Sepsis-induced organ failure is associated with high morbidity and mortality rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.

Sepsis-induced organ failure is associated with high morbidity and mortality rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.

Sepsis-induced organ failure is associated with high morbidity and mortality rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.

Nos últimos anos, houve uma tendência na busca por substâncias reguladoras que pudessem otimizar o processo de cicatrização de membranas timpânicas (MTs) perfuradas. Objetivos: Determinar os efeitos da utilização da insulina tópica e da biomembrana de látex natural, de forma isolada e em associação, no processo de cicatrização de perfurações traumáticas de MTs. Materiais e Métodos: MTs de 61 ratos Wistar foram perfuradas nas porções anterior e posterior ao cabo do martelo. Os animais foram divididos em quatro grupos: Controle, Insulina, Látex e Insulina+Látex. No grupo Insulina, as perfurações foram tratadas com uso tópico de insulina regular. No grupo Látex, tratadas com biomembrana de látex natural. No grupo Insulina+Látex, tratadas com associação da insulina e da biomembrana de látex. As MTs foram avaliadas por técnicas histológicas com três, cinco e sete dias após sua perfuração traumática. Foram analisadas as morfometrias das espessuras das camadas epitelial, fibrosa e mucosa; tamanho da perfuração; área de secção transversal da MT; avaliação semiquantitativa e qualitativa da produção de colágeno por microscopia de polarização; e avaliação imuno-histoquímica das células epiteliais, dos miofibroblastos e da vascularização. Resultados: A insulina e a biomembrana de látex anteciparam o fechamento das perfurações traumáticas de MTs (p<0,01); estimularam precocemente o aumento da espessura da camada epitelial externa (p<0,01); promoveram aumento precoce da espessura da camada fibrosa (p<0,01); contribuíram para a maior identificação do anticorpo anti-panqueratina como marcador epitelial (p<0,05); aumentaram a marcação do anticorpo anti-alfa-actina de músculo liso (p<0,05), caracterizando maior proliferação de miofibroblastos. A insulina, isoladamente, provocou maior formação do colágeno tecidual (p<0,05), com fibras colágenas mais espessas e melhor organizadas (p<0,05). Conclusão: A insulina e a biomembrana de látex natural, de forma isolada e em associação, aceleraram o processo de cicatrização de perfurações traumáticas de MTs. / In recent years, there has been a tendency to search for regulatory substances that can optimize the healing process of perforated tympanic membranes (TMs). Objectives: To determine the effects of using topical insulin and natural latex biomembrane, alone or in combination, in the healing process of traumatic perforations of TMs. Methods: TMs of 61 Wistar rats were perforated in two sections, anterior and posterior to the malleus. The rats were divided into 4 groups: Control, Insulin, Latex, and Insulin+Latex. The Insulin group was treated with topical regular insulin. The Latex group was treated with natural latex biomembrane. The Insulin+Latex group was treated with a combination of insulin plus latex biomembrane. The TMs were histologically examined 3, 5, and 7 days post-perforation through morphometric analysis of the thickness of the epithelial, fibrous, and mucosal layers; size of the perforation; cross sectional area of the TM; semiquantitative and qualitative evaluation of the collagen production by polarization microscopy, and immunohistochemical evaluation of epithelial cells, myofibroblasts, and vascularization markers. Results: Insulin and latex biomembrane accelerated the healing process of the perforated TMs (p<0.01); stimulated early thickening of the outer epithelial layer (p<0.01); promoted premature increase in the thickness of the fibrous layer (p<0.01); contributed to a larger identification of anti-pankeratin antibody as epithelial marker (p<0.05); increased labeling of anti-alpha smooth muscle actin antibody (p<0.05), indicating greater proliferation of myofibroblasts. When insulin was used alone, it resulted in greater formation of collagen tissue (p<0.05), with thicker and better-organized collagen fibers (p<0.05). Conclusion: Insulin and natural latex biomembrane, used alone or in combination, accelerated the healing process of traumatic perforations of TMs.

Abstract Patients with orofacial clefts must overcome problems associated with their deformity including multiple surgeries, facial scarring, speech difficulties, dental problems and hearing loss. This study considered dental and hearing problems faced by cleft lip and palate patients in Northern Finland. The research aimed to determine prevalence of dental anomalies in cleft children, assess restorative treatment need and examine dental treatment necessary under general anesthesia. Other aims were to identify middle ear problems, need for ventilation tubes (VTs) among cleft children and examine the relationship between cleft severity, palatoplasty technique and hearing outcomes in cleft children aged between 3 and 9-years. The material comprised 214 cleft patients treated at Oulu University Hospital. In the dental study 26.6% had at least one dental anomaly while 17.9% had 2 or 3, most commonly missing or supernumerary teeth. In the general anesthesia study 11.5% had a syndrome and 52.4% of those with a syndrome aged 6-years-old needed restorative treatment. General anesthesia was required for dental treatment in 17.5% of cleft patients, mostly in those with a syndrome. In the middle ear study 79% had secretions in the middle ear during the study period. On average 3 VTs were placed in each patient. The prevalence of tympanic perforation was 35.9% and cholesteatoma occurred in 3.3%. In the hearing study pure tone average did not significantly differ between right and left ears and was unrelated to cleft severity or palatoplasty technique. Based on the dental study the severity of clefting increased with the prevalence of dental anomalies. The general anesthesia study found that need for restorations increased with cleft severity. The presence of a syndrome increased the need for dental treatment under general anesthesia. The middle ear study found that patients with cleft lip and palate and isolated cleft palate had more extensive clefts affecting Eustachian tube function with more frequent middle ear problems requiring more VTs than isolated cleft lip patients. Continuous presence of VTs increased the prevalence of tympanic perforation and cholesteatoma. The hearing study concluded that most of the 3 to 9 year-old cleft patients had normal hearing thresholds unaffected by cleft severity or palatoplasty technique. / Tiivistelmä Huuli- ja suulakihalkioihin liittyy monia haasteita kuten useita leikkauksia, näkyviä arpia, puheongelmia, hampaiston ongelmia ja kuulonalenemaa. Tässä tutkimuksessa perehdyttiin halkiolasten hampaiden ja kuulon ongelmiin Pohjois-Suomessa. Tutkimus selvitti halkiopotilaiden hampaiden anomalioiden esiintyvyyttä, hampaiden korjaavan hoidon tarvetta sekä hampaiden hoidon tarvetta yleisanestesiassa. Lisäksi selvitettiin välikorvaongelmia, ilmastointiputkien tarvetta sekä kuulontutkimustulosten yhteyttä halkion vakavuuden ja suulaen leikkaustekniikan välillä 3-9-vuotiailla halkiolapsilla. Aineisto koostui 214 halkiopotilaasta jotka hoidettiin Oulun yliopistollisessa sairaalassa. Potilaista 26,6%:lla oli vähintään yksi ja 17,9%:lla kaksi tai kolme hammasanomaliaa. Yleisin anomalia oli puuttuvat tai ylilukuiset hampaat. Yleisanestesiassa hoidetuista potilaista 11,5%:lla oli syndrooma eli oireyhtymä, kaikkiaan yleisanestesiaa tarvitsi 17,5%. 6-vuotiaista syndroomapotilaista 52,4% tarvitsi hampaiden korjaavaa hoitoa. Korvien tutkimuksessa 79%:lla potilaista oli eritettä välikorvissa tutkimusjakson aikana. Jokaiselle potilaalle laitettiin ilmastointiputket keskimäärin 3 kertaa. Tärykalvon perforaatio havaittiin 35,9%:lla ja kolesteatooma todettiin 3,3%:lla. Oikean ja vasemman korvan välillä ei ollut merkittävää eroa kuulontutkimustuloksissa eikä niillä havaittu yhteyttä halkion vakavuuden tai suulaen leikkaustekniikan kanssa. Halkion vakavuus lisäsi hammasanomalioiden esiintyvyyttä sekä korjaavan hoidon tarvetta yleisanestesiassa. Syndrooma lisäsi myös korjaavan hoidon tarvetta yleisanestesiassa. Huuli- ja suulakihalkiopotilailla sekä suulakihalkiopotilailla laaja halkio vaikutti voimakkaasti korvatorven toimintaan ja näin ollen se lisäsi putkituksia vaativia korvaongelmia toisin kuin huulihalkiopotilailla joilla suulaki oli ehjä. Jatkuva ilmastointiputkien läsnäolo lisäsi tärykalvon perforaatioita ja kolesteatoomia. Kuitenkin enemmistöllä 3-9-vuotiaista halkiopotilaista kuulotutkimustulokset olivat normaalit.

Sepsis-induced organ failure is associated with high morbidity and mortality rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.

El presente trabajo de investigación está orientado a la mejora de la fragmentación de rocas de la zona de Machu Picchu, la misma que se encuentra en el tajo Santa rosa de la Empresa Administradora Cerro S.A.C. Mediante el diseño de la malla de perforación, se considera la modificación de los parámetros como longitud y diámetro de taladro, así mismo con la aplicación de la nueva tecnología plasma. Se usó esta innovadora opción por tener como limitación la cercanía de zona urbana a unos 120 metros aproximadamente del proyecto. Aunque esta nueva opción permitía cumplir con la norma, no logró ser idóneo por los resultados en la fragmentación del macizo rocoso, generando un 64% de bancos mayores de 18''. Con este indicador se debió usar equipos adicionales generando un aumento en los costos operativos. Por consiguiente, se desarrollaron diversas pruebas con las mallas de perforación, y con la distribución de carga, considerando el tipo del macizo rocoso del proyecto, siendo Regular B, con RMR 49. Al finalizar el análisis de esta información se diseñó la propuesta de solución que consistió en la modificación de los parámetros de la malla de perforación, adecuados como el burden, espaciamiento, y altura de los taladros de producción. En el desarrollo del presente trabajo se tuvo resultados favorables en la disminución del tamaño de las rocas obtenidas después del disparo. / This research work aimed at improving rock fragmentation in the Machu Picchu area, the same one that found in the Santa Rosa Tagus of Empresa Administradora Cerro S.A.C. Through the design of the perforation mesh, consideration and modification of the parameters such as length and diameter of the hole, applying the new plasma technology. This innovative option used because it limited by the proximity of an urban area approximately 120 meters from the project. Although this new option allowed us to comply with the standard, it was not suitable due to the results in the fragmentation of the rocky massif, generating 64 % of banks larger than 18". With this indicator, additional equipment had to used, generating an increase in operating costs. Consequently, various tests developed with the drilling meshes and with the load distribution, considering the type of the rocky massif of the project, being Regular B, with RMR 49. At the end analysis of this information, the solution proposal was designed which consisted of modifying the parameters of the drilling mesh, suitable as the burden, spacing, and height of the production holes. In the development of the present work, favorable results were obtained in the reduction of the size of the rocks obtained after the shot. / Tesis

El presente trabajo de investigación, comprende la implementación de un diseño de malla de perforación en base a los criterios fundamentales de la ingeniería de voladura para analizar y controlar la dilución del mineral en yacimientos de vetas angostas de una mina subterránea polimetálica en el Perú. Por tal motivo, primero es analizar la base de datos proporcionados por la empresa minera con respecto a las condiciones geológicas para la clasificación del macizo rocoso de la caja techo, caja piso y la veta con el objetivo de determinar la calidad de la roca. Por otro lado, se debe examinar las leyes de mineral, potencia de la veta y el porcentaje de dilución para posteriormente determinar la continuidad y grosor de la veta en un bloque determinado, así mismo, analizar la dilución en función a los criterios fundamentales de la ingeniería de voladura. Este criterio está profundamente arraigado a la geología, perforación, voladura, planeamiento y al proceso de explotación. En esta investigación, se analiza la aplicabilidad de un diseño de la ingeniería de voladura en vetas angostas de una mina subterránea empleado en un contexto peruano de vetas a través de la recolección y observación de datos, utilizando el sistema de clasificación geomecánica de macizo rocoso de Bieniawski, ponderación promedio de la potencia de la veta, dilución geológica y operativa de los tajeos. La generación de soluciones será bajo el enfoque de la fórmula de McCarthy, Software Datamine, JK Simblast y el análisis de resultados finales del comportamiento de la dilución obtenido serán comparados en relación con los iniciales. / El presente trabajo de investigación, comprende la implementación de un diseño de malla de perforación en base a los criterios fundamentales de la ingeniería de voladura para analizar y controlar la dilución del mineral en yacimientos de vetas angostas de una mina subterránea polimetálica en el Perú. Por tal motivo, primero es analizar la base de datos proporcionados por la empresa minera con respecto a las condiciones geológicas para la clasificación del macizo rocoso de la caja techo, caja piso y la veta con el objetivo de determinar la calidad de la roca. Por otro lado, se debe examinar las leyes de mineral, potencia de la veta y el porcentaje de dilución para posteriormente determinar la continuidad y grosor de la veta en un bloque determinado, así mismo, analizar la dilución en función a los criterios fundamentales de la ingeniería de voladura. Este criterio está profundamente arraigado a la geología, perforación, voladura, planeamiento y al proceso de explotación. En esta investigación, se analiza la aplicabilidad de un diseño de la ingeniería de voladura en vetas angostas de una mina subterránea empleado en un contexto peruano de vetas a través de la recolección y observación de datos, utilizando el sistema de clasificación geomecánica de macizo rocoso de Bieniawski, ponderación promedio de la potencia de la veta, dilución geológica y operativa de los tajeos. La generación de soluciones será bajo el enfoque de la fórmula de McCarthy, Software Datamine, JK Simblast y el análisis de resultados finales del comportamiento de la dilución obtenido serán comparados en relación con los iniciales. / Tesis

El presente trabajo de investigación busca implementar una metodología de diseño de mallas de perforación y voladura en la empresa Minera Sotrami S.A, perteneciente al rubro de pequeña minería, con fines de estandarizarlo. La ejecución de dicha investigación se realiza mediante la utilización del algoritmo matemático de Holmberg que permite definir un modelo numérico para el diseño de una malla de perforación, y con la consideración de criterios operacionales encontrar una malla técnica que permita mejorar los rendimientos en las labores de exploración y desarrollo. Para el logro del mismo, se consideró como variable fija el tipo de roca (tipo III A) y las características geomecánicas presentes en ella; el diámetro del taladro de perforación como variable fija; y, el tipo de explosivo y accesorio de voladura como cambiantes, ya que se reemplazó la utilización de guías, mecha de seguridad y dinamita por el empleo de detonadores no eléctricos (Exaneles) y emulsiones encartuchadas. La oportuna y pertinente estandarización del proceso de perforación y voladura permitió obtener los siguientes resultados: el avance por disparo pasó a 1.62 m, el factor de carga se redujo a 13.46 kg/m y el factor de potencia disminuyo considerablemente. / This research work seeks to implement a design methodology for drilling and blasting meshes in the company Minera Sotrami S.A, belonging to the small mining sector, with finality to standardize it. This research is carried out by using the Holmberg mathematical algorithm that allows defining a numerical model for the design of a drilling mesh, and with the consideration of operational criteria, finding a technical mesh that allow improving the performance of exploration and development labors. To achieve it, the type of rock (type III - A) and the geomechanical characteristics present in it were considered as a fixed variable; the diameter of the drill as a fixed variable; the type blasting attachment and explosives as changeable, since the use of guides, safety wick and dynamite was replaced with the use of non electric detonators (Exaneles) and encapsulated emulsions. The opportune and pertinent standardization of the drilling and blasting process allowed obtaining the following results: the advance per shot was to 1.62 m, the load factor was reduced to 13.46 kg/m and the power factor decreased considerably. / Tesis

This project is about how we can create architecture that hold the same atmospheric qualities as a tale. By using different media like film, dioramas and technology the tales have been analysed for qualities that have been carried through into architecture. The blend of the real and the unreal is central to any tale and so also to my project; this mixed expression is carried through into the resulting structure. The final product becomes a bath house full of expression, impressions and varying realities.