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The National Research Mentoring Network (NRMN) Strategic Empowerment Tailored for Health Equity Investigators (SETH) study evaluates the value of adding Developmental Network to Coaching in the career advancement of diverse Early-Stage Investigators (ESIs). Focused NIH-formatted Mock Reviewing Sessions (MRS) prior to the submission of grants can significantly enhance the scientific merits of an ESI’s grant application. We evaluated the most prevalent design, analysis-related factors, and the likelihood of grant submissions and awards associated with going through MRS, using descriptive statistics, Chi-square, and logistic regression methods. A total of 62 out of 234 applications went through the MRS. There were 69.4% that pursued R grants, 22.6% career development (K) awards, and 8.0% other grant mechanisms. Comparing applications that underwent MRS versus those that did not (N = 172), 67.7% vs. 38.4% were submitted for funding (i.e., unadjusted difference of 29.3%; OR = 4.8, 95% CI = (2.4, 9.8), p-value < 0.0001). This indicates that, relative to those who did not undergo MRS, ESIs who did, were 4.8 times as likely to submit an application for funding. Also, ESIs in earlier cohorts (1–2) (a period that coincided with the pre COVID-19 era) as compared to those who were recruited at later cohorts (3–4) (i.e., during the peak of COVID-19 period) were 3.8 times as likely to submit grants (p-value < 0.0001). The most prevalent issues that were identified included insufficient statistical design considerations and plans (75%), conceptual framework (28.3%), specific aims (11.7%), evidence of significance (3.3%), and innovation (3.3%). MRS potentially enhances grant submissions for extramural funding and offers constructive feedback allowing for modifications that enhance the scientific merits of research grants.

The COVID-19 pandemic has significantly taxed scientific research and seems to have exacerbated existing inequities within the research field, particularly for early-stage investigators (ESIs). This study examines the effects of the COVID-19 pandemic on traditionally underrepresented ESIs enrolled in an NIH-supported study evaluating the effectiveness of developmental networks, grant writing coaching, and mentoring on research career advancement. The survey consisted of 24 closed-ended (quantitative) and 4 open-ended questions (qualitative) linked to a participant’s ability to meet grant submission deadlines, research and professional development disruptions, stress level, career transition level, self-efficacy and management of scholarly tasks, and familial responsibilities. Results from 32 respondents (53%) suggest that COVID-19 adversely impacted the continuity of research (81%) and grant submissions (63%). On average, grant submissions were delayed by 6.69 months (i.e., greater than one grant cycle). We also conducted additional analyses characterizing nonresponse and found that there were no significant predictors of nonresponse, indicating a limited threat to the validity of our findings. The disruption caused by COVID-19 to the careers of ESIs from underrepresented groups in the biomedical workforce has been profound in the short term. The long-term consequences to the future success of these groups are unknown but is a worthwhile area of research and potential innovation.

As breast cancer relative survival continues to increase, many breast cancer patients face many issues, including recurrence of cancer and cancer-related side effects that impact several aspects of their quality of life. With breast cancer patients living longer, there is more of a concern for negative breast cancer outcomes. Although physical activity is an affordable and relatively convenient way to improve breast cancer outcomes, only about one-third of breast cancer survivors engage in the recommended level of physical activity. This article reviews articles published to date to examine whether home-based physical activity interventions are effective in improving physical activity and other outcomes among breast cancer survivors who have completed primary therapy for the disease. The present review is based upon bibliographic searches in PubMed and CINAHL and relevant search terms. Articles published in English from 1980 through February 28, 2019 were identified. A total of 360 article citations were identified in PubMed and non-duplicates in CINAHL. After screening the abstracts or full texts of these articles and reviewing the references of previous review articles, 20 studies that met the eligibility criteria. Three of the studies were pre-/post-test trials and 17 were randomized controlled trials. home-based exercise programs are effective in improving physical activity among breast cancer survivors who have completed primary therapy for the disease. Home-based exercise programs such as walking programs offer a convenient and affordable option for women who wish to increase their physical activity and maintain a healthy lifestyle.

Green infrastructure systems are often overdesigned. This may be a byproduct of static sizing (e.g., accounting for a design storm’s runoff volume but not exfiltration rates) or may be deliberate (e.g., buffering against performance loss through time). Regardless, overdesign may compromise plants’ access to water in systems where soil pits are embedded in infiltration beds. It could raise the storm size required for water to reach soil pits, reducing water availability between storms, which could ultimately induce plant physiological stress. This study investigated the hydrological dynamics and water relations of a tree trench system suspected to have been overbuilt and identified factors contributing to, compounding, and mitigating the risk of plant stress. Results provided strong evidence that the abovementioned processes played out. Water in the infiltration bed reached soil pits only once in three years, with that event occurring during a hydrant release. Moreover, minimal water was retained in the soil pit during the event due to the hydraulic properties of the soil media. Through a growing season, one of the two tree types frequently experienced water stress, while the other did so only rarely. These contrasting responses can likely be attributed to roots either being largely confined to the soil pits or reaching a deeper water source. Implications of these results for green infrastructure design are considered.

Classical biocontrol constitutes the importation of natural enemies from a native range to control a non-native pest. This is challenging when the target organism is phylogenetically close to a sympatric non-target form. Recent papers have proposed and recommended that two European moths (Archanara spp.) be introduced to North America to control non-native Phragmites australis australis, claiming they would not adversely affect native P. australis americanus. We assert that these papers overlooked research contradicting their conclusions and that the authors recommended release of the non-native moths despite results of their own studies indicating that attack on native Phragmites is possible after field release. Furthermore, their open-field, host-specificity tests were conducted in non-wetland fields in Switzerland using potted plants, reflecting considerably different conditions than those of North American wetlands. Also, native Phragmites in eastern North America has declined, increasing its potential vulnerability to any new stressors. Because all inadvertently introduced, established, Phragmites-specialist, herbivorous insects have done more harm to native than non-native Phragmites, native Phragmites may experience more intense herbivory than non-native Phragmites from the introduction of Archanara spp. due to demographic mechanisms (e.g., increase in density of the biocontrol agent and spillover onto alternate hosts) or because the herbivores may undergo genetic change. In addition to the risk to native Phragmites, significant biomass reduction of non-native Phragmites may decrease important ecosystem services, including soil accretion in wetlands affected by sea level rise. We strongly caution against the approval of Archanara spp. as biocontrol agents for non-native Phragmites in North America.

Objectives To describe the frequency of postnatal discussions about withdrawal or withholding of life-sustaining therapy (WWLST), ensuing WWLST, and outcomes of infants surviving such discussions. We hypothesized that such survivors have poor outcomes. Study design This retrospective review included registry data from 18 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Infants born at 22-28 weeks of gestation who survived >12 hours during 2011-2013 were included. Regression analysis identified maternal and infant factors associated with WWLST discussions and factors predicting ensuing WWLST. In-hospital and 18- to 26-month outcomes were evaluated. Results WWLST discussions occurred in 529 (15.4%) of 3434 infants. These were more frequent at 22-24 weeks (27.0%) compared with 27-28 weeks of gestation (5.6%). Factors associated with WWLST discussion were male sex, gestational age (GA) of ≤24 weeks, birth weight small for GA, congenital malformations or syndromes, early onset sepsis, severe brain injury, and necrotizing enterocolitis. Rates of WWLST discussion varied by center (6.4%-29.9%) as did WWLST (5.2%-20.7%). Ensuing WWLST occurred in 406 patients; of these, 5 survived to discharge. Of the 123 infants for whom intensive care was continued, 58 (47%) survived to discharge. Survival after WWLST discussion was associated with higher rates of neonatal morbidities and neurodevelopmental impairment compared with babies for whom WWLST discussions did not occur. Significant predictors of ensuing WWLST were maternal age >25 years, necrotizing enterocolitis, and days on a ventilator. Conclusions Wide center variations in WWLST discussions occur, especially at ≤24 weeks GA. Outcomes of infants surviving after WWLST discussions are poor. Trial registration ClinicalTrials.gov : NCT00063063 .

Phragmites australis is a cosmopolitan grass and often the dominant species in the ecosystems it inhabits. Due to high intraspecific diversity and phenotypic plasticity, P. australis has an extensive ecological amplitude and a great capacity to acclimate to adverse environmental conditions; it can therefore offer valuable insights into plant responses to global change. Here we review the ecology and ecophysiology of prominent P. australis lineages and their responses to multiple forms of global change. Key findings of our review are that: (1) P. australis lineages are well-adapted to regions of their phylogeographic origin and therefore respond differently to changes in climatic conditions such as temperature or atmospheric CO2; (2) each lineage consists of populations that may occur in geographically different habitats and contain multiple genotypes; (3) the phenotypic plasticity of functional and fitness-related traits of a genotype determine the responses to global change factors; (4) genotypes with high plasticity to environmental drivers may acclimate or even vastly expand their ranges, genotypes of medium plasticity must acclimate or experience range-shifts, and those with low plasticity may face local extinction; (5) responses to ancillary types of global change, like shifting levels of soil salinity, flooding, and drought, are not consistent within lineages and depend on adaptation of individual genotypes. These patterns suggest that the diverse lineages of P. australis will undergo intense selective pressure in the face of global change such that the distributions and interactions of co-occurring lineages, as well as those of genotypes within-lineages, are very likely to be altered. We propose that the strong latitudinal clines within and between P. australis lineages can be a useful tool for predicting plant responses to climate change in general and present a conceptual framework for using P. australis lineages to predict plant responses to global change and its consequences.

Breast cancer continues to be a disease with tremendous public health significance. Primary prevention of breast cancer is still not available, so efforts to promote early detection continue to be the major focus in fighting breast cancer. Since early detection is associated with decreased mortality, one would think that it is important to minimize delays in detection and diagnosis. There are two major types of delay. Patient delay is delay in seeking medical attention after self-discovering a potential breast cancer symptom. System delay is delay within the health care system in getting appointments, scheduling diagnostic tests, receiving a definitive diagnosis, and initiating therapy. Earlier studies of the consequences of delay on prognosis tended to show that increased delay is associated with more advanced stage cancers at diagnosis, thus resulting in poorer chances for survival. More recent studies have had mixed results, with some studies showing increased survival with longer delays. One hypothesis is that diagnostic difficulties could perhaps account for this survival paradox. A rapidly growing lump may suggest cancer to both doctors and patients, while a slow growing lump or other symptom could be less obvious to them. If this is the case, then the shorter delays would be seen with the more aggressive tumors for which the prognosis is worse leading to reduced survival. It seems logical that a tumor that is more advanced at diagnosis would lead to shorter survival; but the several counter-intuitive studies in this review show that it is dangerous to make assumptions.

Feeding intolerance (FI) occurs commonly in the neonatal intensive care unit. Breast milk contains a large pool of transforming growth factor-beta (TGF-β). Few studies describe TGF-β levels in preterm milk, and the relationship to FI remains unexplored. We measured TGF-β levels in preterm breast milk to investigate a correlation with FI in preterm infants. Prospective observational trial of 100 mother–infant pairs, enrolling infants born below 32 wk gestation and less than 1,500 g, and mothers who planned to provide breast milk. TGF-β levels were measured using enzyme-linked immunosorbent assay. Infant charts were reviewed for outcomes. TGF-β declined postnatally, most elevated in colostrum (P < 0.01). TGF-β2 levels were higher than TGF-β1 at all time points (P < 0.01). Colostrum TGF-β levels correlated inversely with birth weight (P < 0.01) and gestational age (P < 0.05). One-week TGF-β2 levels were reduced in growth-restricted infants with FI (P < 0.01). Of infants with necrotizing enterocolitis (NEC), TGF-β2 levels appeared to be low, but small sample size precluded meaningful statistical comparisons. TGF-β levels decline temporally in preterm milk. TGF-β1 colostrum levels correlate inversely with birth weight and gestational age. TGF-β2 may play a role in FI in growth-restricted infants. The relationship of TGF-β2 and NEC merits future investigation.

Energetic costs of tissue construction were compared in two subspecies of Phragmites australis, the common reed – namely the primary native and introduced lineages in North America. Caplan et al. report that the introduced lineage has lower construction costs than the native under all environmental conditions assessed, driven mainly by its lower cost rhizomes. These results highlight the fact that belowground energetics, which are seldom investigated, can influence the performance advantages that drive many plant invasions. The authors also demonstrate that tissue construction costs in organs not typically assessed can shift with global change, suggesting that they may have increasingly important implications into the future., The energetic cost of plant organ construction is a functional trait that is useful for understanding carbon investment during growth (e.g. the resource acquisition vs. tissue longevity tradeoff), as well as in response to global change factors like elevated CO2 and N. Despite the enormous importance of roots and rhizomes in acquiring soil resources and responding to global change, construction costs have been studied almost exclusively in leaves. We sought to determine how construction costs of aboveground and belowground organs differed between native and introduced lineages of a geographically widely dispersed wetland plant species (Phragmites australis) under varying levels of CO2 and N. We grew plants under ambient and elevated atmospheric CO2, as well as under two levels of soil nitrogen. We determined construction costs for leaves, stems, rhizomes and roots, as well as for whole plants. Across all treatment conditions, the introduced lineage of Phragmites had a 4.3 % lower mean rhizome construction cost than the native. Whole-plant construction costs were also smaller for the introduced lineage, with the largest difference in sample means (3.3 %) occurring under ambient conditions. In having lower rhizome and plant-scale construction costs, the introduced lineage can recoup its investment in tissue construction more quickly, enabling it to generate additional biomass with the same energetic investment. Our results suggest that introduced Phragmites has had an advantageous tissue investment strategy under historic CO2 and N levels, which has facilitated key rhizome processes, such as clonal spread. We recommend that construction costs for multiple organ types be included in future studies of plant carbon economy, especially those investigating global change.

Aspects of religiosity are important to health and quality of life of cancer patients. This analysis examined changes in religiosity among community-dwelling cancer survivors. Previously diagnosed and newly diagnosed cancer survivors age 65+ were interviewed at baseline and four years later to understand how components of religiosity may change. Religiosity was assessed as organizational, non-organizational, and intrinsic using the Duke Religiosity Scale. At four years, 45 persons had a new diagnosis of non-skin cancer in addition to the 94 diagnosed at baseline. In comparison to persons without a cancer diagnosis and participants with a baseline diagnosis, newly diagnosed participants were more likely to decrease church attendance. Although not statistically significant, a larger proportion of recently diagnosed persons increased non-organizational religiosity behaviors and intrinsic religiosity compared to those with cancer at baseline and those without cancer. African Americans were more likely than Caucasians to show increased non-organizational religiosity. Caucasians with a cancer diagnosis showed increased intrinsic religiosity, perhaps because of a ceiling effect among African Americans. Although all groups showed declines and increases in the measures, baseline religiosity was the strongest predictor of religiosity at 48 months, indicating stability in religiosity over time, even in the context of a cancer diagnosis.

Experimental observations reveal that the expression levels of different ion channels vary across neurons of a defined type, even when these neurons exhibit stereotyped electrical properties. However, there are robust correlations between different ion channel expression levels, although the mechanisms that determine these correlations are unknown. Using generic model neurons, we show that correlated conductance expression can emerge from simple homeostatic control mechanisms that couple expression rates of individual conductances to cellular readouts of activity. The correlations depend on the relative rates of expression of different conductances. Thus, variability is consistent with homeostatic regulation and the structure of this variability reveals quantitative relations between regulation dynamics of different conductances. Furthermore, we show that homeostatic regulation is remarkably insensitive to the details that couple the regulation of a given conductance to overall neuronal activity because of degeneracy in the function of multiple conductances and can be robust to "antihomeostatic" regulation of a subset of conductances expressed in a cell.

Background— Stem cells are thought to enhance vascular remodeling in ischemic tissue in part through paracrine effects. Using molecular imaging, we tested the hypothesis that treatment of limb ischemia with multipotential adult progenitor cells (MAPCs) promotes recovery of blood flow through the recruitment of proangiogenic monocytes. Methods and Results— Hind-limb ischemia was produced in mice by iliac artery ligation, and MAPCs were administered intramuscularly on day 1. Optical imaging of luciferase-transfected MAPCs indicated that cells survived for 1 week. Contrast-enhanced ultrasound on days 3, 7, and 21 showed a more complete recovery of blood flow and greater expansion of microvascular blood volume in MAPC-treated mice than in controls. Fluorescent microangiography demonstrated more complete distribution of flow to microvascular units in MAPC-treated mice. On ultrasound molecular imaging, expression of endothelial P-selectin and intravascular recruitment of CX 3 CR-1-positive monocytes were significantly higher in MAPC-treated mice than in the control groups at days 3 and 7 after arterial ligation. Muscle immunohistology showed a >10-fold-greater infiltration of monocytes in MAPC-treated than control-treated ischemic limbs at all time points. Intravital microscopy of ischemic or tumor necrosis factor-α–treated cremaster muscle demonstrated that MAPCs migrate to perimicrovascular locations and potentiate selectin-dependent leukocyte rolling. In vitro migration of human CD14 + monocytes was 10-fold greater in response to MAPC-conditioned than basal media. Conclusions— In limb ischemia, MAPCs stimulate the recruitment of proangiogenic monocytes through endothelial activation and enhanced chemotaxis. These responses are sustained beyond the MAPC lifespan, suggesting that paracrine effects promote flow recovery by rebalancing the immune response toward a more regenerative phenotype.

Unlike most biofuel species,Jatropha curcashas promise for use in marginal lands, but it may serve an additional role by stabilizing soils. We evaluated the growth and structural responsiveness of youngJ. curcasplants to diverse soil conditions. Soils included a sand, a sandy-loam, and a clay-loam from eastern Mexico. Growth and structural parameters were analyzed for shoots and roots, although the focus was the plasticity of the primary root system architecture (the taproot and four lateral roots). The sandy soil reduced the growth of both shoot and root systems significantly more than sandy-loam or clay-loam soils; there was particularly high plasticity in root and shoot thickness, as well as shoot length. However, the architecture of the primary root system did not vary with soil type; the departure of the primary root system from an index of perfect symmetry was14±5% (mean ± standard deviation). AlthoughJ. curcasdeveloped more extensively in the sandy-loam and clay-loam soils than in sandy soil, it maintained a consistent root to shoot ratio and root system architecture across all types of soil. This strong genetic determination would make the species useful for soil stabilization purposes, even while being cultivated primarily for seed oil.

Background The large conductance calcium-activated potassium channel alpha-subunit (Slo) is widely distributed throughout the body and plays an important role in a number of diseases. Prior work has shown that Slo, through its S10 region, interacts with β-catenin, a key component of the cytoskeleton framework and the Wnt signaling pathway. However, the physiological significance of this interaction was not clear. Methodology/Principal Findings Using a combination of proteomic and cell biology tools we show the existence of additional multiple binding sites in Slo, and explore in detail β-catenin interactions with the S10 region. We demonstrate that deletion of this region reduces Slo surface expression in HEK cells, which indicates that interaction with beta-catenin is important for Slo surface expression. This is confirmed by reduced expression of Slo in HEK cells and chicken (Gallus gallus domesticus leghorn white) hair cells treated with siRNA to β-catenin. HSlo reciprocally co-immunoprecipitates with β-catenin, indicating a stable binding between these two proteins, with the S10 deletion mutant having reduced binding with β-catenin. We also observed that mutations of the two putative GSK phosphorylation sites within the S10 region affect both the surface expression of Slo and the channel's voltage and calcium sensitivities. Interestingly, expression of exogenous Slo in HEK cells inhibits β-catenin-dependent canonical Wnt signaling. Conclusions and Significance These studies identify for the first time a central role for β-catenin in mediating Slo surface expression. Additionally we show that Slo overexpression can lead to downregulation of Wnt signaling.

The present study tested a mediational model of the role of religious involvement, spirituality, and physical/emotional functioning in a sample of African American men and women with cancer. Several mediators were proposed based on theory and previous research, including sense of meaning, positive and negative affect, and positive and negative religious coping. One hundred patients were recruited through oncologist offices, key community leaders and community organizations, and interviewed by telephone. Participants completed an established measure of religious involvement, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-SP-12 version 4), the Positive and Negative Affect Schedule (PANAS), the Meaning in Life Scale, the Brief RCOPE, and the SF-12, which assesses physical and emotional functioning. Positive affect completely mediated the relationship between religious behaviors and emotional functioning. Though several other constructs showed relationships with study variables, evidence of mediation was not supported. Mediational models were not significant for the physical functioning outcome, nor were there significant main effects of religious involvement or spirituality for this outcome. Implications for cancer survivorship interventions are discussed.

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in neonatal intensive care units, however its pathogenesis is not completely understood. We have previously shown that platelet activating factor (PAF), bacteria and TLR4 are all important factors in the development of NEC. Given that Toll-like receptors (TLRs) are expressed at low levels in enterocytes of the mature gastrointestinal tract, but were shown to be aberrantly over-expressed in enterocytes in experimental NEC, we examined the regulation of TLR4 expression and signaling by PAF in intestinal epithelial cells using human and mouse in vitro cell lines, and the ex vivo rat intestinal loop model. In intestinal epithelial cell (IEC) lines, PAF stimulation yielded upregulation of both TLR4 mRNA and protein expression and led to increased IL-8 secretion following stimulation with LPS (in an otherwise LPS minimally responsive cell line). PAF stimulation resulted in increased human TLR4 promoter activation in a dose dependent manner. Western blotting and immunohistochemical analysis showed PAF induced STAT3 phosphorylation and nuclear translocation in IEC, and PAF-induced TLR4 expression was inhibited by STAT3 and NFκB Inhibitors. Our findings provide evidence for a mechanism by which PAF augments inflammation in the intestinal epithelium through abnormal TLR4 upregulation, thereby contributing to the intestinal injury of NEC.

Human preterm infants with necrotizing enterocolitis (NEC) have increased circulating and luminal levels of platelet-activating factor (PAF) and decreased serum PAF-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF. Formula supplemented with recombinant PAF-AH decreases NEC in a neonatal rat model. We hypothesized that endogenous PAF-AH contributes to neonatal intestinal homeostasis, and therefore developed PAF-AH−/− mice using standard approaches to study the role of this enzyme in the neonatal NEC model. Following exposure to a well-established NEC model, intestinal tissues were evaluated for histology, pro-inflammatory cytokine mRNA synthesis, and death using standard techniques. We found that mortality rates were significantly lower in PAF-AH−/− pups compared to wild-type controls before 24 hours of life but surviving PAF-AH−/− animals were more susceptible to NEC development compared to wild-type controls. Increased NEC incidence was associated with prominent inflammation characterized by elevated intestinal mRNA expression of sPLA2, iNOS and CXCL1. In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and since preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease.

Objectives To compare inter-alpha inhibitor protein (IaIp) levels in neonates with proven necrotizing enterocolitis (NEC) and neonates with other, nonspecific abdominal disorders. Study design This was a prospective observational study of neonates in the neonatal intensive care unit. NEC was diagnosed according to Bell's staging criteria. The nNeonates in the control group had a nonspecific abdominal disorder, but no radiographic evidence of NEC and no disease progression. All neonates with radiographically confirmed NEC were included. Plasma IaIp levels were quantitated by enzyme-linked immunosorbent assay. Results Seventeen neonates had confirmed NEC, and 34 neonates had nonspecific abdominal disorders that improved rapidly. Gestational age, postnatal age, weight, sex, maternal obstetric variables, rupture of membranes, and mode of delivery did not differ between the two groups. Mean IaIp level was significantly lower in the NEC group compared with the control group (137 ± 38 mg/L; 95% confidence interval [CI], 118-157 mg/L vs 258 ± 53 mg/L; 95% CI, 238-277 mg/L; P Conclusions The finding of significantly lower IaIp levels in neonates with NEC suggests that IaIp might be a useful, sensitive biomarker, allowing initiation of appropriate therapy and reducing antibiotic overuse in neonates with suspected but unproven NEC. Administration of IaIp may significantly reduce the severity of systemic inflammation and associated tissue injury.

BACKGROUND: Several studies have attributed racial disparities in cancer incidence and mortality to variances in socioeconomic status and health insurance coverage. However, an Institute of Medicine report found that blacks received lower quality care than whites after controlling for health insurance, income, and disease severity. METHODS: To examine the effects of race on colorectal cancer outcomes within a single setting, the authors performed a retrospective cohort study that analyzed the cancer registry, billing, and medical records of 365 university hospital patients (175 blacks and 190 whites) diagnosed with stage II-IV colon cancer between 2000 and 2005. Racial differences in the quality (effectiveness and timeliness) of stage-specific colon cancer treatment (colectomy and chemotherapy) were examined after adjusting for socioeconomic status, health insurance coverage, sex, age, and marital status. RESULTS: Blacks and whites had similar sociodemographic characteristics, tumor stage and site, quality of care, and health outcomes. Age and diagnostic stage were predictors of quality of care and mortality. Although few patients (5.8%) were uninsured, they were more likely to present at advanced stages (61.9% at stage IV) and die (76.2%) than privately insured and publicly insured patients (p = .002). CONCLUSIONS: In a population without racial differences in socioeconomic status or insurance coverage, patients receive the same quality of care, regardless of racial distinction, and have similar health outcomes. Age, diagnostic stage, and health insurance coverage remained independently associated with mortality. Future studies of disparities in colon cancer treatment should examine sociocultural barriers to accessing appropriate care in various healthcare settings. Cancer 2010. © 2009 American Cancer Society.

Background Delivery of allergens with bacterial adjuvants has been shown to be a successful immunotherapeutic strategy for food allergy treatment in animal models. How microbial signals, acting through the innate immune system, reshape ongoing allergic responses is poorly understood. Objective To investigate the contribution of Toll-like receptors (TLRs) in the response to bacterial adjuvants, we designed an in vitro system to characterize the effect of heat-killed Escherichia coli vector (HKE) on peanut-induced responses of dendritic cells (DCs) and T cells. Methods Wild-type or TLR signaling–deficient bone marrow–derived DCs were pulsed with crude peanut extract (CPE) alone (50 μg/mL) in the presence of HKE (10 6 /mL). DC maturation was analyzed by means of flow cytometry. Treated DCs were cocultured with carboxyfluorescein succinimidyl ester (CFSE)-labeled CD4 + T cells from sensitized mice. Cytokine production from DCs and T cells was measured by using Bioplex assays. Results Peanut-pulsed DCs induced the production of IL-4, IL-5, and IL-13, as well as IL-17 and IFN-γ, from primed T cells. Adding HKE to CPE-pulsed DCs resulted in a significant decrease in T H 2 cytokine production associated with an increase in IFN-γ levels and profound attenuation of T-cell proliferation. These effects were linked to HKE-induced TLR-dependent changes in DC reactivity to CPE, especially the production of polarizing cytokines, such as IL-12. Conclusions TLR signals modulate peanut-induced DC maturation in vitro , leading to changes in the T-cell response to peanut. These TLR effects must be confirmed in vivo and might constitute another alternative for allergen immunotherapies.

Background— We hypothesized that molecular imaging of endothelial cell adhesion molecule expression could noninvasively evaluate prelesion atherogenic phenotype. Methods and Results— Mice deficient for the LDL-receptor and the Apobec-1 editing peptide (DKO mice) were studied as an age-dependent model of atherosclerosis. At 10, 20, and 40 weeks of age, ultrasound molecular imaging of the proximal thoracic aorta was performed with contrast agents targeted to P-selectin and VCAM-1. Atherosclerotic lesion severity and content were assessed by ultrahigh frequency ultrasound, histology, and immunohistochemistry. In wild-type mice at all ages, there was neither aortic thickening nor targeted tracer signal enhancement. In DKO mice, lesions progressed from sparse mild intimal thickening at 10 weeks to widespread severe lesions with luminal encroachment at 40 weeks. Molecular imaging for P-selectin and VCAM-1 demonstrated selective signal enhancement ( P Conclusions— Noninvasive ultrasound molecular imaging of endothelial activation can detect lesion-prone vascular phenotype before the appearance of obstructive atherosclerotic lesions.

Author(s): Anderson, LA; Caplan, LS; Buist, DS; Newton, KM; Curry, SJ; Scholes, D; LaCroix, AZ | Abstract: ObjectiveTo increase our understanding of the factors that impede or promote counseling about hormone replacement therapy, we asked clinicians to provide information concerning barriers and strategies to promote counseling.DesignWe asked clinicians to consider two different scenarios: (1) what they do in they current practice and (2) what they would do if their health care systems implemented the United States Preventive Services Task Force recommendation regarding hormone replacement therapy counseling. A total of 49 of 50 invited clinicians participated in one of six focus group interviews (three women's groups and three men's groups). Our analysis consisted of four steps: (1) identifying segments and classifying them into themes, (2) categorizing themes into topic areas, (3) establishing a final consensus of themes and topics, and (4) ascertaining similarities and contrasts among groups. Transcripts of sessions were analyzed across groups for themes using a text-based analysis system. Conceptualization of themes was derived using a system model of preventive care. Interrater agreement before consensus was good: Kappa (kappa) ranged from 0.70 to 1.00.ResultsFor current practice, identified barriers included lack of information about risks and benefits, unique challenges of counseling, and lack of resources to conduct counseling. The major strategies suggested were to develop and distribute patient education materials. Discussions about barriers to implementing the United States Task Force recommendation focused on lack of information and resources.ConclusionsSuggested strategies were multiple, involving individual-, relationship-, and system-level interventions. We expect the strategies identified to be supportive of future efforts to promote counseling for hormone replacement therapy.

Neurons co-express a multitude of different ion channels that determine the electrophysiological behaviour of the cell. Recent experimental observations have revealed that the expression of different ion channels varies dramatically within neurons of a defined type, even when these neurons exhibit stereotyped electrical properties [1-5]. This variability has a structure visible in the correlations between different ion channel expression levels. Nonetheless,, the underlying mechanism that determines these correlations is unknown, nor is understood how these correlations can coexist with activity-dependent regulation mechanisms that are also known to exist in neurons [6]. We show that these observations are logical consequences of relatively simple control mechanisms that couple the expression levels of individual conductances to a cell-intrinsic readout of activity [7]. Crucially, these correlations are not visible when conductance space is searched to find combinations of conductances that give target behaviour. Therefore, activity-dependent regulation mechanisms constrain the solution space of potential combinations of membrane conductances to a characteristic subset. Furthermore, we show how the shape of the conductance distribution of a population of neurons is determined by the relative rates of expression of different conductances. Finally, degeneracy in the function of multiple ion channels means that regulation mechanisms can have widely-variable parameters yet remain stable; this is exemplified by tolerance to 'anti-homeostatic' regulation of a subset of conductances.