Search

The Sun is the most studied of all stars, and thus constitutes a benchmark for stellar models. However, our vision of the Sun is still incomplete, as illustrated by the current debate on its chemical composition. The problem reaches far beyond chemical abundances and is intimately linked to microscopic and macroscopic physical ingredients of solar models such as radiative opacity, for which experimental results have been recently measured that still await theoretical explanations. We present opacity profiles derived from helioseismic inferences and compare them with detailed theoretical computations of individual element contributions using three different opacity computation codes, in a complementary way to experimental results. We find that our seismic opacity is about 10% higher than theoretical values used in current solar models around 2 million degrees, but lower by 35% than some recent available theoretical values. Using the Sun as a laboratory of fundamental physics, we show that quantitative comparisons between various opacity tables are required to understand the origin of the discrepancies between reported helioseismic, theoretical and experimental opacity values. Opacities are considered to be the source of the disagreement between theoretical solar models and helioseismic data. Here, the authors show solar opacity profiles derived from seismic inferences, which differs from theoretical values used in the solar models. [ABSTRACT FROM AUTHOR]

Laser-driven compact particle accelerators can provide ultrashort pulses of broadband X-rays, well suited for undertaking X-ray absorption spectroscopy measurements on a femtosecond timescale. Here the Extended X-ray Absorption Fine Structure (EXAFS) features of the K-edge of a copper sample have been observed over a 250 eV window in a single shot using a laser wakefield accelerator, providing information on both the electronic and ionic structure simultaneously. This capability will allow the investigation of ultrafast processes, and in particular, probing high-energy-density matter and physics far-from-equilibrium where the sample refresh rate is slow and shot number is limited. For example, states that replicate the tremendous pressures and temperatures of planetary bodies or the conditions inside nuclear fusion reactions. Using high-power lasers to pump these samples also has the advantage of being inherently synchronised to the laser-driven X-ray probe. A perspective on the additional strengths of a laboratory-based ultrafast X-ray absorption source is presented. Laser-driven X-rays can provide ultrashort pulses of broadband light, well suited for femtosecond timescale absorption spectroscopy. Here the authors measure the extended X-ray absorption features of a copper sample using a laser wakefield accelerator, in a single shot; important for studying samples driven to extreme and non-equilibrium states. [ABSTRACT FROM AUTHOR]

The rapid progress that plasma wakefield accelerators are experiencing is now posing the question as to whether they could be included in the design of the next generation of high-energy electron-positron colliders. However, the typical structure of the accelerating wakefields presents challenging complications for positron acceleration. Despite seminal proof-of-principle experiments and theoretical proposals, experimental research in plasma-based acceleration of positrons is currently limited by the scarcity of positron beams suitable to seed a plasma accelerator. Here, we report on the first experimental demonstration of a laser-driven source of ultra-relativistic positrons with sufficient spectral and spatial quality to be injected in a plasma accelerator. Our results indicate, in agreement with numerical simulations, selection and transport of positron beamlets containing N e + ≥ 10 5 positrons in a 5% bandwidth around 600 MeV, with femtosecond-scale duration and micron-scale normalised emittance. Particle-in-cell simulations show that positron beams of this kind can be guided and accelerated in a laser-driven plasma accelerator, with favourable scalings to further increase overall charge and energy using PW-scale lasers. The results presented here demonstrate the possibility of performing experimental studies of positron acceleration in a laser-driven wakefield accelerator. [ABSTRACT FROM AUTHOR]

Beer is made via the fermentation of an aqueous extract predominantly composed of malted barley flavoured with hops. The transforming microorganism is typically a single strain of Saccharomyces cerevisiae, and for the majority of major beer brands the yeast strain is a unique component. The present yeast used to make Guinness stout brewed in Dublin, Ireland, can be traced back to 1903, but its origins are unknown. To that end, we used Illumina and Nanopore sequencing to generate whole-genome sequencing data for a total of 22 S. cerevisiae yeast strains: 16 from the Guinness collection and 6 other historical Irish brewing. The origins of the Guinness yeast were determined with a SNP-based analysis, demonstrating that the Guinness strains occupy a distinct group separate from other historical Irish brewing yeasts. Assessment of chromosome number, copy number variation and phenotypic evaluation of key brewing attributes established Guinness yeast-specific SNPs but no specific chromosomal amplifications. Our analysis also demonstrated the effects of yeast storage on phylogeny. Altogether, our results suggest that the Guinness yeast used today is related to the first deposited Guinness yeast; the 1903 Watling Laboratory Guinness yeast. A genomic analysis of 22 S. cereviseae yeast strains used in beer brewing suggest that yeast used to brew Guinness form a distinct evolutionary sub-clade, and that the modern-day Guinness yeast is closely related to the 1903 Watling Laboratory Guinness yeast. [ABSTRACT FROM AUTHOR]

The emergence of caste-differentiated colonies, which have been defined as 'superorganisms', in ants, bees, and wasps represents a major transition in evolution. Lifetime mating commitment by queens, pre-imaginal caste determination and lifetime unmatedness of workers are key features of these animal societies. Workers in superorganismal species like honey bees and many ants have consequently lost, or retain only vestigial spermathecal structures. However, bumble bee workers retain complete spermathecae despite 25-40 million years since their origin of superorganismality, which remains an evolutionary mystery. Here, we show (i) that bumble bee workers retain queen-like reproductive traits, being able to mate and produce colonies, underlain by queen-like gene expression, (ii) the social conditions required for worker mating, and (iii) that these abilities may be selected for by early queen-loss in these annual species. These results challenge the idea of lifetime worker unmatedness in superorganisms, and provide an exciting new tool for the conservation of endangered bumble bee species. Workers in social insects such as honey bees, bumble bees, and ants are expected to spend their lives helping their mother reproduce. Here the authors show that workers of several bumble bee species can in fact mate and lead colonies of their own. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to demonstrate the effectiveness of spectral photon-counting CT (SPCCT) in quantifying fibrous cap (FC) thickness, FC area, and lipid-rich necrotic core (LRNC) area, in excised carotid atherosclerotic plaques by comparing it with histopathological measurements. Methods: This is a single-center ex vivo cross-sectional observational study. Excised plaques of 20 patients (71 +/- 6 years; 13 men), obtained from carotid endarterectomy were scanned with SPCCT using standardized acquisition settings (120k Vp/19 μA; 7–18 keV, 18–30 keV, 30–45 keV, 45–75 keV, and 75–118 keV). FC thickness, FC area, and LRNC area were quantified and compared between high-resolution 3D multi-energy CT images and histopathology using the Wilcoxon signed-ranks test and Bland–Altman analysis. Images were interpreted twice by two radiologists separately, blinded to the histopathology; inter- and intra-rater reliability were assessed with the intra-class correlation coefficients (ICC). Results: FC thickness and FC area did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements (p value range 0.15–0.51 for FC thickness and 0.053–0.30 for FC area). For the LRNC area, the p value was statistically non-significant for reader 1 (range 0.36–0.81). The Bland-Altman analysis showed mean difference and 95% confidence interval for FC thickness, FC area, and LRNC area, 0.04 (−0.36 to 0.12) square root mm, −0.18 (−0.34 to −0.02) log10 mm2 and 0.10 (−0.088. to 0.009) log10 mm2 respectively. Conclusion: The result demonstrated a viable technique for quantifying FC thickness, FC area, and LRNC area due to the combined effect of high spatial and energy resolution of SPCCT. Key Points: • SPCCT can identify and quantify different components of carotid atherosclerotic plaque in ex vivo study. • Components of atherosclerotic plaque did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements. [ABSTRACT FROM AUTHOR]

In the absence of panel data, researchers have devised alternative methods for estimating synthetic poverty dynamics using repeated cross section surveys. These methods are not only salient in the absence of panel data, but also in contexts where there are concerns over the quality of panel data and/or the panel data are of insufficient length to analyse medium- to long-term mobility trends. Both of these issues afflict the longitudinal element of the European Survey on Income and Living Conditions (EU-SILC) (Hérault and Jenkins, J Econ Inequ 17(1):51–76, 2019). Using the longitudinal element of EU-SILC, this paper assesses the accuracy of the synthetic panel approach put forth by Dang and Lanjouw (2021). For most conventional poverty lines, the DL approach is found to be highly accurate when the true ρ is known. Similar to Hérault and Jenkins (J Econ Inequ 17(1):51–76, 2019) the pseudo-panel approach for estimating ρ is found to be highly sensitive to cohort definition. The longitudinal element of EU-SILC, however, offers a unique route for overcoming this shortcoming. [ABSTRACT FROM AUTHOR]

Objective: Liver lesion characterization is limited by the lack of an established gold standard for precise correlation of radiologic characteristics with their histologic features. The objective of this study was to demonstrate the feasibility of using an ex vivo MRI-compatible sectioning device for radiologic-pathologic co-localization of lesions in resected liver specimens. Methods: In this prospective feasibility study, adults undergoing curative partial hepatectomy from February 2018 to January 2019 were enrolled. Gadoxetic acid was administered intraoperatively prior to hepatic vascular inflow ligation. Liver specimens were stabilized in an MRI-compatible acrylic lesion localization device (27 × 14 × 14 cm3) featuring slicing channels and a silicone gel 3D matrix. High-resolution 3D T1-weighted fast spoiled gradient echo and 3D T2-weighted fast-spin-echo images were acquired using a single channel quadrature head coil. Radiologic lesion coordinates guided pathologic sectioning. A final histopathologic diagnosis was prepared for all lesions. The proportion of successfully co-localized lesions was determined. Results: A total of 57 lesions were identified radiologically and sectioned in liver specimens from 10 participants with liver metastases (n = 8), primary biliary mucinous cystic neoplasm (n = 1), and hepatic adenomatosis (n = 1). Of these, 38 lesions (67%) were < 1 cm. Overall, 52/57 (91%) of radiologically identified lesions were identified pathologically using the device. Of these, 5 lesions (10%) were not initially identified on gross examination but were confirmed histologically using MRI-guided localization. One lesion was identified grossly but not on MRI. Conclusions: We successfully demonstrated the feasibility of a clinical method for image-guided co-localization and histological characterization of liver lesions using an ex vivo MRI-compatible sectioning device. Key Points: • The ex vivo MRI-compatible sectioning device provides a reliable method for radiologic-pathologic correlation of small (< 1 cm) liver lesions in human liver specimens. • The sectioning method can be feasibly implemented within a clinical practice setting and used in future efforts to study liver lesion characterization. • Intraoperative administration of gadoxetic acid results in enhancement in ex vivo MRI images of liver specimens hours later with excellent image quality. [ABSTRACT FROM AUTHOR]

Objectives: 3D chemical shift–encoded (CSE) MRI enables accurate and precise quantification of proton density fat fraction (PDFF) and R2*, biomarkers of hepatic fat and iron deposition. Unfortunately, 3D CSE-MRI requires reliable breath-holding. Free-breathing 2D CSE-MRI with sequential radiofrequency excitation is a motion-robust alternative but suffers from low signal-to-noise-ratio (SNR). To overcome this limitation, this work explores the combination of flip angle–modulated (FAM) 2D CSE imaging with a non-local means (NLM) motion-corrected averaging technique. Methods: In this prospective study, 35 healthy subjects (27 children/8 adults) were imaged on a 3T MRI-system. Multi-echo 3D CSE ("3D") and 2D CSE FAM ("FAM") images were acquired during breath-hold and free-breathing, respectively, to obtain PDFF and R2* maps of the liver. Multi-repetition FAM was postprocessed with direct averaging (DA)– and NLM-based averaging and compared to 3D CSE using Bland-Altmann and regression analysis. Image qualities of PDFF and R2* maps were reviewed by two radiologists using a Likert-like scale (score 1–5, 5 = best). Results: Compared to 3D CSE, multi-repetition FAM-NLM showed excellent agreement (regression slope = 1.0, R2 = 0.996) for PDFF and good agreement (regression slope 1.08–1.15, R2 ≥ 0.899) for R2*. Further, multi-repetition FAM-NLM PDFF and R2* maps had fewer artifacts (score 3.8 vs. 3.2, p < 0.0001 for PDFF; score 3.2 vs. 2.6, p < 0.001 for R2*) and better overall image quality (score 4.0 vs. 3.5, p < 0.0001 for PDFF; score 3.4 vs. 2.7, p < 0.0001 for R2*). Conclusions: Free-breathing FAM-NLM provides superior image quality of the liver compared to the conventional breath-hold 3D CSE-MRI, while minimizing bias for PDFF and R2* quantification. Key Points: • 2D CSE FAM-NLM is a free-breathing method for liver fat and iron quantification and viable alternative for patients unable to hold their breath. • 2D CSE FAM-NLM is a feasible alternative to breath-hold 3D CSE methods, with low bias in proton density fat fraction (PDFF) and no clinically significant bias in R2*. • Quantitatively, multiple repetitions in 2D CSE FAM-NLM lead to improved SNR. [ABSTRACT FROM AUTHOR]

Summary In many countries, osteoporosis is predominantly managed by primary care physicians; however, management after a fragility fracture has not been widely investigated. We describe osteoporosis care gaps in a real-world patient cohort. Our findings help inform initiatives to identify and overcome obstacles to effective management of patients after fragility fracture. Purpose A fragility fracture is a major risk factor for subsequent fracture in adults aged≥50 years. This retrospective observational study aimed to characterize post-fracture management in Canadian primary care. Methods A total of 778 patients with an index fragility fracture (low-trauma, excluding small bones) occurring between 2014 and 2016 were identified from medical records at 76 primary care centers in Canada, with follow-up until January 2018. Results Of 778 patients (80.5% female, median age [IQR] 73 [64–80]), 215 were on osteoporosis treatment and 269 had osteoporosis diagnosis recorded prior to their index fracture. The median follow-up was 363 (IQR 91–808) days. Of patients not on osteoporosis treatment at their index fracture, 60.2% (n=339/563) remained untreated after their index fracture and 62.2% (n=23/37) continued untreated after their subsequent fracture. After their index fracture, fracture risk assessment (FRAX or CAROC) was not performed in 83.2% (n=647/778) of patients, and 59.9% (n=466/778) of patients did not receive bone mineral density testing. Of patients without osteoporosis diagnosis recorded prior to their index date, 61.3% (n=300/489) remained undiagnosed after their index fracture. At least one subsequent fracture occurred in 11.5% (n=86/778) of patients. Conclusion In the primary care setting, fragility fracture infrequently resulted in osteoporosis treatment or fracture risk assessment, even after multiple fragility fractures. These results suggest a fragility fracture is not recognized as a major risk factor for subsequent fracture and its occurrence does not prompt primary care physicians to intervene. These data urge initiatives to identify and overcome obstacles to primary care physicians’ effective management of patients after fragility fractures. [ABSTRACT FROM AUTHOR]

Alcohol withdrawal syndrome (AWS) occurs in 2% of patients admitted to U.K. hospitals. Routine treatment includes thiamine and benzodiazepines. Laboratory studies indicate that thiamine requires magnesium for optimal activity, however this has not translated into clinical practice. Patients experiencing AWS were randomized to three groups: (group 1) thiamine, (group 2) thiamine plus MgSO4 or (group 3) MgSO4. Pre- and 2-h post-treatment blood samples were taken. AWS severity was recorded using the Glasgow Modified Alcohol Withdrawal Score (GMAWS). The primary outcome measure was 15% change in erythrocyte transketolase activity (ETKA) in group 3. Secondary outcome measures were change in plasma lactate concentrations and time to GMAWS = 0. 127 patients were recruited, 115 patients were included in the intention-to-treat analysis. Pre-treatment, the majority of patients had normal or high erythrocyte thiamine diphosphate (TDP) concentrations (≥ 275–675/> 675 ng/gHb respectively) (99%), low serum magnesium concentrations (< 0.75 mmol/L) (59%), and high plasma lactate concentrations (> 2 mmol/L) (67%). Basal ETKA did not change significantly in groups 1, 2 or 3. Magnesium deficient patients (< 0.75 mmol/L) demonstrated less correlation between pre-treatment basal ETKA and TDP concentrations than normomagnesemic patients (R2 = 0.053 and R2 = 0.236). Median plasma lactate concentrations normalized (≤ 2.0 mmol/L) across all three groups (p < 0.001 for all groups), but not among magnesium deficient patients in group 1 (n = 22). The median time to achieve GMAWS = 0 for groups 1, 2 and 3 was 10, 5.5 and 6 h respectively (p < 0.001). No significant difference was found between groups for the primary endpoint of change in ETKA. Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms. ClinicalTrials.gov: NCT03466528. [ABSTRACT FROM AUTHOR]

Brief resolved unexplained events (BRUE) are concerning episodes of short duration (typically < 1 min) characterized by a change in breathing, consciousness, muscle tone (hyper- or hypotonia), and/or skin color (cyanosis or pallor). The episodes occur in a normal-appearing infant in the first year of life, self-resolve, and have no readily identifiable explanation for the cause of the event. Previously called apparent life-threatening events (ALTE), the term BRUE was first defined by the American Academy of Pediatrics (AAP) in 2016. The criteria for BRUE carry greater specificity compared to that of ALTE and additionally are indicative of a diagnosis of exclusion. While most patients with BRUE will have a benign clinical course, important etiologies, including airway, cardiac, gastrointestinal, genetic, infectious, neurologic, and traumatic conditions (including nonaccidental), must be carefully considered. A BRUE is classified as either lower- or higher-risk based on patient age, corrected gestational age, event duration, number of events, and performance of cardiopulmonary resuscitation at the scene. The AAP clinical practice guideline provides recommendations for the management of lower-risk BRUEs, advocating against routine admission, blood testing, and imaging for infants with these events, though a short period of observation and/or an electrocardiogram may be advisable. While guidance exists for higher-risk BRUE, more data are required to better identify proportions and risk factors for serious outcomes among these patients. Conclusion: BRUE is a diagnosis with greater specificity relative to prior definitions and is now a diagnosis of exclusion. Additional research is needed, particularly in the evaluation of higher-risk events. Recent data suggest that the AAP guidelines for the management of lower-risk infants can be safely implemented.This review article summarizes the history, definitional changes, current guideline recommendations, and future research needs for BRUE. What is Known: • BRUE, first described in 2016, is a diagnosis used to describe a well-appearing infant who presents with change in breathing, consciousness, muscle tone (hyper- or hypotonia), and/or skin color (cyanosis or pallor). • BRUE can be divided into higher- and lower-risk events. Guidelines have been published for lower-risk events, with expert recommendations for higher-risk BRUE. What is New: • BRUE carries a low rate of serious diagnoses (< 5%), with the most common representing seizures and airway abnormalities. • Prior BRUE events are associated with serious diagnoses and episode recurrence. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the reproducibility of liver R2* measurements between a 2D cardiac ECG-gated and a 3D breath-hold liver CSE-MRI acquisition for liver iron quantification. Methods: A total of 54 1.5 T MRI exams from 51 subjects (18 women, 36 men, age 35.2 ± 21.8) were included. These included two sub-studies with 23 clinical MRI exams from 19 patients identified retrospectively, 24 participants with known or suspected iron overload, and 7 healthy volunteers acquired prospectively. The 2D cardiac and the 3D liver R2* maps were acquired in the same exam. Either acquisitions were reconstructed using a complex R2* algorithm that accounts for the presence of fat and residual phase errors due to eddy currents. Data were analyzed using colocalized ROIs in the liver. Results: Linear regression analysis demonstrated high Pearson's correlation and Lin's concordance coefficient for the overall study and both sub-studies. Bland–Altman analysis also showed good agreement, except for a slight increase of the mean R2* value above ~ 400 s−1. The Kolmogorow–Smirnow test revealed a non-normal distribution for (R2* 3D–R2* 2D) values from 0 to 600 s−1 in contrast to the 0–200 s−1 and 0–400 s−1 subpopulations. Linear regression analysis showed no relevant differences other than the intercept, likely due to only 7 measurements above 400 s−1. Conclusions: The results demonstrate that R2*-measurements in the liver are feasible using 2D cardiac R2* maps compared to 3D liver R2* maps as the reference. Liver R2* may be underestimated for R2* > 400 s−1 using the 2D cardiac R2* mapping method. [ABSTRACT FROM AUTHOR]

Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure1, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment2. Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell’s clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation are associated with persister proliferative capacity across multiple cancer types. Impeding oxidative stress or metabolic reprogramming alters the fraction of cycling persisters. In human tumours, programs associated with cycling persisters are induced in minimal residual disease in response to multiple targeted therapies. The Watermelon system enabled the identification of rare persister lineages that are preferentially poised to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence.Lineage tracing by barcoding of individual cells using a lentivirus library shows that cycling and non-cycling drug-tolerant persister cells in cancer arise from different lineages with distinct transcriptional and metabolic programs. [ABSTRACT FROM AUTHOR]

The Greenland ice sheet has been one of the largest sources of sea-level rise since the early 2000s. However, basal melt has not been included explicitly in assessments of ice-sheet mass loss so far. Here, we present the first estimate of the total and regional basal melt produced by the ice sheet and the recent change in basal melt through time. We find that the ice sheet's present basal melt production is 21.4 +4.4/−4.0 Gt per year, and that melt generated by basal friction is responsible for about half of this volume. We estimate that basal melting has increased by 2.9 ± 5.2 Gt during the first decade of the 2000s. As the Arctic warms, we anticipate that basal melt will continue to increase due to faster ice flow and more surface melting thus compounding current mass loss trends, enhancing solid ice discharge, and modifying fjord circulation. Melting at the base of the Greenland Ice Sheet is often disregarded as a source of quantifiable mass loss. In this study, the authors find the basal mass loss is equivalent to 8% of the ice sheet's present imbalance, and that the loss of mass from basal melt is likely to increase in the future. [ABSTRACT FROM AUTHOR]

With high levels of both chronic stress and chronic pain, law enforcement provides a unique population in which to study the potential mitigating impact of cognitive and affective reactivity on the stress–pain link. The primary aim of the present study was to examine the moderating role of mindful nonreactivity in the relationship between chronic stress and pain interference in law enforcement officers (n = 60). A regression analysis was conducted to determine if chronic stress predicted pain interference and, subsequently, to compute an estimate of the interaction effect of the chronic stress and mindful nonreactivity on pain interference. Results demonstrated the overall model was significant, F (3,55) = 5.29, p =.003, R2 =.47. When controlling for mindful nonreactivity, chronic stress significantly predicted pain interference, b =.76, t (55) = 3.40, p =.001, such that every one unit increase in chronic stress was associated with a.76 unit increase in pain interference. Results also demonstrated a significant interaction effect of mindful nonreactivity and chronic stress on pain interference, b = −.04, t (55) = − 2.86, p =.006. The Johnson–Neyman technique was conducted and revealed among individuals with low levels of mindful nonreactivity, chronic stress significantly predicted pain interference. However, for individuals with greater levels of mindful nonreactivity, chronic stress no longer predicted pain interference. Findings contribute to a growing understanding of how mindfulness can mitigate harmful effects of stress. [ABSTRACT FROM AUTHOR]

Electron-impact ionization cross sections are calculated for the ground configuration of the Pb atom. Time-dependent close-coupling cross sections for the direct ionization of the 6s and 6p subshells leading to single ionization are calculated with and without a polarization potential. Configuration-average distorted-wave cross sections for the direct ionization of the 6s and 6p subshells leading to single ionization are also calculated with and without a polarization potential. We find the time-dependent close-coupling cross sections using a polarization potential to be in good agreement with convergent-close-coupling cross sections using a polarization potential. The total direct ionization cross sections are compared to two sets of experimental measurements. The differences between the direct ionization cross sections and the experimental measurements are mainly due to indirect ionization cross sections coming from the 6 s 2 6 p 2 → 6 s 6 p 3 excitation followed by autoionization. [ABSTRACT FROM AUTHOR]

Purpose: To determine the feasibility of ultra-short echo time (UTE) MRA for assessment of inferior vena cava (IVC) filters and evaluate the impact of different imaging protocols at 3.0 T, using conventional Cartesian MRA (cMRA) as the reference standard. Methods: Patients with IVC-filters were recruited for this prospective IRB-approved, HIPAA-compliant study. Subjects underwent contrast-enhanced breath-held and a free-breathing 3D radial acquisition UTE-MRA (bhUTE, fbUTE) at three different flip angles (FA: 10°, 15°, 20°) to optimize T1-weighted image quality. Two radiologists performed a direct comparison consensus reading to assess the optimal FA. Image quality (IQ) of both UTE techniques at the best FA was rated independently on a 4-point Likert scale (0 = non-diagnostic, 3 = excellent) and compared to 3D T1-weighted breath-held cMRA. Results: Nine subjects were recruited. Low FAs of 10° were rated best for both UTE techniques. fbUTE was excellent (3, IQR: 2; 3) and significantly better for IVC-filter depiction than cMRA (2, IQR: 0.75; 2, p = 0.001) and bhUTE (1.5, IQR: 0.75; 2, p < 0.001). Both UTE techniques showed significantly less filter-related artifacts (fbUTE: 28%, bhUTE: 33%) than cMRA (89%, p = 0.001 and p = 0.002, respectively). However, IQ of bhUTE was generally degraded due to high image noise and low image contrast. IQ of the IVC venogram was best with cMRA. Clinically relevant signal voids were only observed with the cage-shaped OptEase filter. Conclusion: UTE-MRA is feasible at 3.0 T for the assessment of IVC-filters, particularly using a free-breathing protocol. Larger studies are needed to investigate the clinical utility of free-breathing UTE-MRA for assessment of IVC-filter-related complications. [ABSTRACT FROM AUTHOR]

Background: Goals of care (GOC) is a communication and decision-making process that occurs between a clinician and a patient (or surrogate decision-maker) during an episode of care to facilitate a plan of care that is consistent with the patient's preferences and values. Little is known about patients' experiences of these discussions. Objective: This study explored patients' perspectives of the GOC discussion in the hospital setting. Design: An explorative qualitative design was used within a social constructionist framework. Participants: Adult patients were recruited from six Australian hospitals across two states. Eligible patients had had a GOC discussion and they were identified by the senior nurse or their doctor for informed consent and interview. Approach: Semi-structured individual or dyadic interviews (with the carer/family member present) were conducted at the bedside or at the patient's home (for recently discharged patients). Interviews were audio-recorded and transcribed verbatim. Data were analysed for themes. Key Results: Thirty-eight patient interviews were completed. The key themes identified were (1) values and expectations, and (2) communication (sub-themes: (i) facilitators of the conversation, (ii) barriers to the conversation, and (iii) influence of the environment). Most patients viewed the conversation as necessary and valued having their preferences heard. Effective communication strategies and a safe, private setting were facilitators of the GOC discussion. Deficits in any of these key elements functioned as a barrier to the process. Conclusions: Effective communication, and patients' values and expectations set the stage for goals of care discussions; however, the environment plays a significant role. Communication skills training and education designed to equip clinicians to negotiate GOC interactions effectively are essential. These interventions must also be accompanied by systemic changes including building a culture supportive of GOC, clear policies and guidelines, and champions who facilitate uptake of GOC discussions. [ABSTRACT FROM AUTHOR]

Background: The relationship between non-Hispanic White (NHW) women's decreased neighborhood income between early-life and adulthood, individual risk-status at delivery, and small for gestational age (weight for gestation < 10th percentile, SGA) rates is unknown. Objective: To determine the extent to which NHW women's exposure to decreased neighborhood income is a risk factor for SGA births, and whether their own birth weight modifies this relationship. Methods: Stratified and multilevel logistic regression analyses were executed on the Illinois transgenerational dataset of mothers (born 1956–1976) and their infants (born 1989–1991) with appended U.S. census income information. Only NHW women with an early-life residence in top income quartile Chicago neighborhoods were studied. Results: NHW women (n = 4889) unexposed to decreased neighborhood income between early-life and adulthood had an SGA rate of 7.1%. In contrast, NHW women exposed to slightly (n = 5112), modestly (n = 2158), or severely (n = 339) decreased neighborhood income by the time of delivery had SGA rates of 8.2%, 10.8%, and 10.8%, respectively; RR (95% CI) equaled 1.2 (1.0–1.3), 1.5 (1.3–1.8) and 1.5 (1.1–2.1), respectively. The relationship between maternal exposure to modestly decreased neighborhood income and SGA rates was present only among former non-low birth weight (> 2500 g, non-LBW) mothers. In multilevel logistic regression models, the adjusted (controlling for age, parity, prenatal care usage, and cigarette smoking) OR of SGA birth for former low birth weight (< 2500 g, LBW) and non-LBW NHW women exposed to modestly (compared to no) decreased neighborhood income equaled 0.7 (0.4, 1.4) and 1.3 (1.1–1.6), respectively. Conclusions for Practice: NHW women's exposure to modestly decreased neighborhood income is associated with an increased risk of SGA birth; this phenomenon is absent among former low birth weight women. [ABSTRACT FROM AUTHOR]

Extreme ultraviolet (EUV) lithography is currently entering high-volume manufacturing to enable the continued miniaturization of semiconductor devices. The required EUV light, at 13.5 nm wavelength, is produced in a hot and dense laser-driven tin plasma. The atomic origins of this light are demonstrably poorly understood. Here we calculate detailed tin opacity spectra using the Los Alamos atomic physics suite ATOMIC and validate these calculations with experimental comparisons. Our key finding is that EUV light largely originates from transitions between multiply-excited states, and not from the singly-excited states decaying to the ground state as is the current paradigm. Moreover, we find that transitions between these multiply-excited states also contribute in the same narrow window around 13.5 nm as those originating from singly-excited states, and this striking property holds over a wide range of charge states. We thus reveal the doubly magic behavior of tin and the origins of the EUV light. Extreme ultraviolet (EUV) light is entering use in nanolithography. Here the authors discuss experimental and theoretical results about the prominent role of multiply-excited states in highly charged tin ions in the mechanism of EUV light emission from laser-produced plasma. [ABSTRACT FROM AUTHOR]

Objectives: Home-based mindfulness practice is a common component of formal mindfulness training (MT) protocols. Obtaining objective data from home-based mindfulness practice is challenging. Interpreting associations between home-based mindfulness practice and clinically impactful outcomes is complicated given the variability in recommendations in length, frequency, and type of practice. In this exploratory study, adherence to home-based practices of Mindfulness-Based Resilience Training (MBRT) was studied in order to evaluate associations with clinical outcomes. Methods: Home practices from 24 (92% male, non-Hispanic White, aged M = 43.20 years) law enforcement officers (LEOs) from the urban Pacific Northwest enrolled in a feasibility and efficacy trial of MBRT were studied using an objective tracking device and self-report data. Outcomes included adherence to home-based mindfulness practices and self-reported aggression. Results: Participants completed 59.12% of the frequency amount of practice assigned in the MBRT curriculum. Frequency of practice was associated with decreased aggression, adjusted R2 =.41, F(3,23) = 6.14, p =.004. Duration of practice also predicted decreased aggression, adjusted R2 =.33, F(3,23) = 4.76, p =.011. Conclusions: Home-based MBRT practices for LEOs, even at low rates of adherence, may reduce aggression. MTs may show beneficial effects for other populations presented with challenges to engage in regular MT practices. [ABSTRACT FROM AUTHOR]

Structural and functional plasticity of dendritic spines is the basis of animal learning. The rapid remodeling of actin cytoskeleton is associated with spine enlargement and shrinkage, which are essential for structural plasticity. The calcium-dependent protein kinase C isoform, PKCα, has been suggested to be critical for this actin-dependent plasticity. However, mechanisms linking PKCα and structural plasticity of spines are unknown. Here, we examine the spatiotemporal activation of actin regulators, including small GTPases Rac1, Cdc42 and Ras, in the presence or absence of PKCα during single-spine structural plasticity. Removal of PKCα expression in the postsynapse attenuated Rac1 activation during structural plasticity without affecting Ras or Cdc42 activity. Moreover, disruption of a PDZ binding domain within PKCα led to impaired Rac1 activation and deficits in structural spine remodeling. These results demonstrate that PKCα positively regulates the activation of Rac1 during structural plasticity. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the feasibility of combined delayed-phase gadoxetic acid (GA) and gadobenate dimeglumine (GD) enhanced liver MRI for improved detection of liver metastases, and to optimize contrast agent dose, timing, and flip angle (FA). Methods: Fourteen healthy volunteers underwent liver MRI at 3.0T at two visits during which they received two consecutive injections: 1. GA (Visit 1 = 0.025 mmol/kg; Visit 2 = 0.05 mmol/kg) and 2. GD (both visits = 0.1 mmol/kg) 20 min after GA administration. Two sub-studies were performed: Experiment-1 Eight subjects underwent multi-phase breath-held 3D-fat-saturated T1-weighted spoiled gradient echo (SGRE) imaging to determine the optimal imaging window for the combined GA + GD protocol to create a homogeneously hyperintense liver and vasculature ("plain-white-liver") with maximum contrast to muscle which served as a surrogate for metastatic lesions in both experiments. Experiment-2 Six subjects underwent breath-held 3D-fat-saturated T1-weighted SGRE imaging at three different FA to determine the optimal FA for best image contrast. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated. Results: Experiment-1 The combined GA + GD protocol created a homogeneously hyperintense liver and vasculature with maximum CNR liver/muscle at approximately 60–120 s after automatic GD-bolus detection. Experiment-2 Flip angles between 25° and 35° at a dose of 0.025 mmol/kg GA provided the best combination that minimized liver/vasculature CNR, while maximizing liver/muscle CNR. CNR performance to achieve a "plain-white-liver" was superior with 0.025 mmol/kg GA compared to 0.05 mmol/kg. Conclusion: Combined GA + GD enhanced T1-weighted MRI is feasible to achieve a homogeneously "plain-white-liver". Future studies need to confirm that this protocol can improve sensitivity of liver lesion detection in patients with metastatic liver disease. [ABSTRACT FROM AUTHOR]

This manuscript discusses global regulatory divergence of dissolution requirements for modified release solid oral dosage forms and the obstacles that must be addressed to be compliant with evolving guidance and legislation. The proliferation of local guidance documents, changing regulatory expectations, and increased legal enforcement has resulted in mismatched country-specific dissolution testing requirements and similarity criteria, and heightens industry's challenges with registration of modified release solid oral dosage forms. The lack of global harmonization and the complexity added by minor regional adaptations contributes to inefficiencies and hinders industry's goal of developing and delivering medicines. Awareness of country-specific similarity requirements and alignment between industry leaders and regulators is needed to facilitate global harmonization which will enable delivering new and improved medicines. The purpose of this manuscript is to compare and contrast in vitro conditions stated in local regulatory guidelines, raise awareness of the need to work toward harmonization of global requirements, and propose an initial study design toward that aspiration. [ABSTRACT FROM AUTHOR]

Background: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. Methods: This prospective, multi-centre study assessed antiplatelet–HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50–99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES − ve. Results: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin–HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin–HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin–HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES − ve subgroup. Discussion: Recently symptomatic moderate–severe carotid stenosis patients had a lower prevalence of aspirin–HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet–HTPR was positively influenced by higher shear stress levels, but not MES status. [ABSTRACT FROM AUTHOR]

Background: As access to open data is increasing, researchers gain the opportunity to build integrated datasets and to conduct more powerful statistical analyses. However, using open access data presents challenges for researchers in understanding the data. Visuals allow researchers to address these challenges by facilitating a greater understanding of the information available. Objectives: This paper illustrates how visuals can address the challenges that researchers face when using open access data, such as: (1) becoming familiar with the data, (2) identifying patterns and trends within the data, and (3) determining how to integrate data from multiple studies. Method: This paper uses data from an integrative data analysis study that combined data from prospective studies of children's responses to four natural disasters: Hurricane Andrew, Hurricane Charley, Hurricane Katrina, and Hurricane Ike. The integrated dataset assessed hurricane exposure, posttraumatic stress symptoms, anxiety, social support, and life events among 1707 participants (53.61% female). The children's ages ranged from 7 to 16 years (M = 9.61, SD = 1.60). Results: Visuals serve as an effective method for understanding new and unfamiliar datasets. Conclusions: In response to the growth of open access data, researchers must develop the skills necessary to create informative visuals. Most research-based graduate programs do not require programming-based courses for graduation. More opportunities for training in programming languages need to be offered so that future researchers are better prepared to understand new data. This paper discusses implications of current graduate course requirements and standard journal practices on how researchers visualize data. [ABSTRACT FROM AUTHOR]

Objectives: Nationally, 5% of the population have been prescribed topical lidocaine patches (TLPs). These patches cost €77–230 per month. The only licensed indication for TLP is post-herpetic neuralgia (PHN). It has not proven to be effective for any other indication including musculoskeletal and post-surgical pain. It is estimated that only 5–10% of patients on TLP have PHN. The aim of this study was to audit the number of inpatients currently prescribed TLP—appropriately and inappropriately—and to examine the prescribing patterns. Methods: The acute inpatient population was audited in August 2017 to determine TLP prevalence. Demographics, indication, prescriber grade, and whether TLP was commenced during the current admission were recorded. Education was given surrounding indications and licensed usage of TLP. The acute inpatient population was subsequently re-audited in February 2018. Results: There were 304 patients included in the initial study and 300 in the repeat study. The most common indication was musculoskeletal pain in each study, 75 and 77.78%, respectively. The number of inpatients on TLP fell from 17.1% (n = 52) to 6% (n = 18) after the intervention. The potential savings between the study periods are therefore €31,418–93,840 in total and €23,100–69,000 in musculoskeletal patients. Conclusion: A large proportion of inpatients are inappropriately prescribed TLP predominantly for musculoskeletal pain, resulting in substantial avoidable cost to the hospital. Education of prescribers and implementation of policies is required to limit inappropriate prescribing. [ABSTRACT FROM AUTHOR]

Marine and estuarine species often exhibit patterns of genetic variability consistent with demographic disequilibrium caused by reduced population sizes, possibly associated with glacial cycles. With one exception, previous studies in southeastern Australia have concentrated on taxa with broad distributions for which convincing scenarios to explain range size reductions are generally lacking. This study investigates the genetic structure of the mussel Austromytilus rostratus, which is a limited-range taxon endemic to the region, to examine the role that demographic instability may have played in its phylogeographic history. A. rostratus presently has no marked geographic structure in mitochondrial cytochrome c oxidase subunit I DNA sequences, although it exhibits very high diversity of haplotypes, with many restricted to one of the three regions where the species is particularly abundant. FST values between these regions are low although they are separated by areas of low population density. Sequence mismatch distributions and population genetic statistics suggest that demographic disequilibrium has occurred in A. rostratus overall and within each region. The species may have experienced population size changes, possibly through a decrease in its distribution during climate cycles to southern refugia at glacial minima or to northern refugia at glacial maxima. Under either scenario, however, the operation of indirect factors such as changes in the ranges of predators, interspecific competition or nutrient availability would probably need to be invoked to explain severe reductions in population size. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Components of carotid atherosclerotic plaque in spectral photon-counting CT with histopathologic comparison" published in the journal European Radiology. The correction addresses an error in the affiliation details for one of the authors, Aamir Y. Raja. The correct affiliation should have been the Department of Physics, Khalifa University, Abu Dhabi, UAE. The original article has been corrected. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives To determine whether affluent-born White mother’s descending neighborhood income is associated with infant mortality rates (< 365 day, IMR). Methods Stratified and multilevel logistic regression analyses were completed on the Illinois transgenerational dataset of singleton births (1989-1991) to non-Latina White mothers (1956-1976) with an early-life residence in affluent neighborhoods (defined as the fourth quartile of income distribution). The breadth of descending neighborhood income was defined by mother’s neighborhood income at the time of delivery. Results Infants of White mothers (n = 4890) who did not suffer descending neighborhood income by the time of delivery had a first-year mortality rate of 5.1/1,000. Infants of White mothers who experienced minor (n = 5112), modest (n = 2158), or extreme (n = 339) descending neighborhood income had IMR of 6.5/1,000, 14.4/1,000, and 11.8/1,000, respectively; RR [95% CI] = 1.3 [0.8, 2.1], 2.8 [1.7, 4.8], and 2.3 [0.8, 6.6], respectively. The incidence of young maternal age, inadequate prenatal care utilization, and cigarette smoking rose as descending neighborhood income increased, p < 0.01. In multilevel logistic regression models, the adjusted (controlling for selected individual-level co-variates) OR [95% CI] of infant mortality for White women with an early-life residence in affluent neighborhoods who subsequently experienced minor or modest to extreme (versus absent) descending neighborhood income equaled 1.0 [0.6, 1.8] and 2.1 [1.1, 3.8] respectively. Conclusions White mother’s modest to extreme descending neighborhood income from early-life residence in affluent neighborhoods is associated with a twofold greater risk of infant mortality independent of selected biologic, medical, and behavioral characteristics. [ABSTRACT FROM AUTHOR]

There has been significant growth in the use of modeling tools to accelerate development and enhance pharmaceutical quality. Among these are empirical and semi-empirical modeling of accelerated stability studies which can be used to predict product shelf-life (Waterman, Pharm Res 24:780-790, 2007; (Wu et al., AAPS Pharm Sci Tech,16:986-991, 2016); (Lavrich, Rapid Development of Robust Stability Models Using Semi-Empirical Design Space, AAPS Webinar, 2016)). These approaches coupled with Lean Stability and Quality by Design (QbD) Analytical Method Development have been discussed at a recent AAPS Workshop (AAPS Workshop, Accelerating Pharmaceutical Development through Predictive Stability Approaches, 2016) with subsequent discussions at a Face-to-Face Focus Group meeting (AAPS, Joint Face-to-Face meeting summary, 6-April, part1, 2017; AAPS, Joint Face-to-Face meeting summary, 6-April, Part II, 2017; Huynh-Ba, et al., Meeting Report, Analytical Approaches to Ensure Product Quality - AAPS Joint Face-to-Face Meeting of the Stability, the Pharmaceutical Impurities, and the CMC Statistics Focus Group, 2017) and the AAPS Annual meeting (AAPS Annual Meeting Sunrise Session, Accelerating Pharmaceutical Development through Predictive Stability Approaches, AAPS Annual Meeting, 2016). A summary/overview and the outcome from the workshop are captured in this publication. The first part focuses on use of Lean Stability Strategies to expedite the development of new chemical entities in early phase development, and to facilitate process, formulation for various dosage forms (solid, liquid, etc.) and product changes throughout development and post-approval. Also, presented, are the global regulatory agencies feedback, challenges and future direction. For Lean Stability and predictive stability approaches to be successful, the methods used must be accurate, precise and consistent across stability time points, analysts, instruments and testing sites, so the data and predictions are meaningful. For both small and large molecules, the use of QbD for analytical method development aids in achieving this goal; and, the second part of this publication discusses such approaches. These approaches are essential to build an overall optimized stability strategy to meet today's challenges to advance new medicines and enhance quality. [ABSTRACT FROM AUTHOR]

The intestinal mucosa provides a selective barrier between the anaerobic lumen and a highly metabolic lamina propria. A number of recent studies indicate that acute inflammation of the mucosa can result in tissue hypoxia and associated shifts in tissue metabolism. The activation of hypoxia-inducible factor (HIF) under these conditions has been demonstrated to function as an endogenous molecular cue to promote resolution of inflammation, particularly through the orchestration of barrier repair toward homeostasis. Given the central role of oxygen in tissue metabolism, ongoing studies have defined metabolic endpoints of HIF stabilization as important biomarkers of disease activity. Such findings make HIF and HIF-associated metabolic pathways particularly attractive therapeutic targets in inflammatory bowel disease (IBD). Here, we review the recent literature related to tissue metabolism in IBD. [ABSTRACT FROM AUTHOR]

Purpose: Ipilimumab was the first FDA-approved agent for advanced melanoma to improve survival and represents a paradigm shift in melanoma and cancer treatment. Its unique toxicity profile and kinetics of treatment response raise novel patient education challenges. We assessed patient perceptions of ipilimumab therapy across the treatment trajectory. Methods: Four patient cohorts were assessed at different time points relative to treatment initiation: (1) prior to initiation of ipilimumab ( n = 10), (2) at weeks 10-12 before restaging studies ( n = 11), (3) at week 12 following restaging studies indicating progression of disease ( n = 10), and (4) at week 12 following restaging studies indicating either a radiographic response or disease stability ( n = 10). Patients participated in a semistructured qualitative interview to assess their experiences with ipilimumab. Quality of life was assessed via the Functional Assessment of Cancer Therapy-General and its Melanoma-specific module. Results: Perceived quality of life was comparable across cohorts, and a majority of the sample understood side effects from ipilimumab and the potential for a delayed treatment response. Patients without progression of disease following restaging studies at week 12 held more positive views regarding ipilimumab compared to patients who had progressed. Conclusion: Patients generally regarded ipilimumab positively despite the risk of unique toxicities and potential for delayed therapeutic responses; however, those with progression expressed uncertainty regarding whether taking ipilimumab was worthwhile. Physician communication practices and patient education regarding realistic expectations for therapeutic benefit as well as unique toxicities associated with ipilimumab should be developed so that patients can better understand the possible outcomes from treatment. [ABSTRACT FROM AUTHOR]