Oxygen assisted focused electron beam induced deposition of silicon dioxide

Focused Electron Beam Induced Deposition (FEBID) is a rapid prototyping technique for the investigation, production and modification of 2 and 3-D nanostructures. The process takes place at room temperature, in the high-vacuum chamber of a Scanning Electron Microscope (SEM). The principle is based on the local FEB decomposition of molecules injected in the chamber and adsorbed on a surface. These molecules, called the precursors, are specifically chosen to contain the element of interest to be deposited. However, the electron induced decomposition results in contaminated materials containing additional parasitic elements from the precursor molecule. These contaminants are incorporated with the element of interest, and downgrade the properties of the materials and prevent therefore their use for many applications. Gas-assisted FEBID, the subject of this thesis, is a promising evolution and solution to the problem that was never extensively studied in literature. It consists in injecting a reactive gas simultaneously to the precursors, which will react in real time with the deposited contaminants to form volatile products, leaving ideally only the interesting material on the surface. This work focused on the Oxygen assisted FEBID of Silicon dioxide (SiO2) and on the understanding of the deposition process. SiO2 it is a high performance material for nano-optic and electronic applications, widely used in research and industry. Modifications were brought to an existing SEM to allow the simultaneous injection of two different and controlled gases, and to allow the in-situ control of growth of optical materials. Si-precursors of three families (alkoxy-, alkyl- and isocyanato-silanes) were compared. The FEBID material could be gradually converted from contaminated Si-materials to pure SiO2, above a [O2]/[precursor] ratio specific to each precursor chemistry and precursor flow. The SiO2 deposited was stoichiometric, C and OH–free, had an estimated density of 2.2, was amorphous and had optical properties close to that of fused silica. Optical structures for nano-optics and plasmonics were produced. Compared to traditional FEBID, O2 assisted FEBID required much lower energy to induce a decomposition reaction, and secondary electrons achieved 90 % of the deposition process in our setup. The electron efficiency could be multiplied by 20 compared to conventional FEBID. O2 assisted FEBID was insensitive to electron density in our setup. The conditions for no C and large deposition rates during O2 assisted FEBID were high molecule reactivity to O2, low sticking coefficient, low acceleration voltage and dwell time ( 60 µs). As function of the precursor chemistry and flow, additional O2 influenced the deposition rate, which could be increased it by a factor of 7. The O2 and precursor molecules co-adsorption resulted in a surface coverage competition, which determined the deposition efficiencies. Limitations due to the residual water in the SEM were demonstrated and characterized. They appeared as Oxygen incorporation in the deposited materials, which influenced the deposition process. Residual water impinging flow was demonstrated to be responsible of the FEBID process deposition efficiency when no Oxygen was injected

Blockade of VEGFR2 and not VEGFR1 can limit diet-induced fat tissue expansion: role of local versus bone marrow-derived endothelial cells.

BACKGROUND: We investigated if new vessel formation in fat involves the contribution of local tissue-derived endothelial cells (i.e., angiogenesis) or bone marrow-derived cells (BMDCs, i.e. vasculogenesis) and if antiangiogenic treatment by blockade of vascular endothelial growth factor (VEGF) receptors can prevent diet-induced obesity (DIO). METHODOLOGY/PRINCIPAL FINDINGS: We performed restorative bone marrow transplantation into wild-type mice using transgenic mice expressing green fluorescent protein (GFP) constitutively (driven by beta-actin promoter) or selectively in endothelial cells (under Tie2 promoter activation) as donors. The presence of donor BMDCs in recipient mice was investigated in fat tissue vessels after DIO using in vivo and ex vivo fluorescence microscopy. We investigated the roles of VEGF receptors 1 and 2 (VEGFR1/VEGFR2) by inducing DIO in mice and treating them with blocking monoclonal antibodies. We found only marginal (less than 1%) incorporation of BMDCs in fat vessels during DIO. When angiogenesis was inhibited by blocking VEGFR2 in mice with DIO, treated mice had significantly lower body weights than control animals. In contrast, blocking VEGFR1 had no discernable effect on the weight gain during DIO. CONCLUSIONS/SIGNIFICANCE: Formation of new vessels in fat tissues during DIO is largely due to angiogenesis rather than de novo vasculogenesis. Antiangiogenic treatment by blockade of VEGFR2 but not VEGFR1 may limit adipose tissue expansion

Extracorporeal support for pulmonary resection: current indications and results.

Extracorporeal assistances are exponentially used for patients, with acute severe but reversible heart or lung failure, to provide more prolonged support to bridge patients to heart and/or lung transplantation. However, experience of use of extracorporeal assistance for pulmonary resection is limited outside lung transplantation. Airways management with standard mechanical ventilation system may be challenging particularly in case of anatomical reasons (single lung), presence of respiratory failure (ARDS), or complex tracheo-bronchial resection and reconstruction. Based on the growing experience during lung transplantation, more and more surgeons are now using such devices to achieve good oxygenation and hemodynamic support during such challenging cases. We review the different extracorporeal device and attempt to clarify the current practice and indications of extracorporeal support during pulmonary resection

Pre-operative localization of solitary pulmonary nodules with computed tomography-guided hook wire: report of 181 patients.

BACKGROUND: Video-assisted thoracic surgery (VATS) is currently performed to diagnose and treat solitary pulmonary nodules (SPN). However, the intra-operative identification of deep nodules can be challenging with VATS as the lung is difficult to palpate. The aim of the study was to report the utility and the results of pre-operative computed tomography (CT)-guided hook wire localization of SPN. METHODS: All records of the patients undergoing CT-guided hook wire localization prior to VATS resection for SPN between 2002 and 2013 were reviewed. The efficacy in localizing the nodule, hook wire complications, necessity to convert VATS to thoracotomy and the histology of SPN are reported. RESULTS: One hundred eighty-one patients (90 females, mean age 63 y, range 28-82 y) underwent 187 pulmonary resections after CT-guided hook wire localization. The mean SPN diameter was 10.3 mm (range: 4-29 mm). The mean distance of the lesion from the pleural surface was 11.6 mm (range: 0-45 mm). The mean time interval from hook wire insertion to VATS resection was 224 min (range 54-622 min). Hook wire complications included pneumothorax requiring chest tube drainage in 4 patients (2.1%) and mild parenchymal haemorrhage in 11 (5.9%) patients. Migration of the hook wire occurred in 7 patients (3.7%) although it did not affect the success of VATS resection (nodule location guided by the lung puncture site). Three patients underwent additional wedge resection by VATS during the same procedure because no lesion was identified in the surgical specimen. Conversion thoracotomy was required in 13 patients (7 %) for centrally localized lesions (6 patients) and pleural adhesions (7 patients). The mean operative time was 60 min (range 18-135 min). Pathological examination revealed a malignant lesion in 107 patients (59 %). The diagnostic yield was 98.3 %. CONCLUSION: VATS resection for SPN after CT-guided hook wire localization for SPN is safe and allows for proper diagnosis with a low thoracotomy conversion rate

Blockade of VEGFR2 and Not VEGFR1 Can Limit Diet-Induced Fat Tissue Expansion: Role of Local versus Bone Marrow-Derived Endothelial Cells

Background: We investigated if new vessel formation in fat involves the contribution of local tissue-derived endothelial cells (i.e., angiogenesis) or bone marrow-derived cells (BMDCs, i.e. vasculogenesis) and if antiangiogenic treatment by blockade of vascular endothelial growth factor (VEGF) receptors can prevent diet-induced obesity (DIO). Methodology/Principal Findings: We performed restorative bone marrow transplantation into wild-type mice using transgenic mice expressing green fluorescent protein (GFP) constitutively (driven by β-actin promoter) or selectively in endothelial cells (under Tie2 promoter activation) as donors. The presence of donor BMDCs in recipient mice was investigated in fat tissue vessels after DIO using in vivo and ex vivo fluorescence microscopy. We investigated the roles of VEGF receptors 1 and 2 (VEGFR1/VEGFR2) by inducing DIO in mice and treating them with blocking monoclonal antibodies. We found only marginal (less than 1%) incorporation of BMDCs in fat vessels during DIO. When angiogenesis was inhibited by blocking VEGFR2 in mice with DIO, treated mice had significantly lower body weights than control animals. In contrast, blocking VEGFR1 had no discernable effect on the weight gain during DIO. Conclusions/Significance: Formation of new vessels in fat tissues during DIO is largely due to angiogenesis rather than de novo vasculogenesis. Antiangiogenic treatment by blockade of VEGFR2 but not VEGFR1 may limit adipose tissue expansion

Photodynamic drug delivery enhancement in tumours does not depend on leukocyte-endothelial interaction in a human mesothelioma xenograft model†

OBJECTIVES The pre-treatment of tumour neovessels by low-level photodynamic therapy (PDT) improves the distribution of concomitantly administered systemic chemotherapy. The mechanism by which PDT permeabilizes the tumour vessel wall is only partially known. We have recently shown that leukocyte-endothelial cell interaction is essential for photodynamic drug delivery to normal tissue. The present study investigates whether PDT enhances drug delivery in malignant mesothelioma and whether it involves comparable mechanisms of actions. METHODS Human mesothelioma xenografts (H-meso-1) were grown in the dorsal skinfold chambers of 28 nude mice. By intravital microscopy, the rolling and recruitment of leukocytes were assessed in tumour vessels following PDT (Visudyne® 400μg/kg, fluence rate 200mW/cm2and fluence 60J/cm2) using intravital microscopy. Likewise, the distribution of fluorescently labelled macromolecular dextran (FITC-dextran, MW 2000kDa) was determined after PDT. Study groups included no PDT, PDT, PDT plus a functionally blocking anti-pan-selectin antibody cocktail and PDT plus isotype control antibody. RESULTS PDT significantly enhanced the extravascular accumulation of FITC-dextran in mesothelioma xenografts, but not in normal tissue. PDT significantly increased leukocyte-endothelial cell interaction in tumour. While PDT-induced leukocyte recruitment was significantly blunted by the anti-pan-selectin antibodies in the tumour xenograft, this manipulation did not affect the PDT-induced extravasation of FITC-dextran. CONCLUSIONS Low-level PDT pre-treatment selectively enhances the uptake of systemically circulating macromolecular drugs in malignant mesothelioma, but not in normal tissue. Leukocyte-endothelial cell interaction is not required for PDT-induced drug delivery to malignant mesotheliom

Local control and short-term outcomes after video-assisted thoracoscopic surgery segmentectomy versus lobectomy for pT1c pN0 non-small-cell lung cancer.

The aim of this study was to compare short-term outcomes and local control in pT1c pN0 non-small-cell lung cancer that were intentionally treated by video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy. Multicentre retrospective study of consecutive patients undergoing VATS lobectomy (VL) or VATS segmentectomy (VS) for pT1c pN0 non-small-cell lung cancer from January 2014 to October 2021. Patients' characteristics, postoperative outcomes and survival were compared. In total, 162 patients underwent VL (n = 81) or VS (n = 81). Except for age [median (interquartile range) 68 (60-73) vs 71 (65-76) years; P = 0.034] and past medical history of cancer (32% vs 48%; P = 0.038), there was no difference between VL and VS in terms of demographics and comorbidities. Overall 30-day postoperative morbidity was similar in both groups (34% vs 30%; P = 0.5). The median time for chest tube removal [3 (1-5) vs 2 (1-3) days; P = 0.002] and median postoperative length of stay [6 (4-9) vs 5 (3-7) days; P = 0.039] were in favour of the VS group. Significantly larger tumour size (mean ± standard deviation 25.1 ± 3.1 vs 23.6 ± 3.1 mm; P = 0.001) and an increased number of lymph nodes removal [median (interquartile range) 14 (9-23) vs 10 (6-15); P < 0.001] were found in the VL group. During the follow-up [median (interquartile range) 31 (14-48) months], no statistical difference was found for local and distant recurrence in VL groups (12.3%) and VS group (6.1%) (P = 0.183). Overall survival (80% vs 80%) was comparable between both groups (P = 0.166). Despite a short follow-up, our preliminary data shows that local control is comparable for VL and VS

Low-Dose Vascular Photodynamic Therapy Decreases Tumor Interstitial Fluid Pressure, which Promotes Liposomal Doxorubicin Distribution in a Murine Sarcoma Metastasis Model.

INTRODUCTION: Solid tumors are known to have an abnormal vasculature that limits the distribution of chemotherapy. We have recently shown that tumor vessel modulation by low-dose photodynamic therapy (L-PDT) could improve the uptake of macromolecular chemotherapeutic agents such as liposomal doxorubicin (Liporubicin) administered subsequently. However, how this occurs is unknown. Convection, the main mechanism for drug transport between the intravascular and extravascular spaces, is mostly related to interstitial fluid pressure (IFP) and tumor blood flow (TBF). Here, we determined the changes of tumor and surrounding lung IFP and TBF before, during, and after vascular L-PDT. We also evaluated the effect of these changes on the distribution of Liporubicin administered intravenously (IV) in a lung sarcoma metastasis model. MATERIALS AND METHODS: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the lung of Fischer rats. Tumor/surrounding lung IFP and TBF changes induced by L-PDT were determined using the wick-in-needle technique and laser Doppler flowmetry, respectively. The spatial distribution of Liporubicin in tumor and lung tissues following IV drug administration was then assessed in L-PDT-pretreated animals and controls (no L-PDT) by epifluorescence microscopy. RESULTS: L-PDT significantly decreased tumor but not lung IFP compared to controls (no L-PDT) without affecting TBF. These conditions were associated with a significant improvement in Liporubicin distribution in tumor tissues compared to controls (P < .05). DISCUSSION: L-PDT specifically enhanced convection in blood vessels of tumor but not of normal lung tissue, which was associated with a significant improvement of Liporubicin distribution in tumors compared to controls