Deep reactive ion etching of auxetic structures: present capabilities and challenges

Auxetic materials (or metamaterials) have negative Poisson ratios (NPR) and display the unexpected properties of lateral expansion when stretched, and equal and opposing densification when compressed. Such auxetic materials are being used more frequently in the development of novel products, especially in the fields of intelligent expandable actuators, shape-morphing structures, and minimally invasive implantable devices. Although several micromanufacturing technologies have already been applied to the development of auxetic materials and devices, additional precision is needed to take full advantage of their special mechanical properties. In this study, we present a very promising approach for the development of auxetic materials and devices based on the use of deep reactive ion etching (DRIE). The process stands out for its precision and its potential applications to mass production. To our knowledge, it represents the first time this technology has been applied to the manufacture of auxetic materials with nanometric details. We take into account the present capabilities and challenges linked to the use of DRIE in the development of auxetic materials and auxetic-based devices.

Aberrant platelet-derived growth factor alpha-receptor transcript as a diagnostic marker for early human germ cell tumors of the adult testis.

Testicular germ cell tumors are the most common form of cancer in young adult males. They result from a derangement of primordial germ cells, and they grow out from a noninvasive carcinoma-in-situ precursor. Since carcinoma in situ can readily be cured by low-dose irradiation, there is a great incentive for non- or minimally invasive methods for detection of carcinoma in situ. We have recently shown that human Tera-2 embryonal carcinoma cells, obtained from a nonseminomatous testicular germ cell tumor, show alternative splicing and alternative promoter use of the platelet-derived growth factor alpha-receptor gene, giving rise to a unique 1.5-kb transcript. In this study we have set up a reverse transcriptase-polymerase chain reaction strategy for characterization of the various transcripts for this receptor. Using this technique, we show that a panel of 18 seminomas and II nonseminomatous testicular germ cell tumors all express the 1.5-kb transcript. In addition, a panel of 27 samples of testis parenchyma with established carcinoma in situ were all found to be positive for the 1.5-kb transcript, while parenchyma lacking carcinoma in situ, placenta, and control semen were all negative. These data show that the 1.5-kb platelet-derived growth factor alpha-receptor transcript can be used as a highly selective marker for detection of early stages of human testicular germ cell tumors.

Desnervação simpática renal e sua utilização no tratamento da hipertensão resistente : caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Hiperparatiroidismo primário assintomático : caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Essays on Entrepreneurship and Founder Pre-entry Knowledge

Thesis (Ph.D.)--University of Washington, 2016-06

A medical management of interstitial ectopic pregnancy: A 5-year clinical study

Background: Medical treatment of the rare interstitial ectopic pregnancy with methotrexate has been considered an alternative to surgical resection. Aim: To determine the treatment success rate with a single-dose intravenous methotrexate/folinic acid regimen and to identify predictors of treatment outcome. Methods: A 5-year audit (April 2000-August 2005) was carried out, collecting clinical imaging data and serum beta-human chorionic gonadotrophin (beta-hCG). Time taken for complete beta-hCG resolution was recorded, and a negative beta-hCG result was used as an endpoint of successful outcome. Results: Of the 13 cases, two required urgent surgery for rupture on presentation. In the remaining 11 cases, intravenous methotrexate (300 mg) was used, with oral folinic acid rescue (15 mg x 4 doses). There were no side-effects. Complete beta-hCG resolution was achieved in 10 of the 11 medically treated cases (91% success rate), requiring 21-129 days. Successful outcome was seen with initial beta-hCG level as high as 106 634 IU/L and gestation sac as large as 6 cm and a live fetus. Conclusion: The methotrexate/folinic acid regimen used as a one-dose treatment is safe and effective for unruptured interstitial pregnancy, with no side-effects and the advantage of avoiding invasive surgery. Subsequent tubal patency and reproductive function are yet to be ascertained.

Ocular biomaterials and the anterior eye

Hydrogels, water swollen polymer matrices, have been utilised in many biomedical applications, as there is the potential to manipulate the properties for a given application by changing the chemical structure of the constituent monomers The eye provides an excellent site to examne the interaction between a synthetic material and a complex biological fluid without invasive surgery. There is a need for the development of new synthetic hydrogels for use in the anterior eye, Three applications of hydrogels in the eye were considered in this thesis. For some patients, the only hope of any visual improvement lies in the use of an artificial cornea, or keratoprosthesis, Preliminary investigations of a series of simple homogeneous hydrogel copolymers revealed that the mechanical properties required to withstand surgery and in eye stresses, were not achieved This lead to work on the development of semi-interpenetrating polymer networks based on the aforementioned copolymers, Manufacture of the device and cell response were also studied. Lasers have been employed in ocular surgery to correct refractive defects. If an irregular surface is ablated, an irregular surface is obtained. A hydrogel system was investigated that could be applied to the eye prior to ablation to create a smooth surface. Factors that may influence ablation rate were explored, Soft contact lenses can be used as a probe to study the interaction between synthetic materials and the biological constituents of tears. This has lead to the development of many sensitive analytical techniques for protein and lipid deposition, one of which is fluorescence spectrophotometry. Various commercially available soft contact lenses were worn for different periods of time and then analysed for protein and lipid deposition using fluorescence spectrophotometry, The influence of water content, degree of ionicity and the lens material on the level and type of deposition was investigated.

Novel hardwired distributive tactile sensing system for medical applications

This thesis described the research carried out on the development of a novel hardwired tactile sensing system tailored for the application of a next generation of surgical robotic and clinical devices, namely a steerable endoscope with tactile feedback, and a surface plate for patient posture and balance. Two case studies are examined. The first is a one-dimensional sensor for the steerable endoscope retrieving shape and ‘touch’ information. The second is a two-dimensional surface which interprets the three-dimensional motion of a contacting moving load. This research can be used to retrieve information from a distributive tactile sensing surface of a different configuration, and can interpret dynamic and static disturbances. This novel approach to sensing has the potential to discriminate contact and palpation in minimal invasive surgery (MIS) tools, and posture and balance in patients. The hardwired technology uses an embedded system based on Field Programmable Gate Arrays (FPGA) as the platform to perform the sensory signal processing part in real time. High speed robust operation is an advantage from this system leading to versatile application involving dynamic real time interpretation as described in this research. In this research the sensory signal processing uses neural networks to derive information from input pattern from the contacting surface. Three neural network architectures namely single, multiple and cascaded were introduced in an attempt to find the optimum solution for discrimination of the contacting outputs. These architectures were modelled and implemented into the FPGA. With the recent introduction of modern digital design flows and synthesis tools that essentially take a high-level sensory processing behaviour specification for a design, fast prototyping of the neural network function can be achieved easily. This thesis outlines the challenge of the implementations and verifications of the performances.

A novel dried blood spot-LCMS method for the quantification of methotrexate polyglutamates as a potential marker for methotrexate use in children

Objective: Development and validation of a selective and sensitive LCMS method for the determination of methotrexate polyglutamates in dried blood spots (DBS). Methods: DBS samples [spiked or patient samples] were prepared by applying blood to Guthrie cards which was then dried at room temperature. The method utilised 6-mm disks punched from the DBS samples (equivalent to approximately 12 μl of whole blood). The simple treatment procedure was based on protein precipitation using perchloric acid followed by solid phase extraction using MAX cartridges. The extracted sample was chromatographed using a reversed phase system involving an Atlantis T3-C18 column (3 μm, 2.1x150 mm) preceded by Atlantis guard column of matching chemistry. Analytes were subjected to LCMS analysis using positive electrospray ionization. Key Results: The method was linear over the range 5-400 nmol/L. The limits of detection and quantification were 1.6 and 5 nmol/L for individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglutamates, respectively. The method has been applied successfully to the determination of DBS finger-prick samples from 47 paediatric patients and results confirmed with concentrations measured in matched RBC samples using conventional HPLC-UV technique. Conclusions and Clinical Relevance: The methodology has a potential for application in a range of clinical studies (e.g. pharmacokinetic evaluations or medication adherence assessment) since it is minimally invasive and easy to perform, potentially allowing parents to take blood samples at home. The feasibility of using DBS sampling can be of major value for future clinical trials or clinical care in paediatric rheumatology. © 2014 Hawwa et al.

A novel 3-D segmentation algorithm for anatomic liver and tumor volume calculations for liver cancer treatment planning

Three-Dimensional (3-D) imaging is vital in computer-assisted surgical planning including minimal invasive surgery, targeted drug delivery, and tumor resection. Selective Internal Radiation Therapy (SIRT) is a liver directed radiation therapy for the treatment of liver cancer. Accurate calculation of anatomical liver and tumor volumes are essential for the determination of the tumor to normal liver ratio and for the calculation of the dose of Y-90 microspheres that will result in high concentration of the radiation in the tumor region as compared to nearby healthy tissue. Present manual techniques for segmentation of the liver from Computed Tomography (CT) tend to be tedious and greatly dependent on the skill of the technician/doctor performing the task. ^ This dissertation presents the development and implementation of a fully integrated algorithm for 3-D liver and tumor segmentation from tri-phase CT that yield highly accurate estimations of the respective volumes of the liver and tumor(s). The algorithm as designed requires minimal human intervention without compromising the accuracy of the segmentation results. Embedded within this algorithm is an effective method for extracting blood vessels that feed the tumor(s) in order to plan effectively the appropriate treatment. ^ Segmentation of the liver led to an accuracy in excess of 95% in estimating liver volumes in 20 datasets in comparison to the manual gold standard volumes. In a similar comparison, tumor segmentation exhibited an accuracy of 86% in estimating tumor(s) volume(s). Qualitative results of the blood vessel segmentation algorithm demonstrated the effectiveness of the algorithm in extracting and rendering the vasculature structure of the liver. Results of the parallel computing process, using a single workstation, showed a 78% gain. Also, statistical analysis carried out to determine if the manual initialization has any impact on the accuracy showed user initialization independence in the results. ^ The dissertation thus provides a complete 3-D solution towards liver cancer treatment planning with the opportunity to extract, visualize and quantify the needed statistics for liver cancer treatment. Since SIRT requires highly accurate calculation of the liver and tumor volumes, this new method provides an effective and computationally efficient process required of such challenging clinical requirements.^

Interventional radiology and the care of the oncology patient.

Interventional Radiology (IR) is occupying an increasingly prominent role in the care of patients with cancer, with involvement from initial diagnosis, right through to minimally invasive treatment of the malignancy and its complications. Adequate diagnostic samples can be obtained under image guidance by percutaneous biopsy and needle aspiration in an accurate and minimally invasive manner. IR techniques may be used to place central venous access devices with well-established safety and efficacy. Therapeutic applications of IR in the oncology patient include local tumour treatments such as transarterial chemo-embolisation and radiofrequency ablation, as well as management of complications of malignancy such as pain, organ obstruction, and venous thrombosis.

C-MEMS Based Micro Enzymatic Biofuel Cells

Miniaturized, self-sufficient bioelectronics powered by unconventional micropower may lead to a new generation of implantable, wireless, minimally invasive medical devices, such as pacemakers, defibrillators, drug-delivering pumps, sensor transmitters, and neurostimulators. Studies have shown that micro-enzymatic biofuel cells (EBFCs) are among the most intuitive candidates for in vivo micropower. In the fisrt part of this thesis, the prototype design of an EBFC chip, having 3D intedigitated microelectrode arrays was proposed to obtain an optimum design of 3D microelectrode arrays for carbon microelectromechanical systems (C-MEMS) based EBFCs. A detailed modeling solving partial differential equations (PDEs) by finite element techniques has been developed on the effect of 1) dimensions of microelectrodes, 2) spatial arrangement of 3D microelectrode arrays, 3) geometry of microelectrode on the EBFC performance based on COMSOL Multiphysics. In the second part of this thesis, in order to investigate the performance of an EBFC, behavior of an EBFC chip performance inside an artery has been studied. COMSOL Multiphysics software has also been applied to analyze mass transport for different orientations of an EBFC chip inside a blood artery. Two orientations: horizontal position (HP) and vertical position (VP) have been analyzed. The third part of this thesis has been focused on experimental work towards high performance EBFC. This work has integrated graphene/enzyme onto three-dimensional (3D) micropillar arrays in order to obtain efficient enzyme immobilization, enhanced enzyme loading and facilitate direct electron transfer. The developed 3D graphene/enzyme network based EBFC generated a maximum power density of 136.3 μWcm-2 at 0.59 V, which is almost 7 times of the maximum power density of the bare 3D carbon micropillar arrays based EBFC. To further improve the EBFC performance, reduced graphene oxide (rGO)/carbon nanotubes (CNTs) has been integrated onto 3D mciropillar arrays to further increase EBFC performance in the fourth part of this thesisThe developed rGO/CNTs based EBFC generated twice the maximum power density of rGO based EBFC. Through a comparison of experimental and theoretical results, the cell performance efficiency is noted to be 67%.

Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease

Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1. Implementation of next generation sequencing platforms for molecular diagnostics in non-small-cell lung cancer is increasingly common, allowing testing of multiple genetic variants from a single sample. The use of next generation sequencing to recruit for molecularly stratified clinical trials is discussed in the context of the UK Stratified Medicine Programme and The UK National Lung Matrix Trial.

Laparoscopic versus open total mesorectal excision for stage I-III mid and low rectal cancer: a retrospective 5 years analysis

Introduction. Total mesorectal excision (TME) is the cornerstone of a correct surgical therapy for extraperitoneal rectal cancer. Aim of the study is to evaluate our 5 years experience confronting retrospectively laparoscopic (lap) TME in respect to its laparotomic (open) counterpart. Patients and Methods. 30 patients were treated laparoscopically for stage I-III extraperitoneal rectal cancer and retrospectively compared to a homogeneous group, stratified for sex, age, comorbidities and stage of disease. Results. 30 days mortality was zero for both groups, while morbidity was 20% for the lap group and 36.6% for the open group. Mean lymph nodes harvested was 24 ± 12 for the lap group, 26 ± 14 for the open group (p > 0.05). Five years overall and disease free survival was respectively 82.2% and 81.4% in the lap group, 79.9% and 79.6% in the open group, without statistical significance (p>0.05). Discussion. Minimally invasive TME resulted a safe, effective and oncologically adequate procedure when retrospectively compared to its laparotomic counterpart, with 5 years overall survival and disease free survival reaching no statistical significance compared to the open approach, but with all the advantages of the laparoscopy such as less pain and blood loss, faster recovery, less morbidity and better cosmetics. Conclusions. Our study has retrospectively demonstrated that laparoscopic TME is feasible and oncologically effective, even if it remains a complex minimally invasive procedure, requiring adequate skill. More prospective, randomized studies are necessary to define such a procedure as the new gold standard in treatment of stage I-III extraperitoneal rectal cancer.

Endovascular treatment of multiple anomalous splenic artery aneurysms in a Jehovah witness

Purpose. The present report describes a full endovascular treatment of a multiple anomalous (Splenic artery aneurysms) SAA with combination of coils embolization and proximal occlusion of the splenic artery with the Amplatzer vascular plug. Case report. A 53-year-old Jehovah witness woman presented with multiple aneurysms arising from an anomalous splenic artery. An endovascular treatment was performed by implantation of multiple coils and an Amplatzer Vascular Plug. A CT scan 2 months after the procedure showed complete thrombosis of the aneurysms. Discussion. Aneurysms involving an anomalous or aberrant splenic artery are rarely reported in the literature. Their surgical treatment involves potential difficulties as a consequence of anatomical position and vascular anomalies. A fully endovascular technique can be much more attractive compared to any surgical management, providing an effective and minimally invasive option. Splenic artery - Aberrant splenic artery - Aneurysm - Endovascular treatment - Jehovah witness.