APPROACHES AND DEVICES USED IN PULMONARY DRUG DELIVERY SYSTEM: A REVIEW

Targeting drug delivery into the lungs has become one of the most important aspects of systemic or local drug delivery.Consequently, in the last few years, techniques and new drug delivery devices intended to deliver drugs into the lungs havebeen widely developed. Currently, the main drug targeting regimens include direct application of a drug into the lungs,mostly by inhalation therapy using either pressurized metered dose inhalers (pMDI) or dry powder inhalers (DPI).Intratracheal administration is commonly used as a first approach in lung drug delivery in vivo. To convey a sufficient doseof drug to the lungs, suitable drug carriers are required. These can be solid, liquid, or gaseous excipients. Liposomes, nanoand microparticles, cyclodextrins, microemulsions, micelles, suspensions, or solutions are all examples of this type ofpharmaceutical carrier that have been successfully used to target drugs into lungs. The use of micro reservoir type systemsoffers clear advantages, such as high loading capacity and possibility of controlling size and permeability, and thus ofcontrolling the release kinetics of the drugs from the carrier systems. These systems make it possible to use relatively smallnumbers of vector molecules to deliver substantial amounts of a drug to the target. This review discusses the approaches anddevices required to be administer drug into the lungs

Evaluation of the Interfacial Sliding Stress of Ceramic Matrix Composites Under Tensile Loading

The fundamental strain mechanisms of Ceramic Matrix Composites are the matrix microcracking that induces a loss of stiffness and the fiber-matrix debonding that leads to interfacial frictional sliding [1]. The interfacial sliding stress is thus a key parameter in the global behavior. The use of an experimental device coupling an ultrasonic immersion tank to a tensile machine and an extensometer allows to detect the anisotropy of the damage mechanisms of a material as well as to perform a strain partition under load because it makes it possible to identify the elastic tensor variation. The inelastic strain identified this way comes from the transverse cracks opening due to both the fiber/matrix elasticity mismatch and relative sliding at the interface. It is then possible to assess the value of the interfacial sliding stress with a micromechanical model derived from the analytical expressions of the elastic properties of a fibrous composite containing cracks and a shear-lag analysis. This can be done because the experimental variation of the compliances gives access to the constitutive law of the transverse crack densities and allows to estimate the debonding length.</p

SUPREME-HN: a retrospective biomarker study assessing the prognostic value of PD-L1 expression in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND:Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although its role as a prognostic factor is controversial. This study investigates whether tumoral expression of PD-L1 is a prognostic marker in patients with recurrent and/or metastatic (R/M) HNSCC treated with standard chemotherapy. METHODS:This retrospective, multicenter, noninterventional study assessed PD-L1 expression on archival R/M HNSCC tissue samples using the VENTANA PD-L1 (SP263) Assay. PD-L1 high was defined as PD-L1 staining of ≥ 25% TC, with exploratory scoring at TC ≥ 10% and TC ≥ 50%. The primary objective of this study was to estimate the prognostic value of PD-L1 status in terms of overall survival (OS) in patients with R/M HNSCC. RESULTS:412 patients (median age, 62.0 years; 79.9% male; 88.2% Caucasian) were included from 19 sites in seven countries. 132 patients (32.0%) had TC ≥ 25% PD-L1 expression; 199 patients (48.3%) and 85 patients (20.6%) had TC ≥ 10% and ≥ 50%, respectively. OS did not differ significantly across PD-L1 expression (at TC ≥ 25% cutoff median OS: 8.2 months vs TC &lt; 25%, 10.1 months, P = 0.55) or the ≥ 10% and ≥ 50% cutoffs (at TC ≥ 10%, median OS: 9.6 months vs TC &lt; 10%, 9.4 months, P = 0.32, and at TC ≥ 50%, median OS 7.9 vs TC &lt; 50%, 10.0 months, P = 0.39, respectively). CONCLUSIONS:PD-L1 expression, assessed using the VENTANA PD-L1 (SP263) Assay, was not prognostic of OS in patients with R/M HNSCC treated with standard of care chemotherapies. Trial registration ClinicalTrials.gov, NCT02543476. Registered September 4, 2015

Fast fatigue limit estimation of woven composite materials by self-heating analysis

Abstract The fatigue limit of materials is usually difficult to estimate, and requires an expensive experimental campaign to test every sample under a large number of cycles in order to determine the asymptote of the S-N curve. An experimental study is here reported with the purpose to show an efficient and fast way to estimate the fatigue limit of a woven composite using only one sample. The studied material is subjected to stepped fatigue cycles, for increasing values of stress, with a fixed frequency and a constant stress ratio. The surface temperature variation and its heating rate are analyzed. Nomenclatur

RetroSpective cohort stUdy of PD-L1 expression in REcurrent and/or MEtastatic squamous cell carcinoma of the head and neck (SUPREME-HN)

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Elastic Characterization of Orthotropic Composite Materials from Ultrasonic Inspection through Non-Principal Planes

Transmission of bulk ultrasonic waves through materials immersed in water is a well appropriated method to measure the stiffness matrix of anisotropic composite materials. This matrix can be deduced from velocities measurements by simple [1,2,3] or double transmission [4,5] or from amplitudes of double reflected bulk waves [4]. All these methods are working very well for unidirectional composites when transverse isotropy is assumed and the stiffness matrix has only five independent elastic constants.</p

The Generation R Study: design and cohort update 2010

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children

Can environmental or occupational hazards alter the sex ratio at birth? A systematic review

More than 100 studies have examined whether environmental or occupational exposures of parents affect the sex ratio of their offspring at birth. For this review, we searched Medline and Web of Science using the terms ‘sex ratio at birth’ and ‘sex ratio and exposure’ for all dates, and reviewed bibliographies of relevant studies to find additional articles. This review focuses on exposures that have been the subject of at least four studies including polychlorinated biphenyls (PCBs), dioxins, pesticides, lead and other metals, radiation, boron, and g-forces. For paternal exposures, only dioxins and PCBs were consistently associated with sex ratios higher or lower than the expected 1.06. Dioxins were associated with a decreased proportion of male births, whereas PCBs were associated with an increased proportion of male births. There was limited evidence for a decrease in the proportion of male births after paternal exposure to DBCP, lead, methylmercury, non-ionizing radiation, ionizing radiation treatment for childhood cancer, boron, or g-forces. Few studies have found higher or lower sex ratios associated with maternal exposures. Studies in humans and animals have found a reduction in the number of male births associated with lower male fertility, but the mechanism by which environmental hazards might change the sex ratio has not yet been established