Evaluation of Thiel cadaveric model for MRI-guided stereotactic procedures in neurosurgery

BACKGROUND: Magnetic resonance imaging (MRI)-guided deep brain stimulation (DBS) and high frequency focused ultrasound (FUS) is an emerging modality to treat several neurological disorders of the brain. Developing reliable models to train and assess future neurosurgeons is paramount to ensure safety and adequate training of neurosurgeons of the future. METHODS: We evaluated the use of Thiel cadaveric model to practice MRI-guided DBS implantation and high frequency MRI-guided FUS in the human brain. We performed three training sessions for DBS and five sonications using high frequency MRI-guided FUS in five consecutive cadavers to assess the suitability of this model to use in training for stereotactic functional procedures. RESULTS: We found the brains of these cadavers preserved in an excellent anatomical condition up to 15 months after embalmment and they were excellent model to use, MRI-guided DBS implantation and FUS produced the desired lesions accurately and precisely in these cadaveric brains. CONCLUSION: Thiel cadavers provided a very good model to perform these procedures and a potential model to train and assess neurosurgeons of the future

Risk factors for moderate-to-severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

AbstractAmong 810 consecutive hematopoietic stem cell transplantation (HSCT) patients, 679 survived more than 3 months and were evaluated for chronic GVHD. The aim of this study was to find predisposing factors increasing the risk of development of moderate-to-severe chronic GVHD. Many of the donors were HLA-identical siblings or related (n = 435), 185 were HLA-matched unrelated, and 59 were mismatched related or unrelated donors. Most of the patients had a hematological malignancy (n = 568), but 111 patients with a nonmalignant disease were included. Two hundred twenty-three patients (33%) developed mild, 41 (6%) moderate, and 15 (2.2%) severe chronic GVHD. The 5-year probability of development of moderate-to-severe chronic GVHD was 10%. We analyzed 30 potential risk factors for chronic GVHD. In the multivariate analysis, acute GVHD grades II to IV (relative hazard [RH], 2.30; 95% CI, 1.29- 4.10; P = .005), CML diagnosis (RH, 2.37; CI, 1.38-4.08; P = .002) and transplantation from an immunized female donor to a male recipient (RH, 2.16; CI, 1.14-4.11; P = .02) were independent risk factors for moderate-to-severe chronic GVHD. Recipient age also was significant (RH, 2.42; CI, 1.23-4.77; P = .01) if CML was not included in the analysis. In patients with no risk factors, the 5-year probability of development of moderate-to-severe chronic GVHD was 5%. In patients with 1 risk factor, the probability was 13%; 2 risk factors, 23%; and 3 risk factors, 45%. Among patients who developed chronic GVHD (n = 279), acute GVHD grades II to IV (RH, 2.18; CI, 1.23-3.86; P < .01) was the only predictive factor for moderate-to-severe chronic GVHD versus mild disease. Patients with previous acute GVHD grades II to IV may benefit from more aggressive initial treatment. This possibility would have to be examined in clinical trials.Biol Blood Marrow Transplant 2002;8(12):674-82

The smaller the market, the better the rent capturing: electrification in North Portugal during the Interwar Period

This article analyses the origin of the persistently high level of electricity prices that hampered the expansion of electricity consumption during the interwar period in Porto. Initially, the rent-seeking behaviour of both the supply firm and the City Hall at the local level affected the expansion of the local electricity market. During the 1930s, this collusion at municipal level coincided with unpredictable energy policies at state level. This circumstance impeded the indispensable increase of scale and the building of a regional market of electricity in north Portugal. The literature on regulation and institutional analysis has proved very useful. Finally, though equally important, primary sources from company archives and institutional bodies were also employed.Este artículo analiza el origen de los elevados precios de la electricidad en Oporto entre las dos guerra mundiales y su secuela, su lenta electrificación. La colusión entre la compañía suministradora y el municipio limitó la expansión al comenzar el servicio hidroeléctrico; luego, la expectativa reiteradamente frustrada de una mayor intervención gubernamental fue en detrimento de mayores inversiones. Se impidió así el necesario aumento de escala, la plena integración del mercado eléctrico del Norte de Portugal y, en consecuencia, los precios eléctricos se mantuvieron elevados y la electrificación sufrió un persistente atraso. La adopción de una perspectiva institucional se ha revelado muy útil para esclarecer el funcionamiento de este mercado, que se ha examinado consultando fuentes empresariales, municipales y gubernamentales.This research has been financed by the Fundaçao Ciência e Tecnologia de Portugal

Technical Change and Industrial Dynamics as Evolutionary Processes

Technical Change and Industrial Dynamics as Evolutionary Processes

The developing rat kidney : the dopamine system and related serine/threonine kinases and phosphatases

The kidney originates from the fusion and conversion of two tissues: the metanephric mesenchyme and the ureter epithelium, an evagination from the Wolffian duct. Although a number of candidate molecules have been shown to be of importance for the differentiation of the embryonic kidney, many of the signalling pathway leading to this development are still obscure. A large proportion of important functions in eukaryotic cells is meticulously regulated by reversible protein phosphorylation, carried out by protein kinases and phosphates. This thesis presents data from five studieson serine/threonine protein phosphorylation during the foetal and postnatal development of the rat kidney. The isoforms of protein phosphatases (PP) 1 and PP2A had differential and age-dependent expression patterns, initially with a general distribution, shifting to restricted distributions later in nephrogenesis. All were present in the peripheral, nephrogenic, zone. Inhibition of PP1 and PP2A with okadaic acid in metanephric culture severely disturbed growth and differentiation and induced apoptosis. Protein kinase C (PKC) isoforms [alpha], [delta], [zeta] and [lambda]were age-dependently expressed with individual distribution patterns. Inhibition of PKC in primary culture of proximal tubule cells and in metanephric organ culture resulted in disrupted morphogenesis, increased apoptosis and age-dependent growth inhibition. Inhibitor-1, an endogenous and specific inhibitor of PP1, was specifically expressed in uninduced metanephric mesenchyme at embryonic day (E) 15. Inhibitor-1 is the first known marker of these cells. DARPP-32, another specific PP1 inibitor with a central position in dopaminergic cell signalling, was not detected until E 18. From that age, DARPP-32 was highly concentrated in ureter bud tips, the inducing tissue. The same distribution of DARPP-32 was observed in foetal mouse kidneys. Mice deficient in DARPP-32 had a 28% nephron deficit. They were also unable to regulate natriuresis in response to atrial natriuretic peptide. Furthermore, these mice were hypertensive. Dopamine and its synthesizing (AADC) and metabolizing (COMT) enzymes, as well as the dopamine D1A receptor, were all detected in foetal rat kidneys, each with specific distribution. Conclusion: Reversible protein phosphorylation is an important intracellular modulating system for kidney morphogenesis. This study also presents, for the first time, data indicating important roles for dopamine and dopamine-related signalling during nephrogenesis. The DARPP-32 deficient mice constitute a new model for limited nephron deficit and may be valuable in future research on renal insufficiency and hypertension