induced AKI disrupted renal development assessed by imaging (CFE-MRI). METHODS: Neonatal New Zealand rabbits received indomethacin and gentamicin (AKI) or saline (control) for four days followed by cationic ferritin (CF) at six weeks. Ex vivo images were acquired using a gradient echo pulse sequence on 7 T MRI. Glomerular number (Nglom) and apparent glomerular volume (aVglom) were determined. CF toxicity was assessed at two and 28 days in healthy rabbits. RESULTS: Nglom was lower in the AKI group as compared to controls (74,034 vs 198,722, p < 0.01). aVglom was not different (AKI: 7.3 × 10-4 vs control: 6.2 × 10-4 mm3, p = 0.69). AKI kidneys had a band of glomeruli distributed radially in the cortex that were undetectable by MRI. Following CF injection, there was no difference in body or organ weights except for the liver, and transient changes in serum iron, platelets and white blood cell count. CONCLUSIONS: Brief nephrotoxin exposure during nephrogenesis results in fewer glomeruli and glomerular maldevelopment in a unique pattern detectable by MRI. Whole kidney evaluation by CFE-MRI may provide an important tool to understand the development of CKD following AKI.

A Solid-State Support for Separating Astatine-211 from Bismuth.

Increasing access to the short-lived α-emitting radionuclide astatine-211 (211At) has the potential to advance targeted α-therapeutic treatment of disease and to solve challenges facing the medical community. For example, there are numerous technical needs associated with advancing the use of 211At in targeted α-therapy, e.g., improving 211At chelates, developing more effective 211At targeting, and characterizing in vivo 211At behavior. There is an insufficient understanding of astatine chemistry to support these efforts. The chemistry of astatine is one of the least developed of all elements on the periodic table, owing to its limited supply and short half-life. Increasing access to 211At could help address these issues and advance understanding of 211At chemistry in general. We contribute here an extraction chromatographic processing method that simplifies 211At production in terms of purification. It utilizes the commercially available Pre-Filter resin to rapidly (<1.5 h) isolate 211At from irradiated bismuth targets (Bi decontamination factors ≥876 000), in reasonable yield (68-55%) and in a form that is compatible for subsequent in vivo study. We are excited about the potential of this procedure to address 211At supply and processing/purification problems.

Visual displays for cyber network defense.

Five computer network Defence displays (one Alphanumeric and four graphical displays: Radial Traffic Analyser, Bar Graph, Cube, and Treemap) were evaluated. Two experiments were conducted using different methodological procedures. Participants responded to questions that were structured to approximate various ways in which analysts might need to consider network traffic. Numerous significant effects were obtained and a fairly clear rank ordering of performance for the four graphical displays was obtained across experiments (from best to worst): Bar Graph, Cube, Radial Traffic Analyser, and Treemap. The results are interpreted from the perspective of ecological interface design: the quality of performance is directly related to the quality of semantic mapping between work domain, display, and human constraints. Factors that may have contributed to the poor performance for the Radial Traffic Analyser and Treemap displays are discussed. General implications for display and interface design are provided. Practitioner summary: Proposed displays for computer network Defence are evaluated; the results are interpreted from the perspective of ecological interface design. The associated design principles are applicable to all analogical graphical displays. Abbreviation: CND: cyber network defence; CSE: cognitive systems engineering; EID: ecological interface design; ICMP: internet control message protocol; IP: internet protocol; RTA: radial traffic analyzer; TCP: transmission control protocol; UDP: user datagram protocol.

Self-directed down-regulation of auditory cortex activity mediated by real-time fMRI neurofeedback augments attentional processes, resting cerebral perfusion, and auditory activation.

In this work, we investigated the use of real-time functional magnetic resonance imaging (fMRI) with neurofeedback training (NFT) to teach volitional down-regulation of the auditory cortex (AC) using directed attention strategies as there is a growing interest in the application of fMRI-NFT to treat neurologic disorders. Healthy participants were separated into two groups: the experimental group received real feedback regarding activity in the AC; the control group was supplied sham feedback yoked from a random participant in the experimental group and matched for fMRI-NFT experience. Each participant underwent five fMRI-NFT sessions. Each session contained 2 neurofeedback runs where participants completed alternating blocks of "rest" and "lower" conditions while viewing a continuously-updated bar representing AC activation and listening to continuous noise. Average AC deactivation was extracted from each closed-loop neuromodulation run and used to quantify the control over AC (AC control), which was found to significantly increase across training in the experimental group. Additionally, behavioral testing was completed outside of the MRI on sessions 1 and 5 consisting of a subjective questionnaire to assess attentional control and two quantitative tests of attention. No significant changes in behavior were observed; however, there was a significant correlation between changes in AC control and attentional control. Also, in a neural assessment before and after fMRI-NFT, AC activity in response to continuous noise stimulation was found to significantly decrease across training while changes in AC resting perfusion were found to be significantly greater in the experimental group. These results may be useful in formulating effective therapies outside of the MRI, specifically for chronic tinnitus which is often characterized by hyperactivity of the primary auditory cortex and altered attentional processes. Furthermore, the modulation of attention may be useful in developing therapies for other disorders such as chronic pain.