Brain perfusion in sepsis.

Brain dysfunction is a frequent complication of sepsis, usually defined as "sepsis-associated encephalopathy" (SAE). Its pathophysiology is complex and related to numerous processes and pathways, while the exact mechanisms producing neurological impairment in septic patients remain incompletely elucidated. Alterations of the cerebral blood flow (CBF) may represent a key component for the development of SAE. Reduction of CBF may be caused by cerebral vasoconstriction, either induced by inflammation or hypocapnia. Endothelial dysfunction associated with sepsis leads to impairment of microcirculation and cerebral metabolic uncoupling that may further reduce brain perfusion so that CBF becomes inadequate to satisfy brain cellular needs. The natural autoregulatory mechanisms that protect the brain from reduced/ inadequate CBF can be impaired in septic patients, especially in those with shock or delirium, and this further contributes to cerebral ischemia if blood pressure drops below critical thresholds. Sedative agents alter cerebro-vascular reactivity and may significantly reduce CBF. Although disorders of brain perfusion and alteration of CBF and cerebral autoregulation are frequently observed in humans with sepsis, their exact role in the pathogenesis of SAE remains unknown. Brain perfusion can further become inadequate due to cerebral microcirculatory dysfunction, as evidenced in the experimental setting. Microvascular alterations can be implicated in the development of electrophysiological abnormalities observed during sepsis and contribute to neurological alterations in septic animals. The aim of this review is to provide an update on the pathophysiology of brain perfusion in sepsis, with a particular focus on human clinical investigation and novel tools for CBF monitoring in septic patients.

Methylprednisolone concentrations in the vitreous and the serum after pulse therapy.

PURPOSE: Intravenous (i.v.) pulse of corticosteroids has been used to treat severe eye inflammation from different origins. Whether such large doses result in vitreous levels that differ either in magnitude or duration from more conventional corticotherapy remain unsolved issues. The authors therefore determined levels of methylprednisolone hemisuccinate and methylprednisolone in the vitreous and serum of patients at different times after a single i.v. perfusion of methylprednisolone hemisuccinate. METHODS: Fifty patients scheduled for a first vitrectomy received an i.v. injection of 500 mg hemisuccinate methylprednisolone at different times before surgery (from 15-24 hours). Patients were divided into two groups: those with (n = 21) and without (n = 29) retinal detachment (RD). Pure vitreous samples were analyzed by high-pressure liquid chromatography. RESULTS: Both the ester and the nonester methylprednisolone forms were sampled in the vitreous, showing a slower rate of hydrolysis compared to the serum. On average, the highest concentration of total methylprednisolone in the vitreous was found at 2.5 hours and rapidly decreased for the group of patients with RD. In the group of patients without RD, the highest concentration was reached at 6 hours and then slowly decreased. The antiinflammatory potency in the nondetached retina eyes was approximately 500 times more than in the physiologic vitreous, but despite the route of administration (i.v. or oral), only 1/10 of the corticosteroid serum concentration was measured in the vitreous. CONCLUSION: High concentration of methylprednisolone is achieved by i.v. pulse therapy without changing the kinetic of entry in the vitreous of nondetached retina eyes when compared to conventional oral corticotherapy. Hydrolysis occurs in the vitreous resulting in high rate of active form. Pulse therapy could be considered in cases of severe ocular inflammation involving the posterior segment of the eye.

Regional Innovation Policy: Effect on SMEs in Five EU-Regions

Valtaosa eurooppalaisista yrityksistä on pk-yrityksiä, mutta tästä huolimatta seudullisen innovaatiopolitiikan vaikutusta juuri pk-yrityksiin on tutkittu melko vähän. Tämän tutkimuksen tarkoituksena on luoda yleiskuva pk-yritysten näkemykseen oman seutunsa innovaatiopolitiikasta viidellä EU:n alueella sijaitsevalla seudulla. Kirjallisuuden perusteella rakennettiin seudullista innovaatiopolitiikkaa kuvaava kysely, johon joukko pk-yrityksiä viideltä seudulta vastasi. Kyselyn tulokset kuvailtiin graafisesti, minkä lisäksi etsittiin vastauksiin vaikuttaneita tekijöitä ja yhteyksiä yritysten vastausten välillä. Tutkimus oli luonteeltaan lähinnä kvantitatiivinen. Tutkimus osoittaa, että seudullisessa innovaatiopolitiikassa on vielä paljon kehitettävää, jotta se tavoittaisi kattavasti pk-yritykset. Pk-yritysten tietoisuutta tulisi lisätä, sillä nämä eivät yleisesti ottaen näytä pitävän seudullista innovaatiopolitiikkaa menetykseen vaikuttavana tekijänä tai siihen liittyviä yhteistyömahdollisuuksia tärkeinä omalle toiminnalleen. Erot innovaatiotoiminnan seudullisessa roolissa tulivat esiin tuloksissa. Yritysten vastauksia selittäviä tekijöitä löydettiin, samoin yhteyksiä vastausten välillä, mutta varsinaisten johtopäätösten tekeminen edellyttänee laajempaa tutkimusta.

El Museo Regional del Rif (Marruecos). Proyecto científico y cultural sobre la constitución de un museo de sociedad del Rif.

The end of this paper is to offer a Planning Project aimed to the prospective museum of the Rif society. The authors, unaware of the actual purpose of both political and cultural institutions, which eventually will decide about the museum and its location, just want to attract the attention of those responsible for some aspects and the chronological periods that the Planning Project must take into account to assure the success of this new Riffian cultural institution.

Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey.

BACKGROUND: Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine the patterns of RNI. METHODS: A web-questionnaire, including several clinical scenarios, was distributed to 88 EORTC-affiliated centers. Responses were received between July 2013 and January 2014. RESULTS: A total of 84 responses were analyzed. While three-dimensional (3D) radiotherapy (RT) planning is carried out in 81 (96%) centers, nodal areas are delineated in only 51 (61%) centers. Only 14 (17%) centers routinely link internal mammary chain (IMC) and supraclavicular node (SCN) RT indications. In patients undergoing total mastectomy (TM) with ALND, SCN-RT is recommend by 5 (6%), 53 (63%) and 51 (61%) centers for patients with pN0(i+), pN(mi) and pN1, respectively. Extra-capsular extension (ECE) is the main factor influencing decision-making RNI after breast conserving surgery (BCS) and TM. After primary systemic therapy (PST), 49 (58%) centers take into account nodal fibrotic changes in ypN0 patients for RNI indications. In ypN0 patients with inner/central tumors, 23 (27%) centers indicate SCN-RT and IMC-RT. In ypN1 patients, SCN-RT is delivered by less than half of the centers in patients with ypN(i+) and ypN(mi). Twenty-one (25%) of the centers recommend ALN-RT in patients with ypN(mi) or 1-2N+ after ALND. Seventy-five (90%) centers state that age is not considered a limiting factor for RNI. CONCLUSION: The NORA survey is unique in evaluating the impact of SLNB/ALND status on adjuvant RNI decision-making and volumes after BCS/TM with or without PST. ALN-RT is often indicated in pN1 patients, particularly in the case of ECE. Besides the ongoing NSABP-B51/RTOG and ALLIANCE trials, NORA could help to design future specific RNI trials in the SLNB era without ALND in patients receiving or not PST.

Strokes in the anterior circulation: comparison between bridging and intravenous thrombolysis.

BACKGROUND AND PURPOSE: To compare safety and efficacy of bridging approach with intravenous (IV) thrombolysis in patients with acute anterior strokes and proximal occlusions. PATIENTS AND METHODS: Consecutive patients with ischemic anterior strokes admitted within a 4 h 30 min window in two different centers were included. The first center performed IV therapy (alteplase 0.6 mg/kg) during 30 min and, in absence of clinical improvement, mechanical thrombectomy with flow restoration using a Solitaire stent (StS); the second carried out IV thrombolysis (alteplase 0.9 mg/kg) alone. Only T, M1 or M2 occlusions present on CT angiography were considered. Endpoints were clinical outcome and mortality at 3 months. RESULTS: There were 63 patients in the bridging and 163 in the IV group. No significant differences regarding baseline characteristics were observed. At 3 months, 46% (n = 29) of the patients treated in the combined and 23% (n = 38) of those treated in the IV group had a modified Rankin scale (mRS) of 0-1 (P < 0.001). A statistical significant difference was observed for all sites of occlusion. In a logistic regression model, National Institute of Health Stroke Scale (NIHSS) and bridging therapy were independent predictors of good outcome (respectively, P = 0.001 and P = 0.0018). Symptomatic hemorrhage was documented in 6.3% vs 3.7% in the bridging and in the IV group, respectively (P = 0.32). There was no difference in mortality. CONCLUSIONS: Our results suggest that patients treated with a bridging approach were more likely to have minimal or no deficit at all at 3 months as compared to the IV treated group.

La oportunidad de Turquía de posicionarse como líder regional ante la UE : la Primavera Árabe

Las revueltas en el Maghreb y Mashrek entre otras consecuencias han promovido la diversificación de actores en el área mediterránea, de manera que la UE ya no es el único vecino con intereses en la región. Turquía, el eterno candidato a la adhesión, ha sido designada por académicos y políticos como un modelo de Estado secular y multipartidista donde la separación entre la religión y la política representa uno de sus pilares constitucionales. Además, el Primer Ministro Recep Tayyip Erdogan se ha erigido como un líder en la región Mediterránea debido al viraje de la política turca de asuntos exteriores. En otros términos, Turquía ya no es un país completamente aliado del mundo occidental para los árabes, sino que ha asumido su responsabilidad en la escena global. Sin embargo, dicha determinación se ha alcanzado a través de actuar como un poder blando asumiendo como propio la máxima aportación europea a las relaciones internacionales.

Ranking Regional Innovation Policies: DEA-based Benchmarking in an European Setting

Seudullinen innovaatio on monimutkainen ilmiö, joka usein sijaitsee paikallisten toimijoiden keskinäisen vuorovaikutuksen kentässä. Täten sitä on perinteisesti pidetty vaikeasti mitattavana ilmiönä. Työssä sovellettiin Data Envelopment Analysis menetelmää, joka on osoittautunut aiemmin menestyksekkääksi tapauksissa, joissa mitattavien syötteiden ja tuotteiden väliset suhteet eivät ole olleet ilmeisiä. Työssä luotiin konseptuaalinen malli seudullisen innovaation syötteistä ja tuotteista, jonka perusteella valittiin 12 tilastollisen muuttujan mittaristo. Käyttäen Eurostat:ia datalähteenä, lähdedata kahdeksaan muuttujsta saatiin seudullisella tasolla, sekä mittaristoa täydennettiin yhdellä kansallisella muuttujalla. Arviointi suoritettiin lopulta 45 eurooppalaiselle seudulle. Tutkimuksen painopiste oli arvioida DEA-menetelmän soveltuvuutta innovaatiojärjestelmän mittaamiseen, sillä menetelmää ei ole aiemmin sovellettu vastaavassa tapauksessa. Ensimmäiset tulokset osoittivat ylipäätään liiallisen korkeita tehokkuuslukuja. Korjaustoimenpiteitä erottelutarkkuuden parantamiseksi esiteltiin ja sovellettiin, jonka jälkeen saatiin realistisempia tuloksia ja ranking-lista arvioitavista seuduista. DEA-menetelmän todettiin olevan tehokas ja kiinnostava työkalu arviointikäytäntöjen ja innovaatiopolitiikan kehittämiseen, sikäli kun datan saatavuusongelmat saadaan ratkaistua sekä itse mallia tarkennettua.

Análise técnica e econômica do cultivo do cajueiro-anão (Anacardium occidentale L.) na regional de Jales-SP

Objetivou-se estimar os custos de produção e lucratividade do caju in natura na Regional de Jales, noroeste do Estado de São Paulo. Os dados foram levantados junto a produtores, a partir da aplicação de questionário e da elaboração de planilhas, para caracterizar todo o processo produtivo e realizar análise econômica. A produção de fruta para mesa exige um sistema de cultivo mais intensivo, principalmente no controle de pragas e doenças; por sua vez, eleva o custo de produção que, via de regra, é compensada pelos preços alcançados. Os custos de produção são altos, mas o que deve ser destacada é a participação relativa das embalagens que pode chegar a um terço do custo operacional efetivo, seguido pelos custos pós-colheita. Os indicadores de lucratividade mostram que a produção de caju é rentável nesta região, e o índice de lucratividade foi de 46,50%.

Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. METHODS: We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. RESULTS: CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CONCLUSION: CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality.

Regional determinants of firm entry in a developing country

We analyse the determinants of firm entry in developing countries using Argentina as an illustrative case. Our main finding is that although most of the regional determinants used in previous studies analysing developed countries are also relevant here, there is a need for additional explanatory variables that proxy for the specificities of developing economies (e.g., poverty, informal economy and idle capacity).We also find evidence of a core-periphery pattern in the spatial structure of entry that seems to be mostly driven by differences in agglomeration economies. Since regional policies aiming to attract new firms are largely based on evidence from developed countries, our results raise doubts about the usefulness of such policies when applied to developing economies. JEL classification: R12, R30, C33. Key words: Firm entry, Argentina, count data models.