Circulating pre-treatment T-cell receptor repertoire as a predictive biomarker in advanced or metastatic non-small-cell lung cancer patients treated with pembrolizumab alone or in combination with chemotherapy.

BACKGROUND: The circulating T-cell receptor (TCR) repertoire is a dynamic representation of overall immune responses in an individual. MATERIALS AND METHODS: We prospectively collected baseline blood from patients treated with first-line pembrolizumab monotherapy or in combination with chemotherapy. TCR repertoire metrics were correlated with clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and immune-related adverse events (irAEs). We built a logistic regression classifier by fitting all four TCR-ß repertoire metrics to the immune checkpoint inhibitor (ICI) CBR data. In the subsequent receiver operating characteristic (ROC) analysis of the resulting logistic regression model probabilities, the best cut-off value was selected to maximise sensitivity to predict CBR to ICI. RESULTS: We observed an association between reduced number of unique clones and CBR among patients treated with pembrolizumab monotherapy (cohort 1) [risk ratio = 2.86, 95% confidence interval (CI) 1.04-8.73, P = 0.039]. For patients treated with pembrolizumab plus chemotherapy (cohort 2), increased number of unique clones [hazard ratio (HR) = 2.96, 95% CI 1.28-6.88, P = 0.012] and Shannon diversity (HR = 2.73, 95% CI 1.08-6.87, P = 0.033), and reduced evenness (HR = 0.43, 95% CI 0.21-0.90, P = 0.025) and convergence (HR = 0.41, 95% CI 0.19-0.90, P = 0.027) were associated with improved PFS, while only an increased number of unique clones (HR = 4.62, 95% CI 1.52-14.02, P = 0.007) were associated with improved OS. Logistic regression models combining the TCR repertoire metrics improved the prediction of CBR (cohorts 1 and 2) and were strongly associated with PFS (cohort 1, HR = 0.38, 95% CI 0.19-0.78, P = 0.009) and OS (cohort 2, HR = 0.20, 95% CI 0.05-0.76, P < 0.0001). Reduced TCR conversion was associated with increased frequency of irAEs needing systemic steroid treatment. CONCLUSION: Combined pre-treatment circulating TCR metrics might serve as a predictive biomarker for clinical outcomes among patients with advanced non-small-cell lung cancer treated with pembrolizumab alone or in combination with chemotherapy.

Nitrogen Incorporation in Potassic and Micro- and Meso-Porous Minerals: Potential Biogeochemical Records and Targets for Mars Sampling.

We measured the N concentrations and isotopic compositions of 44 samples of terrestrial potassic and micro- and meso-porous minerals and a small number of whole-rocks to determine the extent to which N is incorporated and stored during weathering and low-temperature hydrothermal alteration in Mars surface/near-surface environments. The selection of these minerals and other materials was partly guided by the study of altered volcanic glass from Antarctica and Iceland, in which the incorporation of N as NH4+ in phyllosilicates is indicated by correlated concentrations of N and the LILEs (i.e., K, Ba, Rb, Cs), with scatter likely related to the presence of exchanged, occluded/trapped, or encapsulated organic/inorganic N occurring within structural cavities (e.g., in zeolites). The phyllosilicates, zeolites, and sulfates analyzed in this study contain between 0 and 99,120 ppm N and have δ15Nair values of -34‰ to +65‰. Most of these minerals, and the few siliceous hydrothermal deposits that were analyzed, have δ15N consistent with the incorporation of biologically processed N during low-temperature hydrothermal or weathering processes. Secondary ion mass spectrometry on altered hyaloclastites demonstrates the residency of N in smectites and zeolites, and silica. We suggest that geological materials known on Earth to incorporate and store N and known to be abundant at, or near, the surface of Mars should be considered targets for upcoming Mars sample return with the intent to identify any signs of ancient or modern life.

An update on oral cavity cancer: epidemiological trends, prevention strategies and novel approaches in diagnosis and prognosis.

In the UK, the incidence of oral cavity cancer continues to rise, with an increase of around 60% over the past 10 years. Many patients still present with advanced disease, often resulting in locoregional recurrence and poor outcomes, which has not changed significantly for over four decades. Changes in aetiology may also be emerging, given the decline of smoking in developed countries. Therefore, new methods to better target prevention, improve screening and detect recurrence are needed. High-throughput 'omics' technologies appear promising for future individual-level diagnosis and prognosis. However, given this is a relatively rare cancer with significant intra-tumour heterogeneity and variation in patient response, reliable biomarkers have been difficult to elucidate. From a public health perspective, implementing these novel technologies into current services would require substantial practical, financial and ethical considerations. This may be difficult to justify and implement at present, therefore focus remains on early detection using new patient-led follow-up strategies. This paper reviews the latest evidence on epidemiological trends in oral cavity cancer to help identify at risk groups, population-based approaches for prevention, in addition to potential cutting-edge approaches in the diagnosis and prognosis of this disease.

Average SAR prediction, validation, and evaluation for a compact MR scanner head-sized RF coil.

A recently developed compact 3 T (C3T) MRI scanner with high performance gradients [1, 2] has a dedicated radiofrequency (RF) transmit coil that exposes only the head, neck and a small portion of the upper body region during head-first scanning. Due to the unique coil geometry and patient positioning, the established SAR model used for a conventional whole-body scanner cannot be directly translated to the C3T. Here a specific absorption rate (SAR) estimation and validation framework was developed and used to implement a dedicated and accurate SAR prediction model for the C3T. Two different SAR prediction models for the C3T were defined and evaluated: one based on an anatomically derived exposed mass, and one using a fixed anatomical position located caudally to the RF coil to determine the exposed mass. After coil modeling and virtual human body simulation, the designed SAR prediction model was implemented on the C3T and verified with calorimetry and in vivo scan power monitoring. The fixed-demarcation exposed mass model was selected as appropriate exposed mass region to accurately estimate the SAR deposition in the patient on the C3T.

Variation in chemotherapy prescribing rates and mortality in early breast cancer over two decades: a national data linkage study.

BACKGROUND: Regional variation in clinical practice may identify differences in care, reveal inequity in access, and explain inequality in outcomes. The study aim was to measure geographical variation in Scotland for adjuvant chemotherapy use and mortality in early-stage breast cancer. PATIENTS AND METHODS: In this retrospective cohort study using population cancer registry-based data linkage, patients with surgically treated early breast cancer between 2001 and 2018 were identified from the Scottish Cancer Registry. Geographical regions considered were based on NHS Scotland organisational structure including 14 territorial Health Boards as well as three regional Cancer Networks. Regional variation in the proportion receiving chemotherapy, breast cancer mortality and all-cause mortality was investigated. Inter-regional comparisons of chemotherapy use were adjusted for differences in case mix using logistic regression. Comparison of breast cancer-specific mortality and all-cause mortality used regression with a parametric survival model. Time trends were assessed using moving average plots. RESULTS: Chemotherapy use ranged from 35% to 46% of patients across Health Boards without adjustment. Variation reduced between 2001 and 2018. Following adjustment for clinical case mix, variation between cancer networks was within 3 percentage points, but up to 10 percentage points from the national average in some Health Boards. Differences in breast cancer mortality and all-cause mortality between cancer networks were modest, with hazard ratios of between 0.933 (95% confidence interval 0.893-0.975) and 1.041 (1.002-1.082) compared with the national average. Survival improved over the time period studied. CONCLUSION: With adequate case mix adjustment, variation in adjuvant chemotherapy use for early breast cancer in Scotland is small, with a trend towards greater convergence in practice and improved mortality outcomes in more recent cohorts. This suggests very limited regional inequity in access and convergence of clinical practice towards risk-stratified treatment recommendations. Outliers require assessment to understand the reasons for variance.

Risk of missing colorectal cancer with a COVID-adapted diagnostic pathway using quantitative faecal immunochemical testing.

BACKGROUND: COVID-19 has brought an unprecedented challenge to healthcare services. The authors' COVID-adapted pathway for suspected bowel cancer combines two quantitative faecal immunochemical tests (qFITs) with a standard CT scan with oral preparation (CT mini-prep). The aim of this study was to estimate the degree of risk mitigation and residual risk of undiagnosed colorectal cancer. METHOD: Decision-tree models were developed using a combination of data from the COVID-adapted pathway (April-May 2020), a local audit of qFIT for symptomatic patients performed since 2018, relevant data (prevalence of colorectal cancer and sensitivity and specificity of diagnostic tools) obtained from literature and a local cancer data set, and expert opinion for any missing data. The considered diagnostic scenarios included: single qFIT; two qFITs; single qFIT and CT mini-prep; two qFITs and CT mini-prep (enriched pathway). These were compared to the standard diagnostic pathway (colonoscopy or CT virtual colonoscopy (CTVC)). RESULTS: The COVID-adapted pathway included 422 patients, whereas the audit of qFIT included more than 5000 patients. The risk of missing a colorectal cancer, if present, was estimated as high as 20.2 per cent with use of a single qFIT as a triage test. Using both a second qFIT and a CT mini-prep as add-on tests reduced the risk of missed cancer to 6.49 per cent. The trade-off was an increased rate of colonoscopy or CTVC, from 287 for a single qFIT to 418 for the double qFIT and CT mini-prep combination, per 1000 patients. CONCLUSION: Triage using qFIT alone could lead to a high rate of missed cancers. This may be reduced using CT mini-prep as an add-on test for triage to colonoscopy or CTVC.

Calibration of the WHO 5th IS for Blood Coagulation Factor IX, Concentrate and Ph. Eur. Human Coagulation Factor IX Concentrate Biological Reference Preparation Batch 3 and investigation of the suitability of an IS as potency standard for purified full-length recombinant FIX.

A joint World Health Organization (WHO) - European Directorate for the Quality of Medicines & HealthCare (EDQM) study was run to calibrate the WHO 5th International Standard (IS) for Blood Coagulation Factor IX (FIX), Concentrate, and European Pharmacopoeia (Ph. Eur.) Human Coagulation Factor IX concentrate Biological Reference Preparation (BRP) Batch 3. The suitability of the 4th IS as a potency standard for purified full-length recombinant FIX (rFIX) was also investigated. Forty-nine laboratories contributed data for the calibration of 2 plasma-derived FIX candidates, relative to the 4th IS, from clotting and chromogenic assays. The intra-laboratory variability was reasonably low; the inter-laboratory variation was lower for sample B (14/148) than for sample C (14/162). Although there were no discrepancies between clotting and chromogenic assays, a significantly lower potency was obtained for sample C with clotting assays when buffer rather than FIX-deficient plasma was used as pre-diluent. A significant assay discrepancy was observed with estimates for the 4th IS for Blood Coagulation Factors FII, VII, IX, X, Plasma against the 4th IS, resulting in a clotting to chromogenic activity ratio of 1.11. The study also investigated the comparability of the plasma-derived concentrate standard with the rFIX products and considered the establishment of an IS for rFIX. The 3 rFIX products currently licensed were represented in this study. Data from 49 laboratories for 2 rFIX candidates were received, with additional results for another full-length rFIX test sample returned by 6 laboratories. The intra-laboratory variability when the rFIX samples were assayed against the 4th IS was acceptably low. Although the full-length rFIX could be assayed against the plasma-derived 4th IS and provided statistically valid results, there were large discrepancies among the clotting assays using different APTT reagents. The inter-laboratory variability of the chromogenic assays was similarly high. There were also significant clotting and chromogenic assay discrepancies. The data from the present study indicate that a recombinant standard for rFIX products will minimise assay discrepancies and improve inter-laboratory agreement. However, they also underline that the value assignment of the 1st rFIX IS needs careful consideration. The Expert Committee on Biological Standardization (ECBS) of WHO was therefore not requested to consider the establishment of an IS for rFIX. In order to ensure continued harmonised standards, sample B (14/148) was established as the WHO 5th IS for Blood Coagulation Factor IX, Concentrate, and as Ph. Eur. Human Coagulation Factor IX, concentrate BRP Batch 3 with the functional activity of 10.5 IU/ampoule.

A meta-analysis comparing the diagnostic performance of abbreviated MRI and a full diagnostic protocol in breast cancer.

AIM: To undertake a meta-analysis of the diagnostic performance of abbreviated (ABB) magnetic resonance imaging (MRI) and full diagnostic protocol MRI (FDP-MRI) in breast cancer. MATERIALS AND METHODS: This meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guidelines. The PubMed and EMBASE databases were searched through August 2019 for studies comparing the diagnostic performance of ABB-MRI and FDP-MRI in the breast. Studies were reviewed by two authors independently according to eligibility and exclusion criteria and split into two subgroups (screening population studies and studies using cohorts enriched with known cancers) to avoid bias. Quality assessment and bias for diagnostic accuracy was determined with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The diagnostic accuracy for each subgroup was pooled using a bivariate random effects model and summary receiver operating characteristic (sROC) curves produced. Sensitivities and specificities were compared using a paired t-test. RESULTS: Five screening (62/2,588 cancers/patients) and eight enriched cohort (540/1,432 cancers/patients) studies were included in the meta-analysis. QUADAS-2 assessment showed a low risk of bias in most studies. The pooled sensitivity/specificity/area under the receiver operating characteristic curve (AUC) for screening studies was 0.90/0.92/0.94 for ABB-MRI and 0.92/0.95/0.97 for FDP-MRI. The pooled sensitivity/specificity/AUC for enriched cohort studies was 0.93/0.83/0.94 for ABB-MRI and 0.93/0.84/0.95 for FDP-MRI. There was no significant difference in sensitivity or specificity using ABB-MRI or FDP-MRI (p=0.18 and 0.27, p=0.18 and 0.93, respectively). CONCLUSION: The diagnostic performances of the ABB-MRI and FDP-MRI protocols used in either screening or enriched cohorts were comparable. There was a large variation in patient population, study methodology, and abbreviated protocols reported.

Stopping targeted therapy for complete responders in advanced BRAF mutant melanoma.

BRAF inhibitors revolutionised the management of melanoma patients and although resistance occurs, there is a subgroup of patients who maintain durable disease control. For those cases with durable complete response (CR) it is not clear whether it is safe to cease therapy. Here we identified 13 patients treated with BRAF +/- MEK inhibitors, who cease therapy after prolonged CR (median = 34 months, range 20-74). Recurrence was observed in 3/13 (23%) patients. In the remaining 10 patients with sustained CR off therapy, the median follow up after discontinuation was 19 months (range 8-36). We retrospectively measured ctDNA levels using droplet digital PCR (ddPCR) in longitudinal plasma samples. CtDNA levels were undetectable in 11/13 cases after cessation and remained undetectable in patients in CR (10/13). CtDNA eventually became detectable in 2/3 cases with disease recurrence, but remained undetectable in 1 patient with brain only progression. Our study suggests that consideration could be given to ceasing targeted therapy in the context of prolonged treatment, durable response and no evidence of residual disease as measured by ctDNA.

"There is a Place": impacts of managed alcohol programs for people experiencing severe alcohol dependence and homelessness.

BACKGROUND: The twin problems of severe alcohol dependence and homelessness are associated with precarious living and multiple acute, social and chronic harms. While much attention has been focused on harm reduction services for illicit drug use, there has been less attention to harm reduction for this group. Managed alcohol programs (MAPs) are harm reduction interventions that aim to reduce the harms of severe alcohol use, poverty and homelessness. MAPs typically provide accommodation, health and social supports alongside regularly administered sources of beverage alcohol to stabilize drinking patterns and replace use of non-beverage alcohol (NBA). METHODS: We examined impacts of MAPs in reducing harms and risks associated with substance use and homelessness. Using case study methodology, data were collected from five MAPs in five Canadian cities with each program constituting a case. In total, 53 program participants, 4 past participants and 50 program staff were interviewed. We used situational analysis to produce a series of "messy", "ordered" and "social arenas" maps that provide insight into the social worlds of participants and the impact of MAPs. RESULTS: Prior to entering a MAP, participants were often in a revolving world of cycling through multiple arenas (health, justice, housing and shelters) where abstinence from alcohol is often required in order to receive assistance. Residents described living in a street-based survival world characterized by criminalization, unmet health needs, stigma and unsafe spaces for drinking and a world punctuated by multiple losses and disconnections. MAPs disrupt these patterns by providing a harm reduction world in which obtaining accommodation and supports are not contingent on sobriety. MAPs represent a new arena that focuses on reducing harms through provision of safer spaces and supply of alcohol, with opportunities for reconnection with family and friends and for Indigenous participants, Indigenous traditions and cultures. Thus, MAPs are safer spaces but also potentially spaces for healing. CONCLUSIONS: In a landscape of limited alcohol harm reduction options, MAPs create a new arena for people experiencing severe alcohol dependence and homelessness. While MAPs reduce precarity for participants, programs themselves remain precarious due to ongoing challenges related to lack of understanding of alcohol harm reduction and insecure program funding.

Leaf:wood allometry and functional traits together explain substantial growth rate variation in rainforest trees.

Plant growth rates drive ecosystem productivity and are a central element of plant ecological strategies. For seedlings grown under controlled conditions, a large literature has firmly identified the functional traits that drive interspecific variation in growth rate. For adult plants, the corresponding knowledge is surprisingly poorly understood. Until recently it was widely assumed that the key trait drivers would be the same (e.g. specific leaf area, or SLA), but an increasing number of papers has demonstrated this not to be the case, or not generally so. New theory has provided a prospective basis for understanding these discrepancies. Here we quantified relationships between stem diameter growth rates and functional traits of adult woody plants for 41 species in an Australian tropical rainforest. From various cost-benefit considerations, core predictions included that: (i) photosynthetic rate would be positively related to growth rate; (ii) SLA would be unrelated to growth rate (unlike in seedlings where it is positively related to growth); (iii) wood density would be negatively related to growth rate; and (iv) leaf mass:sapwood mass ratio (LM:SM) in branches (analogous to a benefit:cost ratio) would be positively related to growth rate. All our predictions found support, particularly those for LM:SM and wood density; photosynthetic rate was more weakly related to stem diameter growth rates. Specific leaf area was convincingly correlated to growth rate, in fact negatively. Together, SLA, wood density and LM:SM accounted for 52 % of variation in growth rate among these 41 species, with each trait contributing roughly similar explanatory power. That low SLA species can achieve faster growth rates than high SLA species was an unexpected result but, as it turns out, not without precedent, and easily understood via cost-benefit theory that considers whole-plant allocation to different tissue types. Branch-scale leaf:sapwood ratio holds promise as an easily measurable variable that may help to understand growth rate variation. Using cost-benefit approaches teamed with combinations of leaf, wood and allometric variables may provide a path towards a more complete understanding of growth rates under field conditions.

Hypervelocity collision and water-rock interaction in space preserved in the Chelyabinsk ordinary chondrite.

A comprehensive geochemical study of the Chelyabinsk meteorite reveals further details regarding its history of impact-related fragmentation and melting, and later aqueous alteration, during its transit toward Earth. We support an ∼30 Ma age obtained by Ar-Ar method (Beard et al., 2014) for the impact-related melting, based on Rb-Sr isotope analyses of a melt domain. An irregularly shaped olivine with a distinct O isotope composition in a melt domain appears to be a fragment of a silicate-rich impactor. Hydrogen and Li concentrations and isotopic compositions, textures of Fe oxyhydroxides, and the presence of organic materials located in fractures, are together consistent with aqueous alteration, and this alteration could have pre-dated interaction with the Earth's atmosphere. As one model, we suggest that hypervelocity capture of the impact-related debris by a comet nucleus could have led to shock-wave-induced supercritical aqueous fluids dissolving the silicate, metallic, and organic matter, with later ice sublimation yielding a rocky rubble pile sampled by the meteorite.

A standardised protocol for the evaluation of small extracellular vesicles in plasma by imaging flow cytometry.

Flow cytometry provides robust, multi-parametric and quantitative information on single cells which also exhibits enormous potential as a tool for small particle characterisation. Small extracellular vesicle (sEV) detection by flow cytometry remains compromised due to the high prevalence of swarm detection, which is defined by the simultaneous illumination of more than one sEV, recorded as a single event. Detection of sEVs by imaging flow cytometry presents a major advantage by having the ability to resolve single particles from swarm detection based on the image features recorded for each event. In this study, we provide a simplified protocol that facilitates the removal of both swarm events and aggregated particles to improve the accuracy of sEV analysis. Our results indicate that imaging flow cytometry should be at the forefront as a robust and sensitive technique for sEV characterisation.

Joint Position Sense Testing in Young Children.

The standard physical examination evaluation for a proprioception abnormality depends upon the patient's ability to follow directions and respond to the examiner, a skill not yet developed in toddlers. This study demonstrates a new proprioception examination method that may allow for better localization of lesions and determines whether healthy toddlers would cooperate with this test. By placing stickers on children's hands, covering their eyes, and then moving their hands, the examiner can see whether the children reach for where their hands and stickers were previously located or to their new location, which serves as an indicator of proprioception ability. When tested on 12- to 36-month-old children without known neurologic issues, we found that older children were more cooperative during the test but that the ability to successfully find the sticker did not depend on age. We have optimized the test for efficient usage in a clinic setting and propose that this is a useful test that can be applied in children, with no change in confidence based on age. No children with known deficits in proprioception were tested, so sensitivity could not be assessed.

Improved White Matter Cerebrovascular Reactivity after Revascularization in Patients with Steno-Occlusive Disease.

BACKGROUND AND PURPOSE: One feature that patients with steno-occlusive cerebrovascular disease have in common is the presence of white matter (WM) lesions on MRI. The purpose of this study was to evaluate the effect of direct surgical revascularization on impaired WM cerebrovascular reactivity in patients with steno-occlusive disease. MATERIALS AND METHODS: We recruited 35 patients with steno-occlusive disease, Moyamoya disease (n = 24), Moyamoya syndrome (n = 3), atherosclerosis (n = 6), vasculitis (n = 1), and idiopathic stenosis (n = 1), who underwent unilateral brain revascularization using a direct superficial temporal artery-to-MCA bypass (19 women; mean age, 45.8 ± 16.5 years). WM cerebrovascular reactivity was measured preoperatively and postoperatively using blood oxygen level-dependent (BOLD) MR imaging during iso-oxic hypercapnic changes in end-tidal carbon dioxide and was expressed as %Δ BOLD MR signal intensity per millimeter end-tidal partial pressure of CO2. RESULTS: WM cerebrovascular reactivity significantly improved after direct unilateral superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass in the revascularized hemisphere in the MCA territory (mean ± SD, -0.0005 ± 0.053 to 0.053 ± 0.046 %BOLD/mm Hg; P < .0001) and in the anterior cerebral artery territory (mean, 0.0015 ± 0.059 to 0.021 ± 0.052 %BOLD/mm Hg; P = .005). There was no difference in WM cerebrovascular reactivity in the ipsilateral posterior cerebral artery territory nor in the vascular territories of the nonrevascularized hemisphere (P < .05). CONCLUSIONS: Cerebral revascularization surgery is an effective treatment for reversing preoperative cerebrovascular reactivity deficits in WM. In addition, direct-STA-MCA bypass may prevent recurrence of preoperative symptoms.

Melanoma circulating tumor cells: Benefits and challenges required for clinical application.

The implementation of novel therapeutic interventions has improved the survival rates of melanoma patients with metastatic disease. Nonetheless, only 33% of treated cases exhibit long term responses. Circulating tumor cell (CTC) measurements are currently of clinical value in breast, prostate and colorectal cancers. However, the clinical utility of melanoma CTCs (MelCTCs) is still unclear due to challenges that appear intrinsic to MelCTCs (i.e. rarity, heterogeneity) and a lack of standardization in their isolation, across research laboratories. Here, we review the latest developments, pinpoint the challenges in MelCTC isolation and address their potential role in melanoma management.

The effect of increasing the sulfation level of chondroitin sulfate on anticoagulant specific activity and activation of the kinin system.

Oversulfated chondroitin sulfate (OSCS) was identified as a contaminant in certain heparin preparations as the cause of adverse reactions in patients. OSCS was found to possess both plasma anticoagulant activity and the ability to activate prekallikrein to kallikrein. Differentially sulfated chondroitin sulfates were prepared by synthetic modification of chondroitin sulfate and were compared to the activity of OSCS purified from contaminated heparin. Whilst chondroitin sulfate was found to have minimal anticoagulant activity, increasing sulfation levels produced an anticoagulant response which we directly show for the first time is mediated through heparin cofactor II. However, the tetra-sulfated preparations did not possess any higher anticoagulant activity than several tri-sulfated variants, and also had lower heparin cofactor II mediated activity. Activation of prekallikrein was concentration dependent for all samples, and broadly increased with the degree of sulfation, though the di-sulfated preparation was able to form more kallikrein than some of the tri-sulfated preparations. The ability of the samples to activate the kinin system, as measured by bradykinin, was observed to be through kallikrein generation. These results show that whilst an increase in sulfation of chondroitin sulfate did cause an increase in anticoagulant activity and activation of the kinin system, there may be subtler structural interactions other than sulfation at play given the different responses observed.

Racial Differences in Eating Patterns and Food Purchasing Behaviors among Urban Older Women.

OBJECTIVE: To examine differences in diet and food purchasing behaviors between Black and White older women living in urban neighborhoods. DESIGN: Cross-sectional observational study. SETTING: Urban neighborhoods in Washington, DC, USA. PARTICIPANTS: Community-dwelling White and Black women of age 65 and older. MEASUREMENTS: Participants were queried on diet via 24-hour recalls, food purchasing habits, their use of neighborhood resources and local travel patterns. Frequency and location of self-reported food purchasing and consumption were compared by race. RESULTS: In 2014 and 2015, 49 White and 44 Black older women were enrolled in the study. Compared to Whites, Blacks reported lower daily caloric intake (mean (SD) 1314 (404) vs. 1529 (448), p=0.02), with a higher percent of calories from protein and fat 1.8 (7.0), p=0.03), and a slightly higher polyunsaturated to saturated fat ratio (p=0.05). Blacks had substantially lower alternate healthy eating index (AHEI) (33.5 (10.2) vs. 43.9 (10.8) of 80 possible points, p<0.001), daily intake (grams) of total fiber (15.3 (8.1) vs. 22.9 (8.5), p<0.001), insoluble fiber (10.8 (6.9) vs. 15.9 (6.5), p<0.001), and soluble fiber (4.5 (2.0) vs. 6.9 (2.8), p<0.001). Blacks had lower intake of micronutrients, alcohol and caffeine. Blacks shopped for groceries less often (4.4 (3.0) vs. 6.2 (3.0) monthly; p=0.006) and spent a longer time traveling to stores (15.8 (9.1) vs. 11.5 (7.2) minutes per trip, p=0.02). A lower percent of Blacks walked to stores (14% vs. 40%, p=0.003) and a higher percent of Blacks rode in a car with someone else (33% vs. 6%, p<0.001). CONCLUSIONS: In an urban setting, food consumption and purchasing behaviors differed substantially between older Black and White women, which should be further investigated and considered to promote healthy eating in older populations.

Racial Differences in Misclassification of Healthy Eating Based on Food Frequency Questionnaire and 24-Hour Dietary Recalls.

OBJECTIVES: To examine the agreement in nutrient intake and alternate healthy eating indices (AHEI) between a self-administered Food Frequency Questionnaire (FFQ) and 24-hour recall (24HR) measurements of diet by race, among urban older women. DESIGN: Cross-sectional observational study. SETTING: Urban neighborhoods in Washington, DC, USA. PARTICIPANTS: Community-dwelling White and Black women aged 65 and older. MEASUREMENTS: In 2014 and 2015, 49 White and 44 Black older women were queried on diet using both FFQ and 24-hour recalls. The correlation coefficients of 55 nutrient intake measures and agreements on healthy eating classification between the two instruments were compared overall and by race. RESULTS: The mean correlation coefficient (rho) was 0.46 for Whites and 0.23 for Blacks. For 47 measures, rho was lower for Blacks. Whites had a strong correlation of ≥0.5 for 28 items, while Blacks had strong correlations for only 3 items. Based on FFQ, the mean (SD) of AHEI were 54.0 (10.3) for Whites and 45.9 (8.8) for Blacks (p<0.001). Based on 24HR, the mean (SD) were 43.9 (10.8) for Whites and 33.2 (9.6) for Blacks (p<0.001). Using 32 as the cutoff (40% of maximum AHEI score), 50% of Blacks and 14% of Whites were classified as eating unhealthy based on the 24HR, versus 2.6% and 0% based on the FFQ. CONCLUSION: The FFQ has limited ability to accurately assess nutrient intake among older Black women, and tends to underestimate racial differences in healthy eating. The FFQ should be further improved for use in racial disparities research of healthy eating in older age, using a larger sample of older women with racial and geographic diversities.

Gender and Age Differences in Levels, Types and Locations of Physical Activity among Older Adults Living in Car-Dependent Neighborhoods.

BACKGROUND: A thorough understanding of gender differences in physical activity is critical to effective promotion of active living in older adults. OBJECTIVES: To examine gender and age differences in levels, types and locations of physical activity. DESIGN: Cross-sectional observation. SETTING: Car-dependent urban and rural neighborhoods in Worcester County, Massachusetts, USA. PARTICIPANTS: 111 men and 103 women aged 65 years and older. MEASUREMENTS: From 2012 to 2014, participants were queried on type, frequency and location of physical activity. Participants wore an accelerometer for 7 consecutive days. RESULTS: Compared to women, men had a higher mean daily step count (mean (SD) 4385 (2122) men vs. 3671(1723) women, p=0.008). Men reported higher frequencies of any physical activity and moderate-to-vigorous physical activity, and a lower frequency of physical activity inside the home. Mean daily step counts and frequency of physical activity outside the home decreased progressively with age for both men and women. Women had a sharper decline in frequencies of self-reported physical activity. Men had a significant decrease in utilitarian walking, which women did not (p=0.07). Among participants who reported participation in any physical activity (n=190), more women indicated exercising indoors more often (59% vs. 44%, p=0.04). The three most commonly cited locations for physical activity away from home for both genders were streets or sidewalks, shopping malls, and membership-only facilities (e.g., YMCA or YWCA). The most common types of physical activity, performed at least once in a typical month, with over 40% of both genders reporting, included light housework, brisk walking, leisurely walking, and stretching. CONCLUSION: Levels, types and location preferences of physical activity differed substantially by gender. Levels of physical activity decreased progressively with age, with greater decline among women. Consideration of these gender differences is necessary to improve the effectiveness of active living promotion programs among older adults.