Peripheral T Cell Cytokine Responses for Diagnosis of Active Tuberculosis

BACKGROUND: A test for diagnosis of active Tuberculosis (TB) from peripheral blood could tremendously improve clinical management of patients. METHODS: Of 178 prospectively enrolled patients with possible TB, 60 patients were diagnosed with pulmonary and 27 patients with extrapulmonary TB. The frequencies of Mycobacterium tuberculosis (MTB) specific CD4(+) T cells and CD8(+) T cells producing cytokines were assessed using overnight stimulation with purified protein derivate (PPD) or early secretory antigenic target (ESAT)-6, respectively. RESULTS: Among patients with active TB, an increased type 1 cytokine profile consisting of mainly CD4(+) T cell derived interferon (IFN)-γ was detectable. Despite contributing to the cytokine profile as a whole, the independent diagnostic performance of one cytokine producing T cells as well as polyfunctional T cells was poor. IFN-γ/Interleukin(IL)-2 cytokine ratios discriminated best between active TB and other diseases. CONCLUSION: T cells producing one cytokine and polyfunctional T cells have a limited role in diagnosis of active TB. The significant shift from a "memory type" to an "effector type" cytokine profile may be useful for further development of a rapid immune-diagnostic tool for active TB

Distinct Effector Memory CD4+ T Cell Signatures in Latent Mycobacterium tuberculosis Infection, BCG Vaccination and Clinically Resolved Tuberculosis

Two billion people worldwide are estimated to be latently infected with Mycobacterium tuberculosis (Mtb) and are at risk for developing active tuberculosis since Mtb can reactivate to cause TB disease in immune-compromised hosts. Individuals with latent Mtb infection (LTBI) and BCG-vaccinated individuals who are uninfected with Mtb, harbor antigen-specific memory CD4+ T cells. However, the differences between long-lived memory CD4+ T cells induced by latent Mtb infection (LTBI) versus BCG vaccination are unclear. In this study, we characterized the immune phenotype and functionality of antigen-specific memory CD4+ T cells in healthy BCG-vaccinated individuals who were either infected (LTBI) or uninfected (BCG) with Mtb. Individuals were classified into LTBI and BCG groups based on IFN-γ ELISPOT using cell wall antigens and ESAT-6/CFP-10 peptides. We show that LTBI individuals harbored high frequencies of late-stage differentiated (CD45RA−CD27−) antigen-specific effector memory CD4+ T cells that expressed PD-1. In contrast, BCG individuals had primarily early-stage (CD45RA−CD27+) cells with low PD-1 expression. CD27+ and CD27− as well as PD-1+ and PD-1− antigen-specific subsets were polyfunctional, suggesting that loss of CD27 expression and up-regulation of PD-1 did not compromise their capacity to produce IFN-γ, TNF-α and IL-2. PD-1 was preferentially expressed on CD27− antigen-specific CD4+ T cells, indicating that PD-1 is associated with the stage of differentiation. Using statistical models, we determined that CD27 and PD-1 predicted LTBI versus BCG status in healthy individuals and distinguished LTBI individuals from those who had clinically resolved Mtb infection after anti-tuberculosis treatment. This study shows that CD4+ memory responses induced by latent Mtb infection, BCG vaccination and clinically resolved Mtb infection are immunologically distinct. Our data suggest that differentiation into CD27−PD-1+ subsets in LTBI is driven by Mtb antigenic stimulation in vivo and that CD27 and PD-1 have the potential to improve our ability to evaluate true LTBI status

Obsolescence Challenges for Product-Service Systems in Aerospace and Defence Industry

Organised by: Cranfield UniversityThe aerospace and defence industries are moving towards new types of agreement such as availability contracts based on Product-Service System (PSS) business models. Obsolescence has become one of the main problems that will impact on many areas of the system during its life cycle. This paper presents the major challenges to managing obsolescence for availability contracts, identified by means of a comprehensive literature review and several interviews and forums with experts in obsolescence management. It is observed that there is a lack of understanding of the impact of obsolescence on whole life cost. Experts agree that the development of a framework to support estimation, management, and mitigation of these costs is desirable, but the difficulty in forecasting future obsolescence issues constrains industry to a reactive approach rather than proactive.Mori Seiki – The Machine Tool Compan

Kovapintaiset maisemat muutoksessa - Malmin kiitotie 18/36

This thesis deals with the urban voids of the city structure, seemingly empty space in the tight urban knit. The term hardscape is used to describe urban streets and squares, public outdoor spaces inside the city that are mostly paved. In this thesis a hardscape exceed being just a physical configuration: it is a combination of form and function, a man-made urban landscape often mostly paved and for the public use of people. The purpose of this thesis is to find guidelines for the design of a liveable hardscape prepared for future needs and apply them later to a case site situated in the current Malmi Airport. The first chapters contribute to the development of a new design criteria, whereas the latter present the application of it on a case site, the Malmi Runway 18/36. At present time, the case site is a fully functioning runway, but plans to turn it into the main hardscape of a newly planned residential area are in action. As an introduction, in the theoretical part of this thesis features of liveable hardscapes are determined and their evolution studied. For a basis of a new criteria list, three existing lists are explored. They are compared and tested in an evaluation of hardscapes around Europe to find out how the guidelines work, what they concentrate on and if they lack some aspects to achieve liveability. The findings are elaborated into the basis of a new criteria list and completed with attributes related to future and functionality. The new criteria list fills the gaps found on the existing lists and makes them better suited for the future, more comprehensive in different scales and emphasise liveability. The new criteria list is easily adjustable to any hardscape, but has been done with Helsinki and the Nordic environment in mind. The site design part of this thesis follows the principles set by the design criteria list. The starting point of the design is an existing disposition plan of the Malmi Airport made at the City Planning Department in 2015−2016. In the existing plan, the runway’s long shape is retained open and public in respect to the aviation history and the hardscape is developed as the main street widening into liveable squares. In the thesis design, first, the Runway 18/36’s shape together with its first surrounding blocks are transformed to best fulfil the new design criteria list created. The final result is a master plan for the Runway 18/36 aiming to find the best possible solutions as the hardscape artery of the newly developed neighbourhood gathering residents and resonating history.Tämä diplomityö käsittelee kaupunkitiloja rakennusten välissä, tiiviin rakenteen näennäisesti tyhjiä paikkoja. Kovapintaisella maisemalla tarkoitetaan kaupunkien katuja ja aukioita; julkisia ulkotiloja kaupungin sisällä, jotka ovat pääosin päällystettyjä. Tässä työssä kovapintainen maisema on muutakin kuin vain tilan fyysiset ominaisuudet: se on yhdistelmä muodonantoa ja toimintoja, rakennettu maisema, joka on tarkoitettu ihmisten käyttöön. Työn tarkoitus on kehittää suunnitteluohjeet eläväiselle kovapintaiselle ulkotilalle, joka vastaa tulevaisuuden tarpeisiin. Suunnitteluohjeet otetaan käyttöön nykyisellä Malmin lentokenttäalueella sijaitsevan kohdealueen suunnittelussa. Työn ensimmäisissä kappaleissa luodaan pohja ja lopullinen muoto suunnitteluohjeistolle, ja jälkimmäisellä puoliskolla ohjeistoa sovelletaan suunnittelukohteeseen, Malmin Kiitotie 18/36:lle. Nykyisellään kohdealue on täydessä toiminnassa oleva kiitorata, mutta suunnittelu sen muuttamiseksi uuden asuinalueen tärkeimmäksi kovapintaiseksi maisemaksi on käynnissä. Diplomityön teoreettisessa osuudessa määritellään kovapintaisten maisemien ominaisuuksia ja käydään niiden historiaa ja kehitystä läpi. Kolmea olemassa olevaa kriteerilistaa vertaillaan ja testataan neljän eurooppalaisen kovapintaisen alueen arvioinnissa. Löydösten pohjalta luodaan pohja uudelle suunnitteluohjeistolle, jota täydentämään lisätään ominaisuuksia liittyen tulevaisuuteen ja toimintoihin. Uusi suunnitteluohjeisto paikkaa olemassa olevien listojen arvioituja puutteita ja sopeutuu edeltäjiään paremmin tulevaisuuden suunnitteluhaasteisiin, ottaa huomioon usean mittakaavan elementtejä ja korostaa elävyyttä. Suunnitteluohjeisto on sovellettavissa mille tahansa kovapintaiselle ulkotilalle, mutta se on tehty Helsinki ja pohjoinen ympäristö mielessä. Kiitotie 18/36:n suunnittelu noudattelee suunnitteluohjeistossa määriteltyjä periaatteita. Suunnitelma pohjautuu olemassa olevaan Malmin lentokenttäalueen kaavarunkoon, joka on tehty Helsingin kaupunkisuunnitteluvirastossa vuosien 2015‒2016 aikana. Kaavarungossa kiitotien pitkä muoto säilytetään avoimena ja julkisena kunnioituksena lentokenttähistorialle ja siitä kehitetään alueen tärkein kovapintainen ulkotila, alueen pääkatu, joka laajenee kolmeksi eläväiseksi aukioksi. Diplomityön suunnitteluosuudessa Kiitotie 18/36:n muoto sekä ympäröivät korttelit otetaan ensin käsittelyyn ja niitä muokataan parhaiten suunnitteluohjeiston kriteerit täyttäviksi. Lopputuloksena suunnitteluosuudessa on Kiitotie 18/36:n ideatasoinen yleissuunnitelma, jonka tarkoitus on löytää parhaat mahdolliset ratkaisut uuden asuinalueen kovapintaiselle selkärangalle, joka kokoaa asukkaita ja muistuttaa historiasta

Recurrent Barrett's esophagus and adenocarcinoma after esophagectomy

<p>Abstract</p> <p>Background</p> <p>Esophagectomy is considered the gold standard for the treatment of high-grade dysplasia in Barrett's esophagus (BE) and for noninvasive adenocarcinoma (ACA) of the distal esophagus. If all of the metaplastic epithelium is removed, the patient is considered "cured". Despite this, BE has been reported in patients who have previously undergone esophagectomy. It is often debated whether this is "new" BE or the result of an esophagectomy that did not include a sufficiently proximal margin. Our aim was to determine if BE recurred in esophagectomy patients where the entire segment of BE had been removed.</p> <p>Methods</p> <p>Records were searched for patients who had undergone esophagectomy for cure at our institution. Records were reviewed for surgical, endoscopic, and histopathologic findings. The patients in whom we have endoscopic follow-up are the subjects of this report.</p> <p>Results</p> <p>Since 1995, 45 patients have undergone esophagectomy for cure for Barrett's dysplasia or localized ACA. Thirty-six of these 45 patients underwent endoscopy after surgery including 8/45 patients (18%) with recurrent Barrett's metaplasia or neoplasia after curative resection.</p> <p>Conclusion</p> <p>Recurrent Barrett's esophagus or adenocarcinoma after esophagectomy was common in our patients who underwent at least one endoscopy after surgery. This appears to represent the development of metachronous disease after complete resection of esophageal disease. Half of these patients have required subsequent treatment thus far, either repeat surgery or photodynamic therapy. These results support the use of endoscopic surveillance in patients who have undergone "curative" esophagectomy for Barrett's dysplasia or localized cancer.</p