Genetic association analyses reveal a role for vitamin D insufficiency in hepatitis C virus-associated hepatocellular carcinoma development

Background: V itamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. Methods: Associations between t he r isk o f HCV-related HCC development and CYP2R1 , GC, and DHCR7 genotypes, which are genetic determinants of reduced 25-OH-vitamin D3 (25[OH]D3) serum levels, were determined. Results: A t otal of 5604 HCV-infected patients, 1279 with a nd 4325 without progression to HCC, w ere identified. The well-known association between 25(OH)D3 s erum levels and variations in CYP2R1 ( rs1993116, rs10741657), GC ( rs2282679), a nd DHCR7 ( rs7944926, rs12785878) g enotypes was also apparent in patients w ith chronic hepatitis C. The same genotypes of t hese single nucleotide polymorphisms (SNPs), w hich are associated with reduced 25(OH)D3 s erum levels, were significantly associated with HCV-associated HCC (P=0.07 [OR=1.13] for CYP2R1 , P=0.007 [OR=1.56] for GC, P=0.003 [OR=1.42] for DHCR7; ORs for risk genotypes). In contrast, no association between t hese genetic variations and the o utcome of antiviral therapy with pegylated interferon-α and ribavirin ( P>0.2 for e ach SNP) or liver fibrosis progression rate (P>0.2 for each SNP) was observed, s uggesting a specific influence o f the genetic d eterminants of 25(OH)D3 s erum levels o n hepatocarcinogenesis. Conclusions: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related HCC development. Controlled clinical trials to assess the benefit of vitamin D supplementation in HCVinfected patients with advanced liver fibrosis or cirrhosis are warranted.

Autonvalmistajan toimitusketjun tehostaminen Suomen sisäisellä yhteistyöllä

Tutkimuksen tavoitteena on selvittää, kuinka globaalin autonvalmistajan toimitusketjua voidaan tehostaa Suomen sisäisten yhteistyökumppaneiden kesken.Tarkoituksena on saada yksittäisten yritysten välisestä yhteistyöstä mahdollisimman paljon synergiaa koko toimitusketjun tehostamiseksi. Tutkimuksessa on käytetty hyväksi alan kirjallisuutta, case- yrityksen tietokantoja ja kerätty aineistoa haastattelemalla toimitusketjussa toimivien yritysten edustajia. Informaatiotekniikan kehitys on ollut runsasta viime vuosikymmenien aikana, mikä on mahdollistanut reaaliaikaisen yhteistyön globaaleissa toimitusketjuissa. Toimivan yhteistyöverkoston edellytyksenä ovat kuitenkin hyvin rakennetut toimintamallit, joissa toimitaan tehokkaasti koko toimitusketjun edun saavuttamiseksi. Tutkimuksen empiirisessä osassa esitellään vaihtoehtoisia toimintamalleja, joilla voidaan lisätä yhteistyötä jokaista osapuolta hyödyttävällä tavalla. Näintoimitusketjusta saadaan karsittua osaoptimointia ja tehotonta toimintaa. Tämänlisäksi annetaan ehdotuksia informaatiotekniikan laajempaan hyväksikäyttöön toimitusketjun eri yritysten välillä.

Patterns and factors associated with low adherence to psychotropic medications during pregnancy-a cross-sectional, multinational web-based study.

BACKGROUND: No previous studies have explored how closely women follow their psychotropic drug regimens during pregnancy. This study aimed to explore patterns of and factors associated with low adherence to psychotropic medication during pregnancy. METHODS: Multinational web-based study was performed in 18 countries in Europe, North America, and Australia. Uniform data collection was ensured via an electronic questionnaire. Pregnant women were eligible to participate. Adherence was measured via the 8-item Morisky Medication Adherence Scale (MMAS-8). The Beliefs about Prescribed Medicines Questionnaire (BMQ-specific), the Edinburgh Postnatal Depression Scale (EPDS), and a numeric rating scale were utilized to measure women's beliefs, depressive symptoms, and antidepressant risk perception, respectively. Participants reporting use of psychotropic medication during pregnancy (n = 160) were included in the analysis. RESULTS: On the basis of the MMAS-8, 78 of 160 women (48.8%, 95% CI: 41.1-56.4%) demonstrated low adherence during pregnancy. The rates of low adherence were 51.3% for medication for anxiety, 47.2% for depression, and 42.9% for other psychiatric disorders. Smoking during pregnancy, elevated antidepressant risk perception (risk≥6), and depressive symptoms were associated with a significant 3.9-, 2.3-, and 2.5-fold increased likelihood of low medication adherence, respectively. Women on psychotropic polytherapy were less likely to demonstrate low adherence. The belief that the benefit of pharmacotherapy outweighed the risks positively correlated (r = .282) with higher medication adherence. CONCLUSIONS: Approximately one of two pregnant women using psychotropic medication demonstrated low adherence in pregnancy. Life-style factors, risk perception, depressive symptoms, and individual beliefs are important factors related to adherence to psychotropic medication in pregnancy.

Randomized clinical trial on epidural versus patient-controlled analgesia for laparoscopic colorectal surgery within an enhanced recovery pathway.

OBJECTIVE: To compare epidural analgesia (EDA) to patient-controlled opioid-based analgesia (PCA) in patients undergoing laparoscopic colorectal surgery. BACKGROUND: EDA is mainstay of multimodal pain management within enhanced recovery pathways [enhanced recovery after surgery (ERAS)]. For laparoscopic colorectal resections, the benefit of epidurals remains debated. Some consider EDA as useful, whereas others perceive epidurals as unnecessary or even deleterious. METHODS: A total of 128 patients undergoing elective laparoscopic colorectal resections were enrolled in a randomized clinical trial comparing EDA versus PCA. Primary end point was medical recovery. Overall complications, hospital stay, perioperative vasopressor requirements, and postoperative pain scores were secondary outcome measures. Analysis was performed according to the intention-to-treat principle. RESULTS: Final analysis included 65 EDA patients and 57 PCA patients. Both groups were similar regarding baseline characteristics. Medical recovery required a median of 5 days (interquartile range [IQR], 3-7.5 days) in EDA patients and 4 days (IQR, 3-6 days) in the PCA group (P = 0.082). PCA patients had significantly less overall complications [19 (33%) vs 35 (54%); P = 0.029] but a similar hospital stay [5 days (IQR, 4-8 days) vs 7 days (IQR, 4.5-12 days); P = 0.434]. Significantly more EDA patients needed vasopressor treatment perioperatively (90% vs 74%, P = 0.018), the day of surgery (27% vs 4%, P < 0.001), and on postoperative day 1 (29% vs 4%, P < 0.001), whereas no difference in postoperative pain scores was noted. CONCLUSIONS: Epidurals seem to slow down recovery after laparoscopic colorectal resections without adding obvious benefits. EDA can therefore not be recommended as part of ERAS pathways in laparoscopic colorectal surgery.

Osuuskunta hyvinvointipalvelujen vaihtoehtoisena tuottajana

The purpose of this thesis is to describe the meaning of cooperation for the entrepreneurs who have planned to establish a co-operative. The objective is to understand what kind of benefits, expectations and challenges entrepreneurs see in the co-operative business and its establishment. The context of the study is welfare sector. As the population ages, increases the need for welfare services and the role of private service providers emphasizes. The study is based on qualitative theme interview. The empirical material was collected by interviewing eleven entrepreneurs in home care and home nursing sectors. The interviews were executed during the summer and autumn 2006. As an additional material there have been used five interviews of entrepreneurs who are members of co-operatives in different sectors. These interviews were executed during the spring 2007. The results show that the entrepreneurs experience that cooperation brings noticeable added value to their business activity. Cooperation is believed to be a channel to develop business activities. Besides development, co-operative business is expected to reply to the collective needs of entrepreneurs. The biggest challenges of functional cooperation are opportunistic behavior and finding a trustworthy group of entrepreneurs to establish the co-operative. Successful cooperation with the public sector would be the mutual benefit of government, companies and clients.

Treball social i responsabilitat social corporativa, reflexions i sinergies. Explorant noves perspectives de participació.

Les empreses en tant que formen part de la comunitat, tenen una responsabilitat vers la mateixa i la realitat social que la forma. Les accions que es realitzen no són neutres, generant comportaments que cal saber preveure en benefici comú de totes les parts implicades directament o indirectament. Parlar de Responsabilitat Social Corporativa (RSC) ja és en si un fet positiu que dibuixa nous horitzons cap a societats més responsables i justes. L'incorporació de la RSC en el debat econòmic, social, ambiental, cultural i polític, fa preveure un recorregut llarg en el temps on cada vegada més empreses, entitats i organitzacions sumen esforços al seu voltant. El Treball Social com a professió coneixedora de la realitat social i les dificultats existents ha de poder jugar un paper proactiu en la RSC conjuntament amb d´altres actors. Des d'un treball col·laboratiu que afavoreixi espais de sinergia, on es sumin esforços per assolir una societat més humana, justa, solidària i responsable. En definitiva amb un missatge adreçat a treballar, des de diferents àmbits professionals, per garantir uns mínims de qualitat de vida per a totes les persones que formem part de la societat.

Points to consider for prioritizing clinical genetic testing services: a European consensus process oriented at accountability for reasonableness.

Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set of prioritization criteria would be desirable. A decision process following the accountability for reasonableness framework was undertaken, including a multidisciplinary EuroGentest/PPPC-ESHG workshop to develop shared prioritization criteria. Resources are currently too limited to fund all the beneficial genetic testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit of information for important life decisions, benefit for other people apart from the person tested and the patient-specific likelihood of being affected by the condition tested for. It may be subject to a finite time window. Health need includes the severity of the condition tested for and its progression at the time of testing. Further discussion and better evidence is needed before clearly defined recommendations can be made or a prioritization algorithm proposed. To our knowledge, this is the first time a clinical society has initiated a decision process about health-care prioritization on a European level, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management.

Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with significantly increased cardiovascular morbidity and mortality. Fluid overload may promote obstructive sleep apnea in patients with ESRD through an overnight fluid shift from the legs to the neck soft tissues. Body fluid shift and severity of obstructive sleep apnea before and after hemodialysis were compared in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventeen patients with hemodialysis and moderate to severe obstructive sleep apnea were included. Polysomnographies were performed the night before and after hemodialysis to assess obstructive sleep apnea, and bioimpedance was used to measure fluid overload and leg fluid volume. RESULTS: The mean overnight rostral fluid shift was 1.27±0.41 L prehemodialysis; it correlated positively with fluid overload volume (r=0.39; P=0.02) and was significantly lower posthemodialysis (0.78±0.38 L; P<0.001). There was no significant difference in the mean obstructive apnea-hypopnea index before and after hemodialysis (46.8±22.0 versus 42.1±18.6 per hour; P=0.21), but obstructive apnea-hypopnea index was significantly lower posthemodialysis (-10.1±10.8 per hour) in the group of 12 patients, with a concomitant reduction of fluid overload compared with participants without change in fluid overload (obstructive apnea-hypopnea index +8.2±16.1 per hour; P<0.01). A lower fluid overload after hemodialysis was significantly correlated (r=0.49; P=0.04) with a lower obstructive apnea-hypopnea index. Fluid overload-assessed by bioimpedance-was the best predictor of the change in obstructive apnea-hypopnea index observed after hemodialysis (standardized r=-0.68; P=0.01) in multivariate regression analysis. CONCLUSIONS: Fluid overload influences overnight rostral fluid shift and obstructive sleep apnea severity in patients with ESRD undergoing intermittent hemodialysis. Although no benefit of hemodialysis on obstructive sleep apnea severity was observed in the whole group, the change in obstructive apnea-hypopnea index was significantly correlated with the change in fluid overload after hemodialysis. Moreover, the subgroup with lower fluid overload posthemodialysis showed a significantly lower obstructive sleep apnea severity, which provides a strong incentive to further study whether optimizing fluid status in patients with obstructive sleep apnea and ESRD will improve the obstructive apnea-hypopnea index.

Product Launch in Industrial Markets – Financial Risks in New AMD Elevator Door Launch

Tuotekehitys ja uusien tuotteiden lanseeraus on teollisen yrityksen menestyksekkään liiketoiminnan elinehtoja tämän päivän kilpailussa. Teollisuusyrityksen tuotteiden innovaatioaikakausia on ollut lukuisia, samoin kuin uuden tuotteen lanseerauksen lähtökohtia. Aikakausista, jolloin tuotteita kehitettiin yrityksen omista lähtökohdista, kuten valmistuksellisista eduista, on edetty tilanteeseen, jossa markkinoiden tarpeita tulee ottaa yhä enemmän huomioon. Kuitenkin, teollisuudessa esitellään tuotteita yhä puhtaasti tuotantolähtöisesti, ja tutkimuksen tavoitteena on selvittää taloudellisia riskejä, joita liittyy puhtaasti teknologiavetoiseen tuotteiden kehitystyöhön, valmistukseen ja lanseeraukseen. Normatiivisena tutkimuksena työ pyrkii asiakastarpeita ja teollisuusyrityksen loppuasiakkaiden näkökulmia huomioon ottaen osoittamaan markkinoinnin keinojen merkityksen tuotantolähtöisen tuotelanseerauksen taloudellisten riskien minimoimiseksi. Uuden teollisen tuotteen asiakastarpeita on selvitetty kyselymuotoisen markkinointitutkimuksen menetelmiä hyväksikäyttäen. Tuotteen tärkeimpien ominaisuuksien, kuten turvallisuuden, kestävyyden ja hinnan merkitystä voidaan hyödyntää ennen tuotteen kaupallista esittelyä potentiaalisten asiakassegmenttien kartoitukseen ja menestyksellisen lanseerauksen edesauttamiseksi.

Teknologiayrityksen laajentuminen epävarmassa tilanteessa – reaalioptiolähtöinen kannattavuustarkastelu

Investoinnit ovat välttämättömiä, jotta yritys voi parantaa asemaansa toimintaympäristössään ja ylläpitää saavutettua kilpailuetua. Siksi investointien kannattavuuden tutkiminen on tärkeää. Reaalioptioiden avulla voidaan hyödyntää tulevaisuuden mahdollisuuksia ja vähentää uhkia, jolloin kannattavuuslaskentaan saadaan uusia näkökulmia. Reaalioptiot ovat strategisen suunnittelun työkaluja. Työssä tutkittiin reaalioptioiden mahdollisuuksia teknologiayrityksen päätöksenteon tukena. Tarkastelu tehtiin kohdeyrityksen näkökulmasta keskittyen informaation tuottamiseen ja reaalioptioiden soveltamiseen kerätyssä aineistossa. Reaalioptiot ovat tärkeitä riskienhallintavälineitä, joiden avulla tulevaisuuden muutokset voidaan ottaa muuttujiksi investointeja arvotettaessa. Reaalioptioiden soveltava käyttö on ollut vielä vähäistä niiden monimutkaisuudesta ja muuttujien hallinnan vaikeudesta johtuen. Reaalioptioita on tutkittu tieteellisessä kirjallisuudessa jo merkittävästi. Suomessa käytännön sovellukset ovat olleet vähäisiä. Reaalioptioiden strategisesta luonteesta johtuen tulokset ovat usein myös salaisia. Tässä työssä käytetään kohdeyrityksen pyynnöstä Case-osuudessa kohteista muutettuja nimiä ja arvoja.

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures.

Transiliac bone biopsies, while widely considered to be the standard for the analysis of bone microstructure, are typically restricted to specialized centers. The benefit of Trabecular Bone Score (TBS) in addition to areal bone mineral density (aBMD) for fracture risk assessment has been documented in cross-sectional and prospective studies. The aim of this study was to test if TBS may be useful as a surrogate to histomorphometric trabecular parameters of transiliac bone biopsies. Transiliac bone biopsies from 80 female patients (median age 39.9years-interquartile range, IQR 34.7; 44.3) and 43 male patients (median age 42.7years-IQR 38.9; 49.0) with idiopathic osteoporosis and low traumatic fractures were included. Micro-computed tomography values of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), structural model index (SMI) as well as serum bone turnover markers (BTMs) sclerostin, intact N-terminal type 1 procollagen propeptide (P1NP) and cross-linked C-telopeptide (CTX) were investigated. TBS values were higher in females (1.282 vs 1.169, p< 0.0001) with no differences in spine aBMD, whereas sclerostin levels (45.5 vs 33.4pmol/L) and aBMD values at the total hip (0.989 vs 0.971g/cm(2), p<0.001 for all) were higher in males. Multiple regression models including: gender, aBMD and BTMs revealed TBS as an independent, discriminative variable with adjusted multiple R(2) values of 69.1% for SMI, 79.5% for Tb.N, 68.4% for Tb.Sp, and 83.3% for BV/TV. In univariate regression models, BTMs showed statistically significant results, whereas in the multiple models only P1NP and CTX were significant for Tb.N. TBS is a practical, non-invasive, surrogate technique for the assessment of cancellous bone microarchitecture and should be implemented as an additional tool for the determination of trabecular bone properties.

Thermoregulation and microhabitat choice in the polymorphic asp viper (Vipera aspis).

In ectotherms, thermoregulation strongly depends on environmental conditions, as well as on intrinsic factors, such as skin colour. Indeed, due to its physical properties, melanin pigments allow melanistic morphs to benefit of a more efficient thermoregulation compared to non-melanistic ones. Despite thermal benefits of melanism have often been highlighted under experimental conditions, such field data remain scarce. In this study, we investigated the influence of colouration on body temperature and microhabitat choice in a montane population of colour polymorphic asp viper (Vipera aspis) characterized by a strong presence of melanism (64%). Results highlighted a difference in internal body temperature, but only within gravid females, with melanistic individuals having higher body temperatures compared to non-melanistic ones. No differences were found when considering both sexes. We also showed that melanistic and non-melanistic vipers were found in different microhabitat types, i.e. melanistic snakes used areas marked by a scarcer sun exposure and by higher vegetation cover compared to non-melanistic ones. This result has important implications. Indeed, besides providing a possible explanation for the lack of difference in body temperature (except for gravid females), it confirms that melanistic individuals can potentially use their efficient thermoregulation in order to inhabit less exposed and thermally unfavourable microhabitats.

Sairaanhoitajan opiskelijaohjaustaidot sekä ohjaajakoulutuksen tarve ja hyöty hoitotyön ohjatun harjoittelun oppimisympäristössä

A Nurse's Preceptorship Skills of Guiding Students and the Need for and Benefit from Preceptorship Education Guided practical training in units of health services is an essential part of the education of nurses. Nurses take care of a student's preceptorship during these periods, and their role in supporting a student's learning has been shown to be the most important factor in the learning environment of guided practical training. Education for preceptors in various educational units has been organized to develop their skills of guiding students. The aim of this study was both to investigate preceptors' skills of guiding students, the differences in the student guiding skills of those who have and who have not received preceptorship education and to describe their experiences of their own need for preceptorship education and of the benefit of such education. Any activities that promote a student's learning were included in nurses' preceptorship skills. On the basis of research knowledge, the preceptorship skills were divided into the following subdomains: proficiency in nursing; creation of a preceptorship relationship; planning of preceptorship; implementation of preceptorship; combination of theory and practice; and evaluation. The target group comprised all those nurses (n=128) in a hospital in southern Finland who guided future nurses. The material was gathered by means of a questionnaire with structural and open questions. Preceptorship skills were studied with the structured questions and the need for and benefit from preceptorship education with the open questions. The material was interpreted by means of a statistical SAS programme and qualitative content analysis. The preceptorship skills in all domains of guiding skills proved good. Those who had received preceptorship education had better skills than those who had not received such education in all domains but “creation of a preceptorship relationship”. However, the differences were not statistically significant. The need for preceptorship education was highest in evaluation and in setting goals for a student. To support these, the preceptors wanted information on education and students' requirements. Most of all, preceptorship education had benefited the creation of a preceptorship relationship and the implementation of evaluation. The preceptors were of the opinion that their skills of guiding students were good. However, education is needed, which makes the results inconsistent in this respect. The results can be used in developing preceptorship skills and in planning preceptorship education.

Net Neutrality: Measuring the Problem, Assessing the Legal Risks

Network neutrality is a growing policy controversy. Traffic management techniques affect not only high-speed, high-money content, but by extension all other content too. Internet regulators and users may tolerate much more discrimination in the interests of innovation. For instance, in the absence of regulatory oversight, ISPs could use Deep Packet Inspection (DPI) to block some content altogether, if they decide it is not to the benefit of ISPs, copyright holders, parents or the government. ISP blocking is currently widespread in controlling spam email, and in some countries in blocking sexually graphic illegal images. In 1999 this led to scrutiny of foreclosure of Instant Messaging and video and cable-telephony horizontal merger. Fourteen years later, there were in 2013 net neutrality laws implemented in Slovenia, the Netherlands, Chile and Finland, regulation in the United States and Canada , co-regulation in Norway, and self-regulation in Japan, the United Kingdom and many other European countries . Both Germany and France in mid-2013 debated new net neutrality legislation, and the European Commission announced on 11 September 2013 that it would aim to introduce legislation in early 2014. This paper analyses these legal developments, and in particular the difficulty in assessing reasonable traffic management and ‘specialized’ (i.e. unregulated) faster services in both EU and US law. It also assesses net neutrality law against the international legal norms for user privacy and freedom of expression

The pseudo-high-risk prevention strategy

Key Messages: A fundamental failure of high-risk prevention strategies is their inability to prevent disease in the large part of the population at a relatively small average risk and from which most cases of diseases originate. The development of individual predictive medicine and the widening of high-risk categories for numerous (chronic) conditions lead to the application of pseudo-high-risk prevention strategies. Widening the criteria justifying individual preventive interventions and the related pseudo-high-risk strategies lead to treating, individually, ever healthier and larger strata of the population. The pseudo-high-risk prevention strategies raise similar problems compared with high-risk strategies, however on a larger scale and without any of the benefit of population-based strategies. Some 30 years ago, the strengths and weaknesses of population-based and high-risk prevention strategies were brilliantly delineated by Geoffrey Rose in several seminal publications (Table 1).1,2 His work had major implications not only for epidemiology and public health but also for clinical medicine. In particular, Rose demonstrated the fundamental failure of high-risk prevention strategies, that is, by missing a large number of preventable cases.