Skogsbränslets elementära sammansättning med tanke på förbränningsprocessen och för näringsämnesförluster i ekosystemet

There are several reasons for increasing the usage of forest biomass for energy in Finland. Apart from the fact that forest biomass is a CO2 -neutral energy source, it is also a domestic resource distributed throughout the country. Usage of forest biomass in the form of logging residues decreases Finland’s dependence of energy import and increases both incomes and employment. Wood chips are mainly made from logging residues, which constitute 64 % of the raw material. A large-scale use of forest biomass requires heed also to the potential negative aspects. Forest bioenergy is used extensively, but its impacts on the forests soil nutrition and carbon balance has not been studied much. Nor have there been many studies on the heavy metal or chlorine content of logging residues. The goal of this study was to examine the content of carbon, macronutrients, heavy metals and other for the combustion harmful substances in Scots pine and Norway spruce wood chips, and to estimate the effect of harvesting of logging residues on the forests carbon and nutrient balance. Another goal was to examine the energy content of the clear cut remains. The Wood chips for this study were gathered from pine and spruce dominated clear cut sites in southern Finland, in the costal forests between Hankoo and Siuntio. The number of sample locations were 29, and the average area was 3,15 ha and the average timber volume 212,6 m3 ha -1. The average logged timber volume was for Scots pine timber 70 m3 ha -1 and for Norway spruce timber 124 m3 ha -1 and for deciduous timber (birch and alder) 18,5 m3 ha -1. The proportion of spruce in the logging residues and the stand-volume were relevant for how much nutrients were taken from the forest ecosystem when harvesting logging residues. In this study it was noted that the nutrient content of the logging residues clearly increased when the percentage of spruce in the timber volume increased. The S, K, Na and Cl -contents in the logging residues in this study increased with an increasing percentage of spruce, which is probably due to the fact that the spruce is an effective collector of atmospheric dry-deposition. The amounts of nutrients that were lost when harvesting logging residues were less than those referred to in the literature. Within a circulation period (100 years), the forest soil gets substantially more nutrients from atmospheric deposition, litter fall and weathering than is lost through harvesting of logging residues after a clear cut. Harvesting of the logging residues makes for a relatively modest increase of the quantity of carbon that is removed from the forest compared to traditional forestry. Due to the fact that the clear cut remains in my study showed a high content of chlorine, there is a risk of corrosion in connection to the incineration of the logging residues in power plants especially at coastal areas/forests. The risk of sulphur -related corrosion is probably rather small, because S concentrations are relatively low in woodchips. The clear cut remains showed rather high heavy metal contents. If the heavy metal contents in this study are representative for the clear cut remains in the coastal forests generally, there might be reason to exert some caution when using the ash for forest fertilizing purposes.

Synthetic Modifications of Estrogens and Androgens

Estrogens the female sex hormones have numerous biological actions. Estradiol is the most abundant estrogen in women before menopause. It influences the development, maturation and function of the female reproductive tract. It also plays a role in mammary cancer. Accordingly determinations of estradiol level in body fluids assist in the evaluation of ovarian function and diagnosis for malignancies. Estriol is the primary estrogen in pregnant women and secreted from the fetoplacental unit. Measurement of estriol in maternal body fluids is the basis of fetoplacental monitoring test. Concentration of estrogens in body fluids is determined by immunoassay. Accuracy of this measurement depends on the availability of a specific antibody. As estrogens are not antigenic, their derivatives (haptens) are coupled with a carrier and this hapten-protein conjugate is used to generate antibodies. Specificity of the generated antibody largely depends on the structure of hapten. Therefore the synthesis of a hapten with a right structure is crucial for the accurate measurement of a steroid. We have synthesised new haptens for estradiol and estriol by adding an alkyl or alkoxy side chain at the C-7 of estrane skeleton. The side chains carry a terminal amino group, which can be used for conjugation with a carrier molecule. Estrogens and their biosynthetic precursor androgens both exist as fatty acid esters. They are known to act as hormone storage but their physiological role is not completely known yet. Our collaborator is studying their effect in cardiovascular diseases. We synthesised fatty acid ester derivatives of several steroids in high yield by a very rapid procedure (in 1 min) under microwave irradiation in an ionic liquid (IL). An expedient regioselective hydrolysis at C-3 of estradiol diesters is also reported. 8-Isoestrogens are compounds of pharmaceutical interests, their synthesis, structure, conformation and biological activity studies are ongoing. 7-Hydroxy-8-isoestradiol and 7-alkyl ether of it were synthesised as well. During this study we have developed a selective O-debenzylation method. A mild route for selective removal of benzylic protection on phenol in presence of benzyl protected alcohol was explored.

Minä kirjoittajana : Identiteetit, subjektit ja persoonat lukion 1. vuoden opiskelijoiden omaa kirjoittamista pohdiskelevissa teksteissä

Tutkimuksessani tarkastelen kirjoittajaidentiteettejä teksteissä, joissa lukion ensimmäisen vuoden opiskelijat pohdiskelevat omaa kirjoittamistaan. Lähtökohtanani on ajatus narratiivisesta identiteetistä: identiteetti nähdään hermeneuttisena itsen ymmärtämisen prosessina sen sijaan, että sitä pidettäisiin kuvauksena, jonka totuusarvoa olisi relevanttia arvioida. Tutkimuskohteena on kirjoittajaidentiteetti, joten lähestyn aineistoni tekstejä osana prosessia, jossa ihminen ottaa etäisyyttä omaan kirjoittamiseensa ja siten lisää omaa ymmärrystään siitä. Myös sosiaalinen konteksti vaikuttaa tähän identiteettiprosessiin. Lähestyn kirjoittajaidentiteettejä yhteisöllisestä ja yksilöllisestä näkökulmasta, mutta jaossa ei ole kysymys dikotomiasta vaan kahdenlaisesta valotuksesta samaan asiaan: myös yksilö tarvitsee yhteisön, josta erottua. Yhteisöllisyyttä pohtiessani käsittelen nollapersoonakonstruktiota näkökulman jakamisen ja samastumisen tarjoamisen välineenä. Aineistossani nollapersoonakonstruktio on yhtäältä keino käsitellä omaa kokemusta ja toisaalta keino kurkottaa lukijan puoleen ja saada tämä ymmärtämään kirjoittajaa. Hyvin samanlainen merkitys on aineistossani yleistävällä yksikön 2. persoonalla. Molemmat kielen keinot ilmentävät kirjoittajaidentiteettien sosiaalisuutta: lukija edustaa kirjoittajalle sosiaalista yhteisöä, joka halutaan saada ymmärtämään kirjoittajan ratkaisuja ja kokemuksia. Yhteisöllisyyden valossa tarkastelen myös erilaisia keinoja luoda kirjoittajien kollektiivia. Aineistoni lukiolaiset määrittävät teksteissään erilaisia ryhmiä käyttämällä monikon 1. persoonaa tai passiivia. Monikon 1. persoonaa käyttämällä voidaan luoda myös yhteyttä kirjoittajan ja lukijan välillä. Kirjoittajaidentiteetit näyttäytyvät sosiaalisena, sillä kuuluminen johonkin ryhmään esitetään oman kirjoittamisen kannalta olennaisena asiana. Yksilöllisyyttä tuodaan esiin mm. yksikön 1. persoonaa käyttämällä, kun kirjoittaja asettaa itsensä lausuman subjektiksi, joka erottuu puhuteltavasta sinästä. Kirjoittaja ikään kuin määrittää rajansa ja eronsa suhteessa toiseen. Yksikön 1. persoonan lisäksi myös sana itse nostaa esiin eron muihin. Tässäkin suhteessa kirjoittajaidentiteetit näyttäytyvät sosiaalisina. Erilaisten kielellisten keinojen käyttö tuo näkyviin, kuinka ihminen jäsentää omaa suhdettaan toisiin: mihin hän kuuluu ja mistä hän eroaa. Sosiokulttuurisessa kontekstissa on subjektipositioita, joiden välityksellä identiteetit rakentuvat. Tutkimuksessani pohdin yhteisöllisyyttä ja yksilöllisyyttä myös kahden aineistosta konstruoimani subjektiposition avulla. Ensinnäkin esittelen hyvän kirjoittajan malliposition, johon asettuvan kirjoittajan tekstit ovat mm. pitkiä, monipuolisia ja normatiivisen kieliopin mukaisia. Kirjoittajat suhteuttavat itseään tähän positioon: he joko hyväksyvät sen tai asettuvat vastustamaan sitä. Toiseksi esittelen romanttisen kirjoittajan malliposition, johon liittyy mm. inspiraatio ja kirjoittamisen näkeminen itseilmaisuna. Kirjoittajat projisoivat teksteissään itseään ja omaa kirjoittamistaan suhteessa näihin subjektipositioihin, ja kirjoittajaidentiteetti muodostuu kirjoittajan ja tekstiyhteisön välisessä vuorovaikutuksessa. Avainsanat: kirjoittaminen, identiteetti, nollapersoona, persoonareferenssi

Inpatient hospital care and its costs among type 1 diabetic patients in Finland : a nationwide longitudinal study

Background. In Finland, the incidence of type 1 diabetes mellitus (T1DM) is the highest in the world, and it continues to increase steadily. No effective preventative interventions exist either for individuals at high risk or for the population as a whole. In addition to problems with daily lifelong insulin replacement therapy, T1DM patients with long-lasting disease suffer from various diabetes related complications. The complications can lead to severe impairments and reductions in functional capacity and quality of life and in the worst case they can be fatal. Longitudinal studies on the costs of T1DM are extremely rare, especially in Finland. Typically, in these studies, distinctions between the various types of diabetes have not been made, and costs have not been calculated separately for the sexes. Aims. The aim of this study was to describe inpatient hospital care and costs of inpatient care in a cohort of 5,166 T1DM patients by sex during 1973-1998 in Finland. Inpatient care and costs of care due to T1DM without complications, due to T1DM with complications and due to other causes were calculated separately. Material and Methods. The study population consisted of all Finnish T1DM patients diagnosed before the age of 18 years between January 1st in 1965 and December 31st in 1979 and derived from the Finnish population based T1DM register (N=5,120 in 1979 and N=4,701 in 1997). Data on hospitalisations were obtained from the Finnish Hospital Discharge Register. Results. In the early stages of T1DM, the majority of the use of inpatient care was due to the treatment of T1DM without complications. There were enormous increases in the use of inpatient care for certain complications when T1DM lasted longer (from 9.5 years to 16.5 years). For women, the yearly number of bed-days for renal complications increased 4.8-fold, for peripheral vascular disease 4.3-fold and for ophthalmic complications 2.5-fold. For men, the corresponding increases were as follows: 5-fold, 6.9-fold and 2.5-fold. The yearly bed-days for glaucoma increased 8-fold, nephropathy 7-fold and microangiopathy 6-fold in the total population. During these 7 years, the yearly numbers of bed-days for T1DM without complications dropped dramatically. The length of stay in inpatient care decreased notably, but hospital visits became more frequent when the length of duration of T1DM increased from 9.5 years to 16.5 years. The costs of treatments due to complications increased when T1DM lasted longer. Costs due to inpatient care of complications in the cohort 2.5-folded as duration of T1DM increased from 9.5 years to 16.5 years, while the total costs of inpatient care in the cohort dropped by 22% due to an 80% decrease in the costs of care of T1DM without complications. Treating complications of female patients was more expensive than treating complications of men when T1DM had lasted 9.5 years; the mean annual costs for inpatient care of a female diabetic (any cause) were 1,642 , and the yearly costs of care of complications were 237 . The corresponding yearly mean costs for a male patient were 1,198 and 167 . Treating complications of female patients was more expensive than that of male patients also when the duration of diabetes was 16.5 years, although the difference in average annual costs between sexes was somewhat smaller. Conclusions. In the early phases of T1DM, the treatment of T1DM without complications causes a considerable amount of hospital bed-days. The use of inpatient care due to complications of T1DM strongly increases with ageing of patients. The economic burden of inpatient care of T1DM is substantial.

Type 1 and type 2 diabetes among young adults in Finland : Incidence and perinatal exposures

This study aimed to examine the incidence of young adult-onset T1DM and T2DM among Finns, and to explore the possible risk factors for young adult-onset T1DM and T2DM that occur during the perinatal period and childhood. In the studies I-II, the incidence of diabetes was examined among 15-39-year-old Finns during the years 1992-2001. Information on the new diagnoses of diabetes was collected from four sources: standardized national reports filled in by diabetes nurses, the Hospital Discharge Register, the Drug Reimbursement Register, and the Drug Prescription Register. The type of diabetes was assigned using information obtained from these four data sources. The incidence of T1DM was 18 per 100,000/year, and there was a clear male predominance in the incidence of T1DM. The incidence of T1DM increased on average 3.9% per year during 1992-2001. The incidence of T2DM was 13 per 100,000/year, and it displayed an increase of 4.3% per year. In the studies III-V, the effects of perinatal exposures and childhood growth on the risk for young adult-onset T1DM and T2DM were explored in a case-control setting. Individuals diagnosed with T1DM (n=1,388) and T2DM (n=1,121) during the period 1992-1996 were chosen as the diabetes cases for the study, and two controls were chosen for each case from the National Population Register. Data on the study subjects parents and siblings was obtained from the National Population Register. The study subjects original birth records and child welfare clinic records were traced nationwide. The risk for young adult-onset T2DM was the lowest among the offspring of mothers aged about 30 years, whereas the risk for T2DM increased towards younger and older maternal ages. Birth orders second to fourth were found protective of T2DM. In addition, the risk for T2DM was observed to decrease with increasing birth weight until 4.2 kg, after which the risk began to increase. A high body mass index (BMI) at the BMI rebound between ages 3-11 years substantially increased the risk for T2DM, and the excess weight gain in individuals diagnosed with T2DM began in early childhood. Maternal age, birth order, or body size at birth had no effect on the risk for young adult-onset T1DM. Instead, individuals with T1DM were observed to have a higher maximum BMI before the age of 3 than their control subjects. In conclusion, the increasing trend in the development of both T1DM and T2DM among young Finnish adults is alarming. The high risk for T1DM among the Finnish population extends to at least 40 years of age, and at least 200-300 young Finnish adults are diagnosed with T2DM every year. Growth during the fetal period and childhood notably affects the risk for T2DM. T2DM prevention should also target childhood obesity. Rapid growth during the first years of life may be a risk factor for late-onset T1DM.

Stanniocalcin-1 in cell stress and differentiation

Stanniocalcin-1 (STC-1) is a 56 kD homodimeric protein which was originally identified in bony fish, where it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. STC-1 was considered unique to fish until the cloning of cDNA for human STC-1 in 1995 and mouse Stc-1 in 1996. STC-1 is conserved through evolution with human and salmon STC-1 sharing 60% identity and 80% similarity. The surprisingly high homology between mammalian and fish STC-1 and the protective actions of STC-1 in terminally differentiated neurons, originally reported by my colleagues, prompted me to further study the role of STC-1 in cell stress and differentiation. One purpose was to determine whether there is an inter-relationship between terminally differentiated cells and STC-1 expression. The study revealed an accumulation of STC-1 in mature megakaryocytes and adipocytes, i.e. postmitotic cells with limited or lost proliferative capacity. Still proliferating uninduced cells were negative for STC-1 mRNA and protein, whereas differentiating cells accumulated STC-1 in their cytoplasm. Interestingly, in liposarcomas the grade inversely correlated with STC-1 expression. Another aim was to study how STC-1 gene expression is regulated. Given that IL-6 is a cytokine with neuroprotective actions, by unknown mechanisms, we examined whether IL-6 regulates STC-1 gene expression. Treatment of human neural Paju cells with IL-6 induced a dose-dependent upregulation of STC-1 mRNA levels. This induction of STC-1 expression by IL-6 occurred mainly through the MAPK signaling pathway. Furthermore, I studied the role of IL-6-mediated STC-1 expression as a mechanism of cytoprotection conferred by hypoxic preconditioning (HOPC) in brain and heart. My findings show that Stc-1 was upregulated in brain after hypoxia treatment. In the brain of IL-6 deficient mice, however, no upregulation of Stc-1 expression was evident. After induced brain injury the STC-1 response in brains of IL-6 transgenic mice, with IL-6 overexpression in astroglial cells, was stronger than in brains of WT mice. These results indicate that IL-6-mediated expression of STC-1 is one molecular mechanism of HOPC-induced tolerance to brain ischemia. The protection conferred by HOPC in heart occurs during a bimodal time course comprising early and delayed preconditioning. Interestingly, my results showed that the expression of Stc-1 in heart was upregulated in a biphasic manner during HOPC. IL-6 deficient mice did not, however, show a similar biphasic manner of Stc-1 upregulation as did WT mice. Instead, only an early upregulation of Stc-1 expression was evident. The results suggest that the upregulation of Stc-1 during the delayed preconditioning is IL-6-dependent. The upregulated expression of Stc-1 during the early preconditioning, however, is only partly IL-6-dependent and possibly also directly mediated by HIF-1. These findings suggest that STC-1 is a pro-survival protein for terminally differentiated cells and that STC-1 expression may in fact be regulated by stress. In addition, I show that STC-1 gene upregulation, mediated in part by IL-6, is a new mechanism of protection conferred by HOPC in brain and heart. Because of its importance for fundamental biological processes, such as differentiation and cytoprotection, STC-1 may have therapeutic implications for management of stroke, neurodegenerative diseases, cancer, and obesity.

Organic contaminants - occurrence and biological effects in the Baltic Sea

The Baltic Sea was studied with respect to selected organic contaminants and their ecotoxicology. The research consisted of analyses of total hydrocarbons, polycyclic aromatic hydrocarbons, bile metabolites, hepatic ethoxyresorufin-O-deethylase (EROD) activity, polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). The contaminants were measured from various matrices, such as seawater, sediment and biota. The methods of analysis were evaluated and refined to comparability of the results. Polyaromatic hydrocarbons, originating from petroleum, are known to be among the most harmful substances to the marine environment. In Baltic subsurface water, seasonal dependence of the total hydrocarbon concentrations (THCs) was seen. Although concentrations of parent polycyclic aromatic hydrocarbons (PAHs) in sediment surface varied between 64 and 5161 ug kg-1 (dw), concentrations above 860 ug kg-1 (dw) were found in all the studied sub-basins of the Baltic Sea. Concentrations commonly considered to substantially increase the risk of liver disease and reproductive impairment in fish, as well as potential effects on growth (above 1000 ug kg-1 dw), were found in all the studied sub-basins of the Baltic Sea except Kattegat. Thus, considerable pollution in sediments was indicated. In bivalves, the sums of 12 PAHs varied on a wet weight basis between 44 and 298 ug kg-1 (ww). The predominant PAHs were high molecular weight and the PAH profiles of M. balthica differed from those found in sediment from the same area. The PAHs were both pyrolytic and petrogenic in origin, and a contribution from diesel engines was found, which indicates pollution of the Baltic Sea, most likely caused by the steadily increasing shipping in the area. The HPLC methods developed for hepatic EROD activity and bile metabolite measurements proved to be fast and suitable for the study of biological effects. A mixed function oxygenase enzyme system in Baltic Sea perch collected from the Gulf of Finland was induced slightly: EROD activity in perch varied from 0.30 14 pmol min-1 mg-1 protein. This range can be considered to be comparable to background values. Recent PAH exposure was also indicated by enhanced levels (213 and 1149 ug kg-1) of the bile metabolite 1-hydroxypyrene. No correlation was indicated between hepatic EROD activity and concentration of 1-hydroxypyrene in bile. PCBs and OCPs were observed in Baltic Sea sediment, bivalves and herring. Sums of seven CBs in surface sediment (0 5 cm) ranged from 0.04 to 6.2 ug kg-1 (dw) and sums of three DDTs from 0.13 to 5.0 ug kg-1 (dw). The highest levels of contaminants were found in the most eastern area of the Gulf of Finland where the highest total carbon and nitrogen content was found and where the lowest percentage proportion of p,p -DDT was found. The highest concentrations of CBs and the lowest concentration of DDTs were found in M. balthica from the Gulf of Finland. The highest levels of DDTs were found in M. balthica from the Hanö Bight, which is the outer part of the Bornholm Basin close to the Swedish mainland. In bivalves, the sums of seven CBs were 72 108 ug kg-1 (lw) and the sums of three DDTs were 66 139 ug kg-1 (lw). Results from temporal trend monitoring showed, that during the period 1985 2002, the concentrations of seven CBs in two-year-old female Baltic herring were clearly decreased, from 9 16 to 2 6 ug kg-1 (ww) in the northern Baltic Sea. At the same time, concentrations of three DDTs declined from 8 15 to 1 5 ug kg-1 (ww). The total concentration of the fat-soluble CBs and DDTs in Baltic herring muscle was shown to be age-dependent; the average concentrations in ten-year-old Baltic herring were three to five-fold higher than in two-year-old herring. In Baltic herring and bivalves, as well as in surface sediments, CB 138 and CB153 were predominant among CBs, whereas among DDTs p,p'-DDD predominated in sediment and p,p'-DDE in bivalves and Baltic herring muscle. Baltic Sea sediments are potential sources of contaminants that may become available for bioaccumulation. Based on ecotoxicological assessment criteria, cause for concern regarding CBs in sediments was indicated for the Gulf of Finland and the northern Baltic Proper, and for the northern Baltic Sea regarding CBs in Baltic herring more than two years old. Statistical classification of selected organic contaminants indicated high-level contamination for p,p'-DDT, p,p'-DDD, p,p'-DDE, total DDTs, HCB, CB118 and CB153 in muscle of Baltic herring in age groups two to ten years; in contrast, concentrations of a-HCH and g-HCH were found to be moderate. The concentrations of DDTs and CBs in bivalves is sufficient to cause biological effects, and demonstrates that long-term biological effects are still possible in the case of DDTs in the Hanö Bight.

Min-preposition kääntäminen Septuagintan Pentateukissa

Tässä tutkimuksessa tarkastellaan preposition min kääntämistä Septuagintan Pentateukissa. Työssä selvitetään, millaisia käännösvastineita Pentateukin kirjojen kääntäjät käyttävät ja millaista kreikkaa lopputulos on. Lisäksi tutkitaan, poikkeavatko Pentateukin kirjojen käännökset toisistaan. Työ on Septuagintan käännöstekniikan tutkimusta. Tämä tarkoittaa pyrkimystä ymmärtää, millaisia kriteerejä kääntäjillä on ollut ja miksi tietynlaiseen käännökseen on päädytty. Metodisesti työ liittyy Helsingin yliopistossa aiemmin tehtyyn Septuagintan käännöstekniikan tutkimukseen. Tässä työssä tutkimuskohteeksi on valittu yksi heprean syntaksin osaalue, min-prepositio. Valittu osa-alue voidaan nähdä yhtenä näkökulmana tai "mittarina" Septua-gintan käännöstekniikan tutkimukseen. Tutkimus on siten osa kokonaiskuvaa, joka saadaan, kun otetaan huomioon Septuagintan käännöstekniikkaa mahdollisimman monesta eri osa-alueesta. Tutkimuksessa on analysoitu min-preposition esiintymät Pentateukissa. Työn ulkopuolelle on rajattu min-prepositiot, jotka esiintyvät yhdistetyn preposition tai puolipreposition osana sekä min-prepositiot, jotka esiintyvät infinitiivin tai komparatiivisen ilmauksen kanssa. Analysointia varten aineisto on luokiteltu erityyppisten tapausten mukaan: 1) lokaaliset tapaukset; 2) kuvainnollisesti lokaaliset tapaukset; 3) partitiiviset tapaukset; 4) temporaaliset tapaukset; 5) kausaaliset ja instrumentaaliset tapaukset sekä agentti; 6) rektiotapaukset ja 7) erikoistapaukset. Tutkimuksessa on käynyt ilmi, että yleisimmät käännösvastineet ovat ??? (48 %) ja ?? (33 %), joita käytetään lähes aina kun se on mahdollista. Näiden kahden yleisimmän käännöksen lisäksi kääntäjät ovat monissa yksittäistapauksissa käyttäneet monia erilaisia käännöksiä. Kokonaisuutena Pentateukin kirjat näyttävät melko yhtenäiseltä. Selvimmin Pentateukista erottuu Exodus muita vapaampana käännöksenä. Kreikan kielen kannalta käännökset ovat hyvin suureksi osaksi sujuvia. Muutamat piirteet käännöksissä ovat hepraistisia. Kyse on yleensä siitä, että jokin ilmiö esiintyy Septuagintassa useammin kuin kreikkalaisessa aineistossa yleensä. Min-preposition käännöksissä Septuagintan kielessä on havaittavissa kaksi kreikan kielelle ominaista ajan ilmiötä: sijamuotojen korvautuminen prepositioilla sekä preposition ?? sulautuminen prepositioon ???.

Liver fat in the metabolic syndrome and type 2 diabetes

Introduction: The epidemic of obesity has been accompanied by an increase in the prevalence of the metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). However, not all obese subjects develop these metabolic abnormalities. Hepatic fat accumulation is related to hepatic insulin resistance, which in turn leads to hyperglycemia, hypertriglyceridemia, and a low HDL cholesterol con-centration. The present studies aimed to investigate 1) how intrahepatic as compared to intramyocellular fat is related to insulin resistance in these tissues and to the metabolic syndrome (Study I); 2) the amount of liver fat in subjects with and without the metabolic syndrome, and which clinically available markers best reflect liver fat content (Study II); 3) the effect of liver fat on insulin clearance (Study III); 4) whether type 2 diabetic patients have more liver fat than age-, gender-, and BMI-matched non-diabetic subjects (Study IV); 5) how type 2 diabetic patients using exceptionally high doses of insulin respond to addition of a PPARγ agonist (Study V). Subjects and methods: The study groups consisted of 45 (Study I), 271 (Study II), and 80 (Study III) non-diabetic subjects, and of 70 type 2 diabetic patients and 70 matched control subjects (Study IV). In Study V, a total of 14 poorly controlled type 2 diabetic patients treated with high doses of insulin were studied before and after rosiglitazone treatment (8 mg/day) for 8 months. In all studies, liver fat content was measured by proton magnetic resonance spectroscopy, and sub-cutaneous and intra-abdominal fat content by MRI. In addition, circulating markers of insulin resistance and serum liver enzyme concentrations were determined. Hepatic (i.v. insulin infusion rate 0.3 mU/kg∙min combined with [3-3H]glucose, Studies I, III, and V) and muscle (1.0 mU/kg min, Study I) insulin sensitivities were measured by the euglycemic hyperinsulinemic clamp technique. Results: Fat accumulation in the liver rather than in skeletal muscle was associated with features of insulin resistance, i.e. increased fasting serum (fS) triglycerides and decreased fS-HDL cholesterol, and with hyperinsulinemia and low adiponectin concentrations (Study I). Liver fat content was 4-fold higher in subjects with as compared to those without the metabolic syndrome, independent of age, gender, and BMI. FS-C-peptide was the best correlate of liver fat (Study II). Increased liver fat was associated with both impaired insulin clearance and hepatic insulin resistance independent of age, gender, and BMI (Study III). Type 2 diabetic patients had 80% more liver fat than age-, weight-, and gender-matched non-diabetic subjects. At any given liver fat content, S-ALT underestimated liver fat in the type 2 diabetic patients as compared to the non-diabetic subjects (Study IV). In Study V, hepatic insulin sensitivity increased and glycemic control improved significantly during rosiglitazone treatment. This was associated with lowering of liver fat (on the average by 46%) and insulin requirements (40%). Conclusions: Liver fat is increased both in the metabolic syndrome and type 2 diabetes independent of age, gender, and BMI. A fatty liver is associated with both hepatic insulin resistance and impaired insulin clearance. Rosi-glitazone may be particularly effective in type 2 diabetic patients who are poorly controlled despite using high insulin doses.

Individualized immunosuppression after renal transplantation in childhood

Pediatric renal transplantation (TX) has evolved greatly during the past few decades, and today TX is considered the standard care for children with end-stage renal disease. In Finland, 191 children had received renal transplants by October 2007, and 42% of them have already reached adulthood. Improvements in treatment of end-stage renal disease, surgical techniques, intensive care medicine, and in immunosuppressive therapy have paved the way to the current highly successful outcomes of pediatric transplantation. In children, the transplanted graft should last for decades, and normal growth and development should be guaranteed. These objectives set considerable requirements in optimizing and fine-tuning the post-operative therapy. Careful optimization of immunosuppressive therapy is crucial in protecting the graft against rejection, but also in protecting the patient against adverse effects of the medication. In the present study, the results of a retrospective investigation into individualized dosing of immunosuppresive medication, based on pharmacokinetic profiles, therapeutic drug monitoring, graft function and histology studies, and glucocorticoid biological activity determinations, are reported. Subgroups of a total of 178 patients, who received renal transplants in 1988 2006 were included in the study. The mean age at TX was 6.5 years, and approximately 26% of the patients were <2 years of age. The most common diagnosis leading to renal TX was congenital nephrosis of the Finnish type (NPHS1). Pediatric patients in Finland receive standard triple immunosuppression consisting of cyclosporine A (CsA), methylprednisolone (MP) and azathioprine (AZA) after renal TX. Optimal dosing of these agents is important to prevent rejections and preserve graft function in one hand, and to avoid the potentially serious adverse effects on the other hand. CsA has a narrow therapeutic window and individually variable pharmacokinetics. Therapeutic monitoring of CsA is, therefore, mandatory. Traditionally, CsA monitoring has been based on pre-dose trough levels (C0), but recent pharmacokinetic and clinical studies have revealed that the immunosuppressive effect may be related to diurnal CsA exposure and blood CsA concentration 0-4 hours after dosing. The two-hour post-dose concentration (C2) has proved a reliable surrogate marker of CsA exposure. Individual starting doses of CsA were analyzed in 65 patients. A recommended dose based on a pre-TX pharmacokinetic study was calculated for each patient by the pre-TX protocol. The predicted dose was clearly higher in the youngest children than in the older ones (22.9±10.4 and 10.5±5.1 mg/kg/d in patients <2 and >8 years of age, respectively). The actually administered oral doses of CsA were collected for three weeks after TX and compared to the pharmacokinetically predicted dose. After the TX, dosing of CsA was adjusted according to clinical parameters and blood CsA trough concentration. The pharmacokinetically predicted dose and patient age were the two significant parameters explaining post-TX doses of CsA. Accordingly, young children received significantly higher oral doses of CsA than the older ones. The correlation to the actually administered doses after TX was best in those patients, who had a predicted dose clearly higher or lower (> ±25%) than the average in their age-group. Due to the great individual variation in pharmacokinetics standardized dosing of CsA (based on body mass or surface area) may not be adequate. Pre-Tx profiles are helpful in determining suitable initial CsA doses. CsA monitoring based on trough and C2 concentrations was analyzed in 47 patients, who received renal transplants in 2001 2006. C0, C2 and experienced acute rejections were collected during the post-TX hospitalization, and also three months after TX when the first protocol core biopsy was obtained. The patients who remained rejection free had slightly higher C2 concentrations, especially very early after TX. However, after the first two weeks also the trough level was higher in the rejection-free patients than in those with acute rejections. Three months after TX the trough level was higher in patients with normal histology than in those with rejection changes in the routine biopsy. Monitoring of both the trough level and C2 may thus be warranted to guarantee sufficient peak concentration and baseline immunosuppression on one hand and to avoid over-exposure on the other hand. Controlling of rejection in the early months after transplantation is crucial as it may contribute to the development of long-term allograft nephropathy. Recently, it has become evident that immunoactivation fulfilling the histological criteria of acute rejection is possible in a well functioning graft with no clinical sings or laboratory perturbations. The influence of treatment of subclinical rejection, diagnosed in 3-month protocol biopsy, to graft function and histology 18 months after TX was analyzed in 22 patients and compared to 35 historical control patients. The incidence of subclinical rejection at three months was 43%, and the patients received a standard rejection treatment (a course of increased MP) and/or increased baseline immunosuppression, depending on the severity of rejection and graft function. Glomerular filtration rate (GFR) at 18 months was significantly better in the patients who were screened and treated for subclinical rejection in comparison to the historical patients (86.7±22.5 vs. 67.9±31.9 ml/min/1.73m2, respectively). The improvement was most remarkable in the youngest (<2 years) age group (94.1±11.0 vs. 67.9±26.8 ml/min/1.73m2). Histological findings of chronic allograft nephropathy were also more common in the historical patients in the 18-month protocol biopsy. All pediatric renal TX patients receive MP as a part of the baseline immunosuppression. Although the maintenance dose of MP is very low in the majority of the patients, the well-known steroid-related adverse affects are not uncommon. It has been shown in a previous study in Finnish pediatric TX patients that steroid exposure, measured as area under concentration-time curve (AUC), rather than the dose correlates with the adverse effects. In the present study, MP AUC was measured in sixteen stable maintenance patients, and a correlation with excess weight gain during 12 months after TX as well as with height deficit was found. A novel bioassay measuring the activation of glucocorticoid receptor dependent transcription cascade was also employed to assess the biological effect of MP. Glucocorticoid bioactivity was found to be related to the adverse effects, although the relationship was not as apparent as that with serum MP concentration. The findings in this study support individualized monitoring and adjustment of immunosuppression based on pharmacokinetics, graft function and histology. Pharmacokinetic profiles are helpful in estimating drug exposure and thus identifying the patients who might be at risk for excessive or insufficient immunosuppression. Individualized doses and monitoring of blood concentrations should definitely be employed with CsA, but possibly also with steroids. As an alternative to complete steroid withdrawal, individualized dosing based on drug exposure monitoring might help in avoiding the adverse effects. Early screening and treatment of subclinical immunoactivation is beneficial as it improves the prospects of good long-term graft function.

Measurement of the Λb0 Lifetime in Λb0→Λc+π- Decays in pp̅ Collisions at √s=1.96 TeV

We report a measurement of the lifetime of the Lambda_b baryon in decays to the Lambda_C+ pi- final state in a sample corresponding to 1.1 fb^-1 collected in p-pbar collisions at sqrt(s) = 1.96 TeV by the CDF II detector at the Tevatron collider. Using a sample of about 3000 fully reconstructed Lambda_b events we measure tau(Lambda_b) = 1.401 +- 0.046 (stat) +- 0.035 (syst) ps (corresponding to c.tau(Lambda_b) = 420.1 +- 13.7 (stat) +- 10.6 (syst) um, where c is the speed of light). The ratio of this result and the world average B^0 lifetime yields tau(Lambda_b)/tau(B^0) = 0.918 +- 0.038 (stat and syst), in good agreement with recent theoretical predictions.

An optimal local approximation algorithm for max-min linear programs

In a max-min LP, the objective is to maximise ω subject to Ax ≤ 1, Cx ≥ ω1, and x ≥ 0 for nonnegative matrices A and C. We present a local algorithm (constant-time distributed algorithm) for approximating max-min LPs. The approximation ratio of our algorithm is the best possible for any local algorithm; there is a matching unconditional lower bound.

Local approximability of max-min and min-max linear programs

In a max-min LP, the objective is to maximise ω subject to Ax ≤ 1, Cx ≥ ω1, and x ≥ 0. In a min-max LP, the objective is to minimise ρ subject to Ax ≤ ρ1, Cx ≥ 1, and x ≥ 0. The matrices A and C are nonnegative and sparse: each row ai of A has at most ΔI positive elements, and each row ck of C has at most ΔK positive elements. We study the approximability of max-min LPs and min-max LPs in a distributed setting; in particular, we focus on local algorithms (constant-time distributed algorithms). We show that for any ΔI ≥ 2, ΔK ≥ 2, and ε > 0 there exists a local algorithm that achieves the approximation ratio ΔI (1 − 1/ΔK) + ε. We also show that this result is the best possible: no local algorithm can achieve the approximation ratio ΔI (1 − 1/ΔK) for any ΔI ≥ 2 and ΔK ≥ 2.

Finlandismer och språkvård från 1800-talet till i dag

The aim of the study is to investigate the use of finlandisms in an historical perspective, how they have been viewed from the mid-19th century to this day, and the effect of language planning on their use. A finlandism is a word, a phrase, or a structure that is used only in the Swedish varieties used in Finland (i.e. in Finland Swedish), or used in these varieties in a different meaning than in the Swedish used in Sweden. Various aspects of Finland-Swedish language planning are discussed in relation to language planning generally; in addition, the relation of Finland Swedish to Standard Swedish and standard regional varieties is discussed, and various types of finlandisms are analysed in detail. A comprehensive picture is provided of the emergence and evolution of the ideology of language planning from the mid-19th century up until today. A theoretical model of corpus planning is presented and its effect on linguistic praxis described. One result of the study is that the belief among Finland-Swedish language planners that the Swedish language in Finland must not be allowed to become distanced from Standard Swedish, has been widely adopted by the average Finland Swede, particularly during the interwar period, following the publication of Hugo Bergroth s work Finlandssvenska in 1917. Criticism of this language-planning ideology started to appear in the 1950s, and intensified in the 1970s. However, language planning and the basis for this conception of language continue to enjoy strong support among Swedish-speaking Finns. I show that the editing of Finnish literary texts written in Swedish has often been somewhat amateurish and the results not always linguistically appropriate, and that Swedish publishers have in fact adopted a rather liberal attitude towards finlandisms. My conclusion is that language planning has achieved rather modest results in its resistance to finlandisms. Most of the finlandisms used in 1915 were still in use in 2005. Finlandisms occur among speakers of all ages, and even among academically educated people despite their more elevated style. The most common finlandisms were used by informants of all ages. The ones that are firmly rooted are the most established, in other words those that are stylistically neutral, seemingly genuinely Swedish, but which are nevertheless strongly supported by Finnish, and display a shift in meaning as compared with Standard Swedish.