”In a perfect world we don’t need them or want them – but the world isn’t perfect” : the United Nations and the private arms

Tutkielma on temaattisesti kiinnostunut erityisesti 1990-luvulla räjähdysmäisesti kasvaneista yksityisistä sotilas –ja turvallisuusalan yrityksistä. Työn tarkoituksena on avata näiden yritysten sekä Yhdistyneiden kansakuntien (YK) välistä yhteyttä sekä tutkia, millaista toimijuutta YK yrityksistä tuottaa. Tutkielman lähtökohtana on asetelma, jossa YK on itse perinteisestä normatiivisesta suhtautumisestaan huolimatta toimialan merkittävä asiakas, sekä lukuisista eri tekijöistä sekä kehityssuunnista johtuen kasvavasti kiinnostunut yritysten tuottamista palveluista. Työ lähestyy tutkimusaineistoa vahvan teoreettisesta näkökulmasta. Teoria koostuu Sarah Percyn teoksessa Mercenaries: The History of a Norm in International Relations (2007) esitetystä kieltävän normin käsitteestä. Teorian ydinajatuksena on kansainvälisissä suhteissa läpi historian vaikuttanut kieltävä normi, joka esittää palkkasoturit moraalisesti ongelmallisina, sillä he ovat yksinomaan motivoituneet rahasta – ja he eivät näin ollen toimi aatteesta – ja toisekseen, toimivat legitiimiksi koetun kontrollin ulkopuolella. Analyysin tehtävänä on peilata tätä kieltävää normia tutkimusaineistoon ja tutkia, kuinka voimakkaasti normi on aineistossa havaittavissa. Kysymys on kiinnostava ottaen huomioon toisaalta YK:n aiemman, vahvasti normatiivisen diskurssin sekä toisaalta sen oman, edelleen kasvavan riippuvuussuhteen yksityisistä sotilas –ja turvallisuusalan yrityksistä. Analyysi osoittaa, että kieltävä normi vaikuttaa edelleen YK:n tuottamassa puheessa. Yksityiset sotilas –ja turvallisuusalan yritykset nähdään melko verrannollisina palkkasotureihin, joskin tämä diskurssi vaimenee mitä myöhäisemmästä aineistosta on kyse. Tämä näkyy muun muassa siinä, että yritysten sekä niiden työntekijöiden nähdään omaavan yksinomaan rahallisia intressejä. Yhtä lailla, yritysten toiminta nähdään uhkana valtion harjoittamalle väkivallan monopolille. Tästä huolimatta yritykset nähdään myös YK:lle tarpeellisina, sekä niiden läsnäolon lopullisuus YK:n kontekstissa tunnustetaan

Priorities for health economic methodological research: Results of an expert consultation

Background: The importance of economic evaluation in decision making is growing with increasing budgetary pressures on health systems. Diverse economic evidence is available for a range of interventions across national contexts within Europe, but little attention has been given to identifying evidence gaps that, if filled, could contribute to more efficient allocation of resources. One objective of the Research Agenda for Health Economic Evaluation project is to determine the most important methodological evidence gaps for the ten highest burden conditions in the European Union (EU), and to suggest ways of filling these gaps. Methods: The highest burden conditions in the EU by Disability Adjusted Life Years were determined using the Global Burden of Disease study. Clinical interventions were identified for each condition based on published guidelines, and economic evaluations indexed in MEDLINE were mapped to each intervention. A panel of public health and health economics experts discussed the evidence during a workshop and identified evidence gaps. Results: The literature analysis contributed to identifying cross-cutting methodological and technical issues, which were considered by the expert panel to derive methodological research priorities. Conclusions: The panel suggests a research agenda for health economics which incorporates the use of real-world evidence in the assessment of new and existing interventions; increased understanding of cost-effectiveness according to patient characteristics beyond the “-omics” approach to inform both investment and disinvestment decisions; methods for assessment of complex interventions; improved cross-talk between economic evaluations from health and other sectors; early health technology assessment; and standardized, transferable approaches to economic modeling

PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice

Recently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel ischemic disease and ischemic stroke most important survival mechanism, such as the recruitment of brain collateral arteries like posterior communicating arteries (PcomAs), remains unknown. Therefore, we applied exome and genome sequencing in a multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic brain small vessel ischemic disease and CADASIL-like Caucasian patients from US, Portugal, Finland, Serbia and Turkey and in 2 C57BL/6J stroke mouse models (bilateral common carotid artery stenosis [BCCAS] and middle cerebral artery occlusion [MCAO]), characterized by different degrees of PcomAs patency. We report 3 very rare coding variants in the small vessel ischemic disease-CADASIL-like cohort (p.Glu198Gln, p.Arg204Gly, p.Val251Leu) and a stop-gain mutation (p.Gln273*) in one MCAO mouse. These coding variants do not cluster in PHACTR1 known pathogenic domains and are not likely to play a critical role in small vessel ischemic disease or brain collateral circulation. We also exclude the possibility that copy number variants (CNVs) or a variant enrichment in Phactr1 may be associated with PcomA recruitment in BCCAS mice or linked to diverse vascular traits (cerebral blood flow pre-surgery, PcomA size, leptomeningeal microcollateral length and junction density during brain hypoperfusion) in C57BL/6J mice, respectively. Genetic variability in PHACTR1 is not likely to be a common susceptibility factor influencing small vessel ischemic disease in patients and PcomA recruitment in C57BL/6J mice. Nonetheless, rare variants in PHACTR1 RPEL domains may influence the stroke outcome and are worth investigating in a larger cohort of small vessel ischemic disease patients, different ischemic stroke subtypes and with functional studies

TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. We report 2 very rare and likely pathogenic TREX1 mutations: a loss of function mutation (p.Ala129fs) clustering in the catalytic domain, in an apparently sporadic 46-year-old patient from the USA and a missense mutation (p.Tyr305Cys) in the well conserved C-terminal region, in a 57-year-old patient with positive family history from Serbia. In concert with recent findings, our study expands the clinical spectrum of diseases associated with TREX1 mutations

TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. We report 2 very rare and likely pathogenic TREX1 mutations: a loss of function mutation (p.Ala129fs) clustering in the catalytic domain, in an apparently sporadic 46-year-old patient from the USA and a missense mutation (p.Tyr305Cys) in the well conserved C-terminal region, in a 57-year-old patient with positive family history from Serbia. In concert with recent findings, our study expands the clinical spectrum of diseases associated with TREX1 mutations

PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice

Recently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel ischemic disease and ischemic stroke most important survival mechanism, such as the recruitment of brain collateral arteries like posterior communicating arteries (PcomAs), remains unknown. Therefore, we applied exome and genome sequencing in a multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic brain small vessel ischemic disease and CADASIL-like Caucasian patients from US, Portugal, Finland, Serbia and Turkey and in 2 C57BL/6J stroke mouse models (bilateral common carotid artery stenosis [BCCAS] and middle cerebral artery occlusion [MCAO]), characterized by different degrees of PcomAs patency. We report 3 very rare coding variants in the small vessel ischemic disease-CADASIL-like cohort (p.Glu198Gln, p.Arg204Gly, p.Val251Leu) and a stop-gain mutation (p.Gln273*) in one MCAO mouse. These coding variants do not cluster in PHACTR1 known pathogenic domains and are not likely to play a critical role in small vessel ischemic disease or brain collateral circulation. We also exclude the possibility that copy number variants (CNVs) or a variant enrichment in Phactr1 may be associated with PcomA recruitment in BCCAS mice or linked to diverse vascular traits (cerebral blood flow pre-surgery, PcomA size, leptomeningeal microcollateral length and junction density during brain hypoperfusion) in C57BL/6J mice, respectively. Genetic variability in PHACTR1 is not likely to be a common susceptibility factor influencing small vessel ischemic disease in patients and PcomA recruitment in C57BL/6J mice. Nonetheless, rare variants in PHACTR1 RPEL domains may influence the stroke outcome and are worth investigating in a larger cohort of small vessel ischemic disease patients, different ischemic stroke subtypes and with functional studies.</p

PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice

Recently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel ischemic disease and ischemic stroke most important survival mechanism, such as the recruitment of brain collateral arteries like posterior communicating arteries (PcomAs), remains unknown. Therefore, we applied exome and genome sequencing in a multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic brain small vessel ischemic disease and CADASIL-like Caucasian patients from US, Portugal, Finland, Serbia and Turkey and in 2 C57BL/6J stroke mouse models (bilateral common carotid artery stenosis [BCCAS] and middle cerebral artery occlusion [MCAO]), characterized by different degrees of PcomAs patency. We report 3 very rare coding variants in the small vessel ischemic disease-CADASIL-like cohort (p.Glu198Gln, p.Arg204Gly, p.Val251Leu) and a stop-gain mutation (p.Gln273*) in one MCAO mouse. These coding variants do not cluster in PHACTR1 known pathogenic domains and are not likely to play a critical role in small vessel ischemic disease or brain collateral circulation. We also exclude the possibility that copy number variants (CNVs) or a variant enrichment in Phactr1 may be associated with PcomA recruitment in BCCAS mice or linked to diverse vascular traits (cerebral blood flow pre-surgery, PcomA size, leptomeningeal microcollateral length and junction density during brain hypoperfusion) in C57BL/6J mice, respectively. Genetic variability in PHACTR1 is not likely to be a common susceptibility factor influencing small vessel ischemic disease in patients and PcomA recruitment in C57BL/6J mice. Nonetheless, rare variants in PHACTR1 RPEL domains may influence the stroke outcome and are worth investigating in a larger cohort of small vessel ischemic disease patients, different ischemic stroke subtypes and with functional studies

Kasvokkaisen kohtaamisen merkitys sähköisiä sosiaalipalveluita kehitettäessä : pälkäneläisten starttipajanuorten kokemuksia palvelujärjestelmästä

Tämä opinnäytetyö toteutettiin Pälkäneen kunnan nuorten starttipajalle kesällä 2019. Tarkoituksenamme oli tuoda esille 17-29 vuotiaiden nuorten näkökulmia sähköisiä palveluita kehitettäessä. Tavoitteenamme oli selvittää, minkälaisesta tuesta starttipajan nuoret kokevat hyötyvänsä. Halusimme myös selvittää, kokevatko nuoret hyötyvänsä sähköisistä palveluista sosiaalialalla sekä minkälainen merkitys fyysisellä läsnäololla ja tuella on nuorille. Opinnäytetyön tietoperustaksi muodostuivat sosiaaliohjaus, moniammatillinen yhteistyö ja palvelujärjestelmä, syrjäytyminen, osallisuus ja osallistuminen, sekä motivaatio. Starttipajan nuorille teetettiin kyselylomake, jonka pohjalta järjestimme kaksi toiminnallista työpajaa. Kyselylomake toimi pohjana työpajoille, joissa aineistonkeruumenetelmänä toimi teemahaastattelu. Toiminnallisten työpajojen tulosten perusteella nuoret kokivat sähköisillä sosiaalipalveluilla olevan paikkansa, mutta kasvokkain tapahtuvaa ohjausta sillä ei voida täysin korvata. Oman työntekijän vaihtumisen koettiin vaikuttavan negatiivisesti palvelukokemukseen. Nuoret kaipasivat starttipajalle enemmän haastetta, jolloin pajalta saatua työkokemusta pystyisi hyödyntämään myös tulevalla työpaikalla. Lisäksi tutkielmassa nousi esiin, että opintoihin liittyvät haasteet juontavat juurensa jo peruskouluun ja siellä tehtävää ohjauksellista työtä olisi syytä lisätä. Sähköisten palvelumuotojen yleistyessä palveluita tulisi kehittää nuorten tarpeita paremmin vastaaviksi. Opinnäytetyössämme on esitelty useita näkökulmia sähköisten palveluiden kehittämiseksi. Työmme tuottaa lisäksi tietoa Pälkäneen starttipajan toiminnan kehittämiseksi.This thesis was implemented at the start of a young people workshop in the municipality of Pälkäne during the summer of 2019. The purpose of this thesis was to acknowledge the point of view of young people (between the age of 17-29) when digital services are developed. Our main goal was to examine what kind of support is most likely beneficial to these young people. We wanted to examine the benefits of the digital services in the field of social sciences and also the meaning of physical presence and support for the young people. The knowledge base of this thesis consisted of; social guidance, multi-professional cooperation and service structure, social exclusion, social inclusion and participation and motivation. The questionnaire was implemented with the young people of the workshop and the functional workshops were organized based on the results of the questionnaire. The questionnaire was the base of the workshops in which focused interview was used as a method to collect the data. Young people see that digital services make a difference (based on the data collected from the functional workshops), but face to face guidance can’ t be totally replaced by that. The lack of a personal instructor was experienced negatively. Young people wanted more challenging activities to the workshops when the gained work experience could be used in possible future work. Furthermore, our thesis revealed that the challenges in the studies have their roots in primary schools and proper guidance should be increased within those schools. The increase of digital services creates a situation in which services should meet young people’s needs better. Our thesis provides perspectives for the development of digital services as well as information to develop the different functions at the start of the workshop in Pälkäne

PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice

Recently, several genome-wide association studies identified PHACTR1 as key locus for five diverse vascular disorders: coronary artery disease, migraine, fibromuscular dysplasia, cervical artery dissection and hypertension. Although these represent significant risk factors or comorbidities for ischemic stroke, PHACTR1 role in brain small vessel ischemic disease and ischemic stroke most important survival mechanism, such as the recruitment of brain collateral arteries like posterior communicating arteries (PcomAs), remains unknown. Therefore, we applied exome and genome sequencing in a multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic brain small vessel ischemic disease and CADASIL-like Caucasian patients from US, Portugal, Finland, Serbia and Turkey and in 2 C57BL/6J stroke mouse models (bilateral common carotid artery stenosis [BCCAS] and middle cerebral artery occlusion [MCAO]), characterized by different degrees of PcomAs patency. We report 3 very rare coding variants in the small vessel ischemic disease-CADASIL-like cohort (p.Glu198Gln, p.Arg204Gly, p.Val251Leu) and a stop-gain mutation (p.Gln273*) in one MCAO mouse. These coding variants do not cluster in PHACTR1 known pathogenic domains and are not likely to play a critical role in small vessel ischemic disease or brain collateral circulation. We also exclude the possibility that copy number variants (CNVs) or a variant enrichment in Phactr1 may be associated with PcomA recruitment in BCCAS mice or linked to diverse vascular traits (cerebral blood flow pre-surgery, PcomA size, leptomeningeal microcollateral length and junction density during brain hypoperfusion) in C57BL/6J mice, respectively. Genetic variability in PHACTR1 is not likely to be a common susceptibility factor influencing small vessel ischemic disease in patients and PcomA recruitment in C57BL/6J mice. Nonetheless, rare variants in PHACTR1 RPEL domains may influence the stroke outcome and are worth investigating in a larger cohort of small vessel ischemic disease patients, different ischemic stroke subtypes and with functional studies.Peer reviewe