Transhepatic ipsilateral right portal vein embolization extended to segment IV: improving hypertrophy and resection outcomes with spherical particles and coils.

PURPOSE: To analyze outcomes after right portal vein embolization extended to segment IV (right PVE + IV) before extended right hepatectomy, including liver hypertrophy, resection rates, and complications after embolization and resection, and to assess differences in outcomes with two different particulate embolic agents. MATERIALS AND METHODS: Between 1998 and 2004, transhepatic ipsilateral right PVE + IV with particles and coils was performed in 44 patients with malignant hepatobiliary disease, including metastases (n = 24), biliary cancer (n = 14), and hepatocellular carcinoma (n = 6). Right PVE + IV was considered if the future liver remnant (FLR; segments II/III with or without I) was less than 25% of the total estimated liver volume (TELV). Tris-acryl microspheres (100-700 microm; n = 21) or polyvinyl alcohol (PVA) particles (355-1,000 microm; n = 23) were administered in a stepwise fashion. Smaller particles were used to occlude distal branches, followed by larger particles to occlude proximal branches until near-complete stasis. Coils were then placed in secondary portal branches. Computed tomographic volumetry was performed before and 3-4 weeks after right PVE + IV to assess FLR hypertrophy. Liver volumes and postembolization and postoperative outcomes were measured. RESULTS: After right PVE + IV with PVA particles, FLR volume increased 45.5% +/- 40.9% and FLR/TELV ratio increased 6.9% +/- 5.6%. After right PVE + IV with tris-acryl microspheres, FLR volume increased 69.0% +/- 30.7% and FLR/TELV ratio increased 9.7% +/- 3.3%. Differences in FLR volume (P = .0011), FLR/TELV ratio (P = .027), and resection rates (P = .02) were statistically significant. Seventy-one percent of patients underwent extended right hepatectomy (86% after receiving tris-acryl microspheres, 57% after receiving PVA). Thirteen patients (29%) did not undergo resection (extrahepatic spread [n = 9], inadequate hypertrophy [n = 3], other reasons [n = 1]). No patient developed postembolization syndrome or progressive liver insufficiency after embolization or resection. One death after resection occurred as a result of sepsis and hemorrhage. Median hospital stays were 1 day after right PVE + IV and 7 days after resection. CONCLUSION: Transhepatic ipsilateral right PVE + IV with use of particles and coils is a safe, effective method for inducing contralateral hypertrophy before extended right hepatectomy. Embolization with small spherical particles provides improved hypertrophy and resection rates compared with larger, nonspherical particles.

Vuosaaren B-voimalaitoksen lauhduttimien merivesikanavaan sijoitettavan pienvesivoimalan kannavuusselvitys

Insinöörityön tavoitteena oli tehdä teknis-taloudellinen selvitystyö pienvesivoimasta Vuosaaren B-voimalaitokselle. Ensimmäiseksi täytyi selvittää laitoksen virtausolosuhteet, putouskorkeus, saavutettavissa oleva teho, konkreettinen sijoittumispaikka laitoksessa, tarvittavat rakenteet, laitteistot, sähköistys ja ohjausjärjestelmät sekä näiden kaikkien kustannukset. Työn alkuosassa käsitellään vesivoimaloiden teoriaa ja niihin liittyviä yleisiä asioita. Loppuosassa tarkastellaan Vuosaaren B-voimalaitosta sekä varsinaista teknis-taloudellista selvitystyötä. Työn teoriaosuuteen tietoja hankittiin kirjallisuudesta sekä Internetistä. Varsinaisessa selvitystyössä tietojen hankkimisessa auttoivat Helsingin Energian sekä muiden yritysten asiantuntijat. Selvitettyjen alkuarvojen ja muiden tietojen perusteella pystyttiin lopuksi tekemään yleisarvio kannattavuudesta sekä arvio investointien kannattavuudesta. Työssä käsiteltiin seuraavia toteutettavissa olleita vaihtoehtoja: yksi turbiini, kaksi turbiinia tai ei turbiinia ollenkaan. Yhdellä turbiinilla vuotuinen käyttöaika olisi ollut laitoksen käyttötietojen perusteella noin 7500 tuntia vuodessa. Kahden turbiinin vaihtoehdossa yhtä turbiinia olisi käytetty 6000 tuntia vuodessa ja kahden turbiinin yhteiskäyttöaika olisi jäänyt vain 1500 tuntiin vuodessa. Näistä syistä johtuen parhaaksi ratkaisuksi muodostui yhden turbiinin vaihtoehto, jossa turbiinin käyttöaika oli optimaalinen ja investointikustannukset pysyivät kohtuullisina. Turbiinin pois jättäminen ei myöskään olisi järkevää, koska turbiinin avulla laitoksen energia tehokkuus paranisi. Selvitystyön avulla Helsingin Energia voi tehdä päätöksen pienvesivoimalaan investoimisesta, mikä selvityksen perusteella vaikuttaisi kannattavalta.

Citrix-terminaalipalvelujen perusteet ja hyödyt yritykselle - esimerkkinä Aurinkomatkat Oy

Tämän insinöörityön lähtökohtana on lähestyä Citrix-tekniikkaa ja sen tuomia hyötyjä ja mahdollisuuksia Oy Aurinkomatkat - Suntours Ltd Ab:n kannalta. Työssä tarkastellaan Citrix-tekniikkaa, joka luo pohjan Citrix-tuotteiden toiminnalle. Keskeisenä aiheena toimii ICA-protokolla, jonka ympärille nivoutuu järjestelmän tehokkuus. Työssä tuodaan esille tyypillisiä Citrix-arkkitehtuurisia ratkaisuja eri etäyhteydenluonti tavoilla. Perustekniikan lisäksi työssä käydään läpi Citrix-tuotteita, joiden kautta selviävät tämän päivän Citrixin tarjoamat palvelut. Jotta ero Windowsin tarjoamien etäyhteysratkaisujen välillä selvenee, on järkevää vertailla Windows-terminaalipalveluita Citrix-terminaalipalveluihin. Lähtökohtaisesti vertailen RDP-protokollaa ICA-protokollaan, jossa selviää ICA:n kyvykkyys monipuolisempiin palveluihin. Aurinkomatkojen suunta on kohti mobiilimpaa ympäristöä, koska matkatoimistojen henkilöstö on jatkuvasti liikkeessä. Tarkastelen ICA-käyttöliittymän käyttöönottoa älypuhelimessa ja tarkastelen muutamia laitevaihtoehtoja. Työn lopussa tutkitaan, kuinka langaton verkko kannattaisi toteuttaa Aurinkomatkojen uudessa ympäristössä tulevaisuutta ajatellen. Citrix-teknologia tuo uusia mahdollisuuksia Aurinkomatkoja ajatellen. ICA-käyttöliittymä tukee lähes kaikkia tämän päivän järjestelmiä. Se istuu hyvin Nokian uusiin älypuhelimiin, toimii hyvin selainpohjaisena ja asentuu kätevästi työkoneisiin sekä kannettaviin. Tarvittaessa yhteyden Citrix-palveluhin saa myös VPN-yhteydellä, josta muutkin sisäverkon palvelut ovat käytettävissä. Citrixin vastaus kustannustehokkuuteen, sen tuomiin mahdollisuuksiin ja käytettävyyteen ilmenee Aurinkomatkoille vasta vuoden tai kahden kuluttua. Tällä hetkellä tärkeimmät sovellukset, kuten käytössä oleva varausjärjestelmä, ovat tuottaneet ongelmia etäohjelmajakeluna. Kun vanha ympäristö saadaan toimimaan Citrixin kautta uudessa ympäristössä, kapenee Aurinkomatkojen hybridi-ympäristö keskitetympään järjestelmään. Tämä tuo aivan uusia mahdollisuuksia Aurinkomatkojen IT-infrastruktuurille. Työ toteutui suurimmaksi osaksi kirjallisuustutkimuksena.

On the use of the likelihood ratio for forensic evaluation: response to Fenton et al.

This letter to the Editor comments on the article When 'neutral' evidence still has probative value (with implications from the Barry George Case) by N. Fenton et al. [[1], 2014].

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

The sand rat, Psammomys obesus, develops type 2 diabetic retinopathy similar to humans.

PURPOSE: Diabetic retinopathy (DR) is a leading cause of blindness, yet pertinent animal models are uncommon. The sand rat (Psammomys obesus), exhibiting diet-induced metabolic syndrome, might constitute a relevant model. METHODS: Adult P. obesus (n = 39) were maintained in captivity for 4 to 7 months and fed either vegetation-based diets (n = 13) or standard rat chow (n = 26). Although plant-fed animals exhibited uniform body weight and blood glucose levels over time, nearly 60% of rat chow-raised animals developed diabetes-like symptoms (test group). Animals were killed, and their eyes and vitreous were processed for immunochemistry. RESULTS: Compared with plant-fed animals, diabetic animals showed many abnormal vascular features, including vasodilation, tortuosity, and pericyte loss within the blood vessels, hyperproteinemia and elevated ratios of proangiogenic and antiangiogenic growth factors in the vitreous, and blood-retinal barrier breakdown. Furthermore, there were statistically significant decreases in retinal cell layer thicknesses and densities, accompanied by profound alterations in glia (downregulation of glutamine synthetase, glutamate-aspartate transporter, upregulation of glial fibrillar acidic protein) and many neurons (reduced expression of protein kinase Cα and Cξ in bipolar cells, axonal degeneration in ganglion cells). Cone photoreceptors were particularly affected, with reduced expression of short- and mid-/long-wavelength opsins. Hypercaloric diet nondiabetic animals showed intermediate values. CONCLUSIONS: Simple dietary modulation of P. obesus induces a rapid and severe phenotype closely resembling human type 2 DR. This species presents a valuable novel experimental model for probing the neural (especially cone photoreceptor) pathogenic modifications that are difficult to study in humans and for screening therapeutic strategies.

Investigation de liens de parenté à l'aide de l'ADN: lecture différentielle de rapports d'expertise

De nos jours, l'ADN apparaît fréquemment dans les affaires judiciaires et la littérature spécialisée. L'évaluation de ce type d'indice est vaste. En général, les débats restent toutefois assez théoriques. Dans la présente contribution, deux types courants d'analyse sont abordés, l'ADN nucléaire et l'ADN mitochondrial, dans le cadre d'une recherche en demi-fraternité. Deux rapports d'expertise seront décortiqués ligne par ligne pour en offrir une lecture critique et cerner la fiabilité et l'utilité des conclusions apportées par les experts.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

In vivo transformation of mouse conventional CD8alpha+ dendritic cells leads to progressive multisystem histiocytosis

Division and proliferation of dendritic cells (DCs) have been proposed to contribute to homeostasis and to prolonged antigen presentation. Whether abnormal proliferation of dendritic cells causes Langerhans cell histiocytosis (LCH) is a highly debated topic. Transgenic expression of simian virus 40 (SV40) T antigens in mature DCs allowed their transformation in vivo while maintaining their phenotype, function, and maturation capacity. The transformed cells were differentiated splenic CD8 alpha-positive conventional dendritic cells with increased Langerin expression. Their selective transformation was correlated with higher steady-state cycling compared with CD8 alpha-negative DCs in wild-type and transgenic mice. Mice developed a DC disease involving the spleen, liver, bone marrow, thymus, and mesenteric lymph node. Surprisingly, lesions displayed key immunohistologic features of Langerhans cell histiocytosis, including expression of Langerin and absence of the abnormal mitoses observed in Langerhans cell sarcomas. Our results demonstrate that a transgenic mouse model with striking similarities to aggressive forms of multisystem histiocytosis, such as the Letterer-Siwe syndrome, can be obtained by transformation of conventional DCs. These findings suggest that conventional DCs may cause some human multisystem LCH. They can reveal shared molecular pathways for human histiocytosis between humans and mice

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts.

Brachial circumference (BC), also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men) of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05) in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.