A combined approach of vesicle formulations and microneedle arrays for transcutaneous immunization against hepatitis B virus

Drug Delivery Technolog

Деформационное упрочнение начально-изотропных металлов при деформировании по траекториям малой кривизны

На примере стали мартенситного класса исследованы закономерности деформационного упрочнения при нагружении по траекториям, имеющим вид двухзвенных ломаных, которым соответствуют траектории деформирования малой кривизны. Показано, что поверхность нагружения, разделяющая области упругого и упругопластического деформирования, смещается в направлении вектора, который соединяет центр поверхности нагружения и изображающую точку на траектории нагружения, при этом не изменяется форма ее фронтальной части. Зависимость величины смещения центра поверхности нагружения от интенсивности накопленных пластических деформаций описывается кривой, инвариантной к виду траектории нагружения.На прикладі сталі мартенситного класу досліджено закономірності деформаційного зміцнення при навантаженні по траєкторіях, що мають вигляд дволанкових ламаних, яким відповідають траєкторії деформування малої кривини. Показано, що поверхня навантаження, яка розділяє області пружного та пружнопластичного деформування, зміщується у напрямку вектора, який з ’єднує центр поверхні навантаження та відображуючу точку на траєкторії навантаження, при цьому форма фронтальної частини не змінюється. Залежність величини зміщення центра поверхні навантаження від інтенсивності накопичених пластичних деформацій описується кривою, яка є інваріантною відносно траєкторії навантаження.By the example of martensitic steel we study regularities of strain hardening under loading along two-section broken lines corresponding to slightly curved strain paths. It is shown that the loading surface separating domains of elastic and elastoplastic strains (yield surface) is displaced in the direction of a vector connecting the surface center with the loading trajectory image point, while the shape of its frontal part remains unchanged. The yield surface center displacement versus the intensity of accumulated plastic strains is described by a curve invariant to the loading trajectory

Development and external validation of a prediction model for tube feeding dependency for at least four weeks during chemoradiotherapy for head and neck cancer

Background & aims: Patients who receive chemoradiotherapy or bioradiotherapy (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates interfering with oral intake, causing tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF exceeds 4 weeks. We aimed to develop and externally validate a prediction model to identify patients who need TF ≥ 4 weeks and would benefit from prophylactic gastrostomy insertion. Methods: A retrospective multicenter cohort study was performed in four tertiary head and neck cancer centers in the Netherlands. The prediction model was developed using data from University Medical Center Utrecht and the Netherlands Cancer Institute and externally validated using data from Maastricht University Medical Center and Radboud University Medical Center. The primary endpoint was TF dependency ≥4 weeks initiated during CRT/BRT or within 30 days after CRT/BRT completion. Potential predictors were extracted from electronic health records and radiotherapy dose–volume parameters were calculated. Results: The developmental and validation cohort included 409 and 334 patients respectively. Multivariable analysis showed predictive value for pretreatment weight change, texture modified diet at baseline, ECOG performance status, tumor site, N classification, mean radiation dose to the contralateral parotid gland and oral cavity. The area under the receiver operating characteristics curve for this model was 0.73 and after external validation 0.62. Positive and negative predictive value for a risk of 90% or higher for TF dependency ≥4 weeks were 81.8% and 42.3% respectively. Conclusions: We developed and externally validated a prediction model to estimate TF-dependency ≥4 weeks in LAHNSCC patients treated with CRT/BRT. This model can be used to guide personalized decision-making on prophylactic gastrostomy insertion in clinical practice

Metabolic syndrome is an independent predictor of cardiovascular events in high-risk patients with occlusive and aneurysmatic peripheral arterial disease

Objective: Metabolic syndrome (MetSyn) is a well-known risk factor for cardiovascular (CV) disease in the general population; however, the additional predictive value for CV events in high-risk patients with peripheral arterial disease (PAD) is unknown. The aims of the current study were to assess and compare: (1) prevalence of MetSyn, and (2) predictive value of MetSyn for CV events, in patients with either occlusive or aneurysmatic PAD. Methods: We screened 2069 patients scheduled for lower occlusive arterial revascularization (n = 1031) or abdominal aortic aneurysm repair (n = 1038) for the presence of MetSyn. Adult Treatment Panel III report (ATP III) was used for de. ning MetSyn. Central obesity was defined as body-mass-index >30 kg/m(2). Main outcomes were the occurrence of CV events and CV mortality during a median follow-up of 6 years (IQR 2-9 years). Results: Metabolic syndrome was diagnosed in 421 (41%) and 432 (42%) patients with occlusive and aneurysmatic PAD, respectively (p = 0.72). Patients with occlusive or aneurysmatic PAD and MetSyn had an increased risk for the development of CV events, when compared to patients without MetSyn (27% vs. 18% and 27% vs. 19%, p < 0.001, respectively). In occlusive and aneurysmatic PAD, MetSyn was independently associated with an increased risk of CV events (HR = 1.6; 95% CI 1.2-2.1 and HR = 1.4; 95% CI 1.1-1.8). No significant association between the presence of MetSyn and CV mortality was observed. Conclusions: Metabolic syndrome is highly prevalent in high-risk PAD patients. In occlusive and aneurysmatic PAD patients, MetSyn is an independent predictor of long-term CV events. (C) 2009 Elsevier Ireland Ltd. All rights reserved.Vascular Biology and Interventio

Association of COPD with carotid wall intima-media thickness in vascular surgery patients

Introduction: There is increasing evidence that non-invasive imaging modalities such as ultrasonography may be able to detect subclinical atherosclerotic lesions, and as such may be useful tools for risk-stratification. However, the clinical relevance of these observations remains unknown in patients with COPD. Therefore we investigated the association between COPD and carotid wall intima-media thickness (IMT) in patients undergoing vascular surgery and its relationship with mortality in these patients. Methods: Carotid wall IMT was measured in 585 patients who underwent lower extremity, aortic aneurysm or stenosis repair. Primary study endpoint was increased carotid wall IMT which was defined as IMT >= 1.25 mm. Secondary study endpoints included total and cardiovascular mortality over a mean follow-up of 1.5 years. Results: Thirty-two percent of patients with mild COPD and 36% of the patients with moderate/severe COPD had increased carotid wall IMT, while only 23% had an increased carotid wall IMT in patients without COPD (p < 0.01). COPD was independently associated with an increased carotid wall IMT (OR 1.60; 95% Cl 1.08-2.36). Among patients with COPD, increased carotid wall IMT was associated with an increased risk of total (HR, 3.18 95% CI 1.93-5.24) and cardiovascular mortality (HR 7.28, 95% Cl 3.76-14.07). Conclusions: COPD is associated with increased carotid wall IMT independent of age and smoking status. Increased carotid wall IMT is associated with increased total and cardiovascular mortality in patients with COPD suggesting that carotid wall measurements may be a good biomarker for morbidity and mortality in these patients. (C) 2009 Elsevier Ltd. All rights reserved.Vascular Biology and Interventio