Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study.

BACKGROUND: Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. METHODS: Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1-6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. RESULTS: Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. CONCLUSIONS: Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study.

Klammt's elastic open activator: Ricketts' cephalometrics results

The purpose of this study is to investigate the orthodontic and orthopaedic real effects of the Klammt's Elastic Open Activator (EOA) in 25 Class II Division 1 patients in growing period. We wanted to determine statistically the cephalometrics changes produced in the patients, comparing the lateral cranium teleradiographies we took for the diagnosis with the ones we took at the end of treatment. At the end of this study we confirm that by using the EOA we obtained the desired effects, especially reducing the molar relation 2.53 mm and the overjet 2.56 mm. The EOA corrected the inclination and protrusion of incisors, although we cannot avoid the use of fixed appliances to round off. The reduction of 2.48 mm of facial convexity stands out as the most important skeletal effect; the facial depth angle increases 0.8 degree, and the maxillary depth decreases 1.16 degrees. The length of the mandibular corpus also increases 6.7 mm, although this change is mainly due to the growth of the patient. The changes in the aesthetic profile do not stand out

Molecular Analysis of NOTCH2 in Patients with Primary Open-Angle Glaucoma.

BACKGROUND AND PURPOSE: Transgenic mice overexpressing Notch2 in the uvea exhibit a hyperplastic ciliary body leading to increased IOP and glaucoma. The aim of this study was to investigate the possible presence of NOTCH2 variants in patients with primary open-angle glaucoma (POAG). METHODS: We screened DNA samples from 130 patients with POAG for NOTCH2 variants by denaturing high-performance liquid chromatography after PCR amplification and validated our data by direct Sanger sequencing. RESULTS: No mutations were observed in the coding regions of NOTCH2 or in the splice sites. 19 known SNPs (single nucleotide polymorphisms) were detected. An SNP located in intron 24, c.[4005+45A>G], was seen in 28.5% of the patients (37/130 patients). As this SNP is reported to have a minor allele frequency of 7% in the 1000 genomes database, it could be associated with POAG. However, we evaluated its frequency in an ethnic-matched control group of 96 subjects unaffected by POAG and observed a frequency of 29%, indicating that it was not related to POAG. CONCLUSION: NOTCH2 seemed to be a good candidate for POAG as it is expressed in the anterior segment in the human eye. However, mutational analysis did not show any causative mutation. This study also shows that proper ethnic-matched control groups are essential in association studies and that values given in databases are sometimes misleading.

Osakevaihto yhtiöoikeudessa ja vero-oikeudessa

Tutkielman tavoitteena on ollut selvittää, kuinka osakevaihto tulee toteuttaa, jotta vältetään luovutusvoittoverotus ja samalla noudatetaan säännöksiä suunnatusta apportista. Tämän selvittämiseksi on tutkittu erityisesti vero-oikeuden ja yhtiöoikeuden säännöksiä. Tutkimus on toteutettu lainopillisena tutkimuksena tutkien pääasiassa kansallisen lainsäädännön vaikutusta osakevaihtoon. Tarkoituksena on ollut analysoida lainsäädännön, kirjallisuuden ja oikeustapausten avulla yhtiöoikeuden ja vero-oikeuden asettamia mahdollisuuksia ja rajoituksia osakevaihdon toteuttamiseen. Oikeustapauksia on käytetty myös esimerkkeinä selventämään eräitä tulkinnanvaraisia kohtia arvioitaessa osakevaihtoa. Oikeusvertailua tutkielmassa on suoritettu vain yritysjärjestelydirektiivin ja kansallisen lainsäädännön eräiden tulkintaerojen osalta. Tutkielmassa havaittiin, että osakevaihdon huolellinen etukäteissuunnittelu on tärkeää, koska osakevaihdossa saatava verotuksen lykkääntymisen etu voidaan menettää sekä yhtiöoikeuden että vero-oikeuden säännösten perusteella.

Net communication strategy planning and management

Tutkielman tavoitteena on selvittää kuinka suunnitella ja hallita tehokasta verkkoviestintää, joka vastaa kohdeyleisön ja palvelun ylläpitäjien kasvaviin vaatimuksiin. Tutkielma on normatiivinen tapaustutkimus, jonka tuloksena syntyy konstruktiivinen askelmalli kokonaisvaltaisen verkkoviestintäprojektin toteuttamiseen. Tutkimus esittää myös teoreettisesti merkittävän näkökulman verkkopalvelujen sisällön hallintaongelmien ratkaisemiseen. Tosielämän verkkoviestintäprojektin toteutusta seurataan TietoEnator Forestissa, jossa tutkielman kirjoittaja työskentelee. Tutkimusmateriaalina käytetään 11 TietoEnator Forestissa toteutettua haastattelua, TietoEnator konsernin dokumentaatiota ja osallistuvaa havainnointia. Haastattelulomake sisältää 13 avointa kysymystä, jotka käsittelevät verkkoviestintästrategian perusasioita. Tunnistetut verkkoviestinnän avainmenestystekijät ovat vahva sisäinen sitoutuminen hajautettuihin ylläpitorooleihin ja perinpohjainen asiakastarpeiden tunnistaminen. Teknisesti on tärkeää, että eritason verkkoympäristöt, Internet, Intranet ja Extranet, hallitaan samoilla sisällönhallinta työkaluilla. Näin pystytään rationalisoimaan ylläpitotoiminnot.

Formulation of Business Strategy for China. Case: Kemira Agro Oy

Tutkielman tavoitteena on tutkia kansainvälisen liiketoimintastrategian kehittämiseen liittyviä osa-alueita ja tarjota ehdotuksia Kemira Agro Oy:lle liiketoimintastrategian kehittämiseksi. Tutkielman teoreettisessa osassa analysoidaan liiketoimintastrategian osa-alueita. Tutkielman empiirisessä osassa liiketoimintastrategian osa-alueet analysoidaan Kemira Agro Oy:n Kiinan liiketoimintastrategian kannalta ja esitetään ehdotuksia liiketoimintastrategian kehittämiseksi. Tutkielma on normatiivinen case-tutkimus. Tutkielma on jaettu teoreettiseen ja empiiriseen osaan. Empiirisessä osassa tutkimuskohteina on Suomessa tehdyt vapaamuotoiset haastattelut ja Kiinassa puoli-strukturoituina toteutetut haastattelut. Tutkimus määrittää Kiinan vaikeaksi markkina-alueeksi, joka kuitenkin tarjoaa suuria kasvumahdollisuuksia. Tutkielman tutkimustuloksissa ehdotetaan markkinointitoimenpiteiden lisäämistä sekä tutkimaan mahdollisuutta oman jakelukanavan luomiseen ja tuotevalikoiman laajentamiseen sekä korostetaan segmentoinnin tärkeyttä.

Optimal Exchange Rate Policy in a Growing Semi-Open Economy

This paper considers an alternative perspective to China's exchange rate policy. It studies a semi-open economy where the private sector has no access to international capital markets but the central bank has full access. Moreover, it assumes limited financial development generating a large demand for saving instruments by the private sector. The paper analyzes the optimal exchange rate policy by modeling the central bank as a Ramsey planner. Its main result is that in a growth acceleration episode it is optimal to have an initial real depreciation of the currency combined with an accumulation of reserves, which is consistent with the Chinese experience. This depreciation is followed by an appreciation in the long run. The paper also shows that the optimal exchange rate path is close to the one that would result in an economy with full capital mobility and no central bank intervention.

Secondhand tobacco smoke exposure in open and semi-open settings: a systematic review

Background: Some countries have recently extended smoke-free policies to particular outdoor settings; however, there is controversy regarding whether this is scientifically and ethically justifiable. Objectives: The objective of the present study was to review research on secondhand smoke (SHS) exposure in outdoor settings. Data sources: We conducted different searches in PubMed for the period prior to September 2012. We checked the references of the identified papers, and conducted a similar search in Google Scholar. Study selection: Our search terms included combinations of"secondhand smoke,""environmental tobacco smoke,""passive smoking" OR"tobacco smoke pollution" AND"outdoors" AND"PM" (particulate matter),"PM2.5" (PM with diameter ≤ 2.5 µm),"respirable suspended particles,""particulate matter,""nicotine,""CO" (carbon monoxide),"cotinine,""marker,""biomarker" OR"airborne marker." In total, 18 articles and reports met the inclusion criteria. Results: Almost all studies used PM2.5 concentration as an SHS marker. Mean PM2.5 concentrations reported for outdoor smoking areas when smokers were present ranged from 8.32 to 124 µg/m3 at hospitality venues, and 4.60 to 17.80 µg/m3 at other locations. Mean PM2.5 concentrations in smoke-free indoor settings near outdoor smoking areas ranged from 4 to 120.51 µg/m3. SHS levels increased when smokers were present, and outdoor and indoor SHS levels were related. Most studies reported a positive association between SHS measures and smoker density, enclosure of outdoor locations, wind conditions, and proximity to smokers. Conclusions: The available evidence indicates high SHS levels at some outdoor smoking areas and at adjacent smoke-free indoor areas. Further research and standardization of methodology is needed to determine whether smoke-free legislation should be extended to outdoor settings.

Pelin kehitys win32-alustalla käyttäen Open Source -työkaluja

Peliteollisuus on nykyään erittäin suuri ohjelmistokehityksen ala, joten on ajankohtaista tutustua ilmaisten työkalujen ja kirjastojen tarjoamiin mahdollisuuksiin. Visuaalisen viihteen tuottamiseen tarvitaan yleensä C++-ohjelmointitaidon lisäksi mallinnustaitoa ja kuvankäsittelytaitoa. Tämän lisäksi äänten tuottaminen on erittäin suuri osa toimivan kokonaisuuden saavuttamiseksi. Tässä työssä käsitellään kaikki osa-alueet ja tutkitaan Open Source -työkalujen soveltuvuutta pelin kehitykseen win32-alustalla. Lopputuloksena syntyy täysin pelattava, tosin yksinkertainen peli CrazyBunny. Työn alussa esitellään kaikki käytettävät työkalut jotka kuuluvat tarvittavaan kehitysympäristöön. Tähän esittelyyn kuuluvat myös olennaisena osana työkalujen asennuksen läpikäynti sekä käyttöönotto. Työn perustana on käytetty OGRE-ohjelmistokehystä, joka ei ole varsinainen pelimoottori. Puuttuvia ominaisuuksia on lisätty käyttämällä CEGUI-kirjastoa käyttöliittymien tekoon sekä FMOD-kirjastoa äänijärjestelmän toteutukseen. Muita käytet-tyjä työkaluja ovat Code::Blocks-kehitysympäristö, Blender-mallinnusohjelma ja Audacity-äänieditori. Pelisovelluksen toteutuksen pohjana on käytetty State-sunnittelumalliin perustuvaa järjes-telmää pelitiloja hallintaan. Tässä mallissa pelin päävalikko, pelitila ja pelin loppu on ero-tettu omiksi tilaluokikseen, jolloin sovelluksesta saadaan helpommin hallittava. Päävali-kossa tärkein osa on itse valikoiden toteutus CEGUI-kirjaston avulla. Pelitilan toteutukses-sa tutustutaan OGRE:n visuaalisiin ominaisuuksiin kuten ympäristöön, valoihin, varjoihin, kuva-alustoihin ja visuaalisiin tehosteisiin. Tämän lisäksi peliin on toteutettu äänet suosi-tulla FMOD-kirjastolla, jota useat isot alan yritykset käyttävät kaupallisissa tuotteissaan.

A thematic analysis of delusion with religious content in schizophrenia: open, closed, and mixed dynamics

The aim of the present study was to elicit how patients with delusions with religious contents conceptualized or experienced their spirituality and religiousness. Sixty-two patients with present or past religious delusions went through semistructured interviews, which were analyzed using the three coding steps described in the grounded theory. Three major themes were found in religious delusions: ''spiritual identity,'' ''meaning of illness,'' and ''spiritual figures.'' One higher-order concept was found: ''structure of beliefs.'' We identified dynamics that put these personal beliefs into a constant reconstruction through interaction with the world and others (i.e., open dynamics) and conversely structural dynamics that created a complete rupture with the surrounding world and others (i.e., closed structural dynamics); those dynamics may coexist. These analyses may help to identify psychological functions of delusions with religious content and, therefore, to better conceptualize interventions when dealing with it in psychotherapy.

STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

BACKGROUND: The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. METHODS/DESIGN: STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. DISCUSSION: The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. TRIAL REGISTRATION: STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013. STRATEGIC-1 is registered at EudraCT-No.: 2013-001928-19, 25 April, 2013.

Endovascular Versus Open Abdominal Aortic Aneurysm: Best Decision.

Since the first implantation of an endograft in 1991, endovascular aneurysm repair (EVAR) rapidly gained recognition. Historical trials showed lower early mortality rates but these results were not maintained beyond 4 years. Despite newer-generation devices, higher rates of reintervention are associated with EVAR during follow-up. Therefore, the best therapeutic decision relies on many parameters that the physician has to take in consideration. Patient's preferences and characteristics are important, especially age and life expectancy besides health status. Aneurysmal anatomical conditions remain probably the most predictive factor that should be carefully evaluated to offer the best treatment. Unfavorable anatomy has been observed to be associated with more complications especially endoleak, leading to more re-interventions and higher risk of late mortality. Nevertheless, technological advances have made surgeons move forward beyond the set barriers. Thus, more endografts are implanted outside the instructions for use despite excellent results after open repair especially in low-risk patients. When debating about AAA repair, some other crucial points should be analysed. It has been shown that strict surveillance is mandatory after EVAR to offer durable results and prevent late rupture. Such program is associated with additional costs and with increased risk of radiation. Moreover, a risk of loss of renal function exists when repetitive imaging and secondary procedures are required. The aim of this article is to review the data associated with abdominal aortic aneurysm and its treatment in order to establish selection criteria to decide between open or endovascular repair.

Granulomatous Reaction to Pneumocystis jirovecii Diagnosed in a Bronchoalveolar Lavage: A Case Report.

BACKGROUND: Granulomatous reaction to Pneumocystis jirovecii is a rare but well-known pathological finding encountered in the setting of immunosuppression, HIV infection being the most common cause. It can also potentially complicate the treatment of hematological malignancies, typically when drugs lowering the count and function of lymphocytes are used. Lung biopsy is considered the gold standard for the diagnosis of granulomatous P. jirovecii pneumonia, whereas the diffuse alveolar form is usually detected cytologically in bronchoalveolar lavage (BAL). CASE: A female patient pursuing R-CHOP chemotherapy for the treatment of multiple hematological malignancies developed a rapidly progressing dyspnea. Chest CT scans revealed a worsening of a known infiltrative lung disease thought to be secondary to her chemotherapy. Alterations compatible with a drug-induced interstitial lung disease and well-formed focally necrotizing granulomas were observed on an open lung biopsy, but no microorganism was identified with special stains. Eventually, a granulomatous reaction to P. jirovecii was found in a BAL and allowed appropriate treatment with rapid improvement of the dyspnea. CONCLUSION: Because granulomas are tissue-bound structures, they are rarely described in BAL. This article describes the first reported cytological diagnosis of a granulomatous reaction to P. jirovecii and the potential diagnostic interest of such a peculiar finding.