Near-zero stiffness accelerometer with buckling of tunable electrothermal microbeams.

Pre-shaped microbeams, curved or inclined, are widely used in MEMS for their interesting stiffness properties. These mechanisms allow a wide range of positive and negative stiffness tuning in their direction of motion. A mechanism of pre-shaped beams with opposite curvature, connected in a parallel configuration, can be electrothermally tuned to reach a near-zero or negative stiffness behavior at the as-fabricated position. The simple structure helps incorporate the tunable spring mechanism in different designs for accelerometers, even with different transduction technologies. The sensitivity of the accelerometer can be considerably increased or tuned for different applications by electrothermally changing the stiffness of the spring mechanism. Opposite inclined beams are implemented in a capacitive micromachined accelerometer. The measurements on fabricated prototypes showed more than 55 times gain in sensitivity compared to their initial sensitivity. The experiments showed promising results in enhancing the resolution of acceleration sensing and the potential to reach unprecedent performance in micromachined accelerometers.

Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development.

Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demonstrate that CRC diversity is forged by asynchronous forms of molecular alterations, where mutational and chromosomal instability collectively boost CRC genetic and microenvironment intra-tumor heterogeneity. We were able to depict predictor signatures of cancer-related genes that can foresee heterogeneity levels across the different tumor consensus molecular subtypes (CMS) and primary tumor location. Finally, we show that high genetic and microenvironment heterogeneity are associated with lower metastatic potential, whereas late-emerging copy number variations favor metastasis development and polyclonal seeding. This study provides an exhaustive portrait of the interplay between genetic and microenvironment intra-tumor heterogeneity across CMS subtypes, depicting molecular events with predictive value of CRC progression and metastasis development.

Python-Based Open-Source Electro-Mechanical Co-Optimization System for MEMS Inertial Sensors.

The surge in fabrication techniques for micro- and nanodevices gave room to rapid growth in these technologies and a never-ending range of possible applications emerged. These new products significantly improve human life, however, the evolution in the design, simulation and optimization process of said products did not observe a similarly rapid growth. It became thus clear that the performance of micro- and nanodevices would benefit from significant improvements in this area. This work presents a novel methodology for electro-mechanical co-optimization of micro-electromechanical systems (MEMS) inertial sensors. The developed software tool comprises geometry design, finite element method (FEM) analysis, damping calculation, electronic domain simulation, and a genetic algorithm (GA) optimization process. It allows for a facilitated system-level MEMS design flow, in which electrical and mechanical domains communicate with each other to achieve an optimized system performance. To demonstrate the efficacy of the methodology, an open-loop capacitive MEMS accelerometer and an open-loop Coriolis vibratory MEMS gyroscope were simulated and optimized-these devices saw a sensitivity improvement of 193.77% and 420.9%, respectively, in comparison to their original state.

Micromachined Accelerometers with Sub-µg/√Hz Noise Floor: A Review.

This paper reviews the research and development of micromachined accelerometers with a noise floor lower than 1 µg/√Hz. Firstly, the basic working principle of micromachined accelerometers is introduced. Then, different methods of reducing the noise floor of micromachined accelerometers are analyzed. Different types of micromachined accelerometers with a noise floor below 1 µg/√Hz are discussed. Such sensors can mainly be categorized into: (i) micromachined accelerometers with a low spring constant; (ii) with a large proof mass; (iii) with a high quality factor; (iv) with a low noise interface circuit; (v) with sensing schemes leading to a high scale factor. Finally, the characteristics of various micromachined accelerometers and their trends are discussed and investigated.

[Esophageal cancer: surgical strategies]. / Cancro do Esófago: Estratégia de Abordagem Cirúrgica.

INTRODUCTION: Oesophagectomy for cancer is associated to a significant morbidity and mortality. The superiority of transthoracic vs transhiatal is still a matter of controversy. The aim of this paper is to discuss the results of a series of patients submitted to either a transthoracic or a transhiatal according to the anatomic location regarding the carina. MATERIAL AND METHODS: Retrospective analysis of 52 consecutive patients, with oesophageal carcinoma, 7 female and 45 males, median age 64 [46-85] years. Location: cervical - 1; above carina - 22; below or at carina level - 19; cardia type I -10. 19 adenocarcinoma, 32 squamous cells, 1 lymphoma. Twenty patients (40%) - neo-adjuvant therapy. Thoracoabdominal approach - 3, cervico-thoracoabdominal - 20, transhiatal - 27, exploratory thoracotomy - 2. Gastric pull-up 49 (cervical anastomosis - 46; thoracic - 3); cervical oesofagocoloplasty -1. RESULTS: Pathologic staging: complete remission - 8; Ib - 3; IIa - 9; IIb - 4; IIa - 11; IIIb -2; IIIc - 10; IV - 1; non-stageable - 3. Major complications: 37%. Resectability: 96% (50/52). Mortality: 4th week - 6%; in-hospital - 14%. Median survival 18 months [3-80]. Survival Curves (Kaplan-Meier): 2 years - 47%; 5 years - 19% (transthoracic vs transhiatal p > 0.05). DISCUSSION: Selection of surgical approach based on the anatomic location of the tumour regarding the carina was safe, the resectability was high and similar when a transthoracic or a transhiatal was planed and carry-on. CONCLUSIONS: In this series of oesophageal cancer patients, in advanced pathologic condition (52% p Stages III/IV) the overall survival was similar for transthoracic and transhiatal. Neo-adjuvant treatments definitively contributed to enhance resectability.

Introdução: A ressecção transmediastínica e a ressecção transtorácica têm mortalidade hospitalar (1,4% -14%) e sobrevivência (± 25% aos cinco anos) semelhantes. A terapêutica neo-adjuvante é opção em estádios avançados. A intenção deste trabalho é apresentar uma série consecutiva de 52 doentes - opção operatória baseada na localização anatómica: tumores infra-carinais e cervicais submetidos a ressecção transmediastínica e restantes ressecções transtorácicas.Material e Métodos: O estudo incluiu 52 doentes consecutivos, sete mulheres e 45 homens, mediana de idade: 64 anos [46- 85]. Localização: cervical – um; montante da carina - 22; jusante da carina -19; cárdia tipo I –10. Histologia: 19 adenocarcinomas, 32 carcinomas pavimento-celulares, um linfoma. Vinte doentes (40%) - terapêutica neoadjuvante. Abordagem tóraco-abdominal – três, tóraco-abdómino-cervical – 20, transhiatal – 27, toracotomia exploradora – dois. Transposição gástrica 49 (anastomose cervical – 46; torácica - três); esofagocoloplastia cervical - um.Resultados: Estadiamento patológico: regressão completa - 8; Ib – 3; IIa – 9; IIb - 4; IIa – 11; IIIb -2; IIIc – 10; IV – 1; linfoma - um; não classificáveis – três. Complicações major: 37%. Ressecabilidade: 96% (50/52). Mortalidade: quatro semanas - 6%; hospitalar - 14%. Sobrevida mediana 18 meses [3-80]. Curvas de sobrevida (Kaplan-Meier): dois anos - 47%; cinco anos - 19%.Discussão: Não tendo sido demonstrada vantagem oncológica para a ressecção transtorácica ou a ressecção transmediastínica,basear a opção operatória na localização do tumor permitiu-nos com segurança e eficácia, planear e executar as ressecções esofágicas desta série.Conclusão: As curvas de sobrevida foram sobreponíveis para ressecção transtorácica e ressecção transmediastínica e bastantefavoráveis numa população com 52 % de estádios pIII/IV. A quimio-radioterapia contribuiu para aumentar a ressecabilidade.

An unusual fat-containing presacral tumor in an elderly patient.

The authors present a case of a presacral myelolipoma diagnosed in an 84-year-old male patient with longstanding pelvic pain and past medical history of bladder cancer. Pelvic computed tomography (CT) revealed a well-encapsulated and lobulated presacral mass, with mixed fat and soft-tissue attenuation. Magnetic resonance (MR) imaging provided further confirmation of macroscopic intralesional fat and excluded either adjacent bone invasion or bladder cancer recurrence. A presacral myelolipoma was suspected based on imaging findings, with liposarcoma and teratoma having also been considered for the differential diagnosis. The histological confirmation of the tumor was only attained postoperatively. This case report alerts to the possible presacral location of myelolipomas, which should be considered for every fat-containing lesion detected in this region. The main clinical, imaging, and differential diagnoses of this entity are reviewed in this paper.

Rare and severe complications of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a case report.

INTRODUCTION: We report the case of a patient with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency who presented with unusual anatomical and biochemical features, namely massively enlarged adrenal glands, adrenogenital rest tissue and an unexpected endocrine profile. The contribution of the adrenocortical cells in the adrenals and testicles was determined by a cosyntropin stimulation test before and after adrenalectomy. To the best of our knowledge this is the first report of such a case in the literature. CASE PRESENTATION: A 35-year-old Caucasian man was admitted to the emergency room with an Addisonian crisis. He had been diagnosed with congenital adrenal hyperplasia in the neonatal period. He acknowledged poor adherence to treatment and irregular medical assistance. Physical examination revealed marked cutaneous and gingival hyperpigmentation, hypotension, and hard nodules in the upper pole of both testicles. Blood analysis showed mild anemia and hyponatremia and no evidence of acute infection. Endocrine evaluation showed very low cortisol levels, low dehydroepiandrosterone-sulfate and elevated corticotropin, 11-deoxycortisol and delta-4-androstenedione. The concentration of 17-hydroxyprogesterone was 20,400ng/dL. After the cosyntropin stimulation test the pattern was similar and there was no significant increase in cortisol or 17-hydroxyprogesterone. The abdominal computed tomography scan revealed grossly enlarged and heterogeneous adrenal glands (left, 12cm; and right, six cm). A bilateral adrenalectomy was performed and pathologic examination revealed adrenal myelolipomas with nodular cortical hyperplasia. The sonogram showed bilateral heterogeneous masses on the upper pole of both testes which corresponded to the nodular hyperplasia of adrenal rest tissues. The genetic study revealed compound heterozigoty (mutations R124H and R356W), suggestive of a phenotypically moderate disease. We performed a cosyntropin stimulation test after adrenalectomy. The steroidogenic profile displayed the same unusual features, indicating an important contribution from the adrenogenital cells. CONCLUSION: This case illustrates that congenital adrenal hyperplasia due to 21-hydroxylase deficiency can progress to severe acute and chronic complications. The masses in the patient's adrenal glands and testicles resulted from chronically elevated adrenocorticotropic hormone and growth of adrenocortical cells. The basal and stimulated steroid profile, before and after adrenalectomy, revealed an unexpected pattern, suggesting significant contribution of the testicular adrenal cells to the steroidogenesis.

Alpha blockade with doxazosin in pheochromocytoma--report of three cases.

Pheochromocytoma is a catecholamine-secreting tumor, for which the treatment of choice is complete surgical resection, when possible. Some form of preoperative pharmacological preparation is indicated. Most centers use alpha blockade, phenoxybenzamine being the preferred drug. There is little experience with the use of other alpha-blocking agents. The authors report three different cases in which doxazosin was used: as preoperative preparation of a patient with pheochromocytoma, as preparation for therapy in I-131-MIBG of a patient with a malignant pheochromocytoma, and as a pre-cesarean preparation in a pregnant woman with multiple endocrine neoplasia type 2A (MEN-2A). Doxazosin provided a safe alternative to phenoxybenzamine in the three cases described, with some advantages that the authors summarize.

Veia mediana cubital: sua utilizaçäo na cirurgia dos acessos vasculares para hemodiálise / Medial-ulnar vein: use in surgery of the hemodialysis vascular access

Nos vasculares para hemodiálise, efectuados a nível do antebraço, utilizam-se, em regra, os vasos das suas faces anterior ou ântero-externa. A face posterior daquela regiäo é por todos reconhecida como a "zona esquerda". Nos útimos quatro anos, os AA. tiveram a oportunidade de utilizar a veia mediana-cubital por 11 vezes em 10 doentes. Após a sua transposiçäo para a face anterior, foram efectuadas: Em sete doentes, F.A.V. em "loop", com anastomose à arteria radial a nível do sangradouro; Em dois doentes, F.A.V. com anastomose T-L à artéria radial (no seu 1/3 médio); Nos dois últimos, com anastomose T-L à veia radial, em segmento ainda funcionante. Apenas num dos doentes ocorreu a oclusäo do acesso, por hipotensäo intra-dialítica prolongada, tendo-se realizado um novo acesso com a veia mediana-cubital, no membro oposto. Num outro doente, procedeu-se a ressecçäo de zona pré-oclusiva e sua substituiçäo por segmento de veia safena interna, autóloga. Todos os acessos se encontram, presentemente, funcionantes. Os bons resultados obtidos com a experiência citada levam os AA. a considerar a veia mediana-cubital como óptica alternativa, em circunstância de insucesso ou complicaçöes dos acessos vasculares efectuados com veias da face ântero-externa do antebraço