Assessment of TUFT1 and Rac1-GTP levels in triple-negative breast cancer patients: clinical and pathological correlations.

OBJECTIVE: The primary goal of this study was to investigate the expressions of TUFT1 (Tuftelin) and Rac1-GTP in the cancerous tissues of individuals with triple-negative breast cancer (TNBC). Additionally, we aimed to explore the correlation between TUFT1 and Rac1-GTP expressions and examine the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients. METHODS: Ninety-six patients diagnosed with TNBC, scheduled for surgery between May 2022 and November 2022, were enrolled in this study. Cancerous tissue specimens were collected from these patients, and immunohistochemistry was employed to evaluate the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues. Subsequent to data collection, a comprehensive analysis was conducted to examine the correlation between TUFT1 and Rac1-GTP expressions. Furthermore, we sought to assess the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients. RESULTS: The TUFT1 protein was expressed in both the membrane and cytoplasm of TNBC cancer cells, with notably higher expression observed in the cytoplasm. Rac1-GTP was primarily expressed in the cytoplasm. There was a positive correlation between the levels of TUFT1 and Rac1-GTP expressions (χ2 = 9.816, P < 0.05). The levels of TUFT1 and Rac1-GTP protein expressions showed no correlation with patient age (χ2 = 2.590, 2.565, P > 0.05); however, they demonstrated a positive correlation with tumor size (χ2 = 5.592,5.118), histological grading (χ2 = 6.730, 5.443), and lymph node metastasis (χ2 = 8.221, 5.180) (all with a significance level of P < 0.05). CONCLUSION: A significant correlation was identified between the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues of patients with TNBC, suggesting a close association with the progression of TNBC. The two molecules play significant roles in facilitating an early diagnosis and treatment of TNBC.

A Low-Cost, Sensitive Reporter System Using Membrane-Tethered Horseradish Peroxidase for Efficient Gene Expression Analysis.

Reporter gene assays are essential for high-throughput analysis, such as drug screening or determining downstream signaling activation/inhibition. However, use of this technology has been hampered by the high cost of the substrate (e.g., d-Luciferin (d-Luc)) in the most common firefly luciferase (FLuc) reporter gene assay. Although alternate luciferase is available worldwide, its substrate has remained expensive, and a more affordable option is still in demand. Here, we present a membrane-tethered horseradish peroxidase (mHRP), a new reporter system composed of a cell membrane expressing HRP that can preserve its enzymatic function on the cell surface, facilitates contact with HRP substrates (e.g., ABTS and TMB), and avoids the cell lysis process and the use of the high-priced luciferase substrate. An evaluation of the light signal sensitivity of mHRP compared to FLuc showed that both had comparable signal sensitivity. We also identified an extended substrate half-life of more than 5-fold that of d-Luc. Of note, this strategy provided a more stable detection signal, and the cell lysis process is not mandatory. Furthermore, with this strategy, we decreased the total amount of time taken for analysis and increased the time of detection limit of the reporter assay. Pricing analysis showed a one-third to one twenty-eighth price drop per single test of reporter assay. Given the convenience and stability of the mHRP reporter system, we believe that our strategy is suitable for use as an alternative to the luciferase reporter assay.

Home-Based Walking Exercise and Supervised Treadmill Exercise in Patients With Peripheral Artery Disease: An Individual Participant Data Meta-Analysis.

Importance: Few people with lower extremity peripheral artery disease (PAD) participate in supervised treadmill exercise covered by the Center for Medicare and Medicaid Services. In people with PAD, the benefits of home-based walking exercise, relative to supervised exercise, remain unclear. Objective: To study whether home-based walking exercise improves 6-minute walk (6MW) more than supervised treadmill exercise in people with PAD (defined as Ankle Brachial Index ≤0.90). Data Sources: Data were combined from 5 randomized clinical trials of exercise therapy for PAD using individual participant data meta-analyses, published from 2009 to 2022. Study Selection: Of the 5 clinical trials, 3 clinical trials compared supervised treadmill exercise to nonexercise control (N = 370) and 2 clinical trials compared an effective home-based walking exercise intervention to nonexercise control (N = 349). Data Extraction and Synthesis: Individual participant-level data from 5 randomized clinical trials led by 1 investigative team were combined. The 5 randomized clinical trials included 3 clinical trials of supervised treadmill exercise and 2 effective home-based walking exercise interventions. Main Outcomes and Measures: Change in 6MW distance, maximum treadmill walking distance, and Walking Impairment Questionnaire at 6-month follow-up. The supervised treadmill exercise intervention consisted of treadmill exercise in the presence of an exercise physiologist, conducted 3 days weekly for up to 50 minutes per session. Home-based walking exercise consisted of a behavioral intervention in which a coach helped participants walk for exercise in or around home for up to 5 days per week for 50 minutes per session. Results: A total of 719 participants with PAD (mean [SD] age, 68.8 [9.5] years; 46.5% female) were included (349 in a home-based exercise clinical trial and 370 in a supervised exercise trial). Compared with nonexercise control, supervised treadmill exercise was associated with significantly improved 6MW by 32.9 m (95% CI, 20.6-45.6; P < .001) and home-based walking exercise was associated with significantly improved 6MW by 50.7 m (95% CI, 34.8-66.7; P < .001). Compared with supervised treadmill exercise, home-based walking exercise was associated with significantly greater improvement in 6MW distance (between-group difference: 23.8 m [95% CI, 3.6, 44.0; P = .02]) but significantly less improvement in maximum treadmill walking distance (between-group difference:-132.5 m [95% CI, -192.9 to -72.1; P < .001]). Conclusions and Relevance: In this individual participant data meta-analyses, compared with supervised exercise, home-based walking exercise was associated with greater improvement in 6MW in people with PAD. These findings support home-based walking exercise as a first-line therapy for walking limitations in PAD.

A frequentist approach to dynamic borrowing.

There has been growing interest in leveraging external control data to augment a randomized control group data in clinical trials and enable more informative decision making. In recent years, the quality and availability of real-world data have improved steadily as external controls. However, information borrowing by directly pooling such external controls with randomized controls may lead to biased estimates of the treatment effect. Dynamic borrowing methods under the Bayesian framework have been proposed to better control the false positive error. However, the numerical computation and, especially, parameter tuning, of those Bayesian dynamic borrowing methods remain a challenge in practice. In this paper, we present a frequentist interpretation of a Bayesian commensurate prior borrowing approach and describe intrinsic challenges associated with this method from the perspective of optimization. Motivated by this observation, we propose a new dynamic borrowing approach using adaptive lasso. The treatment effect estimate derived from this method follows a known asymptotic distribution, which can be used to construct confidence intervals and conduct hypothesis tests. The finite sample performance of the method is evaluated through extensive Monte Carlo simulations under different settings. We observed highly competitive performance of adaptive lasso compared to Bayesian approaches. Methods for selecting tuning parameters are also thoroughly discussed based on results from numerical studies and an illustration example.

Assessment of Median and Mean Survival Time in Cancer Clinical Trials.

This cohort study assesses the relative stability of median and mean survival time estimates reported in cancer clinical trials.

Barriers to participation in supervised exercise therapy reported by people with peripheral artery disease.

OBJECTIVE: This study identified barriers to participation in supervised exercise therapy covered by the Centers for Medicare and Medicaid Services (CMS), reported by people with lower extremity peripheral artery disease (PAD). METHODS: People with PAD participating in research studies of walking impairment due to PAD in the Chicagoland area were asked to complete a questionnaire between March 15, 2019, and July 12, 2022, assessing their experience and attitudes about supervised exercise therapy. Participants were identified using mailed postcards to people aged 50 and older in Chicagoland, from medical centers in Chicago, and using bus and train advertisements. The questionnaire was developed based on focus group feedback from people with PAD. RESULTS: Of 516 participants with PAD approached, 489 (94.8%) completed the questionnaire (mean age: 71.0 years [standard deviation: 8.7], mean ankle-brachial index: 0.71 [standard deviation: 0.25]; 204 [41.7%] women and 261 [53.4%] Black). Of the 489 participants, 416 (85.1%) reported that their physician had never prescribed or recommended supervised exercise therapy. Overall, 357 (73.2%) reported willingness to travel three times weekly to the medical center for supervised exercise participation. However, of these, 214 (59.9%) reported that they were unwilling or unable to pay the $11 per exercise session copay required for supervised exercise covered by CMS. Of 51 people with PAD who reported prior participation in supervised exercise, only 5 (9.8%) completed the 12 weeks of supervised exercise therapy covered by CMS and 29 (56.9%) completed 6 or fewer weeks. Of 131 (26.8%) unwilling to travel three times weekly to a center for supervised exercise, the most common reasons for unwillingness to participate were "too time-consuming" (55.0%), "too inconvenient" (45.8%), and "lack of interest in treadmill exercise" (28.2%). CONCLUSIONS: Approximately 2 to 4 years after CMS began covering supervised exercise for PAD, most people with PAD in this study from a large urban area had not participated in supervised exercise therapy. Of those who participated, most completed fewer than half of the sessions covered by CMS. The required CMS copayment was a common barrier to supervised exercise participation by people with PAD.

Factors that influence beef meat production in Tanzania. A Cobb-Douglas production function estimation approach.

Beef meat production is the key to reducing poverty, achieving food security and nutrition, promoting exports, economic growth, and industrialization. Despite a large number of beef cattle, Tanzania continues to import beef meat and its contribution to GDP is low. Thus, this study used time-series panel data to analyze the beef meat industry in Tanzania from 1990 to 2019, with a particular focus on identifying the reasons and direction of the correlation between beef meat output and its determinants in the production processes. The study applied both descriptive statistics and the Cobb-Douglas production function model, using the Ordinary Least Squares (OLS) based estimator to analyze the data. Descriptive analyses revealed that Tanzania's beef meat production increased by 283,871 tons (59.3%-a positive trend) between 1990 and 2019. This increase was accompanied by approximately 29.75%, 53.05%, and 42.42% increases in beef cattle yield (carcass weight (hg) per head, beef cattle inventory, and the number of beef cattle slaughtered, respectively). However, the analysis further revealed that a 2.8% decrease in beef cattle extraction (low harvesting) rate due to low market participation, continues to be a critical barrier to increasing beef meat production in Tanzania. Furthermore, econometric estimates showed that the key factors that positively influenced beef meat output at a 5% significance level (P < 0.05) included beef cattle population (inventory), beef cattle yield (carcass weight (kg) per head, and the number of beef cattle slaughtered, with elasticity coefficients of 0.146, 0.469, and 0.564, respectively). While the number of beef cattle exported positively influenced beef meat production at the 10% significance level (P < 0.1) with an elasticity coefficient of 0.028. Surprisingly, invested credit to agriculture (farm credits) and imported pure-bred beef cattle had a negative impact on beef meat output but were statistically insignificant at P < 0.05. The results of this study have implications as to what factors need to be addressed to further improve beef meat production, thereby reducing its reliance on imports. We suggest that the Tanzania government and policymakers need to establish balanced policies for beef farmers and appropriately manage them so that beef meat development can be induced, contributing to poverty reduction, food security, and economic development.

Towards developing a beef meat export oriented policy in Tanzania: -Exploring the factors that influence beef meat exports.

The purpose of this study was to investigate the factors that influence beef meat exports in Tanzania, with a particular focus on the years 1985 to 2020, in enhancing the development of beef meat export-oriented policy in Tanzania, thereby enhancing beef exports in Tanzania. A time-series panel dataset was analyzed using both descriptive statistics and ordinary least squares (OLS) linear regression analyses models. As per the descriptive analyses, beef meat exports reached the highest pick of 4,300 tons per year in 1990, whereas from 1991 to date, beef meat exportation in Tanzania has been in declining trends despite an increase in beef meat output and trade openness from 162,500 to 486,736 tons and 7.6 to 98.7%, respectively. Nevertheless, while the prospect of Tanzanian beef meat exports appears bright and promising, the industry will continue to encounter trade barriers and must stay competitive to produce enough volume and quality beef meat to meet the needs of its existing and expanding markets. This is because, Tanzanian beef meat competes for market share with beef meat from other countries in the global markets, where customers pay a premium for lines of beef meat that meet quality standards while discarding those that do not. This indicates that the quantity of beef meat produced has no relevance to its world market share, but its quality standards do. Furthermore, the econometric results revealed that the coefficients of the terms of trade, Tanzania GDP per capita, global beef meat consumption, trade openness, and beef meat outputs were found to be significantly positive (P < 0.05) influencing beef meat exports in Tanzania, whereas the trading partners' GDP per capita and exchange rate were not. The findings have varying implications as to what factors need to be addressed to further improve beef meat exports. From the farmer's perspective, better access to adequate funds as a result of increased income benefit from export will assist in improving beef cattle productivity and quality to compete effectively in the global markets. From the government's perspective, because trade openness promotes economic growth through export benefits, the Tanzania government and policymakers need to establish balanced policies to strengthen bilateral trade relationships to generate more opportunities in global markets.

Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh, India: A community-based, cluster randomized, open-label controlled trial.

BACKGROUND: Hospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings. METHODS AND FINDINGS: This was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation. CONCLUSIONS: In this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility-community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function. TRIAL REGISTRATION: ISRCTN Registry ISRCTN38965585 and Clinical Trials Registry-India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.

Estimation of municipal solid waste amount based on one-dimension convolutional neural network and long short-term memory with attention mechanism model: A case study of Shanghai.

Municipal solid waste (MSW) amount has direct influence on MSW management, policy-decision making, and MSW treatment methods. Machine learning has great potential for prediction, but few studies apply the approaches of deep learning to forecast the quantity of MSW. Therefore, the aim of this study is to evaluate the feasibility and practicability of employing the methods of supervised learning, including Attention, one-dimension Convolutional Neural Network (1D-CNN) and Long Short-Term Memory (LSTM) to predict the MSW Amount in Shanghai. Integrated 1D-CNN and LSTM with Attention model, the new structure model (1D-CNN-LSTM-Attention, 1D-CLA), is designed to forecast MSW amount. In addition, the influence of socioeconomic factors on MSW amount, the structure and layers distribution of Attention, 1D-CNN, LSTM and 1D-CLA are also discussed. The results indicate that the correlation coefficients of Attention, one-dimension CNN, LSTM, and proposed 1D-CLA model to predict the MSW in Shanghai are 78%, 86.6%, 90%, and 95.3%, respectively, suggesting the feasible and practicable. The values of 24, 0.01, 50 and 25 for the number of neurons, dropout, the value of epoch number and Batch size best fit 1D-CLA to predict the amount of MSW in Shanghai. Furthermore, the performance of 1D-CLA is better than any single model or two model's combination (R2 is 95.3%) and the mechanism of 1D-CLA is contributed by three former models following the order: LSTM>CNN>Attention.

Occurrence of pharmaceuticals and personal care products in bottled water and assessment of the associated risks.

The occurrence of 187 pharmaceuticals and personal care products (PPCPs) was investigated in bottled water samples (35 and 33 from Chinese and foreign brands, respectively). Forty-four compounds belonging to 14 PPCP categories were detected in 56 of the 68 bottled water samples. Further, more than 35% of water samples contained at least three PPCPs, and in one particular sample, 11 different PPCPs were detected. Macrolides constituted the most prevalent PPCP category, and salbutamol, erythromycin, and azithromycin showed the highest detection frequency (17.6%). The thermal stabilities of the 187 PPCPs were determined, and the results obtained showed that only 35 out of the 187 compounds were degraded by more than 50% after boiling for 5 min. Even though the risk quotients (RQs) of detected PPCPs showed low risk levels, the RQs of 13 compounds with RQs ≥ 0.0001 were 2-4 fold higher in infants than in other life stages. Moreover, further studies are necessary to evaluate the toxicity of PPCP mixtures, the effects of PPCPs on human intestinal microbiota, and their risk of induction of drug-resistant bacteria and drug-resistant genes.

Impact factor assessment of the uptake and accumulation of polycyclic aromatic hydrocarbons by plant leaves: Morphological characteristics have the greatest impact.

Polycyclic aromatic hydrocarbons (PAHs) have toxic, teratogenic, mutagenic and carcinogenic effects on living organisms. Plants can function as pollutant bioindicators and bioaccumulators due to their wide surface distribution and specific responses to atmospheric pollutants. However, various plants exhibit significant differences in their capacities to accumulate PAHs. At present, research has mainly focused on the effects of leaf morphology and physiological characteristics, and few studies have evaluated the effects of the leaf surface on PAH accumulation. We aimed to assess the factors impacting the uptake and accumulation of PAHs by leaves. We selected 8 common tree species in Shanghai, China, and used supercritical fluid extraction technology to determine the content of PAHs in their leaves. Specific measurements of leaf area, width/length, wax content, and stomatal density were applied to index the morphological and physiological characteristics; surface roughness, surface free energy, polar components, and dispersion components were compiled into an adsorption performance index. Principal component analysis (PCA) and canonical correlation analysis (CCA) were used to assess the effects of different leaf characteristics on PAH accumulation. We found that the mean concentrations of ΣPAHs ranged from 300 to 2000 ng·g-1 and that the proportions of different benzene rings were significantly different among the different tree species. Leaf morphology and physiological characteristics had more significant effects compared to surface adsorption. CCA showed a significant negative correlation between leaf morphological characteristics and wax content, but had no significant correlation with surface adsorption. Low-molecular-weight PAHs were found to be mainly affected by the morphological characteristics, while medium- and high-molecular-weight PAHs were influenced by wax content and adsorption. Our conclusions provide a theoretical basis for the establishment of a reliable plant atmosphere-monitoring system and a method for screening tree species with strong PAH adsorption capacity.

[Construction of ecological security pattern in the agro-pastoral ecotone based on surface humid index: A case study of Hangjin Banner, Inner Mongolia Autonomous Region, China.] / åŸºäºŽåœ°è¡¨æ¹¿æ¶¦æŒ‡æ•°çš„å†œç‰§äº¤é”™å¸¦åœ°åŒºç”Ÿæ€å®‰å ¨æ ¼å±€æž„å»º­­ä»¥å† 蒙古自治区杭锦旗为例.

The construction of regional ecological security pattern can effectively protect regional ecological security and achieve regional sustainable development, which has become one of the key topics in landscape ecology. The construction of regional ecological security pattern is particularly important for the Inner Mongolia Plateau, which is characterized by relatively fragile ecological environment and single land cover type. Considering regional natural environment characteristics, five typical ecosystem services, such as food supply, carbon fixation and oxygen release, soil conservation, water yield and habitat conservation, were selected to assess the importance of natural habitats with Hangjin Banner of Inner Mongolia Autonomous Region as a case study area. Based on comprehensive consideration of single ecosystem service quality and landscape multi-functionality, ecological sources were identified. The basic ecological resistance surface based on the land cover was revised by the surface humid index. The minimum cumulative resistance model was used to identify the ecological corridors, to construct the ecological security pattern of Hangjin Banner. The results showed that the ecological source of Hangjin Banner was 6781.70 km2, accounting for 35.9% of the whole area, which mainly located in the northern Hetao Plain and southern Ordos steppe zone. The total ecological corridor length of Hangjin Banner was 498.51 km, which was divided into two groups from north to south by Kubuqi Desert. Based on the arid and ecologically fragile characteristics in the agro-pastoral ecotone in northern China, this study constructed regional ecological security pattern to provide decision-making guidelines for local economic development and ecological conservation.

Longitudinal assessment of ultrasound-guided complementary microRNA therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the second-leading cause of cancer related deaths worldwide and new strategies to efficiently treat HCC are critically needed. The aim of this study was to assess the longitudinal treatment effects of two complementary miRNAs (miRNA-122 and antimiR-21) encapsulated in biodegradable poly lactic-co-glycolic acid (PLGA) - poly ethylene glycol (PEG) nanoparticles (PLGA-PEG-NPs), administered by an ultrasound-guided and microbubble-mediated delivery approach in doxorubicin-resistant and non-resistant human HCC xenografts. Using in vitro assays, we show that repeated miRNA treatments resulted in gradual reduction of HCC cell proliferation and reversal of doxorubicin resistance. Optimized US parameters resulted in a 9-16 fold increase (p = 0.03) in miRNA delivery in vivo in HCC tumors after two US treatments compared to tumors without US treatment. Furthermore, when combined with doxorubicin (10 mg/kg), longitudinal miRNA delivery showed a significant inhibition of tumor growth in both resistant and non-resistant tumors compared to non-treated, and doxorubicin treated controls. We also found that ultrasound-guided miRNA therapy was not only effective in inhibiting HCC tumor growth but also allowed lowering the dose of doxorubicin needed to induce apoptosis. In conclusion, the results of this study suggest that ultrasound-guided and MB-mediated delivery of miRNA-122 and antimiR-21, when combined with doxorubicin, is a highly effective approach to treat resistant HCC while reducing doxorubicin doses needed for treating non-resistant HCC in longitudinal treatment experiments. Further refinement of this strategy could potentially lead to better treatment outcomes for patients with HCC.

Baseline Assessment of 25-Hydroxyvitamin D Reference Material and Proficiency Testing/External Quality Assurance Material Commutability: A Vitamin D Standardization Program Study.

The Vitamin D Standardization Program (VDSP) coordinated a study in 2012 to assess the commutability of reference materials and proficiency testing/external quality assurance materials for total 25-hydroxyvitamin D [25(OH)D] in human serum, the primary indicator of vitamin D status. A set of 50 single-donor serum samples as well as 17 reference and proficiency testing/external quality assessment materials were analyzed by participating laboratories that used either immunoassay or LC-MS methods for total 25(OH)D. The commutability test materials included National Institute of Standards and Technology Standard Reference Material 972a Vitamin D Metabolites in Human Serum as well as materials from the College of American Pathologists and the Vitamin D External Quality Assessment Scheme. Study protocols and data analysis procedures were in accordance with Clinical and Laboratory Standards Institute guidelines. The majority of the test materials were found to be commutable with the methods used in this commutability study. These results provide guidance for laboratories needing to choose appropriate reference materials and select proficiency or external quality assessment programs and will serve as a foundation for additional VDSP studies.

Baseline Assessment of 25-Hydroxyvitamin D Assay Performance: A Vitamin D Standardization Program (VDSP) Interlaboratory Comparison Study.

The Vitamin D Standardization Program (VDSP) coordinated an interlaboratory study to assess the comparability of measurements of total 25-hydroxyvitamin D [25(OH)D] in human serum, which is the primary marker of vitamin D status. A set of 50 individual donor samples were analyzed by 15 different laboratories representing national nutrition surveys, assay manufacturers, and clinical and/or research laboratories to provide results for total 25(OH)D using both immunoassays (IAs) and LC tandem MS (MS/MS). The results were evaluated relative to bias compared with the target values assigned based on a combination of measurements at Ghent University (Belgium) and the U.S. National Institute of Standards and Technology using reference measurement procedures for the determination of 25(OH)D2 and 25(OH)D3. CV and mean bias for each laboratory and assay platform were assessed and compared with previously established VDSP performance criteria, namely CV ≤ 10% and mean bias ≤ 5%. Nearly all LC-MS/MS results achieved VDSP criteria, whereas only 50% of IAs met the criterion for a ≤10% CV and only three of eight IAs achieved the ≤5% bias. These results establish a benchmark for the evaluation of 25(OH)D assay performance and standardization activities in the future.

Racial differences in functional decline in peripheral artery disease and associations with socioeconomic status and education.

OBJECTIVE: The objective of this study was to determine whether blacks with lower extremity peripheral artery disease (PAD) have faster functional decline than whites with PAD. METHODS: Participants with ankle-brachial index <0.90 were identified from Chicago medical centers and observed longitudinally. Mobility impairment and the 6-minute walk were assessed at baseline and every 6 to 12 months. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or to walk » mile without assistance. RESULTS: Of 1162 PAD participants, 305 (26%) were black. Median follow-up was 46.0 months. Among 711 PAD participants who walked 6 minutes continuously at baseline, black participants were more likely to become unable to walk 6 minutes continuously during follow-up (64/171 [37.4%] vs 156/540 [28.9%]; log-rank, P = .006). Black race was associated with becoming unable to walk 6 minutes continuously, adjusting for age, sex, ankle-brachial index, comorbidities, and other confounders (hazard ratio, 1.45; 95% confidence interval, 1.05-1.99; P = .022). This association was attenuated after adjustment for income and education (P = .229). Among 844 participants without baseline mobility impairment, black participants had a higher rate of mobility loss (64/209 [30.6%] vs 164/635 [25.8%]; log-rank, P = .009). Black race was associated with increased mobility loss, adjusting for potential confounders (hazard ratio, 1.42; 95% confidence interval, 1.04-1.94; P = .028). This association was attenuated after additional adjustment for income and education (P = .392) and physical activity (P = .113). There were no racial differences in average annual declines in 6-minute walk, usual-paced 4-meter walking velocity, or fast-paced 4-meter walking velocity. CONCLUSIONS: Black PAD patients have higher rates of mobility loss and becoming unable to walk for 6 minutes continuously. These differences appear related to racial differences in socioeconomic status and physical activity.

Predicting complication risk in spine surgery: a prospective analysis of a novel risk assessment tool.

OBJECTIVE The ability to assess the risk of adverse events based on known patient factors and comorbidities would provide more effective preoperative risk stratification. Present risk assessment in spine surgery is limited. An adverse event prediction tool was developed to predict the risk of complications after spine surgery and tested on a prospective patient cohort. METHODS The spinal Risk Assessment Tool (RAT), a novel instrument for the assessment of risk for patients undergoing spine surgery that was developed based on an administrative claims database, was prospectively applied to 246 patients undergoing 257 spinal procedures over a 3-month period. Prospectively collected data were used to compare the RAT to the Charlson Comorbidity Index (CCI) and the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator. Study end point was occurrence and type of complication after spine surgery. RESULTS The authors identified 69 patients (73 procedures) who experienced a complication over the prospective study period. Cardiac complications were most common (10.2%). Receiver operating characteristic (ROC) curves were calculated to compare complication outcomes using the different assessment tools. Area under the curve (AUC) analysis showed comparable predictive accuracy between the RAT and the ACS NSQIP calculator (0.670 [95% CI 0.60-0.74] in RAT, 0.669 [95% CI 0.60-0.74] in NSQIP). The CCI was not accurate in predicting complication occurrence (0.55 [95% CI 0.48-0.62]). The RAT produced mean probabilities of 34.6% for patients who had a complication and 24% for patients who did not (p = 0.0003). The generated predicted values were stratified into low, medium, and high rates. For the RAT, the predicted complication rate was 10.1% in the low-risk group (observed rate 12.8%), 21.9% in the medium-risk group (observed 31.8%), and 49.7% in the high-risk group (observed 41.2%). The ACS NSQIP calculator consistently produced complication predictions that underestimated complication occurrence: 3.4% in the low-risk group (observed 12.6%), 5.9% in the medium-risk group (observed 34.5%), and 12.5% in the high-risk group (observed 38.8%). The RAT was more accurate than the ACS NSQIP calculator (p = 0.0018). CONCLUSIONS While the RAT and ACS NSQIP calculator were both able to identify patients more likely to experience complications following spine surgery, both have substantial room for improvement. Risk stratification is feasible in spine surgery procedures; currently used measures have low accuracy.

Intra-Animal Comparison between Three-dimensional Molecularly Targeted US and Three-dimensional Dynamic Contrast-enhanced US for Early Antiangiogenic Treatment Assessment in Colon Cancer.

Purpose To perform an intra-animal comparison between (a) three-dimensional (3D) molecularly targeted ultrasonography (US) by using clinical-grade vascular endothelial growth factor receptor 2 (VEGFR2)-targeted microbubbles and (b) 3D dynamic contrast material-enhanced (DCE) US by using nontargeted microbubbles for assessment of antiangiogenic treatment effects in a murine model of human colon cancer. Materials and Methods Twenty-three mice with human colon cancer xenografts were randomized to receive either single-dose antiangiogenic treatment (bevacizumab, n = 14) or control treatment (saline, n = 9). At baseline and 24 hours after treatment, animals were imaged with a clinical US system equipped with a clinical matrix array transducer by using the following techniques: (a) molecularly targeted US with VEGFR2-targeted microbubbles, (b) bolus DCE US with nontargeted microbubbles, and (c) destruction-replenishment DCE US with nontargeted microbubbles. VEGFR2-targeted US signal, peak enhancement, area under the time-intensity curve, time to peak, relative blood volume (rBV), relative blood flow, and blood flow velocity were quantified. VEGFR2 expression and percentage area of blood vessels were assessed ex vivo with quantitative immunofluorescence and correlated with corresponding in vivo US parameters. Statistical analysis was performed with Wilcoxon signed rank tests and rank sum tests, as well as Pearson correlation analysis. Results Molecularly targeted US signal with VEGFR2-targeted microbubbles, peak enhancement, and rBV significantly decreased (P ≤ .03) after a single antiangiogenic treatment compared with those in the control group; similarly, ex vivo VEGFR2 expression (P = .03) and percentage area of blood vessels (P = .03) significantly decreased after antiangiogenic treatment. Three-dimensional molecularly targeted US signal correlated well with VEGFR2 expression (r = 0.86, P = .001), and rBV (r = 0.71, P = .01) and relative blood flow (r = 0.78, P = .005) correlated well with percentage area of blood vessels, while other US perfusion parameters did not. Conclusion Three-dimensional molecularly targeted US and destruction-replenishment 3D DCE US provide complementary molecular and functional in vivo imaging information on antiangiogenic treatment effects in human colon cancer xenografts compared with ex vivo reference standards. © RSNA, 2016 Online supplemental material is available for this article.