Unconsciousness and sedation as precipitating factors of diabetic ketoacidosis.

The aim of this study was to identify medico-legal situations characterized by increased vitreous glucose concentrations, potentially lethal blood 3-hydroxybutyrate levels and conditions that could either incapacitate or lead to death on their own. The above was investigated in order to verify whether prolonged states of unconsciousness may play a role in precipitating diabetic ketoacidosis. Six groups of medico-legal situations (corresponding to 206 autopsy cases) were identified. Among these, three cases were characterized by pathologically increased vitreous glucose and blood 3-hydroxybutyrate levels. In one case diabetic ketoacidosis coexisted with underlying features that might have potentially incapacitated or lead to death on their own, whereas in two cases it corresponded with potentially lethal or lethal drug concentrations. The results of this study highlight the usefulness of systematically performing biochemistry in order to identify diabetic ketoacidosis-related deaths, even when autopsy and toxicology results provide apparently conclusive findings.

The Effects of Multifactorial Fall Prevention on the Psychological Risk Factors of Falling

Psychological factors, such as depression or depressive symptoms and fear of falling are linked to falls among the aged. According to previous studies, they may increase the risk of falls and injurious falls. In addition, depression or a high amount of depressive symptoms and fear of falling may hinder participation in preventive activities. Despite the severe consequences of both conditions and their high prevalence among the aged, they have rarely been studied in the context of fall prevention. The study aimed to assess the effects of multifactorial fall prevention on the psychological risk factors of falling (depressive symptoms and fear of falling) among the community-dwelling aged at increased risk of falling. In addition, it aimed to determine factors predicting high adherence to preventive activities. Volunteers aged 65 or over, who had fallen during the year previous to randomisation were recruited. Participants (n=591) were randomised into an intervention or a control group. The intervention group received a multifactorial fall prevention programme including geriatric assessment, individual guidance on fall and fracture prevention, group- and home-based physical exercise, psychosocial group activities, lectures and home hazards assessment. The control group had a one-time counselling on fall and fracture prevention. The data on psychological risk factors of falling were collected by self-rated questionnaires. Multifactorial fall prevention was not effective in reducing depressive symptoms or fear of falling compared to one-time counselling in the total sample. However, in subgroup analyses, depressive symptoms reduced statistically significantly more among the men and older participants of the intervention group compared to the control group. Female gender, high physical and cognitive abilities and low self-perceived probability of falling were independent predictors of higher adherence in organised activities. In conclusion, few psychological benefits were gained during this multifactorial fall prevention trial. More attention should be focused on adherence, especially among the aged with functional disabilities.

Role of trabectedin in the treatment of soft tissue sarcoma.

Interest in marine natural products has allowed the discovery of new drugs and trabectedin (ET-743, Yondelis), derived from the marine tunicate Ecteinascidia turbinata, was approved for clinical use in 2007. It binds to the DNA minor groove leading to interferences with the intracellular transcription pathways and DNA-repair proteins. In vitro antitumor activity was demonstrated against various cancer cell lines and soft tissue sarcoma cell lines. In phase I studies tumor responses were observed also in osteosarcomas and different soft tissue sarcoma subtypes. The most common toxicities were myelosuppression and transient elevation of liver function tests, which could be reduced by dexamethasone premedication. The efficacy of trabectedin was established in three phase II studies where it was administered at 1.5 mg/m2 as a 24 h intravenous infusion repeated every three weeks, in previously treated patients. The objective response rate was 3.7%-8.3% and the tumor control rate (which included complete response, partial response and stable disease) was obtained in half of patients for a median overall survival reaching 12 months. In nonpretreated patients the overall response rate was 17%. Twenty-four percent of patients were without progression at six months. The median overall survival was almost 16 months with 72% surviving at one year. Predictive factors of response are being explored to identify patients who are most likely to respond to trabectedin. Combination with other agents are currently studied with promising results. In summary trabectedin is an active new chemotherapeutic agents that has demonstrated its role in the armamentarium of treatments for patients with sarcomas.

Evolution of the epithelial sodium channel and the sodium pump as limiting factors of aldosterone action on sodium transport.

Despite large changes in salt intake, the mammalian kidney is able to maintain the extracellular sodium concentration and osmolarity within very narrow margins, thereby controlling blood volume and blood pressure. In the aldosterone-sensitive distal nephron (ASDN), aldosterone tightly controls the activities of epithelial sodium channel (ENaC) and Na,K-ATPase, the two limiting factors in establishing transepithelial sodium transport. It has been proposed that the ENaC/degenerin gene family is restricted to Metazoans, whereas the α- and β-subunits of Na,K-ATPase have homologous genes in prokaryotes. This raises the question of the emergence of osmolarity control. By exploring recent genomic data of diverse organisms, we found that: 1) ENaC/degenerin exists in all of the Metazoans screened, including nonbilaterians and, by extension, was already present in ancestors of Metazoa; 2) ENaC/degenerin is also present in Naegleria gruberi, an eukaryotic microbe, consistent with either a vertical inheritance from the last common ancestor of Eukaryotes or a lateral transfer between Naegleria and Metazoan ancestors; and 3) The Na,K-ATPase β-subunit is restricted to Holozoa, the taxon that includes animals and their closest single-cell relatives. Since the β-subunit of Na,K-ATPase plays a key role in targeting the α-subunit to the plasma membrane and has an additional function in the formation of cell junctions, we propose that the emergence of Na,K-ATPase, together with ENaC/degenerin, is linked to the development of multicellularity in the Metazoan kingdom. The establishment of multicellularity and the associated extracellular compartment ("internal milieu") precedes the emergence of other key elements of the aldosterone signaling pathway.

Gait disturbances as specific predictive markers of the first fall onset in elderly people: a two-year prospective observational study

Falls are common in the elderly, and potentially result in injury and disability. Thus, preventing falls as soon as possible in older adults is a public health priority, yet there is no specific marker that is predictive of the first fall onset. We hypothesized that gait features should be the most relevant variables for predicting the first fall. Clinical baseline characteristics (e.g., gender, cognitive function) were assessed in 259 home-dwelling people aged 66 to 75 that had never fallen. Likewise, global kinetic behavior of gait was recorded from 22 variables in 1036 walking tests with an accelerometric gait analysis system. Afterward, monthly telephone monitoring reported the date of the first fall over 24 months. A principal components analysis was used to assess the relationship between gait variables and fall status in four groups: non-fallers, fallers from 0 to 6 months, fallers from 6 to 12 months and fallers from 12 to 24 months. The association of significant principal components (PC) with an increased risk of first fall was then evaluated using the area under the Receiver Operator Characteristic Curve (ROC). No effect of clinical confounding variables was shown as a function of groups. An eigenvalue decomposition of the correlation matrix identified a large statistical PC1 (termed "Global kinetics of gait pattern"), which accounted for 36.7% of total variance. Principal component loadings also revealed a PC2 (12.6% of total variance), related to the "Global gait regularity." Subsequent ANOVAs showed that only PC1 discriminated the fall status during the first 6 months, while PC2 discriminated the first fall onset between 6 and 12 months. After one year, any PC was associated with falls. These results were bolstered by the ROC analyses, showing good predictive models of the first fall during the first six months or from 6 to 12 months. Overall, these findings suggest that the performance of a standardized walking test at least once a year is essential for fall prevention.

Cognitive Predictors and Risk Factors of PTSD Following Stillbirth: A Short-Term Longitudinal Study.

This short-term longitudinal study investigated cognitive predictors and risk factors of posttraumatic stress disorder (PTSD) in mothers following stillbirth. After a stillbirth at ≥ 24 weeks gestational age, 65 women completed structured clinical interviews and questionnaires assessing PTSD symptoms, cognitive predictors (appraisals, dysfunctional strategies), and risk factors (perceived social support, trauma history, obstetric history) at 3 and 6 months. PTSD symptoms decreased between 3 and 6 months (Cohen's d ranged .34-.52). Regression analyses also revealed a specific positive relationship between Rumination and concurrent frequency of PTSD symptoms (β = .45). Negative Self-View and Negative World-View related positively and Self-Blame related negatively to concurrent number of PTSD symptoms (β = .48, .44, -.45, respectively). Suppression and Distraction predicted a decrease and Numbing predicted an increase in time-lagged number of PTSD symptoms (β = -.33, -.28, .30, respectively). Risk factors for PTSD symptoms were younger age (β = -.25), lower income (β = -.29), fewer previous pregnancies (β = -.31), and poorer perceived social support (β = -.26). Interventions addressing negative appraisals, dysfunctional strategies, and social support are recommended for mothers with PTSD following stillbirth. Knowledge of cognitive predictors and risk factors of PTSD may inform the development of a screening instrument.

Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance.

Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights into mechanisms associated with chemoresistance, and departing from three distinct CRC cell models, we generated a panel of human colorectal cancer cell lines with acquired resistance to either oxaliplatin or irinotecan. We characterized the resistant cell line variants with regards to their drug resistance profile and transcriptome, and matched our results with datasets generated from relevant clinical material to derive putative resistance biomarkers. We found that the chemoresistant cell line variants had distinctive irinotecan- or oxaliplatin-specific resistance profiles, with non-reciprocal cross-resistance. Furthermore, we could identify several new, as well as some previously described, drug resistance-associated genes for each resistant cell line variant. Each chemoresistant cell line variant acquired a unique set of changes that may represent distinct functional subtypes of chemotherapy resistance. In addition, and given the potential implications for selection of subsequent treatment, we also performed an exploratory analysis, in relevant patient cohorts, of the predictive value of each of the specific genes identified in our cellular models.

External Location Factors of Foreign Direct Investment in Russia – Finnish Perspective

Tämän diplomityön tavoitteena on selvittää, mitä alueellisia tekijöitä suomalaiset yritykset ottavat huomioon valitessaan sopivaa sijaintia suoralle investoinnille Venäjän sisällä. Muutamia yrityksen sisäisiä tekijöitä käytetään taustamuuttujina selittämään sijaintitekijöiden painotuksissa havaittavia eroja erilaisten yritysten välillä. Venäjän alueita vertaillaan lopuksi painotusten valossa. Työn ensimmäisessä osassa keskitytään suorien ulkomaisten investointien teoreettiseen taustaan. Aiempia tutkimuksia käydään läpi, jotta tekijät, joilla on havaittu olevan vaikutusta investointien sijoittumiseen maan sisällä, saadaan kartoitettua. Työn jälkimmäinen osa perustuu yrityskyselyn avulla kerättyyn empiiriseen aineistoon. Aineiston avulla selvitetään mitä tekijöitä suomalaisyritykset huomioivat sijaintipäätöstä tehdessään. Tulosten valossa on ilmeistä, että alueen markkinapotentiaali on suomalaisyrityksissä tärkein huomioitava tekijä investoinnin sijainnista päätettäessä. Myös infrastruktuuri ja kustannushyödyt vaikuttavat päätökseen. Erityyppisten yritysten painotukset ovat hyvin samanlaisia. Moskova ja Pietari vastaavat Venäjän alueista parhaiten suomalaisyritysten investoinnin sijainnille asettamia kriteerejä.

Partial cricotracheal resection for paediatric subglottic stenosis: update of the Lausanne experience with 129 cases.

OBJECTIVES: Partial cricotracheal resection (PCTR) is widely accepted for treating severe paediatric laryngotracheal stenosis (LTS). However, it remains limited to a few experienced centres. Here we report an update of the Lausanne experience in paediatric PCTR performed or supervised by a senior surgeon (Philippe Monnier). METHODS: An ongoing database of 129 paediatric patients who underwent PCTR for benign LTS between March 1978 and July 2012 at our hospital was retrospectively reviewed. Demographic characteristics and information on preoperative status, stenosis and surgery were collected. Primary outcomes were measured as overall and operation-specific decannulation rates (ODR and OSDR, respectively), and secondary outcomes as morbidity, mortality and postoperative functional results. RESULTS: A total of 129 paediatric patients [79 males and 50 females; mean age, 4.1 years (1 month-16 years, median age of 2 years old)] underwent PCTR during the study period. ODR and OSDR were 90 and 81%, respectively. The decannulation rates were significantly superior for single-stage PCTR compared with double-stage PCTR in both ODR and OSDR. Eight patients died postoperatively for reasons unrelated to surgery. Partial anastomotic dehiscence was seen in 13 patients, 9 of whom were successfully treated by revision surgery. Respiratory, voice and swallowing functions were near normal or only minimally impaired in 86, 65 and 81% of patients, respectively. CONCLUSIONS: PCTR is effective and feasible with good ODR and OSDR for highgrade / severe LTS. Glottic involvement and the presence of comorbidities were negative predictive factors of decannulation. Early detection and reintervention of postoperative incipient dehiscence contribute to avoiding the progress to late restenosis; however, voice improvement remains a challenge.

External Location Factors of Finnish Direct Investment in Central and Eastern European Transitional Economies

Tutkimuksen päätavoitteena oli selvittää suomalaisten suorien investointien maan valintaan vaikuttavia tekijöitä Itä- ja Keski-Euroopan kymmenessä siirtymätaloudessa. Empiirisessä osuudessa tarkasteltiin suomalaisten yritysten tärkeimpiä sijaintitekijöitä alueella ja yrityskohtaisten tekijöiden vaikutusta sijaintitekijöihin. Tutkimuksessa selvitettiin myös yritysten päämotiiveja investoida maihin. Laaditun investointikriteeristön mukaan maat pystyttiin laittamaan paremmuusjärjestykseen suomalaisen investoijan kannalta. Empiirisen osuuden aineisto kerättiin postikyselylomakkeella yrityksiltä, joilla on tai jotka ovat suunnittelemassa investointeja näihin maihin. Tutkimusote oli kvantitatiivinen. Tutkimustulokset osoittavat, että suomalaiset investoijat valitsevat Itä- ja Keski-Euroopan maan investointikohteeksi pääasiassa markkinapotentiaalin ja edullisten kustannusten perusteella. Myös infrastruktuuri vaikuttaa maan valintaan. Eri aloilla toimivien yritysten sijaintitekijöiden painotuksissa havaittiin eroja. Yrityksen koko ja päämotiivi vaikuttivat sijaintitekijöiden painotuksiin. Investointikriteereiden mukaan kaksi parasta investointimaata suomalaisille investoijille ovat Puola ja Viro. Vertailtaessa investointikriteereitä toteutuneisiin investointeihin voidaan todeta, että suomalaiset investoijat eivät ole hyödyntäneet investoinneilla saatavia etuja kaikissa kohdemaissa.

Identifying Critical Business Success Factors of Paperboard Tray

Työn tavoitteena oli kartonkivuoan kriittisten menestystekijöiden ja kilpailuaseman selvittäminen jäähdytettyjen ruokatuotteiden markkinoilla Euroopassa. Kilpailija- ja tavoiteanalyysi suoritettiin kahden suomalaisen pakkaajan kesken. Pakkaajien haastattelut toteutettiin joko henkilökohtaisena tai sähköpostihaastatteluna. Muovi on yleisimmin käytetty jäähdytettyjen ruokatuotteiden pakkausmateriaali. Alumiinivuokien osuus on merkittävä erityisesti laatikkoruokien pakkauksena. Kartonkivuoille on kuitenkin havaittavissa selvää menestyspotentiaalia jäähdytettyjen ruokien pakkauksena. Kartonkivuokien hyvä imago ja edistyksellinen tuotekehitystyö mahdollistavat pakkaajien erityisvaatimuksien täyttämisen ja menestymisen markkinoilla. Kartonkivuoilla on useita ainutlaatuisia kilpailuetu- ja menestystekijöitä, kuten hyvä ulkonäkö ja painojälki. Suurin haaste on saada ruokatuotteiden pakkaajat tietoisiksi kartonkivuokien tuomista pakkausmahdollisuuksista.

Success Factors of an Enterprise Resource Planning System

Työn tarkoituksena oli tutkia yrityksen eri yksiköiden toiminnaohjausjärjestelmiä sekä verrata niiden menestystekijöitä Adelakunin malliin tietojärjestelmien laatuulottuvuuksista. Siinä järjestelmän kokonaislaatu jaetaan liiketoiminnalliseen, tekniseen ja käyttäjän kokemaan laatuun. Tulosten perusteella oli myös tavoitteena kehittää kyseisen toiminnanojausjärjestelmän kehittämistä varten malli onnistumistekijöiden keskinäisestä riippuvuudesta. Tutkittavista järjestelmistä ja niiden käytöstä kerättiin tietoja käyttöönottoprojektien dokumentaatiosta, haastatteluin, kyselylomakkein ja järjestelmäanalyysein. Sekä loppukäyttäjät että yritysjohto olivat kyselyjen ja haastattelujen kohderyhmänä. Saatuja tietoja arvioitiin Adelakunin kolmiulotteisen tietojärjestelmän laatutekijämallin mukaisesti ja keskeisiä menestystekijöitä etsittiin. Tutkituissa tapauksissa tietojärjestelmien menestyksen taustalta löytyi alan kirjallisuuden kanssa yhtäpitäviä tekijöitä. Myös Adelakunin laatu-ulottuvuusmalli osoittautui validiksi tutkituissa tapauksissa. Keskeisten menestystekijöiden välisistä vuorovaikutussuhteista rakennettiin malli, jota voidaan hyödyntää kyseisen järjestelmän jatkokehityksessä.

Effect of radar rainfall time resolution on the predictive capability of a distributed hydrologic model

The performance of a hydrologic model depends on the rainfall input data, both spatially and temporally. As the spatial distribution of rainfall exerts a great influence on both runoff volumes and peak flows, the use of a distributed hydrologic model can improve the results in the case of convective rainfall in a basin where the storm area is smaller than the basin area. The aim of this study was to perform a sensitivity analysis of the rainfall time resolution on the results of a distributed hydrologic model in a flash-flood prone basin. Within such a catchment, floods are produced by heavy rainfall events with a large convective component. A second objective of the current paper is the proposal of a methodology that improves the radar rainfall estimation at a higher spatial and temporal resolution. Composite radar data from a network of three C-band radars with 6-min temporal and 2 × 2 km2 spatial resolution were used to feed the RIBS distributed hydrological model. A modification of the Window Probability Matching Method (gauge-adjustment method) was applied to four cases of heavy rainfall to improve the observed rainfall sub-estimation by computing new Z/R relationships for both convective and stratiform reflectivities. An advection correction technique based on the cross-correlation between two consecutive images was introduced to obtain several time resolutions from 1 min to 30 min. The RIBS hydrologic model was calibrated using a probabilistic approach based on a multiobjective methodology for each time resolution. A sensitivity analysis of rainfall time resolution was conducted to find the resolution that best represents the hydrological basin behaviour.

Critical success factors of sales strategy in small and medium- sized ICT-companies

Tyon tavoitteena on selvittaa. mitka myyntistrategian ja siihen liittyvien muiden strategioiden kriittiset osat pienten ja keskisuurten ICT- yritysten toiminnassa. Tutkimusmenetelmana kaytettiin case- tutkimusta, jossa vertailtiin neljan pienen ja keskisuuren ohjelmisto talon toimintaa. Tutkimuksessa tunnistettiin nelja kriittista osa-aluetta, joiden hoitamiseen yritysten erityisesti tulisi kiinnittaa huomiota. Nama olivat: segmentointi ja kohdemarkkinoiden valinta, myyntikanavien valinta, myyntihenkiloston organisointi ja asiakassuuntautuneisuus, ja markkinointi tietojarjestelma. Tutkimus osoitti, etta yrityksen kasvaessa ja omistuksen eriytyessa toimivasta johdosta yrityksen strategia suunnittelusta tulee jarjestelmallisempaa.