The pp-Daugavet property for function spaces

A natural extension of the Daugavet property for $p$-convex Banach function spaces and related classes is analysed. As an application, we extend the arguments given in the setting of the Daugavet property to show that no reflexive space falls into this class

A unique Valanginian paleoenvironment at an iron ore deposit near Zengővárkony (Mecsek Mts, South Hungary), and a possible genetic model

Abstract The spatially restricted Early Valanginian iron ore (limonite) and manganese deposit at Zengõvárkony (Mecsek Mts, southern Hungary) contains a rich, strongly limonitized, remarkably large-sized (specimens are 30–70% larger than those at their type localities) brachiopod-dominated (mainly Lacunosella and Nucleata) megafauna and a diverse crustacean microfauna, which indicates a shallow, nutrient-rich environment possibly linked to an uplifted block, and/or a hydrothermal vent

Predictors and Impact of Intensification of Antihyperglycemic Therapy in Type 2 Diabetes: Translating Research into Action for Diabetes (TRIAD)

ObjectiveThe purpose of this study was to examine the predictors of intensification of antihyperglycemic therapy in patients with type 2 diabetes; its impact on A1C, body weight, symptoms of anxiety/depression, and health status; and patient characteristics associated with improvement in A1C.Research design and methodsWe analyzed survey, medical record, and health plan administrative data collected in Translating Research into Action for Diabetes (TRIAD). We examined patients who were using diet/exercise or oral antihyperglycemic medications at baseline, had A1C >7.2%, and stayed with the same therapy or intensified therapy (initiated or increased the number of classes of oral antihyperglycemic medications or began insulin) over 18 months.ResultsOf 1,093 patients, 520 intensified therapy with oral medications or insulin. Patients intensifying therapy were aged 58 +/- 12 years, had diabetes duration of 11 +/- 9 years, and had A1C of 9.1 +/- 1.5%. Younger age and higher A1C were associated with therapy intensification. Compared with patients who did not intensify therapy, those who intensified therapy experienced a 0.49% reduction in A1C (P < 0.0001), a 3-pound increase in weight (P = 0.003), and no change in anxiety/depression (P = 0.5) or health status (P = 0.2). Among those who intensified therapy, improvement in A1C was associated with higher baseline A1C, older age, black race/ethnicity, lower income, and more physician visits.ConclusionsTreatment intensification improved glycemic control with no worsening of anxiety/depression or health status, especially in elderly, lower-income, and minority patients with type 2 diabetes. Interventions are needed to overcome clinical inertia when patients might benefit from treatment intensification and improved glycemic control

Improved diagnostics of “concealed” metastases in patients with сТ1–2N0М0 oral squamous cell carcinoma

Introduction. Oral squamous cell carcinoma is associated with a high risk of regional metastasis even in early stages (T1–2N0M0). Morphological examination reveals concealed metastases in 20 % of removed clinically unaffected lymph nodes.Objective – to evaluate the effectiveness of flow cytometry for detection of concealed metastases in sentinel lymph nodes as an indication for cervical lymph node dissection in patients with stage сT1–2N0M0 oral squamous cell carcinoma.Materials and methods. This study included 27 patients, including 13 patients (48.1 %) with stage T1N0M0 cancer and 14 patients with stage T2N0M0 cancer (51.9 %). At the first stage, all participants underwent primary tumor removal and cervical lymph node dissection with sentinel lymph node examination. After mobilization, half of these lymph nodes was used for routine morphological examination followed by immunohistochemical examination, while the second half of them was analyzed using flow cytometry. Then we compared the results obtained.Results. We examined 46 removed sentinel lymph nodes from 27 patients. Conventional histological examination revealed 4 concealed metastases (8.7 %). Polymerase chain reaction allowed us to detect another 16 metastases (37.8 %). Levels I, II, and III lymph nodes were most frequently affected. Flow cytometry demonstrated that 20 % of patients with a <4 mm invasion had concealed metastases, whereas patients with a 4 to 8 mm invasion had concealed metastases in 60 % of cases. Median follow-up time was 20.4 ± 11.7 months (range: 2.2 to 42.5 months; median 19.5 months). All participants were alive during this time. Seventeen out of 27 patients with stage T1–2N0M0 disease (63 %) were found to have concealed metastases, while the remaining ten patients (37 %) had no metastasis. One patient with stage T1N0M0 oral floor squamous cell carcinoma underwent the removal of the primary tumor and sentinel lymph node. Morphological examination and flow cytometry showed no metastatic lesions. After 14.8 months, the patient developed ipsilateral regional CN3 metastasis. The three-year progression-free survival rate was 94.7 ± 5.1 %.Conclusion. Highly sensible and rapid flow cytometry can become the method of choice in the diagnosis of metastases and deciding on cervical lymph node dissection in patients with cN0 disease. The study is still ongoing

NextGEM: Next-Generation Integrated Sensing and Analytical System for Monitoring and Assessing Radiofrequency Electromagnetic Field Exposure and Health

The evolution of emerging technologies that use Radio Frequency Electromagnetic Field (RF-EMF) has increased the interest of the scientific community and society regarding the possible adverse effects on human health and the environment. This article provides NextGEM’s vision to assure safety for EU citizens when employing existing and future EMF-based telecommunication technologies. This is accomplished by generating relevant knowledge that ascertains appropriate prevention and control/actuation actions regarding RF-EMF exposure in residential, public, and occupational settings. Fulfilling this vision, NextGEM commits to the need for a healthy living and working environment under safe RF-EMF exposure conditions that can be trusted by people and be in line with the regulations and laws developed by public authorities. NextGEM provides a framework for generating health-relevant scientific knowledge and data on new scenarios of exposure to RF-EMF in multiple frequency bands and developing and validating tools for evidence-based risk assessment. Finally, NextGEM’s Innovation and Knowledge Hub (NIKH) will offer a standardized way for European regulatory authorities and the scientific community to store and assess project outcomes and provide access to findable, accessible, interoperable, and reusable (FAIR) data

Primary Language, Income and the Intensification of Anti-glycemic Medications in Managed Care: the (TRIAD) Study

BACKGROUND Patients who speak Spanish and/or have low socioeconomic status are at greater risk of suboptimal glycemic control. Inadequate intensification of anti-glycemic medications may partially explain this disparity. OBJECTIVE To examine the associations between primary language, income, and medication intensification. DESIGN Cohort study with 18-month follow-up. PARTICIPANTS One thousand nine hundred and thirty-nine patients with Type 2 diabetes who were not using insulin enrolled in the Translating Research into Action for Diabetes Study (TRIAD), a study of diabetes care in managed care. MEASUREMENTS Using administrative pharmacy data, we compared the odds of medication intensification for patients with baseline A1c ≥ 8%, by primary language and annual income. Covariates included age, sex, race/ethnicity, education, Charlson score, diabetes duration, baseline A1c, type of diabetes treatment, and health plan. RESULTS Overall, 42.4% of patients were taking intensified regimens at the time of follow-up. We found no difference in the odds of intensification for English speakers versus Spanish speakers. However, compared to patients with incomes 75,000 (OR 2.22, 1.53-3.24) had increased odds of intensification. This latter pattern did not differ statistically by race. CONCLUSIONS Low-income patients were less likely to receive medication intensification compared to higher-income patients, but primary language (Spanish vs. English) was not associated with differences in intensification in a managed care setting. Future studies are needed to explain the reduced rate of intensification among low income patients in managed care

Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity

<p>Abstract</p> <p>Background</p> <p>Rapamycin, an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined.</p> <p>Methods</p> <p>We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naïve mice.</p> <p>Results</p> <p>Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using <it>ex vivo </it>generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt-1 tumor cell proliferation.</p> <p>Conclusion</p> <p>Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer <it>in vivo </it>that involves inhibition of the mTOR pathway at doses that also suppress host immune responses.</p

Cardiovascular risk associated with the use of glitazones, metformin and sufonylureas: meta-analysis of published observational studies

BACKGROUND: The results of observational studies evaluating and comparing the cardiovascular safety of glitazones, metformin and sufonylureas are inconsistent.To conduct and evaluate heterogeneity in a meta-analysis of observational studies on the risk of acute myocardial infarction (AMI) or stroke in patients with type 2 diabetes using non-insulin blood glucose–lowering drugs (NIBGLD). METHODS: We systematically identified and reviewed studies evaluating NIBGLD in patients with type 2 diabetes indexed in Medline, Embase, or the Cochrane Library that met prespecified criteria. The quality of included studies was assessed with the RTI item bank. Results were combined using fixed- and random-effects models, and the Higgins I(2) statistic was used to evaluate heterogeneity. Sensitivity analyses by study quality were conducted. RESULTS: The summary relative risk (sRR) (95 % CI) of AMI for rosiglitazone versus pioglitazone was 1.13 (1.04–1.24) [I(2) = 55 %]. In the sensitivity analysis, heterogeneity was reduced [I(2) = 16 %]. The sRR (95 % CI) of stroke for rosiglitazone versus pioglitazone was 1.18 (1.02–1.36) [I(2) = 42 %]. There was strong evidence of heterogeneity related to study quality in the comparisons of rosiglitazone versus metformin and rosiglitazone versus sulfonylureas (I(2) ≥ 70 %). The sRR (95 % CI) of AMI for sulfonylurea versus metformin was 1.24 (1.14–1.34) [I(2) = 41 %] and for pioglitazone versus metformin was 1.02 (0.75–1.38) [I(2) = 17 %]. Sensitivity analyses decreased heterogeneity in most comparisons. CONCLUSION/INTERPRETATION: Sulfonylureas increased the risk of AMI by 24 % compared with metformin; an imprecise point estimate indicated no difference in risk of AMI when comparing pioglitazone with metformin. The presence of heterogeneity precluded any conclusions on the other comparisons. The quality assessment was valuable in identifying methodological problems in the individual studies and for analysing potential sources of heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12872-016-0187-5) contains supplementary material, which is available to authorized users

T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers

Introduction: Lymphocyte infiltration (LI) is often seen in breast cancer but its importance remains controversial. A positive correlation of human epidermal growth factor receptor 2 (HER2) amplification and LI has been described, which was associated with a more favorable outcome. However, specific lymphocytes might also promote tumor progression by shifting the cytokine milieu in the tumor. Methods: Affymetrix HG-U133A microarray data of 1,781 primary breast cancer samples from 12 datasets were included. The correlation of immune system-related metagenes with different immune cells, clinical parameters, and survival was analyzed. Results: A large cluster of nearly 600 genes with functions in immune cells was consistently obtained in all datasets. Seven robust metagenes from this cluster can act as surrogate markers for the amount of different immune cell types in the breast cancer sample. An IgG metagene as a marker for B cells had no significant prognostic value. In contrast, a strong positive prognostic value for the T-cell surrogate marker (lymphocyte-specific kinase (LCK) metagene) was observed among all estrogen receptor (ER)-negative tumors and those ER-positive tumors with a HER2 overexpression. Moreover ER-negative tumors with high expression of both IgG and LCK metagenes seem to respond better to neoadjuvant chemotherapy. Conclusions: Precise definitions of the specific subtypes of immune cells in the tumor can be accomplished from microarray data. These surrogate markers define subgroups of tumors with different prognosis. Importantly, all known prognostic gene signatures uniformly assign poor prognosis to all ER-negative tumors. In contrast, the LCK metagene actually separates the ER-negative group into better or worse prognosis