Pharmacokinetics, pharmacodynamics, efficacy, and safety of ravulizumab in pediatric paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease of uncontrolled terminal complement activation leading to intravascular hemolysis, thrombotic events, increased morbidity and mortality. This phase 3, open-label, single-arm multicenter study (NCT03406507) evaluated ravulizumab treatment in eculizumab-naive or -experienced pediatric patients (aged <18 years) with PNH over a 26-week primary evaluation period (PEP) and 4-year extension period (EP). Patients included in the study received weight based intravenous ravulizumab dosing. Primary endpoints were pharmacokinetic and pharmacodynamic parameters to confirm complement component 5 (C5) inhibition by ravulizumab; secondary endpoints assessed the efficacy (including percentage change in lactate dehydrogenase levels over time) and safety of ravulizumab. Thirteen patients, 5 (38.5%) eculizumab-naive and 8 (61.5%) experienced, were enrolled. Ravulizumab Ctrough levels were above the pharmacokinetic threshold of 175 µg/mL in the PEP and EP except in one patient. At the end of the study, pre-and post-infusion mean ± standard deviation serum ravulizumab concentrations were 610.50 ± 201.53 µg/mL and 518.29 ± 109.67 µg/mL for eculizumab-naive and -experienced patients, respectively. After the first ravulizumab infusion, serum free C5 concentrations were <0.5 µg/mL in both cohorts until the end of the study (0.061 ± 0.021 µg/mL and 0.061 ± 0.018 µg/mL for eculizumab-naive and -experienced patients, respectively). Compared with baseline, ravulizumab improved and maintained efficacy outcomes in both groups. Ravulizumab had an acceptable safety profile with no new safety signals identified, and provided immediate, complete, and sustained terminal complement inhibition, translating to clinical benefit for pediatric patients with PNH.

Randomized controlled trial of remote ischemic preconditioning in children having cardiac surgery.

BACKGROUND: Children undergoing cardiac surgery are at risk for acute kidney injury (AKI) and cardiac dysfunction. Opportunity exists in protecting end organ function with remote ischemic preconditioning. We hypothesize this intervention lessens kidney and myocardial injury. METHODS: We conducted a randomized, double blind, placebo controlled trial of remote ischemic preconditioning in children undergoing cardiac surgery. Pre-specified end points are change in creatinine, estimated glomerular filtration rate, development of AKI, B-type natriuretic peptide and troponin I at 6, 12, 24, 48, 72 h post separation from bypass. RESULTS: There were 45 in the treatment and 39 patients in the control group, median age of 3.5 and 3.8 years, respectively. There were no differences between groups in creatinine, cystatin C, eGFR at each time point. There was a trend for a larger rate of decrease, especially for cystatin C (p = 0.042) in the treatment group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of treatment group (p = 0.094). Adjusting for baseline creatinine, the odds ratio for AKI in treatment versus control was 0.31 (p = 0.037); adjusting for clinical characteristics, the odds ratio was 0.34 (p = 0.056). There were no differences in natriuretic peptide or troponin levels between groups. All secondary end points of clinical outcomes were not different. CONCLUSIONS: There is suggestion of RIPC delivering some kidney protection in an at-risk pediatric population. Larger, higher risk population studies will be required to determine its efficacy. Trial registration and date: Clinicaltrials.gov NCT01260259; 2021.

Multi-isotope analysis of bone collagen of Late Pleistocene ungulates reveals niche partitioning and behavioural plasticity of reindeer during MIS 3.

Here we present stable carbon, nitrogen and sulfur isotope ratios of collagen extracted from Rangifer, Equus and Bison bone (n = 128) from different stratigraphic levels at the chronologically well-constrained Middle and Upper Palaeolithic site of Les Cottés, France. Samples were taken from five phases of site use (US08, US06, US04 [upper and lower], and US02; ~ 45.8-35.3 ka cal BP) to explore the dietary and spatial palaeoecology of these ungulate species during MIS 3, and the contemporary climate. Temporal trends in δ15N values of all species broadly align with other climatic indicators at the site and the lowest values in US04 correspond to the Heinrich 4 cooling event, reflecting changes in the composition of soil/plant nitrogen at this time. Rangifer collagen is 13C-enriched compared to the other species throughout, consistent with lichen consumption. However, this isotopic niche partitioning between Rangifer and Equus/Bison is most extensive during US04, indicating plasticity in reindeer feeding behaviour, and potentially overall increased lichen biomass during this cooler/more arid phase. Rangifer δ34S values are consistently lower than Equus and Bison, which could be indicative of their more extensive spatial ranges incorporating greater inland areas. Equus and Bison demonstrate a significant decrease in δ34S values through time, which may be linked to contemporary climatic decline.

Intermediate pressure-normalized principal wall strain values are associated with increased abdominal aortic aneurysmal growth rates.

Introduction: Current abdominal aortic aneurysm (AAA) assessment relies on analysis of AAA diameter and growth rate. However, evidence demonstrates that AAA pathology varies among patients and morphometric analysis alone is insufficient to precisely predict individual rupture risk. Biomechanical parameters, such as pressure-normalized AAA principal wall strain (ερ+¯/PP, %/mmHg), can provide useful information for AAA assessment. Therefore, this study utilized a previously validated ultrasound elastography (USE) technique to correlate ερ+¯/PP with the current AAA assessment methods of maximal diameter and growth rate. Methods: Our USE algorithm utilizes a finite element mesh, overlaid a 2D cross-sectional view of the user-defined AAA wall, at the location of maximum diameter, to track two-dimensional, frame-to-frame displacements over a full cardiac cycle, using a custom image registration algorithm to produce ερ+¯/PP. This metric was compared between patients with healthy aortas and AAAs (≥3 cm) and compared between small and large AAAs (≥5 cm). AAAs were then separated into terciles based on ερ+¯/PP values to further assess differences in our metric across maximal diameter and prospective growth rate. Non-parametric tests of hypotheses were used to assess statistical significance as appropriate. Results: USE analysis was conducted on 129 patients, 16 healthy aortas and 113 AAAs, of which 86 were classified as small AAAs and 27 as large. Non-aneurysmal aortas showed higher ερ+¯/PP compared to AAAs (0.044 ± 0.015 vs. 0.034 ± 0.017%/mmHg, p = 0.01) indicating AAA walls to be stiffer. Small and large AAAs showed no difference in ερ+¯/PP. When divided into terciles based on ερ+¯/PP cutoffs of 0.0251 and 0.038%/mmHg, there was no difference in AAA diameter. There was a statistically significant difference in prospective growth rate between the intermediate tercile and the outer two terciles (1.46 ± 2.48 vs. 3.59 ± 3.83 vs. 1.78 ± 1.64 mm/yr, p = 0.014). Discussion: There was no correlation between AAA diameter and ερ+¯/PP, indicating biomechanical markers of AAA pathology are likely independent of diameter. AAAs in the intermediate tercile of ερ+¯/PP values were found to have nearly double the growth rates than the highest or lowest tercile, indicating an intermediate range of ερ+¯/PP values for which patients are at risk for increased AAA expansion, likely necessitating more frequent imaging follow-up.

Private equity and healthcare firm behavior: Evidence from ambulatory surgery centers.

Healthcare firms regularly seek outside capital; yet, we have an incomplete understanding of external investor influence on provider behavior. We investigate the effects of private equity investment, divestment, and an initial public offering (IPO) on ambulatory surgery centers (ASCs). Throughput is unchanged while charges grow by up to 50% for the same service mix. Affected ASCs witness declines in privately insured cases and rely more on Medicare business. Private equity increases physician ASC ownership stakes, and both simultaneously divest when the ASC is sold. Our findings appear more consistent with private equity influencing the financing of ASCs, rather than treatment approaches.

Dance movement therapy for dementia.

BACKGROUND: Dementia is a syndrome of acquired cognitive impairment which is severe enough to interfere with independent living. Over the course of the illness, people with dementia also experience changes in emotions, behaviour and social relationships. According to Alzheimer's Disease International, dementia affects approximately 55 million people worldwide. The latest NICE guideline for dementia highlights the value of diverse treatment options for the different stages and symptoms of dementia, including non-pharmacological treatments. Relevant literature also argues for the value of interventions that acknowledge the complexity of the condition and address the person as a whole, including their physical, emotional, social and cognitive processes. A growing literature highlights the capacity of the arts and has embodied practices to address this complexity. Dance movement therapy (DMT) is an embodied psychological intervention that can address complexity and thus may be useful for people with dementia, but its effectiveness remains unclear. OBJECTIVES: To assess the effects of dance movement therapy on behavioural, social, cognitive and emotional symptoms of people with dementia in comparison to no treatment, standard care or any other treatment. Also, to compare different forms of dance movement therapy (e.g. Laban-based dance movement therapy, Chacian dance movement therapy or Authentic Movement) SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (Clarivate), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register of the International Clinical Trials Registry Portal until 8 December 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included people with dementia, of any age and in any setting. The DMT intervention had to be delivered by a dance movement therapy practitioner who (i) had received formal training (ii) was a dance movement therapist in training or (iii) was otherwise recognised as a dance movement therapist in the country in which the study was conducted. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and evaluated methodological quality. We expressed effect estimates using the mean difference (MD) between intervention groups and presented associated confidence intervals (CIs). We used GRADE methods to rate our certainty in the results. MAIN RESULTS: We found only one study eligible for inclusion in this review. This was a 3-arm parallel-group RCT conducted in Hong Kong involving 204 adults with mild neurocognitive disorder or dementia. The study examined the effects of short-term (12 weeks) group DMT in comparison with exercise and a waiting-list control group immediately post-intervention and three and nine months later. We found that, at the end of the intervention, DMT may result in little to no difference in neuropsychiatric symptoms assessed with the 12-item Neuropsychiatric Inventory when compared with waiting list (MD 0.3, 95% CI -0.96 to 1.56; low-certainty evidence) or exercise (MD -0.30, 95% CI -1.83 to 1.23; low-certainty evidence). Nor was there any evidence of effects at later time points. Cognitive functioning was assessed with a variety of instruments and there were no statistically significant between-group differences (low-certainty evidence). When compared to exercise or waiting list, DMT may result in little to no difference in cognitive function immediately after the intervention or at follow-up. In comparison to waiting list, DMT may result in a slight reduction in depression assessed with the 4-item Geriatric Depression Scale at the end of therapy (MD -0.60, 95% CI -0.96 to -0.24; low-certainty evidence). This slight positive effect of DMT on depression scores was sustained at three and nine months after the completion of the intervention. DMT may also reduce depression slightly in comparison with exercise at the end of therapy (MD -0.40, 95% CI -0.76 to -0.04, low-certainty evidence), an effect also sustained at three and nine months. Our fourth primary outcome, quality of life, was not assessed in the included study. There were data for two of our secondary outcomes, social and occupational functioning and dropouts (which we used as a proxy for acceptability), but in both cases the evidence was of very low certainty and hence our confidence in the results was very low. For all outcomes, we considered the certainty of the evidence in relation to our review objectives to be low or very low in GRADE terms due to indirectness (because not all participants in the included study had a diagnosis of dementia) and imprecision. AUTHORS' CONCLUSIONS: This review included one RCT with a low risk of bias. Due to the low certainty of the evidence, the true effects of DMT as an intervention for dementia may be substantially different from those found. More RCTs are needed to determine with any confidence whether DMT has beneficial effects on dementia.

When big data initiatives meet: Data sharing between THANADOS and IsoArcH for early medieval cemeteries in Austria.

This paper reports carbon, nitrogen, and sulfur stable isotope data obtained from bone collagen of humans from the early medieval cemeteries of Hemmaberg/Gora svete Heme and Oberleiserberg located in Austria. The Hemmaberg/Gora svete Heme cemetery, dating from the 8th to the 11th century, comprises 29 graves, from which 15 individuals were analyzed. The Oberleiserberg cemetery, established in the first half of the 11th century, includes 71 graves as well as several incidental finds of human bones, from which 75 samples were analyzed. Both cemeteries show comparable δ13C data (mean for Oberleiserberg: -17.5 ± 1.2 ‰, 1σ; mean for Hemmaberg: -16.4 ± 1.6‰, 1σ). However, the δ15N values of individuals from Oberleiserberg (mean: +10.4 ± 1.5‰, 1σ) are slightly higher than those of individuals from Hemmaberg/Gora svete Heme (mean: +8.8 ± 1.1‰,1σ). The δ34S values were only obtained on the individuals from Oberleiserberg, and show a mean value of -0.9 ± 2.0 ‰ (1σ). Beyond the isotopic data presented in this article, we lay the foundations for cooperation between the IsoArcH database (https://isoarch.eu) [1] and the THANADOS (https://thanados.net) [2] project. While IsoArcH primarily stores isotope-related datasets for bioarchaeology, THANADOS stores data on archaeologically and anthropologically researched burials. Moving forward, IsoArcH and THANADOS plan to work closely together to integrate their databases. This collaboration presents a promising opportunity for both projects to pool their resources and knowledge, offering a wealth of information for researchers and the general public who are interested in anthropology and archaeology.

County-level Factors and Treatment Access Among Insured Women With Opioid Use Disorder.

BACKGROUND: An over 40% increase in overdose deaths within the past 2 years and low levels of engagement in treatment call for a better understanding of factors that influence access to medication for opioid use disorder (OUD). OBJECTIVE: To examine whether county-level characteristics influence a caller's ability to secure an appointment with an OUD treatment practitioner, either a buprenorphine-waivered prescriber or an opioid treatment program (OTP). RESEARCH DESIGN AND SUBJECTS: We leveraged data from a randomized field experiment comprised of simulated pregnant and nonpregnant women of reproductive age seeking treatment for OUD among 10 states in the US. We employed a mixed-effects logistic regression model with random intercepts for counties to examine the relationship between appointments received and salient county-level factors related to OUD. MEASURES: Our primary outcome was the caller's ability to secure an appointment with an OUD treatment practitioner. County-level predictor variables included socioeconomic disadvantage rankings, rurality, and OUD treatment/practitioner density. RESULTS: Our sample comprised 3956 reproductive-aged callers; 86% reached a buprenorphine-waivered prescriber and 14% an OTP. We found that 1 additional OTP per 100,000 population was associated with an increase (OR=1.36, 95% CI: 1.08 to 1.71) in the likelihood that a nonpregnant caller receives an OUD treatment appointment from any practitioner. CONCLUSIONS: When OTPs are highly concentrated within a county, women of reproductive age with OUD have an easier time securing an appointment with any practitioner. This finding may suggest greater practitioners' comfort in prescribing when there are robust OUD specialty safety nets in the county.

A Deep Learning Framework to Estimate Elastic Modulus from Ultrasound Measured Displacement Fields.

Ultrasound (US) elastography is a technique that enables non-invasive quantification of material properties, such as stiffness, from ultrasound images of deforming tissue. The displacement field is measured from the US images using image matching algorithms, and then a parameter, often the elastic modulus, is inferred or subsequently measured to identify potential tissue pathologies, such as cancerous tissues. Several traditional inverse problem approaches, loosely grouped as either direct or iterative, have been explored to estimate the elastic modulus. Nevertheless, the iterative techniques are typically slow and computationally intensive, while the direct techniques, although more computationally efficient, are very sensitive to measurement noise and require the full displacement field data (i.e., both vector components). In this work, we propose a deep learning approach to solve the inverse problem and recover the spatial distribution of the elastic modulus from one component of the US measured displacement field. The neural network used here is trained using only simulated data obtained via a forward finite element (FE) model with known variations in the modulus field, thus avoiding the reliance on large measurement data sets that may be challenging to acquire. A U-net based neural network is then used to predict the modulus distribution (i.e., solve the inverse problem) using the simulated forward data as input. We quantitatively evaluated our trained model with a simulated test dataset and observed a 0.0018 mean squared error (MSE) and a 1.14% mean absolute percent error (MAPE) between the reconstructed and ground truth elastic modulus. Moreover, we also qualitatively compared the output of our U-net model to experimentally measured displacement data acquired using a US elastography tissue-mimicking calibration phantom.

Prevalence of Buprenorphine Providers Requiring Cash Payment From Insured Women Seeking Opioid Use Disorder Treatment.

CONTEXT: Medications for opioid use disorder (OUD) are known to be effective, especially in reducing the risk of overdose death. Yet, many individuals suffering from OUD are not receiving treatment. One potential barrier can be the patient's ability to access providers through their insurance plans. DATA AND METHODS: We used an audit (simulated patient) study methodology to examine appointment-granting behavior by buprenorphine prescribers in 10 different US states. Trained callers posed as women with OUD and were randomly assigned Medicaid or private insurance status. Callers request an OUD treatment appointment and then asked whether they would be able to use their insurance to cover the cost of care, or alternatively, whether they would be required to pay fully out-of-pocket. FINDINGS: We found that Medicaid and privately insured women were often asked to pay cash for OUD treatment--40% of the time over the full study sample. Such buprenorphine provider requests happened more than 60% of the time in some states. Areas with more providers or with more generous provider payments were not obviously more willing to accept the patient's insurance benefits for OUD treatment. Rural providers were less likely to require payment in cash in order for the woman to receive care. CONCLUSIONS: State-to-state variation was the most striking pattern in our field experiment data. The wide variation suggests that women of reproductive age with OUD in certain states face even greater challenges to treatment access than perhaps previously thought; however, it also reveals that some states have found ways to curtail this problem. Our findings encourage greater attention to this public health challenge and possibly opportunities for shared learning across states.

Retail Health Clinic Growth as a Potential Primary Care Disruptor.

Retail health clinics (RHCs) have been described as a disruptive model of care delivery. We describe RHC market presence in the United States from 2008 to 2016 with a focus on the characteristics of counties where new clinics open. We merge national data on RHC openings and closings from Merchant Medicine with the Area Health Resources File. We examined county-level counts and ownership of RHCs over time. From 2008 to 2016, we found increasing ownership of RHCs by retail pharmacies, and, contrary to earlier predictions, RHCs continue to be located in affluent counties and did not open in underserved or provider shortage areas. Most new clinics opened in counties where RHCs already had a presence, and these counties also had greater primary care physician, nurse practitioner, and physician assistant density per capita (100,000). As RHCs expand and offer more services, they may place new competitive pressures on nearby primary care providers and practices.

Back to the future: The advantage of studying key events in human evolution using a new high resolution radiocarbon method.

Radiocarbon dating is the most widely applied dating method in archaeology, especially in human evolution studies, where it is used to determine the chronology of key events, such as the replacement of Neanderthals by modern humans in Europe. However, the method does not always provide precise and accurate enough ages to understand the important processes of human evolution. Here we review the newest method developments in radiocarbon dating ('Radiocarbon 3.0'), which can lead us to much better chronologies and understanding of the major events in recent human evolution. As an example, we apply these new methods to discuss the dating of the important Palaeolithic site of Bacho Kiro (Bulgaria).

Physician patient sharing relationships within insurance plan networks.

OBJECTIVE: To quantify shared patient relationships between primary care physicians (PCPs) and cardiologists and oncologists and the degree to which those relationships were captured within insurance networks. DATA SOURCES: Secondary analysis of Vericred data on physician networks, CareSet data on physicians' shared Medicare patients, and insurance plan attributes from Health Insurance Compare. Data validation exercises used data from Physician Compare and IQVIA. STUDY DESIGN: Cross-sectional study of the PCP-to-specialist in-network shared patient percentage (primary outcome). We also categorized networks by insurance market segment (Medicare Advantage [MA], Medicaid managed care, small-group or individually purchased), insurance plan type, and network breadth. DATA EXTRACTION: We analyzed data on 219,982 PCPs, 29,400 cardiologists, and 22,745 oncologists who, in 2021, accepted MA (n = 941 networks), Medicaid managed care (n = 293), and individually-purchased (n = 332) and small-group (n = 501) plans. PRINCIPAL FINDINGS: Networks captured, on average, 64.6% of PCP-cardiology shared patient ties, and 61.8% of PCP-oncologist ties. Less than half of in-network ties (44.5% and 38.9%, respectively) were among physicians with a common organizational affiliation. After adjustment for network breadth, we found no evidence of differences in the shared patient percentage across insurance market segments or networks of different types (p-value >0.05 for all comparisons). An exception was among national versus local and regional networks, where we found that national plans captured fewer shared patient ties, particularly among the narrowest networks (58.4% for national networksvs. 64.7% for local and regional networks for PCP-cardiology). CONCLUSIONS: Given recent trends toward narrower networks, our findings underscore the importance of incorporating additional and nuanced measures of network composition to aid plan selection (for patients) and to guide regulatory oversight.

Three-year results from phase I of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia.

Here we present the 3-year results of ZUMA-4, a phase I/II multicenter study evaluating the safety and efficacy of KTEX19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Phase I explored two dose levels and formulations. The primary endpoint was the incidence of dose-limiting toxicities. Thirty-one patients were enrolled; KTE-X19 was administered to 24 patients (median age 13.5 years, range 3-20; median follow-up 36.1 months). No dose-limiting toxicities were observed. All treated patients had grade ≥3 adverse events, commonly hypotension (50%) and anemia (42%). Grade 3 cytokine release syndrome rates were 33% in all treated patients, 75% in patients given the dose of 2×106 CAR T cells/kg, 27% in patients given the dose of 1×106 cells/kg in the 68 mL formulation, and 22% in patients given the dose of 1×106 cells/kg in the 40 mL formulation; the percentages of patients experiencing grade ≥3 neurologic events were 21%, 25%, 27%, and 11% respectively. Overall complete remission rates (including complete remission with incomplete hematologic recovery) were 67% in all treated patients, 75% in patients given 2×106 CAR T cells/kg, 64% in patients given 1×106 cells/kg in the 68 mL formulation, and 67% in patients given 1×106 cells/kg in the 40 mL formulation. Overall minimal residual diseasenegativity rates were 100% among responders; 88% of responders underwent subsequent allogeneic stem-cell transplantation. In the 1×106 (40 mL) group (recommended phase II dose), the median duration of remission censored at allogeneic stem-cell transplantation and median overall survival were not reached. Pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia achieved high minimal residual disease-negative remission rates with a manageable safety profile after a single dose of KTE-X19. Phase II of the study is ongoing at the dose of 1×106 CAR T cells/kg in the 40 mL formulation. ClinicalTrials.gov: NCT02625480.

"The Perception of Visiting Holocaust Sites on Undergraduate Students Learning Process".

This paper presents the main findings of a qualitative research project. The aim of the research was to explore undergraduate students' perceived knowledge acquisition and awareness of the Holocaust, after visiting Auschwitz concentration camp in Poland. The qualitative study (focus groups & semi-structured questionnaires) involved three cohorts of students and lecturers from a university in the North West of England. The participants visited the Holocaust-related sites in Poland from 2016 to 2019. Findings indicate that students' who actively engaged in visits to Holocaust related sites developed knowledge and awareness of the Holocaust. For many participants, this knowledge and awareness was facilitated via a reflective process that enabled empathic connection between these historical events and the students. The study also highlighted practical strategies that could be implemented to enhance the experience for future cohorts of undergraduate students visiting holocaust related sites. By adding to the limited literature on Holocaust education with undergraduate students, the study highlighted the importance and directions for future research in this area to inform future pedagogic practice.

Changes in intraoperative aortic strain as detected by ultrasound elastography in patients following abdominal endovascular aneurysm repair.

Objective: Predicting success after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) relies on measurements of aneurysm sac regression. However, in the absence of regression, morphometric analysis alone is insufficient to reliably predict the successful remodeling of AAAs after EVAR. Biomechanical parameters, such as pressure-normalized principal strain, might provide useful information in the post-EVAR AAA assessment. Our objective was to assess the feasibility of our novel ultrasound elastography (USE) technique to detect changes in the aortic wall principal strain in patients who had undergone EVAR and determine the temporal nature of the biomechanical changes in the aorta. Methods: USE images were obtained from patients undergoing elective EVAR intraoperatively, immediately before and after endograft implantation, and at their 30-day follow-up. The maximal mean principal strain ( ε ρ + ¯ ) for each scan was assessed using our novel technique, which uses a finite element mesh to track the frame-to-frame displacements of the aortic wall over one cardiac cycle. The ε ρ + ¯ in the user-defined aortic wall was then divided by the pulse pressure at the time of the scan to produce a pressure-normalized strain measurement ( ε ρ + ¯ /PP), a surrogate for tissue stiffness. Paired t tests were used to compare the pre- and postoperative ε ρ + ¯ /PP and the postoperative and 30-day ε ρ + ¯ /PP. Patient 30-day sac regression and endoleak data were collected by a review of 30-day follow-up computed tomography scans. Results: USE analysis of the data from 12 patients demonstrated a significant reduction in aortic wall ε ρ + ¯ /PP (average, 0.191% ± 0.09%/kPa vs 0.087% ± 0.04%/kPa; P = .002) immediately after graft implantation, with a nonsignificant change in the ε ρ + ¯ /PP (0.091% ± 0.04%/kPa vs 0.102% ± 0.05%/kPa; P = .47) from postoperatively to 30-day follow-up. This represents an average 46.5% reduction after stent placement, with a nonsignificant 18.1% increase at 30-day follow-up. All the patients showed sac stability, except for two patients who had demonstrated 7.3-mm and 6.8-mm sac regressions. Conclusions: Our analysis has demonstrated that the presented USE technique is a feasible method for detecting significant reductions in aortic ε ρ + ¯ /PP intraoperatively after EVAR. We found that patients undergoing EVAR will experience large reductions in the ε ρ + ¯ /PP intraoperatively after graft implantation, with stabilization found at their 30-day follow-up. These preliminary data have shown that an intraoperative ε ρ + ¯ /PP reduction could be a promising correlate of post-EVAR aneurysm remodeling. Our results have also suggested that endograft design likely plays a large role in determining the aneurysm biomechanical changes immediately after implantation.

A Neandertal dietary conundrum: Insights provided by tooth enamel Zn isotopes from Gabasa, Spain.

The characterization of Neandertals' diets has mostly relied on nitrogen isotope analyses of bone and tooth collagen. However, few nitrogen isotope data have been recovered from bones or teeth from Iberia due to poor collagen preservation at Paleolithic sites in the region. Zinc isotopes have been shown to be a reliable method for reconstructing trophic levels in the absence of organic matter preservation. Here, we present the results of zinc (Zn), strontium (Sr), carbon (C), and oxygen (O) isotope and trace element ratio analysis measured in dental enamel on a Pleistocene food web in Gabasa, Spain, to characterize the diet and ecology of a Middle Paleolithic Neandertal individual. Based on the extremely low δ66Zn value observed in the Neandertal's tooth enamel, our results support the interpretation of Neandertals as carnivores as already suggested by δ15N isotope values of specimens from other regions. Further work could help identify if such isotopic peculiarities (lowest δ66Zn and highest δ15N of the food web) are due to a metabolic and/or dietary specificity of the Neandertals.

Finding Mycenaeans in Minoan Crete? Isotope and DNA analysis of human mobility in Bronze Age Crete.

We undertook a large-scale study of Neolithic and Bronze Age human mobility on Crete using biomolecular methods (isotope analysis, DNA), with a particular focus on sites dating to the Late Bronze Age ('Late Minoan') period. We measured the strontium and sulphur isotope values of animal remains from archaeological sites around the island of Crete to determine the local baseline values. We then measured the strontium and sulphur values of humans from Late Neolithic and Bronze Age sites. Our results indicate that most of the humans have sulphur and strontium isotope values consistent with being local to Crete, showing no evidence for a wide-scale movement of people from the Greek mainland or other areas away from Crete in these time periods. However, we found four individuals from the late Bronze Age (Late Minoan III) cemetery of Armenoi with sulphur isotope values not typically found in Crete and are instead consistent with an origin elsewhere. This cemetery at Armenoi also has one of only a few examples of the newly adopted Mycenaean Linear B script on Crete found outside of the palace sites, pointing to an influence (trade and possible migration) from the mainland, which may then be the place of origin of these four individuals. DNA (mtDNA) studies of eight Late Bronze Age individuals from Armenoi have results consistent with people living in Aegean region at this time and cannot be used to distinguish between individuals from Crete ('Minoans') and the Greek mainland ['Mycenaeans']).

Micro-punches versus micro-slices for serial sampling of human dentine: Striking a balance between improved temporal resolution and measuring additional isotope systems.

RATIONALE: The last decade has seen a dramatic increase in the application of serial sampling of human dentine in archaeology. Rapid development in the field has provided many improvements in the methodology, in terms of both time resolution as well as the ability to integrate more isotope systems in the analysis. This study provides a comparison of two common sampling approaches, allowing researchers to select the most suitable approach for addressing specific research questions. METHODS: Two common approaches for sequential sampling of human dentine (micro-punches and micro-slices) are compared in terms of viability and efficacy. Using archaeological deciduous second molars and permanent first molars, this study demonstrates how the two approaches capture aspects of the weaning process in different ways. In addition, different aspects related to the extraction protocols, such as the thickness of the central slide and the solubilisation step, are also evaluated. RESULTS: While both approaches show similar intra-tooth isotopic patterns, the micro-punches approach is preferable for research that requires a very fine temporal resolution, while the micro-slices approach is best for research where δ34 S values are needed, or when the samples are poorly preserved. In addition, the solubilisation step has a large effect on collagen yield, and, to a lesser extent, on isotopic compositions. Therefore, it is important to ensure that only samples that have undergone the same pre-treatment protocol are directly compared. CONCLUSIONS: We present the pros and cons of the two micro-sampling approaches and offer possible mitigation strategies to address some of the most important issues related to each approach.

Trading spaces: Medicare's regulatory spillovers on treatment setting for non-Medicare patients.

Medicare pricing is known to indirectly influence provider prices and care provision for non-Medicare patients; however, Medicare's regulatory externalities beyond fee-setting are less well understood. We study how physicians' outpatient surgery choices for non-Medicare patients responded to Medicare removing a ban on ambulatory surgery center (ASC) use for a specific procedure. Following the rule change, surgeons began reallocating both Medicare and commercially insured patients to ASCs. Specifically, physicians became 70% more likely to use ASCs for the policy-targeted procedure among their non-Medicare patients. These novel findings demonstrate that Medicare rulemaking affects physician behavior beyond the program's statutory scope.