949 resultados para Compromise of 1850.


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Suomenlahden lisääntynyt meriliikenne on herättänyt huolta meriliikenteen turvallisuuden tasosta, ja erityisesti Venäjän öljyviennin kasvu on lisännyt öljyonnettomuuden todennäköisyyttä Suomenlahdella. Erilaiset kansainväliset, alueelliset ja kansalliset ohjauskeinot pyrkivät vähentämään merionnettomuuden riskiä ja meriliikenteen muita haittavaikutuksia. Tämä raportti käsittelee meriturvallisuuden yhteiskunnallisia ohjauskeinoja: ohjauskeinoja yleisellä tasolla, meriturvallisuuden keskeisimpiä säätelijöitä, meriturvallisuuden ohjauskeinoja ja meriturvallisuuspolitiikan tulevaisuuden näkymiä, ohjauskeinojen tehokkuutta ja nykyisen meriturvallisuuden ohjausjärjestelmän heikkouksia. Raportti on kirjallisuuskatsaus meriturvallisuuden yhteiskunnalliseen sääntelyn rakenteeseen ja tilaan erityisesti Suomenlahden meriliikenteen näkökulmasta. Raportti on osa tutkimusprojektia ”SAFGOF - Suomenlahden meriliikenteen kasvunäkymät 2007 - 2015 ja kasvun vaikutukset ympäristölle ja kuljetusketjujen toimintaan” ja sen työpakettia 6 ”Keskeisimmät riskit ja yhteiskunnalliset vaikutuskeinot”. Yhteiskunnalliset ohjauskeinot voidaan ryhmitellä hallinnollisiin, taloudellisiin ja tietoohjaukseen perustuviin ohjauskeinoihin. Meriturvallisuuden edistämisessä käytetään kaikkia näitä, mutta hallinnolliset ohjauskeinot ovat tärkeimmässä asemassa. Merenkulun kansainvälisen luonteen vuoksi meriturvallisuuden sääntely tapahtuu pääosin kansainvälisellä tasolla YK:n ja erityisesti Kansainvälisen merenkulkujärjestön (IMO) toimesta. Lisäksi myös Euroopan Unionilla on omaa meriturvallisuuteen liittyvää sääntelyä ja on myös olemassa muita alueellisia meriturvallisuuden edistämiseen liittyviä elimiä kuten HELCOM. Joitakin meriturvallisuuden osa-alueita säädellään myös kansallisella tasolla. Hallinnolliset meriturvallisuuden ohjauskeinot sisältävät aluksen rakenteisiin ja varustukseen, alusten kunnon valvontaan, merimiehiin ja merityön tekemiseen sekä navigointiin liittyviä ohjauskeinoja. Taloudellisiin ohjauskeinoihin kuuluvat esimerkiksi väylä- ja satamamaksut, merivakuutukset, P&I klubit, vastuullisuus- ja korvauskysymykset sekä taloudelliset kannustimet. Taloudellisten ohjauskeinojen käyttö meriturvallisuuden edistämiseen on melko vähäistä verrattuna hallinnollisten ohjauskeinojen käyttöön, mutta niitä voitaisiin varmasti käyttää enemmänkin. Ongelmana taloudellisten ohjauskeinojen käytössä on se, että ne kuuluvat pitkälti kansallisen sääntelyn piiriin, joten alueellisten tai kansainvälisten intressien edistäminen taloudellisilla ohjauskeinoilla voi olla hankalaa. Tieto-ohjaus perustuu toimijoiden vapaaehtoisuuteen ja yleisen tiedotuksen lisäksi tieto-ohjaukseen sisältyy esimerkiksi vapaaehtoinen koulutus, sertifiointi tai meriturvallisuuden edistämiseen tähtäävät palkinnot. Poliittisella tasolla meriliikenteen aiheuttamat turvallisuusriskit Suomenlahdella on otettu vakavasti ja paljon työtä tehdään eri tahoilla riskien minimoimiseksi. Uutta sääntelyä on odotettavissa etenkin liittyen meriliikenteen ympäristövaikutuksiin ja meriliikenteen ohjaukseen kuten meriliikenteen sähköisiin seurantajärjestelmiin. Myös inhimilliseen tekijän merkitykseen meriturvallisuuden kehittämisessä on kiinnitetty lisääntyvissä määrin huomiota, mutta inhimilliseen tekijän osalta tehokkaiden ohjauskeinojen kehittäminen näyttää olevan haasteellista. Yleisimmin lääkkeeksi esitetään koulutuksen kehittämistä. Kirjallisuudessa esitettyjen kriteereiden mukaan tehokkaiden ohjauskeinojen tulisi täyttää seuraavat vaatimukset: 1) tarkoituksenmukaisuus – ohjauskeinojen täytyy olla sopivia asetetun tavoitteen saavuttamiseen, 2) taloudellinen tehokkuus – ohjauskeinon hyödyt vs. kustannukset tulisi olla tasapainossa, 3) hyväksyttävyys – ohjauskeinon täytyy olla hyväksyttävä asianosaisten ja myös laajemman yhteiskunnan näkökulmasta katsottuna, 4) toimeenpano – ohjauskeinon toimeenpanon pitää olla mahdollista ja sen noudattamista täytyy pystyä valvomaan, 5) lateraaliset vaikutukset – hyvällä ohjauskeinolla on positiivisia seurannaisvaikutuksia muutoinkin kuin vain ohjauskeinon ensisijaisten tavoitteiden saavuttaminen, 6) kannustin ja uuden luominen – hyvä ohjauskeino kannustaa kokeilemaan uusia ratkaisuja ja kehittämään toimintaa. Meriturvallisuutta koskevaa sääntelyä on paljon ja yleisesti ottaen merionnettomuuksien lukumäärä on ollut laskeva viime vuosikymmenien aikana. Suuri osa sääntelystä on ollut tehokasta ja parantanut turvallisuuden tasoa maailman merillä. Silti merionnettomuuksia ja muita vaarallisia tapahtumia sattuu edelleen. Nykyistä sääntelyjärjestelmää voidaan kritisoida monen asian suhteen. Kansainvälisen sääntelyn aikaansaaminen ei ole helppoa: prosessi on yleensä hidas ja tuloksena voi olla kompromissien kompromissi. Kansainvälinen sääntely on yleensä reaktiivista eli ongelmakohtiin puututaan vasta kun jokin onnettomuus tapahtuu sen sijaan että se olisi proaktiivista ja pyrkisi puuttumaan ongelmakohtiin jo ennen kuin jotain tapahtuu. IMO:n työskentely perustuu kansallisvaltioiden osallistumiseen ja sääntelyn toimeenpano tapahtuu lippuvaltioiden toimesta. Kansallisvaltiot ajavat IMO:ssa pääasiallisesti omia intressejään ja sääntelyn toimeenpanossa on suuria eroja lippuvaltioiden välillä. IMO:n kyvyttömyys puuttua havaittuihin ongelmiin nopeasti ja ottaa sääntelyssä huomioon paikallisia olosuhteita on johtanut siihen, että esimerkiksi Euroopan Unioni on alkanut itse säädellä meriturvallisuutta ja että on olemassa sellaisia alueellisia erityisjärjestelyjä kuin PSSA (particularly sensitive sea area – erityisen herkkä merialue). Merenkulkualalla toimii monenlaisia yrityksiä: toisaalta yrityksiä, jotka pyrkivät toimimaan turvallisesti ja kehittämään turvallisuutta vielä korkeammalle tasolle, ja toisaalta yrityksiä, jotka toimivat niin halvalla kuin mahdollista, eivät välitä turvallisuusseikoista, ja joilla usein on monimutkaiset ja epämääräiset omistusolosuhteet ja joita vahingon sattuessa on vaikea saada vastuuseen. Ongelma on, että kansainvälisellä merenkulkualalla kaikkien yritysten on toimittava samoilla markkinoilla. Vastuuttomien yritysten toiminnan mahdollistavat laivaajat ja muut alan toimijat, jotka suostuvat tekemään yhteistyötä niiden kanssa. Välinpitämätön suhtautuminen turvallisuuteen johtuu osaksi myös merenkulun vanhoillisesta turvallisuuskulttuurista. Verrattaessa meriturvallisuuden sääntelyjärjestelmää kokonaisuutena tehokkaiden ohjauskeinoihin kriteereihin, voidaan todeta, että monien kriteerien osalta nykyistä järjestelmää voidaan pitää tehokkaana ja onnistuneena. Suurimmat ongelmat lienevät sääntelyn toimeenpanossa ja ohjauskeinojen kustannustehokkuudessa. Lippuvaltioiden toimeenpanoon perustuva järjestelmä ei toimi toivotulla tavalla, josta mukavuuslippujen olemassa olo on selvin merkki. Ohjauskeinojen, sekä yksittäisten ohjauskeinojen että vertailtaessa eri ohjauskeinoja keskenään, kustannustehokkuutta on usein vaikea arvioida, minkä seurauksena ohjauskeinojen kustannustehokkuudesta ei ole saatavissa luotettavaa tietoa ja tuloksena voi olla, että ohjauskeino on käytännössä pienen riskin eliminoimista korkealla kustannuksella. Kansainvälisen tason meriturvallisuus- (ja merenkulku-) politiikan menettelytavoiksi on ehdotettu myös muita vaihtoehtoja kuin nykyinen järjestelmä, esimerkiksi monitasoista tai polysentristä hallintojärjestelmää. Monitasoisella hallintojärjestelmällä tarkoitetaan järjestelmää, jossa keskushallinto on hajautettu sekä vertikaalisesti alueellisille tasoille että horisontaalisesti ei-valtiollisille toimijoille. Polysentrinen hallintojärjestelmä menee vielä askeleen pidemmälle. Polysentrinen hallintojärjestelmä on hallintotapa, jonka puitteissa kaikentyyppiset toimijat, sekä yksityiset että julkiset, voivat osallistua hallintoon, siis esimerkiksi hallitukset, edunvalvontajärjestöt, kaupalliset yritykset jne. Kansainvälinen lainsäädäntö määrittelee yleiset tasot, mutta konkreettiset toimenpiteet voidaan päättää paikallisella tasolla eri toimijoiden välisessä yhteistyössä. Tämän tyyppisissä hallintojärjestelmissä merenkulkualan todellinen, kansainvälinen mutta toisaalta paikallinen, toimintaympäristö tulisi otetuksi paremmin huomioon kuin järjestelmässä, joka perustuu kansallisvaltioiden keskenään yhteistyössä tekemään sääntelyyn. Tällainen muutos meriturvallisuuden hallinnassa vaatisi kuitenkin suurta periaatteellista suunnanmuutosta, jollaisen toteutumista ei voi pitää kovin todennäköisenä ainakaan lyhyellä tähtäimellä.

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Despite the increase in research regarding mild head injury (MHI), relatively little has investigated whether, or the extent to which, premorbid factors (i.e., personality traits) influence, or otherwise account for, outcomes post-MHI. The current study examined the extent to which postinjury outcome after MHI is analogous to the outcome post-moderate or- severe traumatic brain injury (by comparing the current results to previous literature pertaining to individuals with more severe brain injuries) and whether these changes in function and behaviour are solely, or primarily, due to the injury, or reflect, and are possibly a consequence of, one’s preinjury status. In a quasi-experimental, test-retest design, physiological indices, cognitive abilities, and personality characteristics of university students were measured. Since the incidence of MHI is elevated in high-risk activities (including high-risk sports, compared to other etiologies of MHI; see Laker, 2011) and it has been found that high-risk athletes present with unique, risk-taking behaviours (in terms of personality; similar to what has been observed post-MHI) compared to low-risk and non-athletes. Seventy-seven individuals (42% with a history of MHI) of various athletic statuses (non-athletes, low-risk athletes, and high-risk athletes) were recruited. Consistent with earlier studies (e.g., Baker & Good, 2014), it was found that individuals with a history of MHI displayed decreased physiological arousal (i.e., electrodermal activation) and, also, endorsed elevated levels of sensation seeking and physical/reactive aggression compared to individuals without a history of MHI. These traits were directly associated with decreased physiological arousal. Moreover, athletic status did not account for this pattern of performance, since low- and high-risk athletes did not differ in terms of personality characteristics. It was concluded that changes in behaviour post-MHI are associated, at least in part, with the neurological and physiological compromise of the injury itself (i.e., physiological underarousal and possible subtle OFC dysfunction) above and beyond influences of premorbid characteristics.

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Many studies have focused on the concept of humanization of birth in normal pregnancy cases or at low obstetric risk, but no studies, at our knowledge, have so far specifically focused on the humanization of birth in both high-risk, and low risk pregnancies, in a highly specialized hospital setting. The present study thus aims to: 1) define the specific components of the humanized birth care model which bring satisfaction to women who seek obstetrical care in highly specialized hospitals; and 2) explore the organizational and cultural dimensions which act as barriers or facilitators for the implementation of humanized birth care practices in a highly specialized, university affiliated hospital in Quebec. A single case study design was chosen for this thesis. The data were collected through semi-structured interviews, field notes, participant observations, selfadministered questionnaire, relevant documents, and archives. The samples comprised: 11 professionals from different disciplines, 6 administrators from different hierarchical levels within the hospital, and 157 women who had given birth at the hospital during the study. The performed analysis covered both quantitative descriptive and qualitative deductive and inductive content analyses. The thesis comprises three articles. In the first article, we proposed a conceptual framework, based on Allaire and Firsirotu’s (1984) organizational culture theory. It attempts to examine childbirth patterns as an organizational cultural phenomenon. In our second article, we answered the following specific question: according to the managers and multidisciplinary professionals practicing in a highly specialized hospital as well as the women seeking perinatal care in this hospital setting, what is the definition of humanized care? Analysis of the data collected uncovered the following themes which explained the perceptions of what humanized birth was: personalized care, recognition of women’s rights, humanly care for women, family-centered care,women’s advocacy and companionship, compromise of security, comfort and humanity, and non-stereotyped pregnancies. Both high and low risk women felt more satisfied with the care they received if they were provided with informed choices, were given the right to participate in the decision-making process and were surrounded by competent care providers. These care providers who humanly cared for them were also able to provide relevant medical intervention. The professionals and administrators’ perceptions of humanized birth, on the other hand, mostly focused on personalized and family-centered care. In the third article of the thesis, we covered the dimensions of the internal and external components of an institution which can act as factors that facilitate or barriers that prevent, a specialized and university affiliated hospital in Quebec from adopting a humanized child birthing care. The findings revealed that both the external dimensions of a highly specialized hospital -including its history, society, and contingency-; and its internal dimensions -including culture, structure, and the individuals present in the hospital-, can all affect the humanization of birth care in such an institution, whether separately, simultaneously or in interaction. We thus hereby conclude that the humanization of birth care in a highly specialized hospital setting, should aim to meet all the physiological, as well as psychological aspects of birth care, including respect of the fears, beliefs, values, and needs of women and their families. Integration of competent and caring professionals and the use of obstetric technology to enhance the level of certainty and assurance in both high-risk and low risk women are both positive factors for the implementation of humanized care in a highly specialized hospital. Finally, the humanization of birth care approach in a highly specialized and university affiliated hospital setting demands a new healthcare policy. Such policy must offer a guarantee for women to have the place of birth, and the health care professional of their choice as well as those, which will enable women to make informed choices from the beginning of their pregnancy.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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BACKGROUND: Paracoccidioidomycosis is a systemic mycosis of dermatological interest due to the frequency of cutaneous and mucosal lesions. The involvement of the external genitalia is extremely rare and few cases have been reported.OBJECTIVE: To study the prevalence of external genitalia lesions in paracoccidioidomycosis patients, identify clinical characteristics and compare with what is observed in the specific literature.METHODS: This is a cross-sectional, descriptive study, with focus on paracoccidioiodomycosis patients with external genitalia lesions. The demographic and clinical aspects of cases were compared with what has been reported so far on LILACS, SciELO e MEDLINE data bases.RESULTS: Data of 483 cases of paracoccidioidomycosis were studied in a 42-year period. Six (1.2%) patients showed specific lesions on external genitalia. Five patients were male with mean age of 47.2 years and all of them presented with the chronic multifocal clinical form. Only one, a 15-year-old female patient was observed who showed a subacute clinical form, juvenile type.CONCLUSIONS: Compromise of the genitourinary tract among paracoccidioidomycosis patients is rare and even rarer when only the external genitalia are considered. As observed in the classical picture of paracoccidioidomycosis patients, the male gender and the chronic multifocal clinical form prevailed in the present study.

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Advanced ceramic materials constitute a mature technology with a very broad base of current and potential applications and a growing list of material compositions. Within the advanced ceramics category, silicon nitride based ceramics are wear-resistant, corrosion-resistant and lightweight materials, and are superior to many materials with regard to stability in high-temperature environments. Because of this combination the silicon nitride ceramics have an especially high potential to resolve a wide number of machining problems in the industries. Presently the Si3N4 ceramic cutting tool inserts are developed using additives powders that are pressed and sintered in the form of a cutting tool insert at a temperature of 1850 °C using pressureless sintering. The microstructure of the material was observed and analyzed using XRD, SEM, and the mechanical response of this array microstructure was characterized for hardness Vickers and fracture toughness. The results show that Si3N4/20 wt.% (AlN and Y 2O3) gives the best balance between hardness Vickers and fracture toughness. The Si3N4/15 wt.% (AlN and Y 2O3) composition allows the production of a very fine-grained microstructure with low decreasing of the fracture toughness and increased hardness Vickers. These ceramic cutting tools present adequate characteristics for future application on dry machining. © (2010) Trans Tech Publications.

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Several alloys have been used for prosthodontics restorations in the last years. These alloys have a number of metals that include gold, palladium, silver, nickel, cobalt, chromium and titanium and they are used in oral cavity undergo several corrosion. Corrosion can lead to poor esthetics, compromise of physical properties, or increased biological irritation. The objective of this study was evaluated corrosion resistance of two alloys Ni-Cr and Ni-Cr-Ti in three types of mouthwashes with different active ingredients: 0.5g/l cetylpyridinium chloride + 0.05% sodium fluoride, 0.05% sodium fluoride + 0.03% triclosan (with fluor) and 0.12% chlorohexidine digluconate. The potentiodynamic curves were performed by means of an EG&G PAR 283 potentiostat/galvanostat. The counter electrode was a platinum wire and reference electrode was an Ag/AgCl, KCl saturated. Before each experiment, working electrodes were mechanically polished with 600 and 1200 grade papers, rinsed with distilled water and dried in air. All experiments were carried out at 37.0oC in conventional three-compartment double wall glass cell containing mouthwashes. The microstructures of two alloys were observed in optical microscopy. Analysis of curves showed that Ni-Cr alloy was less reactive in the presence of 0.12% chlorohexidine digluconate while Ni-Cr-Ti alloy was more sensitive for others two types of mouthwashes (0.5g/l cetylpyridinium chloride + 0.05% sodium fluoride  and 0.05% sodium fluoride + 0.03% triclosan). This occurred probably due presence of titanium in this alloy. Microstructural analysis reveals the presence of dendritic and eutectic microstructures for NiCr and Ni-Cr-Ti, respectively.

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The effects of hydration status on cerebral blood flow (CBF) and development of cerebrospinal fluid (CSF) lactic acidosis were evaluated in rabbits with experimental pneumococcal meningitis. As loss of cerebrovascular autoregulation has been previously demonstrated in this model, we reasoned that compromise of intravascular volume might severely affect cerebral perfusion. Furthermore, as acute exacerbation of the inflammatory response in the subarachnoid space has been observed after antibiotic therapy, animals were studied not only while meningitis evolved, but also 4-6 h after treatment with antibiotics to determine whether there would also be an effect on CBF. To produce different levels of hydration, animals were given either 50 ml/kg per 24 h of normal saline ("low fluid") or 150 ml/kg 24 h ("high fluid"). After 16 h of infection, rabbits that were given the lower fluid regimen had lower mean arterial blood pressure (MABP), lower CBF, and higher CSF lactate compared with animals that received the higher fluid regimen. In the first 4-6 h after antibiotic administration, low fluid rabbits had a significant decrease in MABP and CBF compared with, and a significantly greater increase in CSF lactate concentration than, high fluid rabbits. This study suggests that intravascular volume status may be a critical variable in determining CBF and therefore the degree of cerebral ischemia in meningitis.

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Spinal cord injury (SCI) is a devastating condition that affects people in the prime of their lives. A myriad of vascular events occur after SCI, each of which contributes to the evolving pathology. The primary trauma causes mechanical damage to blood vessels, resulting in hemorrhage. The blood-spinal cord barrier (BSCB), a neurovascular unit that limits passage of most agents from systemic circulation to the central nervous system, breaks down, resulting in inflammation, scar formation, and other sequelae. Protracted BSCB disruption may exacerbate cellular injury and hinder neurobehavioral recovery in SCI. In these studies, angiopoietin-1 (Ang1), an agent known to reduce vascular permeability, was hypothesized to attenuate the severity of secondary injuries of SCI. Using longitudinal magnetic resonance imaging (MRI) studies (dynamic contrast-enhanced [DCE]-MRI for quantification of BSCB permeability, highresolution anatomical MRI for calculation of lesion size, and diffusion tensor imaging for assessment of axonal integrity), the acute, subacute, and chronic effects of Ang1 administration after SCI were evaluated. Neurobehavioral assessments were also performed. These non-invasive techniques have applicability to the monitoring of therapies in patients with SCI. In the acute phase of injury, Ang1 was found to reduce BSCB permeability and improve neuromotor recovery. Dynamic contrast-enhanced MRI revealed a persistent compromise of the BSCB up to two months post-injury. In the subacute phase of injury, Ang1’s effect on reducing BSCB permeability was maintained and it was found to transiently reduce axonal integrity. The SCI lesion burden was assessed with an objective method that compared favorably with segmentations from human raters. In the chronic phase of injury, Ang1 resulted in maintained reduction in BSCB permeability, a decrease in lesion size, and improved axonal integrity. Finally, longitudinal correlations among data from the MRI modalities and neurobehavioral assays were evaluated. Locomotor recovery was negatively correlated with lesion size in the Ang1 cohort and positively correlated with diffusion measures in the vehicle cohort. In summary, the results demonstrate a possible role for Ang1 in mitigating the secondary pathologies of SCI during the acute and chronic phases of injury.

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PURPOSE To assess the extent of early recoil in patients with critical limb ischemia (CLI) undergoing conventional tibial balloon angioplasty. METHODS Our hypothesis was that early recoil, defined as lumen compromise >10%, is frequent and accounts for considerable luminal narrowing after tibial angioplasty, promoting restenosis. To test this theory, 30 consecutive CLI patients (18 men; mean age 76.2±12.1 years) were angiographically evaluated immediately after tibial balloon angioplasty and 15 minutes later. Half the patients were diabetics. Target lesions included anterior and posterior tibial arteries and the peroneal artery with / without the tibioperoneal trunk. Mean tibial lesion length was 83.8 mm. Early elastic recoil was determined on the basis of minimal lumen diameter (MLD) measurements at baseline (MLDbaseline), immediately after tibial balloon angioplasty (MLDpostdilation), and 15 minutes thereafter (MLD15min). RESULTS Elastic recoil was observed in 29 (97%) patients with a mean luminal compromise of 29% according to MLD measurements (MLDbaseline 0.23 mm, MLD postdilation 2.0 mm, and MLD15min 1.47 mm). CONCLUSION Early recoil is frequently observed in CLI patients undergoing tibial angioplasty and may significantly contribute to restenosis. These findings support the role of dedicated mechanical scaffolding approaches for the prevention of restenosis in tibial arteries.

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PRINCIPLES Patients with carotid artery stenosis (CAS) are at risk of ipsilateral stroke and chronic compromise of cerebral blood flow. It is under debate whether the hypo-perfusion or embolism in CAS is directly related to cognitive impairment. Alternatively, CAS may be a marker for underlying risk factors, which themselves influence cognition. We aimed to determine cognitive performance level and the emotional state of patients with CAS. We hypothesised that patients with high grade stenosis, bilateral stenosis, symptomatic patients and/or those with relevant risk factors would suffer impairment of their cognitive performance and emotional state. METHODS A total of 68 patients with CAS of ≥70% were included in a prospective exploratory study design. All patients underwent structured assessment of executive functions, language, verbal and visual memory, motor speed, anxiety and depression. RESULTS Significantly more patients with CAS showed cognitive impairments (executive functions, word production, verbal and visual memory, motor speed) and anxiety than expected in a normative sample. Bilateral and symptomatic stenosis was associated with slower processing speed. Cognitive performance and anxiety level were not influenced by the side and the degree of stenosis or the presence of collaterals. Factors associated with less cognitive impairment included higher education level, female gender, ambidexterity and treated hypercholesterolemia. CONCLUSIONS Cognitive impairment and increased level of anxiety are frequent in patients with carotid stenosis. The lack of a correlation between cognitive functioning and degree of stenosis or the presence of collaterals, challenges the view that CAS per se leads to cognitive impairment.

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Injury, inflammation, or resection of the small intestine results in severe compromise of intestinal function. Nevertheless, therapeutic strategies for enhancing growth and repair of the intestinal mucosal epithelium are currently not available. We demonstrate that nude mice bearing subcutaneous proglucagon-producing tumors exhibit marked proliferation of the small intestinal epithelium. The factor responsible for inducing intestinal proliferation was identified as glucagon-like peptide 2 (GLP-2), a 33-aa peptide with no previously ascribed biological function. GLP-2 stimulated crypt cell proliferation and consistently induced a marked increase in bowel weight and villus growth of the jejunum and ileum that was evident within 4 days after initiation of GLP-2 administration. These observations define a novel biological role for GLP-2 as an intestinal-derived peptide stimulator of small bowel epithelial proliferation.

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Septic shock is a cytokine-mediated process typically caused by a severe underlying infection. Toxins generated by the infecting organism trigger a cascade of events leading to hypotension, to multiple organ system failure, and frequently to death. Beyond supportive care, no effective therapy is available for the treatment of septic shock. Nitric oxide (NO) is a potent vasodilator generated late in the sepsis pathway leading to hypotension; therefore, NO represents a potential target for therapy. We have previously demonstrated that transforming growth factor (TGF) beta1 inhibits inducible NO synthase (iNOS) mRNA and NO production in vascular smooth muscle cells after its induction by cytokines critical in the sepsis cascade. Thus, we hypothesized that TGF-beta1 may inhibit iNOS gene expression in vivo and be beneficial in the treatment of septic shock. In a conscious rat model of septic shock produced by Salmonella typhosa lipopolysaccharide (LPS), TGF-beta1 markedly reduced iNOS mRNA and protein levels in several organs. In contrast, TGF-beta1 did not decrease endothelium-derived constitutive NOS mRNA in organs of rats receiving LPS. We also performed studies in anesthetized rats to evaluate the effect of TGF-beta1 on the hemodynamic compromise of septic shock; after an initial 25% decrease in mean arterial pressure, TGF-beta1 arrested LPS-induced hypotension and decreased mortality. A decrease in iNOS mRNA and protein levels in vascular smooth muscle cells was demonstrated by in situ hybridization and NADPH diaphorase staining in rats treated with TGF-beta1. Thus these studies suggest that TGF-beta1 inhibits iNOS in vivo and that TGF-beta1 may be of future benefit in the therapy of septic shock.

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Recent results have demonstrated that the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) reduces infarct size due to middle cerebral artery occlusion (MCAO), even when given after ischemia. The objective of the present study was to explore whether PBN influences recovery of energy metabolism. MCAO of 2-hr duration was induced in rats by an intraluminal filament technique. Brains were frozen in situ at the end of ischemia and after 1, 2, and 4 hr of recirculation. PBN was given 1 hr after recirculation. Neocortical focal and perifocal ("penumbra") areas were sampled for analyses of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glycogen, glucose, and lactate. The penumbra showed a moderate-to-marked decrease and the focus showed a marked decrease in PCr and ATP concentrations, a decline in the sum of adenine nucleotides, near-depletion of glycogen, and an increase in lactate concentration after 2 hr of ischemia. Recirculation for 1 hr led to only a partial recovery of energy state, with little further improvement after 2 hr and signs of secondary deterioration after 4 hr, particularly in the focus. After 4 hr of recirculation, PBN-treated animals showed pronounced recovery of energy state, with ATP and lactate contents in both focus and penumbra approaching normal values. Although an effect of PBN on mitochondria cannot be excluded, the results suggest that PBN acts by preventing a gradual compromise of microcirculation. The results justify a reevaluation of current views on the pathophysiology of focal ischemic damage and suggest that a therapeutic window of many hours exists in stroke.