Urban ecosystem services at the plant-soil interface

Continuing urbanization is a crucial driver of land transformation, having widespread impacts on virtually all ecosystems. Terrestrial ecosystems, including disturbed ones, are dependent on soils, which provide a multitude of ecosystem services. As soils are always directly and/or indirectly impacted through land transformation, land cover change causes soil change. Knowledge of ecosystem properties and functions in soils is increasing in importance as humans continue to concentrate into already densely-populated areas. Urban soils often have hampered functioning due to various disturbances resulting from human activity. Innovative solutions are needed to bring the lacking ecosystem services and quality of life to these urban environments. For instance, the ecosystem services of the urban green infrastructure may be substantially improved through knowledge of their functional properties. In the research forming this thesis, the impacts of four plant species (Picea abies, Calluna vulgaris, Lotus corniculatus and Holcus lanatus) on belowground biota and regulatory ecosystem services were investigated in two different urban soil types. The retention of inorganic nitrogen and phosphorus in the plant-soil system, decomposition of plant litter, primary production, and the degradation of polycyclic aromatic hydrocarbons (PAHs) were examined in the field and under laboratory conditions. The main objective of the research was to determine whether the different plant species (representing traits with varying litter decomposability) will give rise to dissimilar urban belowground communities with differing ecological functions. Microbial activity as well as the abundance of nematodes and enchytraeid worm biomass was highest below the legume L. corniculatus. L. corniculatus and the grass H. lanatus, producing labile or intermediate quality litter, enhanced the proportion of bacteria in the soil rhizosphere, while the recalcitrant litter-producing shrub C. vulgaris and the conifer P. abies stimulated the growth of fungi. The loss of nitrogen from the plant-soil system was small for H. lanatus and the combination of C. vulgaris + P. abies, irrespective of their energy channel composition. These presumably nitrogen-conservative plant species effectively diminished the leaching losses from the plant-soil systems with all the plant traits present. The laboratory experiment revealed a difference in N allocation between the plant traits: C. vulgaris and P. abies sequestered significantly more N in aboveground shoots in comparison to L. corniculatus and H. Lanatus. Plant rhizosphere effects were less clear for phosphorus retention, litter decomposition and the degradation of PAH compounds. This may be due to the relatively short experimental durations, as the maturation of the plant-soil system is likely to take a considerably longer time. The empirical studies of this thesis demonstrated that the soil communities rapidly reflect changes in plant coverage, and this has consequences for the functionality of soils. The energy channel composition of soils can be manipulated through plants, which was also supported by the results of the separate meta-analysis conducted in this thesis. However, further research is needed to understand the linkages between the biological community properties and ecosystem services in strongly human-modified systems.

Perinatal mortality and maternal health in rural China

Background and context Since the economic reforms of 1978, China has been acclaimed as a remarkable economy, achieving 9% annual growth per head for more than 25 years. However, China's health sector has not fared well. The population health gains slowed down and health disparities increased. In the field of health and health care, significant progress in maternal care has been achieved. However, there still remain important disparities between the urban and rural areas and among the rural areas in terms of economic development. The excess female infant deaths and the rapidly increasing sex ratio at birth in the last decade aroused serious concerns among policy makers and scholars. Decentralization of the government administration and health sector reform impacts maternal care. Many studies using census data have been conducted to explore the determinants of a high sex ratio at birth, but no agreement has been so far reached on the possible contributing factors. No study using family planning system data has been conducted to explore perinatal mortality and sex ratio at birth and only few studies have examined the impact of the decentralization of government and health sector reforms on the provision and organization of maternal care in rural China. Objectives The general objective of this study was to investigate the state of perinatal health and maternal care and their determinants in rural China under the historic context of major socioeconomic reforms and the one child family planning policy. The specific objectives of the study included: 1) to study pregnancy outcomes and perinatal health and their correlates in a rural Chinese county; 2) to examine the issue of sex ratio at birth and its determinants in a rural Chinese county; 3) to explore the patterns of provision, utilization, and content of maternal care in a rural Chinese county; 4) to investigate the changes in the use of maternal care in China from 1991 to 2003. Materials and Methods This study is based on a project for evaluating the prenatal care programme in Dingyuan county in 1999-2003, Anhui province, China and a nationwide household health survey to describe the changes in maternal care utilization. The approaches used included a retrospective cohort study, cross sectional interview surveys, informant interviews, observations and the use of statistical data. The data sources included the following: 1) A cohort of pregnant women followed from pregnancy up to 7 days after birth in 20 townships in the study county, collecting information on pregnancy outcomes using family planning records; 2) A questionnaire interview survey given to women who gave birth between 2001 and 2003; 3) Various statistical and informant surveys data collected from the study county; 4) Three national household health interview survey data sets (1993-2003) were utilized, and reanalyzed to described the changes in maternity care utilization. Relative risks (RR) and their confidence intervals (CI) were calculated for comparison between parity, approval status, infant sex and township groups. The chi-square test was used to analyse the disparity of use of maternal care between and within urban and rural areas and its trend across the years in China. Logistic regression was used to analyse the factors associated with hospital delivery in rural areas. Results There were 3697 pregnancies in the study cohort, resulting in 3092 live births in a total population of 299463 in the 20 study townships during 1999-2000. The average age at pregnancy in the cohort was 25.9 years. Of the women, 61% were childless, 38% already had one child and 0.3% had two children before the current pregnancy. About 90% of approved pregnancies ended in a live birth while 73% of the unapproved ones were aborted. The perinatal mortality rate was 69 per thousand births. If the 30 induced abortions in which the gestational age was more than 28 weeks had been counted as perinatal deaths, the perinatal mortality rate would have been as high as 78 per thousand. The perinatal mortality rate was negatively associated with the wealth of the township. Approximately two thirds of the perinatal deaths occurred in the early neonatal period. Both the still birth rate and the early neonatal death rate increased with parity. The risk of a stillbirth in a second pregnancy was almost four times that for a first pregnancy, while the risk of early neonatal deaths doubled. The early neonatal mortality rate was twice as high for female as for male infants. The sex difference in the early neonatal mortality rate was mainly attributable to mortality in second births. The male early neonatal mortality rate was not affected by parity, while the female early neonatal mortality rate increased dramatically with parity: it was about six times higher for second births than for first births. About 82% early neonatal deaths happened within 24 hours after birth, and during that time, girls were almost three times more likely to die than boys. The death rate of females on the day of birth increased much more sharply with parity than that of males. The total sex ratio at birth of 3697 registered pregnancies was 152 males to 100 females, with 118 and 287 in first and second pregnancies, respectively. Among unapproved pregnancies, there were almost 5 live-born boys for each girl. Most prenatal and delivery care was to be taken care of in township hospitals. At the village level, there were small private clinics. There was no limitation period for the provision of prenatal and postnatal care by private practitioners. They were not permitted to provide delivery care by the county health bureau, but as some 12% of all births occurred either at home or at private clinics; some village health workers might have been involved. The county level hospitals served as the referral centers for the township hospitals in the county. However, there was no formal regulation or guideline on how the referral system should work. Whether or not a woman was referred to a higher level hospital depended on the individual midwife's professional judgment and on the clients' compliance. The county health bureau had little power over township hospitals, because township hospitals had in the decentralization process become directly accountable to the township government. In the township and county hospitals only 10-20% of the recurrent costs were funded by local government (the township hospital was funded by the township government and the county hospital was funded by the county government) and the hospitals collected user fees to balance their budgets. Also the staff salaries depended on fee incomes by the hospital. The hospitals could define the user charges themselves. Prenatal care consultations were however free in most township hospitals. None of the midwives made postnatal home visits, because of low profit of these services. The three national household health survey data showed that the proportion of women receiving their first prenatal visit within 12 weeks increased greatly from the early to middle 1990s in all areas except for large cities. The increase was much larger in the rural areas, reducing the urban-rural difference from more than 4 times to about 1.4 times. The proportion of women that received antenatal care visits meeting the Ministry of Health s standard (at least 5 times) in the rural areas increased sharply from 12% in 1991-1993 to 36% in 2001-2003. In rural areas, the proportion increase was much faster in less developed areas than in developed areas. The hospital delivery rate increased slightly from 90% to 94% in urban areas while the proportion increased from 27% to 69% in rural areas. The fastest change was found to be in type 4 rural areas, where the utilization even quadrupled. The overall difference between rural and urban areas was substantially narrowed over the period. Multiple logistic regression analysis shows that time periods, residency in rural or urban areas, income levels, age group, education levels, delivery history, occupation, health insurance and distance from the nearest health care facilities were significantly associated with hospital delivery rates. Conclusions 1. Perinatal mortality in this study was much higher than that for urban areas as well as any reported rate from specific studies in rural areas of China. Previous studies in which calculations of infant mortality were not based on epidemiological surveys have been shown to underestimate the rates by more than 50%. 2. Routine statistics collected by the Chinese family planning system proved to be a reliable data source for studying perinatal health, including still births, neonatal deaths, sex ratio at birth and among newborns. National Household Health Survey data proved to be a useful and reliable data source for studying population health and health services. Prior to this research there were few studies in these areas available to international audiences. 3.Though perinatal mortality rate was negatively associated with the level of township economic development, the excess female early neonatal mortality rate contributed much more to high perinatal mortality rate than economic factors. This was likely a result of the role of the family planning policy and the traditional preferences for sons, which leads to lethal neglect of female newborns and high perinatal mortality. 4. The selective abortions of female foetuses were likely to contribute most to the high sex ratio at birth. The underreporting of female births seemed to have played a secondary role. The higher early neonatal mortality rate in second-born as compared to first-born children, particularly in females, may indicate that neglect or poorer care of female newborn infants also contributes to the high sex ratio at birth or among newborns. Existing family planning policy proved not to effectively control the steadily increased birth sex ratio. 5. The rural-urban gap in service utilization was on average significantly narrowed in terms of maternal healthcare in China from 1991 to 2003. This demonstrates that significant achievements in reducing inequities can be made through a combination of socio-economic development and targeted investments in improving health services, including infrastructure, staff capacities, and subsidies to reduce the costs of service utilization for the poorest. However, the huge gap which persisted among cities of different size and within different types of rural areas indicated the need for further efforts to support the poorest areas. 6. Hospital delivery care in the study county was better accepted by women because most of women think delivery care was very important while prenatal and postnatal care were not. Hospital delivery care was more systematically provided and promoted than prenatal and postnatal care by township hospital in the study area. The reliance of hospital staff income on user fees gave the hospitals an incentive to put more emphasis on revenue generating activities such as delivery care instead of prenatal and postnatal care, since delivery care generated much profits than prenatal and postnatal care . Recommendations 1. It is essential for the central government to re-assess and modify existing family planning policies. In order to keep national sex balance, the existing practice of one couple one child in urban areas and at-least-one-son a couple in rural areas should be gradually changed to a two-children-a-couple policy throughout the country. The government should establish a favourable social security policy for couples, especially for rural couples who have only daughters, with particular emphasis on their pension and medical care insurance, combined with an educational campaign for equal rights for boys and girls in society. 2. There is currently no routine vital-statistics registration system in rural China. Using the findings of this study, the central government could set up a routine vital-statistics registration system using family planning routine work records, which could be used by policy makers and researchers. 3. It is possible for the central and provincial government to invest more in the less developed and poor rural areas to increase the access of pregnant women in these areas to maternal care services. Central government together with local government should gradually provide free maternal care including prenatal and postnatal as well as delivery care to the women in poor and less developed rural areas. 4. Future research could be done to explore if county and the township level health care sector and the family planning system could be merged to increase the effectiveness and efficiency of maternal and child care. 5. Future research could be done to explore the relative contribution of maternal care, economic development and family planning policy on perinatal and child health using prospective cohort studies and community based randomized trials. Key words: perinatal health, perinatal mortality, stillbirth, neonatal death, sex selective abortion, sex ratio at birth, family planning, son preference, maternal care, prenatal care, postnatal care, equity, China

Trends in Pharmaceutical Product Development 2000-2010

Merkittävä osa alkuperäislääkevalmistajien tutkimus- ja tuotekehityskuluista näyttää olevan suunnattu olemassa olevien lääkkeiden kehittämiseen. Tämä voi oletettavasti johtaa kiinnostaviin formulaatiokehitysstrategioihin. Tutkimuksen tarkoituksena oli selvittää, voidaanko farmaseuttisen tuotekehityksen trendejä havaita myönnettyjen myyntilupien perusteella. Tutkimuksen mielenkiinnon kohteena olivat myös suurimpien lääkeyritysten käyttämät elinkaaren hallinnan keinot, joilla suojataan myyvimpiä tuotteita geneeriseltä kilpailulta ja varmistetaan markkinaosuus. Tutkimuksen painopiste oli kiinteissä oraalisissa lääkevalmisteissa. Laadullisten ja määrällisten menetelmien yhdistelmää käytettiin laajan näkökulman saamiseksi tutkittavaan aiheeseen. Suomalaisten myyntilupaviranomaisten haastatteluja käytettiin keräämään taustatietoa tutkimuksen määrällistä osaa varten. Määrällinen osa koostui myyntilupatietokannoista, jotka käsittivät kaikkien menettelyjen kautta Suomessa myönnetyt myyntiluvat, keskitetyn menettelyn kautta EU:ssa myönnetyt myyntiluvat ja maailman kymmenen suurinta lääkeyritystä USA:ssa. Tutkimustulosten perusteella rinnakkaislääkkeiden määrässä tapahtui merkittävä nousu Suomessa kaikkien menettelyjen kautta myönnetyissä myyntiluvissa ja EU:ssa keskitetyn menettelyn kautta myönnetyissä myyntiluvissa vuosina 2000-2010. Tämä muutos saattaa ainakin osaksi johtua lainsäädännöllisistä muutoksista, joilla luotiin kannustimia rinnakkaislääkkeiden käyttöön ja valmistukseen, kuten lääkevaihto ja viitehintajärjestelmä. USA:n tiedot osoittivat suurten lääkevalmistajien kiinnostuksen elinkaaren hallintaan: suurin osa maailman kymmenelle suurimmalle lääkeyritykselle myönnetyistä myyntiluvista vuosina 2005-2010 oli tähän tarkoitukseen. Elinkaaren hallinnan suhde uusiin lääkeaineisiin oli lähes 4:1. Kiinteä oraalinen lääkemuoto on kiistatta kaikista suosituin tapa annostella lääke, minkä vahvistivat sekä arvioijien haastattelut että myyntilupatiedot. Kiinteiden oraalisten rooli oli entistäkin korostuneempi rinnakkaislääkkeiden kohdalla. Kun innovatiivisuutta mitattiin epätyypillisten annosmuotojen määrällä, USA:n tiedot kiinteistä oraalisista lääkemuodoista osoittivat vahvaa innovatiivisuutta Suomen ja EU:n tietoihin verrattuna. Tämä saattaa heijastaa suurten lääkeyritysten innovatiivista tuotevalikoimaa. Epätyypillisten kiinteiden oraalisten annosmuotojen osuus oli huomattavasti pienempi rinnakkaislääkkeissä kuin alkuperäislääkkeissä kaikilla alueilla. Elinkaaren hallinnassa käytetyimmät strategiat olivat uusi formulaatio, uusi vahvuus ja uusi yhdistelmä olemassa olevasta valmisteesta. Kiinteiden oraalisten lääkemuotojen osalta kaksi kolmasosaa uusista elinkaaren hallinnan formulaatioista oli säädellysti vapauttavia valmisteita. Elinkaaren hallinta on olennainen osa suurten lääkeyritysten liiketoimintastrategiaa, ja sen tärkeyttä havainnollistettiin Coreg-tablettien tapausesimerkillä.

Credit Default Swaps and Insurance: Against the Potts Opinion

Little attention has been given to the possibility that CDS transactions might be construed as insurance contracts in English law. This article challenges the widespread “Potts opinion”, which states that CDSs are not insurance, because they do not require the protection buyer to sustain a loss or to have an insurable interest in the subject matter. CDSs often do provide protection against loss that the buyer is exposed to; loss indemnity is not a necessary characterisation of an insurance contract; insurable interest does not form part of the definition of insurance, but is an additional requirement of valid insurance; and what matters is the substance not the form of the contract. The situation in the US and Australia is also briefly considered.

Treatment of illicit opioid and γ-hydroxybutyrate overdose by Helsinki emergency medical services

Aims: To examine the characteristics, incidence, treatment and outcome of presumed opioid, γ-hydroxybutyrate (GHB) and γ-butyrolactone (GBL) overdoses involving users of illicit drugs in Helsinki. GHB/GBL were included in this study, despite not being opioids, due to the relative ease with which they can cause potentially fatal respiratory depression. The incidence and time interval of recurrent opioid toxicity after prehospital administration of naloxone, an opioid antagonist, was studied in presumed heroin overdose patients. Naloxone has been reported to have many adverse effects and the effects of naloxone administered during an opioid overdose on the cardiovascular system and catecholamine levels in piglets were studied. Materials and methods: Patients included in these published retrospective studies were from the following time periods: Study I: 1995-2002, II: 1997-2000, III: 1995-2000, V: 2006-2007. Presumed opioid overdose patients were examined in studies I, II and III. GHB/GBL overdoses among injecting drug users was examined in study V. Recurrent opioid toxicity after prehospital naloxone administration in heroin overdose patients was examined in study III. The effects of naloxone (80 μg/kg i.v.) on the cardiovascular system and catecholamine levels administered during morphine overdose (8mg/kg i.v.) and under propofol anesthesia with spontaneous breathing were studied in eight piglets (IV). In this thesis, previously unpublished data on the incidence of opioid overdose between 2001-2007 and comparison of the characteristics of buprenorphine and heroin overdose patients encountered in 1995-2005 are also included. Results: Helsinki Emergency Medical Service (EMS) ambulances were dispatched annually to 34,153- 45,118 calls from 1995 to 2007. Of them, 7-8% were coded as intoxications or overdoses. During this time, 436 patients were treated by the EMS for presumed opioid overdose. The peak incidence of opioid overdoses was in the year 2000 (113 cases), after which they declined to 6-26 cases annually. The annual incidence of buprenorphine related overdoses increased from 4 (4% of opioid overdoses) in the year 2000 to 8 (30% of opioid overdoses) in 2007. The annual number of GHB related overdose patients treated by Helsinki EMS increased from 21 to 73 between 2004-2007. There appeared to be a peak in the incidence of both GHB/GBL and opioid related overdoses on Saturdays. Characteristics of opioid overdose patients The median age of opioid overdose patients was 28 years (22;33, 25- and 75-percentiles), and 84% were male. Buprenorphine overdose patients had more polydrug, such as alcohol and/or benzodiazepines, use in comparison with heroin overdose patients, 70% versus 33%, respectively. Severe respiratory depression was reported less often with buprenorphine overdoses compared to heroin overdoses, in 67.0% versus 85.4%, respectively. Outcome of heroin overdose patients with cardiac arrest Ninety four patients suffered cardiac arrest due to acute drug poisoning/overdose and were thus considered for resuscitation. Resuscitation was attempted in 72 cases. Cardiac arrest was caused by heroin overdose for 19 patients of which three (16%) were discharged alive. Other agents also induced cardiac arrest in 53 patients, of which six (11%) were discharged alive. The arrest was either EMS witnessed or occurring after the emergency call for all survivors of heroin induced cardiac arrest. Characteristics of GHB/GBL overdose patients The records of 100 GHB/GBL related overdose patients from 2006-2007 were retrieved. The median age of GHB/GBL overdose patients encountered on weekend nights was 24 years (22;27, 25- and 75-percentiles) and 49% were male. Polydrug use was reported in 62-80% of the cases. Thirty nine patients were encountered on Friday-Saturday or Saturday-Sunday night between 11 pm-6 am. The remaining sixty one patients were outside this time frame. There was a statistically significant difference between these two groups in history of chronic injecting drug use (33% vs. 59%, respectively, p=0.012). Recurrent heroin toxicity after prehospital naloxone administration Study III included 145 presumed heroin overdose patients. After prehospital care, 84 patients refused further care and were not transported to an Emergency Department (ED). Seventy one (85%) of them were administered naloxone by the EMS. During a 12-h follow up period, none of these patients developed severe recurrent opioid toxicity. The remaining 61 patients were transported to an ED. Prior to transportation, 52 (85%) patients were administered naloxone by the EMS. Fifteen of them were administered naloxone also in the ED and recurrent opioid toxicity was evident either on arrival at the ED or shortly thereafter. Prehospital naloxone was administered either intravenously, intramuscularly (i.m.) or subcutaneously (s.c.). There was a tendency for more frequent recurrent heroin toxicity among the patients with only intravenous administration of prehospital naloxone (13/36) compared with the patients with intramuscular or subcutaneous prehospital naloxone (2/16), p=0.106. The effects of naloxone on the cardiovascular system and catecholamine levels in piglets The administration of morphine to piglets resulted in an obvious respiratory depression, which was reversed by naloxone. Two severely hypoxemic piglets developed cardiac arrest after naloxone administration. In the other six animals, the administration of naloxone did not provoke arrhythmias, cardiac ischemia or visible evidence of pulmonary edema. There was a statistically significant (p=0.012) increase in norepinephrine levels after morphine administration and before naloxone administration: from 1.9 (1.3-2.3) ng/ml at baseline, to 31.7 (8.3-83.0) ng/ml (median, 25 and 75 percentiles parentheses) after morphine administration. After the administration of naloxone, the catecholamine levels continued to increase in only one of the animals. Conclusions: The incidence of buprenorphine related overdoses increased during the study period, but was still lower in comparison to those involving heroin. Injecting drug users have also started to use GHB/GBL. While recreational drug users use GHB/GBL during weekend nights, a GHB/GBL overdose patient encounter during weekdays has a more probable history of injecting drug use. Patients with cardiac arrest after heroin overdose have a poor prognosis. It appears to be safe to leave heroin overdose patients on scene after prehospital treatment with naloxone. Although no statistically significant difference was observed, it seems prudent to administer part of the total naloxone dose s.c. or i.m. to reduce the risk of recurrent respiratory depression. If transported to an ED, an observation period of one to two hours after the last naloxone dose seems adequate. The treating physician must be vigilant, however, due to the high prevalence of polydrug use and high morbidity after non fatal heroin overdose. Furthermore, care should be taken regarding possible chronic disorders and drug rehabilitation should be addressed. In the experimental animal study, two animals developed cardiac arrest after receiving naloxone while in hypoxemia and bradycardia. Further studies are required to assess the effect of naloxone during opioid-induced hypercapnia and hypoxemia in animals addicted to opioids.

Interfacial Phenomena in Pharmaceutical Low Moisture Content Powder Processing

Powders are essential materials in the pharmaceutical industry, being involved in majority of all drug manufacturing. Powder flow and particle size are central particle properties addressed by means of particle engineering. The aim of the thesis was to gain knowledge on powder processing with restricted liquid addition, with a primary focus on particle coating and early granule growth. Furthermore, characterisation of this kind of processes was performed. A thin coating layer of hydroxypropyl methylcellulose was applied on individual particles of ibuprofen in a fluidised bed top-spray process. The polymeric coating improved the flow properties of the powder. The improvement was strongly related to relative humidity, which can be seen as an indicator of a change in surface hydrophilicity caused by the coating. The ibuprofen used in the present study had a d50 of 40 μm and thus belongs to the Geldart group C powders, which can be considered as challenging materials in top-spray coating processes. Ibuprofen was similarly coated using a novel ultrasound-assisted coating method. The results were in line with those obtained from powders coated in the fluidised bed process mentioned above. It was found that the ultrasound-assisted method was capable of coating single particles with a simple and robust setup. Granule growth in a fluidised bed process was inhibited by feeding the liquid in pulses. The results showed that the length of the pulsing cycles is of importance, and can be used to adjust granule growth. Moreover, pulsed liquid feed was found to be of greater significance to granule growth in high inlet air relative humidity. Liquid feed pulsing can thus be used as a tool in particle size targeting in fluidised bed processes and in compensating for changes in relative humidity of the inlet air. The nozzle function of a two-fluid external mixing pneumatic nozzle, typical for small scale pharmaceutical fluidised bed processes, was studied in situ in an ongoing fluidised bed process with particle tracking velocimetry. It was found that the liquid droplets undergo coalescence as they proceed away from the nozzle head. The coalescence was expected to increase droplet speed, which was confirmed in the study. The spray turbulence was studied, and the results showed turbulence caused by the event of atomisation and by the oppositely directed fluidising air. It was concluded that particle tracking velocimetry is a suitable tool for in situ spray characterisation. The light transmission through dense particulate systems was found to carry information on particle size and packing density as expected based on the theory of light scattering by solids. It was possible to differentiate binary blends consisting of components with differences in optical properties. Light transmission showed potential as a rapid, simple and inexpensive tool in characterisation of particulate systems giving information on changes in particle systems, which could be utilised in basic process diagnostics.