Testing the HTA Core Model: Experiences from two pilot projects

Objectives: The aim of this study was to analyze and describe process and outcomes of two pilot assessments based on the HTA Core Model, discuss the applicability of the model, and explore areas of development. Methods: Data were gathered from HTA Core Model and pilot Core HTA documents, their validation feedback, questionnaires to investigators, meeting minutes, emails, and discussions in the coordinating team meetings in the Finnish Office for Health Technology Assessment (FINOHTA). Results: The elementary structure of the HTA Core Model proved useful in preparing HTAs. Clear scoping and good coordination in timing and distribution of work would probably help improve applicability and avoid duplication of work. Conclusions: The HTA Core Model can be developed into a platform that enables and encourages true HTA collaboration in terms of distribution of work and maximum utilization of a common pool of structured HTA information for national HTA report

Fractal ventilation enhances respiratory sinus arrhythmia

BACKGROUND: Programming a mechanical ventilator with a biologically variable or fractal breathing pattern (an example of 1/f noise) improves gas exchange and respiratory mechanics. Here we show that fractal ventilation increases respiratory sinus arrhythmia (RSA) – a mechanism known to improve ventilation/perfusion matching. METHODS: Pigs were anaesthetised with propofol/ketamine, paralysed with doxacurium, and ventilated in either control mode (CV) or in fractal mode (FV) at baseline and then following infusion of oleic acid to result in lung injury. RESULTS: Mean RSA and mean positive RSA were nearly double with FV, both at baseline and following oleic acid. At baseline, mean RSA = 18.6 msec with CV and 36.8 msec with FV (n = 10; p = 0.043); post oleic acid, mean RSA = 11.1 msec with CV and 21.8 msec with FV (n = 9, p = 0.028); at baseline, mean positive RSA = 20.8 msec with CV and 38.1 msec with FV (p = 0.047); post oleic acid, mean positive RSA = 13.2 msec with CV and 24.4 msec with FV (p = 0.026). Heart rate variability was also greater with FV. At baseline the coefficient of variation for heart rate was 2.2% during CV and 4.0% during FV. Following oleic acid the variation was 2.1 vs. 5.6% respectively. CONCLUSION: These findings suggest FV enhances physiological entrainment between respiratory, brain stem and cardiac nonlinear oscillators, further supporting the concept that RSA itself reflects cardiorespiratory interaction. In addition, these results provide another mechanism whereby FV may be superior to conventional CV

Insulin-like growth factor-I (IGF-I) and thioredoxin are differentially expressed along the reproductive tract of the ewe during the oestrous cycle and after ovariectomy

Insulin-like growth factor-I (IGF-I) and thioredoxin are regulated by gonadal steroids in the female reproductive tract of many species. Oestradiol regulates IGF-I and thioredoxin mRNA levels in the reproductive tract of prepubertal lambs. The physiological status (different endocrine environment) may affect the sensitivity of the reproductive tract to oestradiol and progesterone. We studied the effects of different endocrine milieus (late-follicular and luteal phases of the oestrous cycle, and ovariectomy before or after puberty) on the expression of IGF-I, thioredoxin, oestrogen receptor α (ERα) and progesterone receptor (PR) in sheep. The mRNA levels were determined by a solution hybridisation technique. In the uterus the levels of ERα, PR and thioredoxin mRNA were higher in the late-follicular phase group than in the other three groups, and IGF-I mRNA was high during both the late-follicular and the luteal phases. In the cervix only PR mRNA was significantly higher in the ewes in the late-follicular phase than in the other groups. In the oviducts the levels of thioredoxin and ERα mRNA were highest in the ovariectomised adult ewes, and thioredoxin mRNA was higher than the levels found in the ewes in the late-follicular phase. The IGF-I mRNA levels in the oviduct did not differ between any of the groups. The transcripts of IGF-I, thioredoxin, ERα and PR, varied according to the physiological status and also along the female reproductive tract, suggesting that the regulation of the mRNA levels of these factors by the steroid environment is tissue specific. Koncentrationen av insulin-like growth factor-I (IGF-I) och thioredoxin regleras hos många arter i honors reproduktionsorgan av könssteroider. Sålunda reglerar östradiol IGF-I och thioredoxin mRNA i reproduktionsorganen hos prepubertala lamm. Djurets fysiologiska status (dvs den endokrina miljön) kan påverka känsligheten hos reproduktionsorganen för östradiol och progesteron. Vi studerade effekterna av olika endokrina miljöer (sen follikelfas och lutealfas i östruscykeln, samt ovariektomi före och efter puberteten) på uttrycket av IGF-I, thioredoxin, östrogenreceptor α (ERα) och progesteronreceptorn (PR) hos får. Lösningshybridisering användes för att bestämma mRNA nivåerna. I livmodern var mRNA koncentrationen för ERα, PR och thioredoxin högre i sen follikelfas än i de andra tre grupperna och IGF-I mRNA nivån var hög både under sen follikelfas och i lutealfas. PR mRNA i cervix var signifikant högre hos tackorna under sen follikelfas än i de andra grupperna. I äggledarna var mRNA nivåerna av thioredoxin och ERα högst i de djur som ovariektomerats som vuxna, och thioredoxin mRNA var högre än hos tackorna under sen follikelfas. Det förelåg ingen skillnad vad gäller IGF-I mRNA nivåerna i äggledaren mellan någon av grupperna. IGF-I, thioredoxin, ERα och PR mRNA nivåerna varierade beroende på fysiologisk status och morfologisk lokalisation i reproduktionsorganen. Detta tyder på att steroidhormonernas reglering av dessa faktorers mRNA uttryck också är vävnadsspecifik

Cholesterolinduced changes in macro- and microvessels in rabbits : Effects of antioxidants

Cholesterol induced changes in macro- and microvessels in rabbits. Effects of antioxidants. Anna Freyschuss, Division of Cardiology and Clinical Chemistry, Karolinska Institute at Huddinge University Hospital, Stockholm, Sweden. A hyperlipidemic state induced by cholesterol feeding results in changes in both the structure and function of macro- and microvessels in rabbits. It has been proposed that oxidative modification of lipoproteins might be an important pathophysiological mechanism explaining these effects of hyperlipidemia. This contention has been supported by a number of in vitro studies. The aim of the present study was to investigate whether the use of antioxidants in vivo in a rabbit model interferes with some of the changes induced in vessels by cholesterol feeding. Studies with butylated hydroxytoluene (BHT) demonstrated that this lipophilic anti oxidant had an inhibitory effect on the formation of macroscopic lesions in the thoracic aorta of cholesterol fed New Zealand White rabbits. This effect was present without any decrease in serum levels of cholesterol, triglycerides or high density lipoprotein (HDL). There was a significant correlation between the inhibitory effect of BHT on the extent of aortic lesions and a rise in triglycerides. Furthermore, BHT treatment had a significant inhibitory effect on the resulting inti mal aortic lesions after balloon injury of the thoracic aorta combined with a more moderately cholesterol enriched diet in rabbits. In addition, feeding rabbits a cholesterol enriched diet induced marked changes in the microcirculation in their conjunctivae as demonstrated by in vivo microscopy. BHT treatment counteracted several of the microcirculatory changes induced by the cholesterol diet; more specifically the reduction in blood flow velocity and arteriolar diameter as well as the occurrence of aggregation, stasis and segmental dilations in the microcirculatory vessels. Studies with the aqueous antioxidant ascorbate added to the drinking water did not inhibit the development of macroscopic lesions in the thoracic aorta of cholesterol fed New Zealand White rabbits. In contrast, treatment with ascorbate had significant effects in counteracting some of the microcirculatory effects observed with cholesterol feeding such as reduction in blood flow velocity and the occurrence of aggregation and stasis. The lipophilic antioxidant BHT is shown to interfere with three different processes of interest for the understanding of the development of atherosclerosis. The findings in this study are consistent with the oxidation hypothesis. We cannot exclude the possibi lity however, that the effect is unrelated to the antioxidant properties of BHT. The pre ventive effect of both BHT and the aqueous antioxidant ascorbate on changes in the microcirculation induced by dietary cholesterol, provides strong support for the conten tion that oxidative reactions are of importance for regulation of the microcirculation. However, whether or not oxidized lipoproteins are involved in this regulation remains to be established. The possibility is discussed, that antioxidants may prove useful in the prevention of microcirculatory dysfunction. Key words: Cholesterol, rabbits, oxidative, antioxidants, vessels, microcirculation ISBN 91-628-2543-

Semiconductor Threat, a Securitizing Move Made by the EU? A Qualitative Content Analysis on EU Speech Acts Concerning Semiconductors

Semiconductors (commonly referred to as “chips”) are small electronic components that are essential in all digital devices such as smartphones, computers, and even cars. The European Union has labeled semiconductors as a security threat due to the EU’s dependency on foreign producers to get access to advanced semiconductors. The thesis examines if the securitization theory can identify a securitizing move made from speech acts released by the EU regarding semiconductors and describe the characteristics of the said move. This securitizing move is identified by examining four criteria; referent object, referent subject, existential threat, and extraordinary measures which are based on the criteria outlined by the securitization theory. This is done through a qualitative content analysis of 17 speech acts from the European Commission, Council of the European Union, European Council, and European Parliament covering a time period from 01-01-2021 to 31-12-2023. The results show findings in each of the criteria and a securitizing move can therefore be identified. The move can be described as multifaceted, covering several different areas but the primary theme of the move is based on a presented threat to the economic sector of the EU. The results provide evidence of the possibility of securitizing high-technological multipurpose products like semiconductors. Further research is encouraged to determine whether the targeted audience has accepted or rejected the securitizing move which would conclude if semiconductors can be viewed as securitized

Semiconductor Threat, a Securitizing Move Made by the EU? A Qualitative Content Analysis on EU Speech Acts Concerning Semiconductors

Semiconductors (commonly referred to as “chips”) are small electronic components that are essential in all digital devices such as smartphones, computers, and even cars. The European Union has labeled semiconductors as a security threat due to the EU’s dependency on foreign producers to get access to advanced semiconductors. The thesis examines if the securitization theory can identify a securitizing move made from speech acts released by the EU regarding semiconductors and describe the characteristics of the said move. This securitizing move is identified by examining four criteria; referent object, referent subject, existential threat, and extraordinary measures which are based on the criteria outlined by the securitization theory. This is done through a qualitative content analysis of 17 speech acts from the European Commission, Council of the European Union, European Council, and European Parliament covering a time period from 01-01-2021 to 31-12-2023. The results show findings in each of the criteria and a securitizing move can therefore be identified. The move can be described as multifaceted, covering several different areas but the primary theme of the move is based on a presented threat to the economic sector of the EU. The results provide evidence of the possibility of securitizing high-technological multipurpose products like semiconductors. Further research is encouraged to determine whether the targeted audience has accepted or rejected the securitizing move which would conclude if semiconductors can be viewed as securitized