PET in the evaluation of head and neck cancer treatment - management of the neck

The treatment for head and neck squamous cell carcinoma (HNSCC) is surgery or (chemo)radiotherapy +/- surgery. Side effects related to therapy are long lasting and adversely affects quality of life. The incidence of oropharyngeal cancer is increasing and patients commonly present an advanced tumour stage with neck metastases at the time of diagnosis. The treatment protocol previously comprised radical (chemo)radiotherapy and surgery i.e., neck dissection. However, persistent tumour cells after (chemo)radiotherapy are found in only 20-30% of the neck specimens and a systemic neck dissection have therefore been questioned. The general aim of the present thesis was to explore if positron emission tomography (PET) could be used for radiotherapy response evaluation and adequately determine the need for further therapeutic interventions in patients with HNSCC treated with curative intent. The overall clinical goal with the thesis was to reduce the treatment related morbidity by avoiding unnecessary neck dissection without risking an increase in failures. In studies I and III we evaluated the performance of PET as a tool for assessment of therapy response and the consequences of omitting neck dissections in patients with a complete metabolic response after treatment. Study II focused on therapy response evaluation of the primary site. Lastly, study IV evaluated three different methods for interpreting PET scans in head and neck cancer patients. In conclusion, neither nodal control nor survival is compromised by omitting neck dissection in patients with a complete metabolic response after therapy. A physical examination, preferably supported with a PET scan, is feasible and sufficient for an evaluation of the primary site response. Qualitative interpretation with visual inspection of PET scans is a satisfactory method to assess tumour metabolism and the use of a 5-point Likert scale is a promising tool to reduce the number of scans judged as equivocal to a minimum

Mitochondrial function in sepsis - Temporal evolvement of respiratory capacity in human blood cells

Sepsis is a devastating disease that is caused by the host’s response to an overwhelming infectious process. As sepsis progresses, organs distant from the site of infection become affected and sepsis-induced multiple organ failure ensues. An impaired immunologic response, including dysfunctional peripheral blood immune cells has been described as part of the septic syndrome. Mitochondrial dysfunction has been suggested to be a contributing factor in the pathogenesis of these alterations and restoration of mitochondrial function has been implicated as a prerequisite for the recovery from sepsis. Further, platelets have been proposed to serve as a surrogate tissue in evaluation of systemic mitochondrial dysfunction. The overall aim of this thesis was to evaluate the temporal evolution of mitochondrial respiratory function in platelets and peripheral immune cells during the course of sepsis. In the first study we established methodology and performed a thorough assessment of normal human platelet respiratory function ex vivo from healthy individuals in a wide age-span using high-resolution respirometry. We concluded that freshly isolated platelets, intact or permeabilised, were well suited for studying human mitochondria ex vivo. With different titration protocols, detailed information of the cellular respiratory capacities could be obtained and we deemed this approach suitable for evaluating endogenous mitochondrial capacity as well as alterations of mitochondrial function induced by exogenous factors. In the two subsequent studies we examined mitochondrial respiratory function in platelets and peripheral blood immune cells (PBICs) of patients with severe sepsis or septic shock and studied its evolvement during the first week following admission to the intensive care unit. In both cell types we found that mitochondrial respiration (per cell) gradually increased during the week analysed. In platelets, this increase was higher in patients who subsequently died. Also, in platelets, we observed reduced respiratory control ratios of intact platelets when the cells where suspended in the patient’s own plasma. As markers for mitochondrial content we measured mitochondrial DNA (mtDNA), cytochrome c (Cyt c) and citrate synthase (CS). There was a difference between the two cell types in that the markers were profoundly more increased in PBICs compared to platelets even though they displayed approximately the same levels of increase in mitochondrial respiration. In the final study of this thesis we evaluated cytokines and nitric oxide in the plasma from the septic patient cohort since these signaling molecules have been demonstrated to enhance mitochondrial respiration through stimulation of mitochondrial biogenesis. Of ten different cytokines and NO analysed, IL-8 levels correlated positively with both maximal ATP-generating as well as maximal non-ATP-generating rates of respiration in samples from the latest time point evaluated. Further, the plasma level of IL-8 was higher in non-survivors in samples taken at day 6-7 compared to survivors. In conclusion, this thesis demonstrates that circulating blood cells exhibit increased respiratory capacities throughout the first week of sepsis. This increase seems to be accomplished by different mechanisms; in PBICs by increased mitochondrial mass as indicated by elevated levels of mitochondrial markers, and in platelets possibly by a post-translational regulation of mitochondrial respiratory capacity. In addition, a plasma factor seems to be able to induce increased uncoupling of respiration in platelets during sepsis

Comments of Professor Joan E. Donoghue’s Article, the Public Face of Private International Law: Prospects for a Convention on Foreign State Immunity

Joan E. Donoghue\u27s theories regarding the prospects for a convention on foreign state immunity within the Hague Conference are examined. The prospects for supporting efforts to negotiate an international convention on state immunity are small

Laser, radiofrequency or tympanostomy knife? : Comparison of surgical methods in tympanostomy treatment of young children and predictive value of tympanometry

Objectives: To investigate tympanostomy tube (TT) treatment in young children, with special interest in bloodless surgical methods (laser and radiofrequency), myringosclerosis formation and tympanometric testing.Methods: This prospective study includes 76 children whose 121 ears with middle ear effusion were treated with tympanostomy tubes. Myringotomy was performed with CO2 laser in 37, radiofrequency in 40 and myringotomy knife in 44 ears. The ears were evaluated with otomicroscopy and tympanometry preoperatively and post-operatively every 3-4 months until spontaneous tube extrusion.Results: All tubes extruded spontaneously (mean 12.8 months, range 3-36 months), with no persistent perfora-tions or cholesteatomas. CO2 laser and radiofrequency inserted tympanostomy tubes extruded faster (mean 11 months) compared to incisional myringotomy (mean 15 months, p = 0.002). Myringosclerosis was noted in 25 (21%) ears after treatment. There was a tendency to less myringosclerosis with bloodless techniques, but the difference was not significant. Flat tympanograms on the day of procedure predicted continuation of ventilation problems also after TT treatment (p = 0.003). Ears with preoperative type B tympanogram had significantly more myringosclerosis 21/75 (28%) compared with type A and C tympanograms 4/41 (10%) (p = 0.032).Conclusions: While all myringotomy methods were effective and safe, the traditional incisional myringotomy with a tympanostomy knife is still a good, feasible and cost-effective myringotomy method. No surgical removal of tympanostomy tubes is needed before 3 years of uncomplicated tympanostomy treatment. Tympanometry turned out to be a useful tool in prediction of post TT treatment ventilation problems of the middle ear.Peer reviewe

Arkkitehtuurikasvatus suomalaisessa lastenkirjallisuudessa

Tutkielmassani kartoitan sitä, miten suomalaisissa lasten kuvakirjoissa, faktioissa, lasten tietokirjoissa ja monimuotoisissa lastenkirjoissa on käsitelty arkkitehtuuria ja arkkitehtuurikasvatuksen teemoja. Kuinka yleinen teema arkkitehtuuri on lapsille suunnatussa kirjallisuudessa? Mitä lasten ajatellaan oppivan niistä? Tarkastelen lähemmin kymmentä lastenkirjaa, joissa analysoin niiden rakennetta, sisältöä, tyyliä, tarkoitusta, piilomerkityksiä, tekstin ja kuvan suhdetta, kohdeyleisöä ja oppimis-käsityksiä. Huomion kohteena on erityisesti arkkitehtuurikasvatuksen keskeisten käsitteiden, kuten tilan, paikan, massan, muodon, paikan hengen, mittasuhteiden, rakenteiden, ajan, liikkeen, pintojen, materiaalien, värien, valon ja varjon käsittely kirjoissa. Halusin löytää kirjan, jossa olisi tehty arkkitehtuuria lapsille ymmärrettäväksi näiden käsitteiden kautta. Etsin kirjoja tiedonkeruun menetelmällä, ja rajasin esiteltävät kirjat sillä perusteella, että ne antaisivat mahdollisimman kattavan ja totuudenmukaisen kokonaiskuvan arkkitehtuuriaiheisten suomalaisten lastenkirjojen kentästä. Liitteisiin keräsin esittelyjen ulkopuolelle jäänyttä kirjallisuutta, kyselyn tuloksena kertynyttä muuta arkkitehtuurikasvatuksellista materiaalia, sekä taulukkoon silmäiltävän koosteen esiteltyjen kirjojen ominaisuuksista. Tarkastelin kirjoja lähiluvun ja diskurssianalyysin kontekstissa. Pohdinnan yhteenvedossa totean mm., että aihepiirin kirjoja on vähän saatavilla. Jatkotutkimuksena esitän olemuksen arkkitehtuuria käsittelevän lastenkirjan tekemistä. Tuloksissa pohdin seuraavien kirjojen arkkitehtuurisisältöä: Kunnas, Mauri 1996. Mauri Kunnaksen Koiramäki / …apuna Tarja Kunnas. Helsinki: Otava. Havukainen, Aino – Toivonen, Sami 2012. Tatu ja Patu Helsingissä. Helsinki: Otava. Vainio, Pirkko 1997. Ihmetorni. Helsinki: Lasten keskus. Hämäläinen, Karo – Savolainen, Salla 2011. Hurraa Helsinki! Ikioma kaupunki. Helsinki: Kustannusosakeyhtiö Tammi. Mikkanen, Raili – Valojärvi, Laura 2011. Suomen lasten linnakirja. Helsinki: Minerva Kustannus Oy. Larmola, Maija – Larmola, Yrjö – Lumme, Leena – Mäkiö, Erkki 1987. Kukkulan kortteli : kaupungin kaksi vuosisataa. Helsinki: SKS. Larmola, Maija – Larmola, Antti – Lumme, Leena 2010. Tiikerihevonen ja muita juttuja Kukkulan korttelista. Helsinki: SKS. Finnilä, Anna – Osipow, Penni 2001. Oma Helsinki-kirjani : Helsingin historian, arkkitehtuurin ja kulttuuriympäristön käsikirja. Helsinki: Helsingin kaupunginmuseo. Meskanen, Pihla 2006. Pieni majakirja. Helsinki: Tammi. Grönlund, Hannele 2003: Aineeton tila : matkaopas. Näyttelyluettelo, Helsinki: Rakennustaiteen museo

HEVC-videokoodekin intra-ennustuksen toteutus FPGA-piireille C-kielestä syntesoimalla

High Efficiency Video Coding (HEVC) is the latest video coding standard in video compression. With HEVC, it is possible to compress the video with half the bitrate compared to the previous video coding standard, Advanced Video Coding (AVC), with the same video quality. Now even, the complexity of the encoder is significantly larger. As designs become more and more complex, traditional hardware (HW) description languages (HDLs), such as Very High Speed Integrated Circuit Hardware Description Language (VHDL) or Verilog, can not be used to present the designs without increasing effort. The solution for this is a higher abstraction language for describing HW. High-Level Synthesis (HLS) is a way of using a programming language like C or C++ to describe the HW and automatically generating the HDL from it. This makes the code easier to understand and decreases the time used for implementing the design. This Thesis uses Catapult-C to create an HLS-based implementation of HEVC intra prediction for a Field Programmable Gate Array (FPGA). The HEVC encoder used in this Thesis is open source Kvazaar which has been developed at Tampere University of Technology. The objective is to implement an intra prediction accelerator faster than implementing it with register-transfer level (RTL) using VHDL or Verilog and still get comparable area and performance. This Thesis presents six development versions of the intra prediction accelerator. The complexity of the accelerator grows gradually, as more features were added to it. The final version is able to perform the intra prediction, mode cost computation and mode decision for Full HD video at 24.5 fps using 11 662 adaptive logic modules (ALMs) on an Altera Cyclone V FPGA. This Thesis presents the benefits of Catapult-C and HLS. The implementation results were comparable to hand coded RTL but achieved with a fraction of the estimated time for a VHDL implementation. As a rough estimate, if something takes a month to implement in VHDL, it takes a week with HLS. The biggest gain with HLS is the fast process of changes. Only the C implementation needs to change. The testbench and the RTL-code are generated automatically

Feasibility Study of High-Level Synthesis : Implementation of a Real-Time HEVC Intra Encoder on FPGA

High-Level Synthesis (HLS) on automatisoitu suunnitteluprosessi, joka pyrkii parantamaan tuottavuutta perinteisiin suunnittelumenetelmiin verrattuna, nostamalla suunnittelun abstraktiota rekisterisiirtotasolta (RTL) käyttäytymistasolle. Erilaisia kaupallisia HLS-työkaluja on ollut markkinoilla aina 1990-luvulta lähtien, mutta vasta äskettäin ne ovat alkaneet saada hyväksyntää teollisuudessa sekä akateemisessa maailmassa. Hidas käyttöönottoaste on johtunut pääasiassa huonommasta tulosten laadusta (QoR) kuin mitä on ollut mahdollista tavanomaisilla laitteistokuvauskielillä (HDL). Uusimmat HLS-työkalusukupolvet ovat kuitenkin kaventaneet QoR-aukkoa huomattavasti. Tämä väitöskirja tutkii HLS:n soveltuvuutta videokoodekkien kehittämiseen. Se esittelee useita HLS-toteutuksia High Efficiency Video Coding (HEVC) -koodaukselle, joka on keskeinen mahdollistava tekniikka lukuisille nykyaikaisille mediasovelluksille. HEVC kaksinkertaistaa koodaustehokkuuden edeltäjäänsä Advanced Video Coding (AVC) -standardiin verrattuna, saavuttaen silti saman subjektiivisen visuaalisen laadun. Tämä tyypillisesti saavutetaan huomattavalla laskennallisella lisäkustannuksella. Siksi reaaliaikainen HEVC vaatii automatisoituja suunnittelumenetelmiä, joita voidaan käyttää rautatoteutus- (HW ) ja varmennustyön minimoimiseen. Tässä väitöskirjassa ehdotetaan HLS:n käyttöä koko enkooderin suunnitteluprosessissa. Dataintensiivisistä koodaustyökaluista, kuten intra-ennustus ja diskreetit muunnokset, myös enemmän kontrollia vaativiin kokonaisuuksiin, kuten entropiakoodaukseen. Avoimen lähdekoodin Kvazaar HEVC -enkooderin C-lähdekoodia hyödynnetään tässä työssä referenssinä HLS-suunnittelulle sekä toteutuksen varmentamisessa. Suorituskykytulokset saadaan ja raportoidaan ohjelmoitavalla porttimatriisilla (FPGA). Tämän väitöskirjan tärkein tuotos on HEVC intra enkooderin prototyyppi. Prototyyppi koostuu Nokia AirFrame Cloud Server palvelimesta, varustettuna kahdella 2.4 GHz:n 14-ytiminen Intel Xeon prosessorilla, sekä kahdesta Intel Arria 10 GX FPGA kiihdytinkortista, jotka voidaan kytkeä serveriin käyttäen joko peripheral component interconnect express (PCIe) liitäntää tai 40 gigabitin Ethernettiä. Prototyyppijärjestelmä saavuttaa reaaliaikaisen 4K enkoodausnopeuden, jopa 120 kuvaa sekunnissa. Lisäksi järjestelmän suorituskykyä on helppo skaalata paremmaksi lisäämällä järjestelmään käytännössä minkä tahansa määrän verkkoon kytkettäviä FPGA-kortteja. Monimutkaisen HEVC:n tehokas mallinnus ja sen monipuolisten ominaisuuksien mukauttaminen reaaliaikaiselle HW HEVC enkooderille ei ole triviaali tehtävä, koska HW-toteutukset ovat perinteisesti erittäin aikaa vieviä. Tämä väitöskirja osoittaa, että HLS:n avulla pystytään nopeuttamaan kehitysaikaa, tarjoamaan ennen näkemätöntä suunnittelun skaalautuvuutta, ja silti osoittamaan kilpailukykyisiä QoR-arvoja ja absoluuttista suorituskykyä verrattuna olemassa oleviin toteutuksiin.High-Level Synthesis (HLS) is an automated design process that seeks to improve productivity over traditional design methods by increasing design abstraction from register transfer level (RTL) to behavioural level. Various commercial HLS tools have been available on the market since the 1990s, but only recently they have started to gain adoption across industry and academia. The slow adoption rate has mainly stemmed from lower quality of results (QoR) than obtained with conventional hardware description languages (HDLs). However, the latest HLS tool generations have substantially narrowed the QoR gap. This thesis studies the feasibility of HLS in video codec development. It introduces several HLS implementations for High Efficiency Video Coding (HEVC) , that is the key enabling technology for numerous modern media applications. HEVC doubles the coding efficiency over its predecessor Advanced Video Coding (AVC) standard for the same subjective visual quality, but typically at the cost of considerably higher computational complexity. Therefore, real-time HEVC calls for automated design methodologies that can be used to minimize the HW implementation and verification effort. This thesis proposes to use HLS throughout the whole encoder design process. From data-intensive coding tools, like intra prediction and discrete transforms, to more control-oriented tools, such as entropy coding. The C source code of the open-source Kvazaar HEVC encoder serves as a design entry point for the HLS flow, and it is also utilized in design verification. The performance results are gathered with and reported for field programmable gate array (FPGA) . The main contribution of this thesis is an HEVC intra encoder prototype that is built on a Nokia AirFrame Cloud Server equipped with 2.4 GHz dual 14-core Intel Xeon processors and two Intel Arria 10 GX FPGA Development Kits, that can be connected to the server via peripheral component interconnect express (PCIe) generation 3 or 40 Gigabit Ethernet. The proof-of-concept system achieves real-time. 4K coding speed up to 120 fps, which can be further scaled up by adding practically any number of network-connected FPGA cards. Overcoming the complexity of HEVC and customizing its rich features for a real-time HEVC encoder implementation on hardware is not a trivial task, as hardware development has traditionally turned out to be very time-consuming. This thesis shows that HLS is able to boost the development time, provide previously unseen design scalability, and still result in competitive performance and QoR over state-of-the-art hardware implementations

Cost-effective production of non-fossil energies in the Swedish electricity system including external effects and uncertainty

The objective of this study is to calculate the cost-effective production of non-fossil energies in the Swedish electricity system, considering external effects and uncertainty. The study includes eight non-fossil energy sources in Sweden. For each energy source a unique marginal cost function is assessed, including production costs, external cost and uncertainty based on data from previous studies and publications. Four different models are created: A standard model excluding externalities, a model including externalities, a probabilistic model excluding externalities and a probabilistic model including externalities. The results show that the cost-effective mix of 150TWh is achieved at a total production cost of 58.3 billion SEK. The model finds the cost of externalities to be 7.1 billion SEK and the cost of uncertainty to about 1.7 billion SEK respectively. In all four models, large-scale hydro, nuclear power and onshore wind are included to their full capacity. None of the models have solar PV and wave energy as part of the cost-effective mix. Biomass, offshore wind and small scale hydro are included to a varying extent in the different models. When comparing the results of the four different models the differences in outcome are rather small. However, there are a number of significant findings that may contribute to guidelines for Swedish policy making. Among the discussed implications are: The most effective way to drive down total electricity cost, the role of solar PV incentives and the cost associated with a decommissioning of nuclear power

7α-Hydroxylation of 26-hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid by cytochrome P-450 in pig liver microsomes

AbstractPig liver microsomes were found to catalyze the 7α-hydroxylation of several potential bile acid precursors besides cholesterol. 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid were all efficiently converted into the 7α-hydroxylated products. Two cytochrome P-450 fractions showing 7α-hydroxylase activity could be isolated. One fraction catalyzed 7α-hydroxylation of 26-hydroxycholesterol. 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid but was inactive towards cholesterol. The other fraction catalyzed 7α-hydroxylation of cholesterol in addition to the other substrates. 26-Hydroxycholesterol in equimolar concentration did not inhibit the cholesterol 7α-hydroxylase activity of this fraction. It is concluded that liver microsomes contain a cytochrome P-450 catalyzing 7α-hydroxylation of 26-hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid. The results indicate that this cytochrome P-450 is different from that catalyzing 7α-hydroxylation of cholesterol