Subsampling based variable selection for generalized linear models.

A novel variable selection method for low-dimensional generalized linear models is introduced. The new approach called AIC OPTimization via STABility Selection (OPT-STABS) repeatedly subsamples the data, minimizes Akaike's Information Criterion (AIC) over a sequence of nested models for each subsample, and includes in the final model those predictors selected in the minimum AIC model in a large fraction of the subsamples. New methods are also introduced to establish an optimal variable selection cutoff over repeated subsamples. An extensive simulation study examining a variety of proposec variable selection methods shows that, although no single method uniformly outperforms the others in all the scenarios considered, OPT-STABS is consistently among the best-performing methods in most settings while it performs competitively for the rest. This is in contrast to other candidate methods which either have poor performance across the board or exhibit good performance in some settings, but very poor in others. In addition, the asymptotic properties of the OPT-STABS estimator are derived, and its root-n consistency and asymptotic normality are proved. The methods are applied to two datasets involving logistic and Poisson regressions.

Door-in-Door-out Times for Interhospital Transfer of Patients With Stroke.

Importance: Treatments for time-sensitive acute stroke are not available at every hospital, often requiring interhospital transfer. Current guidelines recommend hospitals achieve a door-in-door-out time of no more than 120 minutes at the transferring emergency department (ED). Objective: To evaluate door-in-door-out times for acute stroke transfers in the American Heart Association Get With The Guidelines-Stroke registry and to identify patient and hospital factors associated with door-in-door-out times. Design, Setting, and Participants: US registry-based, retrospective study of patients with ischemic or hemorrhagic stroke from January 2019 through December 2021 who were transferred from the ED at registry-affiliated hospitals to other acute care hospitals. Exposure: Patient- and hospital-level characteristics. Main Outcomes and Measures: The primary outcome was the door-in-door-out time (time of transfer out minus time of arrival to the transferring ED) as a continuous variable and a categorical variable (≤120 minutes, >120 minutes). Generalized estimating equation (GEE) regression models were used to identify patient and hospital-level characteristics associated with door-in-door-out time overall and in subgroups of patients with hemorrhagic stroke, acute ischemic stroke eligible for endovascular therapy, and acute ischemic stroke transferred for reasons other than endovascular therapy. Results: Among 108 913 patients (mean [SD] age, 66.7 [15.2] years; 71.7% non-Hispanic White; 50.6% male) transferred from 1925 hospitals, 67 235 had acute ischemic stroke and 41 678 had hemorrhagic stroke. Overall, the median door-in-door-out time was 174 minutes (IQR, 116-276 minutes): 29 741 patients (27.3%) had a door-in-door-out time of 120 minutes or less. The factors significantly associated with longer median times were age 80 years or older (vs 18-59 years; 14.9 minutes, 95% CI, 12.3 to 17.5 minutes), female sex (5.2 minutes; 95% CI, 3.6 to 6.9 minutes), non-Hispanic Black vs non-Hispanic White (8.2 minutes, 95% CI, 5.7 to 10.8 minutes), and Hispanic ethnicity vs non-Hispanic White (5.4 minutes, 95% CI, 1.8 to 9.0 minutes). The following were significantly associated with shorter median door-in-door-out time: emergency medical services prenotification (-20.1 minutes; 95% CI, -22.1 to -18.1 minutes), National Institutes of Health Stroke Scale (NIHSS) score exceeding 12 vs a score of 0 to 1 (-66.7 minutes; 95% CI, -68.7 to -64.7 minutes), and patients with acute ischemic stroke eligible for endovascular therapy vs the hemorrhagic stroke subgroup (-16.8 minutes; 95% CI, -21.0 to -12.7 minutes). Among patients with acute ischemic stroke eligible for endovascular therapy, female sex, Black race, and Hispanic ethnicity were associated with a significantly higher door-in-door-out time, whereas emergency medical services prenotification, intravenous thrombolysis, and a higher NIHSS score were associated with significantly lower door-in-door-out times. Conclusions and Relevance: In this US registry-based study of interhospital transfer for acute stroke, the median door-in-door-out time was 174 minutes, which is longer than current recommendations for acute stroke transfer. Disparities and modifiable health system factors associated with longer door-in-door-out times are suitable targets for quality improvement initiatives.

Comparing Radiologist Performance in Diagnosing Clinically Significant Prostate Cancer with Multiparametric versus Hybrid Multidimensional MRI.

Background Variability of acquisition and interpretation of prostate multiparametric MRI (mpMRI) persists despite implementation of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 due to the range of reader experience and subjectivity of lesion characterization. A quantitative method, hybrid multidimensional MRI (HM-MRI), may introduce objectivity. Purpose To compare performance, interobserver agreement, and interpretation time of radiologists using mpMRI versus HM-MRI to diagnose clinically significant prostate cancer. Materials and Methods In this retrospective analysis, men with prostatectomy or MRI-fused transrectal US biopsy-confirmed prostate cancer underwent mpMRI (triplanar T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging) and HM-MRI (with multiple echo times and b value combinations) from August 2012 to February 2020. Four readers with 1-20 years of experience interpreted mpMRI and HM-MRI examinations independently, with a 4-week washout period between interpretations. PI-RADS score, lesion location, and interpretation time were recorded. mpMRI and HM-MRI interpretation time, interobserver agreement (Cronbach alpha), and performance of area under the receiver operating characteristic curve (AUC) analysis were compared for each radiologist with use of bootstrap analysis. Results Sixty-one men (mean age, 61 years ± 8 [SD]) were evaluated. Per-patient AUC was higher for HM-MRI for reader 4 compared with mpMRI (AUCs for readers 1-4: 0.61, 0.71, 0.59, and 0.64 vs 0.66, 0.60, 0.50, and 0.46; P = .57, .20, .32, and .04, respectively). Per-patient specificity was higher for HM-MRI for readers 2-4 compared with mpMRI (specificity for readers 1-4: 48%, 78%, 48%, and 46% vs 37%, 26%, 0%, and 7%; P = .34, P < .001, P < .001, and P < .001, respectively). Diagnostic performance improved for the reader least experienced with HM-MRI, reader 4 (AUC, 0.64 vs 0.46; P = .04). HM-MRI interobserver agreement (Cronbach alpha = 0.88 [95% CI: 0.82, 0.92]) was higher than that of mpMRI (Cronbach alpha = 0.26 [95% CI: 0.10, 0.52]; α > .60 indicates reliability; P = .03). HM-MRI mean interpretation time (73 seconds ± 43 [SD]) was shorter than that of mpMRI (254 seconds ± 133; P = .03). Conclusion Radiologists had similar or improved diagnostic performance, higher interobserver agreement, and lower interpretation time for clinically significant prostate cancer with hybrid multidimensional MRI than multiparametric MRI. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Directional and inter-acquisition variability in diffusion-weighted imaging and editing for restricted diffusion.

PURPOSE: To evaluate and quantify inter-directional and inter-acquisition variation in diffusion-weighted imaging (DWI) and emphasize signals that report restricted diffusion to enhance cancer conspicuity, while reducing the effects of local microscopic motion and magnetic field fluctuations. METHODS: Ten patients with biopsy-proven prostate cancer were studied under an Institutional Review Board-approved protocol. Individual acquisitions of DWI signal intensities were reconstructed to calculate inter-acquisition distributions and their statistics, which were compared for healthy versus cancer tissue. A method was proposed to detect and filter the acquisitions affected by motion-induced signal loss. First, signals that reflect restricted diffusion were separated from the acquisitions that suffer from signal loss, likely due to microscopic motion, by imposing a cutoff value. Furthermore, corrected apparent diffusion coefficient maps were calculated by employing a weighted sum of the multiple acquisitions, instead of conventional averaging. These weights were calculated by applying a soft-max function to the set of acquisitions per-voxel, making the analysis immune to acquisitions with significant signal loss, even if the number of such acquisitions is high. RESULTS: Inter-acquisition variation is much larger than the Rician noise variance, local spatial variations, and the estimates of diffusion anisotropy based on the current data, as well as the published values of anisotropy. The proposed method increases the contrast for cancers and yields a sensitivity of 98 . 8 % $$ 98.8\% $$ with a false positive rate of 3 . 9 % $$ 3.9\% $$ . CONCLUSION: Motion-induced signal loss makes conventional signal-averaging suboptimal and can obscure signals from areas with restricted diffusion. Filtering or weighting individual acquisitions prior to image analysis can overcome this problem.

The optimal 18F-fluoromisonidazole PET threshold to define tumor hypoxia in preclinical squamous cell carcinomas using pO2 electron paramagnetic resonance imaging as reference truth.

PURPOSE: To identify the optimal threshold in 18F-fluoromisonidazole (FMISO) PET images to accurately locate tumor hypoxia by using electron paramagnetic resonance imaging (pO2 EPRI) as ground truth for hypoxia, defined by pO2 [Formula: see text] 10 mmHg. METHODS: Tumor hypoxia images in mouse models of SCCVII squamous cell carcinoma (n = 16) were acquired in a hybrid PET/EPRI imaging system 2 h post-injection of FMISO. T2-weighted MRI was used to delineate tumor and muscle tissue. Dynamic contrast enhanced (DCE) MRI parametric images of Ktrans and ve were generated to model tumor vascular properties. Images from PET/EPR/MRI were co-registered and resampled to isotropic 0.5 mm voxel resolution for analysis. PET images were converted to standardized uptake value (SUV) and tumor-to-muscle ratio (TMR) units. FMISO uptake thresholds were evaluated using receiver operating characteristic (ROC) curve analysis to find the optimal FMISO threshold and unit with maximum overall hypoxia similarity (OHS) with pO2 EPRI, where OHS = 1 shows perfect overlap and OHS = 0 shows no overlap. The means of dice similarity coefficient, normalized Hausdorff distance, and accuracy were used to define the OHS. Monotonic relationships between EPRI/PET/DCE-MRI were evaluated with the Spearman correlation coefficient ([Formula: see text]) to quantify association of vasculature on hypoxia imaged with both FMISO PET and pO2 EPRI. RESULTS: FMISO PET thresholds to define hypoxia with maximum OHS (both OHS = 0.728 [Formula: see text] 0.2) were SUV [Formula: see text] 1.4 [Formula: see text] SUVmean and SUV [Formula: see text] 0.6 [Formula: see text] SUVmax. Weak-to-moderate correlations (|[Formula: see text]|< 0.70) were observed between PET/EPRI hypoxia images with vascular permeability (Ktrans) or fractional extracellular-extravascular space (ve) from DCE-MRI. CONCLUSION: This is the first in vivo comparison of FMISO uptake with pO2 EPRI to identify the optimal FMISO threshold to define tumor hypoxia, which may successfully direct hypoxic tumor boosts in patients, thereby enhancing tumor control.

Pediatric Invasive Fungal Risk Score in Cancer and Hematopoietic Stem Cell Transplantation Patients With Febrile Neutropenia.

BACKGROUND: Invasive fungal diseases (IFDs) are opportunistic infections that result in significant morbidity and mortality in pediatric oncology patients. Predictive risk tools for IFD in pediatric cancer are not available. METHODS: We conducted a 7-year retrospective study of pediatric oncology patients with a diagnosis of febrile neutropenia at UCM Comer Children's Hospitals. Fourteen clinical, laboratory, and treatment-related risk factors for IFD were analyzed. Stepwise variable selection for multiple logistic regression was used to develop a risk prediction model for IFD. Two comparative analyses have been conducted: (i) all suspected IFD cases and (ii) all proven and probable IFD cases. RESULTS: A total of 667 febrile neutropenia episodes were identified in 265 patients. IFD was diagnosed in 62 episodes: 13 proven, 27 probable, and 22 possible. In the final multiple logistic regression models, 5 variables were independently significant for both analyses: fever days, neutropenia days, hypotension, and absolute lymphocyte count <250 at the time of diagnosis. The odds ratio and a relative weight for each factor were then calculated and summed to calculate a predictive score. A risk score of ≤4 and ≤5 (10/11 maximum) for each model signifies low risk, respectively (<1.2% incidence). Model discrimination was evaluated by the area under the receiver operator characteristics curve with an area under the curve of 0.95/0.94 for each model. CONCLUSION: Our prediction IFD risk models perform well, are easy-to-use, and are based on readily available clinical data. Profound lymphopenia absolute lymphocyte count <250 mm3 could serve as a new important prognostic marker for the development of IFD in pediatric cancer and hematopoietic stem cell transplant patients.

Nonparametric inference in the accelerated failure time model using restricted means.

We propose a nonparametric estimate of the scale-change parameter for characterizing the difference between two survival functions under the accelerated failure time model using an estimating equation based on restricted means. Advantages of our restricted means based approach compared to current nonparametric procedures is the strictly monotone nature of the estimating equation as a function of the scale-change parameter, leading to a unique root, as well as the availability of a direct standard error estimate, avoiding the need for hazard function estimation or re-sampling to conduct inference. We derive the asymptotic properties of the proposed estimator for fixed and for random point of restriction. In a simulation study, we compare the performance of the proposed estimator with parametric and nonparametric competitors in terms of bias, efficiency, and accuracy of coverage probabilities. The restricted means based approach provides unbiased estimates and accurate confidence interval coverage rates with efficiency ranging from 81% to 95% relative to fitting the correct parametric model. An example from a randomized clinical trial in head and neck cancer is provided to illustrate an application of the methodology in practice.

Biological validation of electron paramagnetic resonance (EPR) image oxygen thresholds in tissue.

Measuring molecular oxygen levels in vivo has been the cornerstone of understanding the effects of hypoxia in normal tissues and malignant tumors. Here we discuss the advances in a variety of partial pressure of oxygen ( PO2 ) measurements and imaging techniques and relevant oxygen thresholds. A focus on electron paramagnetic resonance (EPR) imaging shows the validation of treating hypoxic tumours with a threshold of PO2  ≤ 10 Torr, and demonstrates utility for in vivo oxygen imaging, as well as its current and future role in cancer studies.

Cytoreductive Surgery for Selected Patients Whose Metastatic Gastric Cancer was Treated with Systemic Chemotherapy.

BACKGROUND: The authors hypothesized that cytoreductive surgery (CRS, comprising gastrectomy combined with metastasectomy) in addition to systemic chemotherapy (SC) is associated with a better survival than chemotherapy alone for patients with metastatic gastric adenocarcinoma (MGA). METHODS: Patients with MGA who received SC between 2004 and 2016 were identified using the National Cancer Database (NCDB). Nearest-neighbor 1:1 propensity score-matching was used to create comparable groups. Overall survival (OS) was compared between subgroups using Kaplan-Meier analyses. Immortal bias analysis was performed among those who survived longer than 90 days. RESULTS: The study identified 29,728 chemotherapy-treated patients, who were divided into the following four subgroups: no surgery (NS, n = 25,690), metastasectomy alone (n = 1170), gastrectomy alone (n = 2248), and CRS (n = 620) with median OS periods of 8.6, 10.9, 14.8, and 16.3 months, respectively (p < 0.001). Compared with the patients who underwent NS, the patients who had CRS were younger (58.9 ± 13.4 vs 62.0 ± 13.1 years), had a lower proportion of disease involving multiple sites (4.6% vs 19.1%), and were more likely to be clinically occult (cM0 stage: 59.2% vs 8.3%) (p < 0.001 for all). The median OS for the propensity-matched patients who underwent CRS (n = 615) was longer than for those with NS (16.4 vs 9.3 months; p < 0.001), including in those with clinical M1 stage (n = 210). In the Cox regression model using the matched data, the hazard ratio for CRS versus NS was 0.56 (95% confidence interval [CI], 0.49-0.63). In the immortal-matched cohort, the corresponding median OS was 17.0 versus 9.5 months (p < 0.001). CONCLUSIONS: In addition to SC, CRS may be associated with an OS benefit for a selected group of MGA patients meriting further prospective investigation.

Optimized variable selection via repeated data splitting.

Model selection in high-dimensional settings has received substantial attention in recent years, however, similar advancements in the low-dimensional setting have been lacking. In this article, we introduce a new variable selection procedure for low to moderate scale regressions (n>p). This method repeatedly splits the data into two sets, one for estimation and one for validation, to obtain an empirically optimized threshold which is then used to screen for variables to include in the final model. In an extensive simulation study, we show that the proposed variable selection technique enjoys superior performance compared with candidate methods (backward elimination via repeated data splitting, univariate screening at 0.05 level, adaptive LASSO, SCAD), being amongst those with the lowest inclusion of noisy predictors while having the highest power to detect the correct model and being unaffected by correlations among the predictors. We illustrate the methods by applying them to a cohort of patients undergoing hepatectomy at our institution.

CommunityRx: A Real-World Controlled Clinical Trial of a Scalable, Low-Intensity Community Resource Referral Intervention.

OBJECTIVES: To test the effect of CommunityRx, a scalable, low-intensity intervention that matches patients to community resources, on mental health-related quality of life (HRQOL) (primary outcome), physical HRQOL, and confidence in finding resources. METHODS: A real-world trial assigned publicly insured residents of Chicago, Illinois, aged 45 to 74 years to an intervention (n = 209) or control (n = 202) group by alternating calendar week, December 2015 to August 2016. Intervention group participants received usual care and an electronic medical record-generated, personalized list of community resources. Surveys (baseline, 1-week, 1- and 3-months) measured HRQOL and confidence in finding community resources to manage health. RESULTS: At 3 months, there was no difference between groups in mental (-1.03; 95% confidence interval [CI] = -3.02, 0.96) or physical HRQOL (0.59; 95% CI = -0.98, 2.16). Confidence in finding resources was higher in the intervention group (odds ratio = 2.08; 95% CI = 1.18, 3.63); the effect increased at each successive time point. Among intervention group participants, 65% recalled receiving the intervention; 48% shared community resource information with others. CONCLUSIONS: CommunityRx did not increase HRQOL, but its positive effect on confidence in finding resources for self-care suggests that this low-intensity intervention may have a role in population health promotion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02435511.

Quercetin Therapy for Selected Patients with PIM1 Kinase-Positive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pilot Study.

We reported that PIM1 kinase is expressed in the lymphocytes of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Quercetin, a naturally occurring flavonoid, is a dietary supplement and inhibits many kinases, including PIM1, in vitro. Under an Institutional Review Board-approved protocol, we performed an open-label, single-arm pilot study to evaluate the antitumor activity of quercetin in patients with CLL/SLL. Q-ForceTM chews were administered orally, 500 mg twice daily, for 3 months. Eligible patients had failed prior therapies, had had no other standard treatment, or refused other therapies. Response was assessed based on objective change in disease parameters. Patients were included if their lymphocyte counts were rising and ≥10,000/µL but not > 100,000/µL. Three patients received quercetin treatment. There was no toxicity. Two responded with stabilization of rising lymphocyte counts (p < 0.001 for each), which remained stable during their follow-up (5 and 11 months after cessation of treatment, respectively). The CLL cells in the nonresponder harbored a TP53 mutation. Although our data from this pilot translational study are based on a small sample, further studies of quercetin as a potential therapeutic agent in selected patients with CLL/SLL appear warranted.

High relative humidity pre-harvest reduces post-harvest proliferation of Salmonella in tomatoes.

Outbreaks of human illness caused by enteric pathogens such as Salmonella are increasingly linked to the consumption of fruits and vegetables. Knowledge on the factors affecting Salmonella proliferation on fresh produce therefore becomes increasingly important to safeguard public health. Previous experiments showed a limited impact of pre-harvest production practices on Salmonella proliferation on tomatoes, but suggested a significant effect of harvest time. We explored the data from two previously published and one unpublished experiment using regression trees, which allowed overcoming the interpretational difficulties of classical statistical models with higher order interactions. We assessed the effect of harvest time by explicitly modeling the climatic conditions at harvest time and by performing confirmatory laboratory experiments. Across all datasets, regression trees confirmed the dominant effect of harvest time on Salmonella proliferation, with humidity-related factors emerging as the most important underlying climatic factors. High relative humidity the week prior to harvest was consistently associated with lower Salmonella proliferation. A controlled lab experiment confirmed that tomatoes containing their native epimicrobiota supported significantly lower Salmonella proliferation when incubated at higher humidity prior to inoculation. The complex interactions between environmental conditions and the native microbiota of the tomato crop remain to be fully understood.

A meta-analysis on the effect of dietary application of exogenous fibrolytic enzymes on the performance of dairy cows.

The aim of this study was to use meta-analytical methods to estimate effects of adding exogenous fibrolytic enzymes (EFE) to dairy cow diets on their performance and to determine which factors affect the response. Fifteen studies with 17 experiments and 36 observations met the study selection criteria for inclusion in the meta-analysis. The effects were compared by using random-effect models to examine the raw mean difference (RMD) and standardized mean difference between EFE and control treatments after both were weighted with the inverse of the study variances. Heterogeneity sources evaluated by meta-regression included experimental duration, EFE type and application rate, form (liquid or solid), and method (application to the forage, concentrate, or total mixed ration). Only the cellulase-xylanase (C-X) enzymes had a substantial number of observations (n = 13 studies). Application of EFE, overall, did not affect dry matter intake, feed efficiency but tended to increase total-tract dry matter digestibility and neutral detergent fiber digestibility (NDFD) by relatively small amounts (1.36 and 2.30%, respectively, or <0.31 standard deviation units). Application of EFE increased yields of milk (0.83 kg/d), 3.5% fat-corrected milk (0.55 kg/d), milk protein (0.03 kg/d), and milk lactose (0.05 kg/d) by moderate to small amounts (<0.30 standard deviation units). Low heterogeneity (I 2 statistic <25%) was present for yields and concentrations of milk fat and protein and lactose yield. Moderate heterogeneity (I 2 = 25 to 50%) was detected for dry matter intake, milk yield, 3.5% fat-corrected milk, and feed efficiency (kg of milk/kg of dry matter intake), whereas high heterogeneity (I 2 > 50%) was detected for total-tract dry matter digestibility and NDFD. Milk production responses were higher for the C-X enzymes (RMD = 1.04 kg/d; 95% confidence interval: 0.33 to 1.74), but were still only moderate, about 0.35 standardized mean difference. A 24% numerical increase in the RMD resulting from examining only C-X enzymes instead of all enzymes (RMD = 1.04 vs. 0.83 kg/d) suggests that had more studies met the inclusion criteria, the C-X enzymes would have statistically increased the milk response relative to that for all enzymes. Increasing the EFE application rate had no effect on performance measures. Application of EFE to the total mixed ration improved only milk protein concentration, and application to the forage or concentrate had no effect. Applying EFE tended to increase dry matter digestibility and NDFD and increased milk yield by relatively small amounts, reflecting the variable response among EFE types.

Distribution and Characterization of Salmonella enterica Isolates from Irrigation Ponds in the Southeastern United States.

Irrigation water has been implicated as a likely source of produce contamination by Salmonella enterica. Therefore, the distribution of S. enterica was surveyed monthly in irrigation ponds (n = 10) located within a prime agricultural region in southern Georgia and northern Florida. All ponds and 28.2% of all samples (n = 635) were positive for Salmonella, with an overall geometric mean concentration (0.26 most probable number [MPN]/liter) that was relatively low compared to prior reports for rivers in this region. Salmonella peaks were seasonal; the levels correlated with increased temperature and rainfall (P < 0.05). The numbers and occurrence were significantly higher in water (0.32 MPN/liter and 37% of samples) than in sediment (0.22 MPN/liter and 17% of samples) but did not vary with depth. Representative isolates (n = 185) from different ponds, sample types, and seasons were examined for resistance to 15 different antibiotics; most strains were resistant to streptomycin (98.9%), while 20% were multidrug resistant (MDR) for 2 to 6 antibiotics. DiversiLab repetitive extragenic palindromic-element sequence-based PCR (rep-PCR) revealed genetic diversity and showed 43 genotypes among 191 isolates, as defined by >95% similarity. The genotypes did not partition by pond, season, or sample type. Genetic similarity to known serotypes indicated Hadar, Montevideo, and Newport as the most prevalent. All ponds achieved the current safety standards for generic Escherichia coli in agricultural water, and regression modeling showed that the E. coli level was a significant predictor for the probability of Salmonella occurrence. However, persistent populations of Salmonella were widely distributed in irrigation ponds, and the associated risks for produce contamination and subsequent human exposure are unknown, supporting continued surveillance of this pathogen in agricultural settings.

Effect of the irrigation regime on the susceptibility of pepper and tomato to post-harvest proliferation of Salmonella enterica.

Raw produce is increasingly recognized as a vehicle of human gastroenteritis. Non-typhoidal Salmonella, pathogenic Escherichia coli, and other human pathogens have been isolated from fruits and vegetables in the field and in the marketplace, which led to the hypothesis that these microbes can use plants as alternate hosts. However, environmental and physiological factors that facilitate persistence of these bacteria in the crop production environment and make produce more vulnerable to post-harvest contamination have not been fully delineated. This study tested the effect of irrigation regimes on the susceptibility of peppers and tomatoes to post-harvest proliferation of Salmonella. The experiments were carried out over three experimental seasons in two locations using seven strains of Salmonella. The irrigation regime per se did not affect susceptibility of tomatoes and peppers to post-harvest proliferation of Salmonella; however, in some of the seasons, irrigation regime-dependent differences were observed. Red peppers and tomatoes were more conducive to proliferation of Salmonella than green fruit in all seasons. Inter-seasonal differences were the strongest factors affecting proliferation of Salmonella in peppers.

Effects of nitrogen and potassium fertilization on the susceptibility of tomatoes to post-harvest proliferation of Salmonella enterica.

Fresh fruits and vegetables are increasingly recognized as vehicles of salmonellosis. Pre- and post-harvest environmental conditions, and physiological, and genetic factors are thought to contribute to the ability of human pathogens to persist in the production environment, attach to, colonize and proliferate in and on raw produce. How field production conditions affect the post-harvest food safety outcomes is not entirely understood. This study tested how varying nitrogen and potassium fertilization levels affected the "susceptibility" of tomatoes to Salmonella infections following the harvest of fruits. Two tomato varieties grown over three seasons under high, medium, and low levels of nitrogen and potassium fertilization in two locations were inoculated with seven strains of Salmonella. Even though the main effects of nitrogen and potassium fertilization on the susceptibility of tomatoes to infections with Salmonella enterica were not statistically significant overall, differences in nitrogen concentrations in plant tissues correlated with the susceptibility of partially ripe tomatoes (cv. Solar Fire) to Salmonella. Tomato maturity and the season in which tomatoes were produced had the strongest effect on the ability of Salmonella to multiply in tomatoes. Tomato phenolics, accumulation of which is known to correlate with rates of the N fertilization, did not inhibit growth of Salmonella in vitro.

Emergency Department Process Times and Door-In-Door-Out Times in Interhospital Transfers After Acute Ischemic Stroke.

Importance: Stroke treatment is exquisitely time sensitive. The door-in-door-out (DIDO) time, defined as the total time spent in the emergency department (ED) at a transferring hospital, is an important quality metric for the care of acute stroke. However, little is known about the contributions of specific process steps to delays and disparities in DIDO time. Objective: To quantify process steps and their association with DIDO times at transferring hospitals among patients with acute ischemic stroke (AIS). Design, Setting, and Participants: This retrospective cohort study analyzed patients in the American Heart Association Get With the Guidelines-Stroke registry with AIS presenting between January 1, 2019, to December 31, 2021, and transferred from the presenting hospital ED to another acute care hospital for evaluation of thrombolytics, endovascular therapy, or postthrombolytic care. Data were analyzed from July 8 to October 13, 2023. Exposures: Intervals of ED care of ischemic stroke: door-to-imaging and imaging-to-door times. Main Outcomes and Measures: The primary outcome was DIDO time. Multivariate generalized estimating equations regression models were performed to compare contributions of interval process times to explain variation in DIDO time, controlling for patient- and hospital-level characteristics. Results: Among 28 887 patients (50.5% male; mean [SD] age, 68.3 [14.8] years; 5.5% Hispanic, 14.7% non-Hispanic Black, and 73.2% non-Hispanic White), mean (SD) DIDO time was 171.4 (149.5) minutes, mean (SD) door-to-imaging time was 18.3 (34.1) minutes, and mean (SD) imaging-to-door time was 153.1 (141.5) minutes. In the model adjusting for door-to-imaging time, the following were associated with longer DIDO time: age 80 years or older (compared with 18-59 years; 5.97 [95% CI, 1.02-10.92] minutes), female sex (5.21 [95% CI, 1.55-8.87] minutes), and non-Hispanic Black race (compared with non-Hispanic White 10.09 [95% CI, 4.21-15.96] minutes). In the model including imaging-to-door time as a covariate, disparities in DIDO by age and female sex became nonsignificant, and the disparity by Black race was attenuated (2.32 [95% CI, 1.09-3.56] minutes). Conclusions and Relevance: In this national cohort study of interhospital transfer of patients with AIS, delays in DIDO time by Black race, older age (≥80 years), and female sex were largely explained by the imaging-to-door period, suggesting that future systems interventions should target this interval to reduce these disparities. While existing guidelines and care resources heavily focus on reducing door-to-imaging times, further attention is warranted to reduce imaging-to-door times in the management of patients with AIS who require interhospital transfer.

Quantification of Collateral Supply with Local-AIF Dynamic Susceptibility Contrast MRI Predicts Infarct Growth.

BACKGROUND AND PURPOSE: In ischemic stroke, leptomeningeal collaterals can provide delayed and dispersed compensatory blood flow to tissue-at-risk despite an occlusion and can impact treatment response and infarct growth. The purpose of this work is to test the hypothesis that inclusion of this delayed and dispersed flow with an appropriately calculated Local Arterial Input Function (Local-AIF) is needed to quantify the degree of collateral blood supply in tissue distal to an occlusion. MATERIALS AND METHODS: Seven experiments were conducted in a pre-clinical middle cerebral artery occlusion model. Dynamic susceptibility contrast MRI was imaged and post-processed to yield quantitative cerebral blood flow (qCBF) maps with both a traditionally chosen single arterial input function applied globally to the whole brain (i.e. "Global-AIF") and a delay and dispersion corrected AIF (i.e. "Local-AIF") that is sensitive to retrograde flow. Leptomeningeal collateral arterial recruitment was quantified with a pial collateral score from x-ray angiograms, and infarct growth calculated from serially acquired diffusion weighted MRI scans. RESULTS: The degree of collateralization at x-ray correlated more strongly with qCBF using the Local-AIF in the ischemic penumbra (R2=0.81) than traditionally chosen Global-AIF (R2=0.05). qCBF using a Local-AIF was negatively correlated (less infarct progression as perfusion increased) with infarct growth (R2 = 0.79) more strongly than a Global-AIF (R2=0.02). CONCLUSIONS: In acute stroke, qCBF calculated with a Local-AIF is more accurate for assessing tissue status and collateral supply than traditionally chosen Global-AIFs. These findings support use of a Local-AIF that corrects for delayed and dispersed retrograde flow in determining quantitative tissue perfusion with collateral supply in occlusive disease. ABBREVIATIONS: MRI = magnetic resonance imaging; DSC = dynamic susceptibility contrast; PCS = pial collateral score; MCAO = middle cerebral artery occlusion; MCA = middle cerebral artery; AIF = arterial input function; rCBF = relative cerebral blood flow; qCBF = quantitative cerebral blood flow.