Post-industrial Intervention : An Activity-Theoretical Expedition Tracing the Proximal Development of Forms of Conducting Interventions

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Cortical processing of musical pitch as reflected by behavioural and electrophysiological evidence

In a musical context, the pitch of sounds is encoded according to domain-general principles not confined to music or even to audition overall but common to other perceptual and cognitive processes (such as multiple pattern encoding and feature integration), and to domain-specific and culture-specific properties related to a particular musical system only (such as the pitch steps of the Western tonal system). The studies included in this thesis shed light on the processing stages during which pitch encoding occurs on the basis of both domain-general and music-specific properties, and elucidate the putative brain mechanisms underlying pitch-related music perception. Study I showed, in subjects without formal musical education, that the pitch and timbre of multiple sounds are integrated as unified object representations in sensory memory before attentional intervention. Similarly, multiple pattern pitches are simultaneously maintained in non-musicians' sensory memory (Study II). These findings demonstrate the degree of sophistication of pitch processing at the sensory memory stage, requiring neither attention nor any special expertise of the subjects. Furthermore, music- and culture-specific properties, such as the pitch steps of the equal-tempered musical scale, are automatically discriminated in sensory memory even by subjects without formal musical education (Studies III and IV). The cognitive processing of pitch according to culture-specific musical-scale schemata hence occurs as early as at the sensory-memory stage of pitch analysis. Exposure and cortical plasticity seem to be involved in musical pitch encoding. For instance, after only one hour of laboratory training, the neural representations of pitch in the auditory cortex are altered (Study V). However, faulty brain mechanisms for attentive processing of fine-grained pitch steps lead to inborn deficits in music perception and recognition such as those encountered in congenital amusia (Study VI). These findings suggest that predispositions for exact pitch-step discrimination together with long-term exposure to music govern the acquisition of the automatized schematic knowledge of the music of a particular culture that even non-musicians possess.

Auditory - Visual Matching in Learning Disabilities : Intervention Studies from Finland and Sweden

The present thesis discusses relevant issues in education: 1) learning disabilities including the role of comorbidity in LDs, and 2) the use of research-based interventions. This thesis consists of a series of four studies (three articles), which deepens the knowledge of the field of special education. Intervention studies (N=242) aimed to examine whether training using a nonverbal auditory-visual matching computer program had a remedial effect in different learning disabilities, such as developmental dyslexia, Attention Deficit Disorder (ADD) and Specific Language Impairment (SLI). These studies were conducted in both Finland and Sweden. The intervention’s non-verbal character made an international perspective possible. The results of the intervention studies confirmed, that the auditory-visual matching computer program, called Audilex had positive intervention effects. In Study I of children with developmental dyslexia there were also improvements in reading skills, specifically in reading nonsense words and reading speed. These improvements in tasks, which are thought to rely on phonological processing, suggest that such reading difficulties in dyslexia may stem in part from more basic perceptual difficulties, including those required to manage the visual and auditory components of the decoding task. In Study II the intervention had a positive effect on children with dyslexia; older students with dyslexia and surprisingly, students with ADD also benefited from this intervention. In conclusion, the role of comorbidity was apparent. An intervention effect was evident also in students’ school behavior. Study III showed that children with SLI experience difficulties very similar to those of children with dyslexia in auditory-visual matching. Children with language-based learning disabilities, such as dyslexia and SLI benefited from the auditory-visual matching intervention. Also comorbidity was evident among these children; in addition to formal diagnoses, comorbidity was explored with an assessment inventory, which was developed for this thesis. Interestingly, an overview of the data of this thesis shows positive intervention effects in all studies despite learning disability, language, gender or age. These findings have been described by a concept inter-modal transpose. Self-evidently these issues need further studies. In learning disabilities the aim in the future will also be to identify individuals at risk rather than by deficit; this aim can be achieved by using research-based interventions, intensified support in general education and inclusive special education. Keywords: learning disabilities, developmental dyslexia, attention deficit disorder, specific language impairment, language-based learning disabilities, comorbidity, auditory-visual matching, research-based interventions, inter-modal transpose

Prevention of type 2 diabetes with lifestyle intervention - emphasis on dietary composition and identification of high-risk individuals

Type 2 diabetes is an increasing, serious, and costly public health problem. The increase in the prevalence of the disease can mainly be attributed to changing lifestyles leading to physical inactivity, overweight, and obesity. These lifestyle-related risk factors offer also a possibility for preventive interventions. Until recently, proper evidence regarding the prevention of type 2 diabetes has been virtually missing. To be cost-effective, intensive interventions to prevent type 2 diabetes should be directed to people at an increased risk of the disease. The aim of this series of studies was to investigate whether type 2 diabetes can be prevented by lifestyle intervention in high-risk individuals, and to develop a practical method to identify individuals who are at high risk of type 2 diabetes and would benefit from such an intervention. To study the effect of lifestyle intervention on diabetes risk, we recruited 522 volunteer, middle-aged (aged 40 - 64 at baseline), overweight (body mass index > 25 kg/m2) men (n = 172) and women (n = 350) with impaired glucose tolerance to the Diabetes Prevention Study (DPS). The participants were randomly allocated either to the intensive lifestyle intervention group or the control group. The control group received general dietary and exercise advice at baseline, and had annual physician's examination. The participants in the intervention group received, in addition, individualised dietary counselling by a nutritionist. They were also offered circuit-type resistance training sessions and were advised to increase overall physical activity. The intervention goals were to reduce body weight (5% or more reduction from baseline weight), limit dietary fat (< 30% of total energy consumed) and saturated fat (< 10% of total energy consumed), and to increase dietary fibre intake (15 g / 1000 kcal or more) and physical activity (≥ 30 minutes/day). Diabetes status was assessed annually by a repeated 75 g oral glucose tolerance testing. First analysis on end-points was completed after a mean follow-up of 3.2 years, and the intervention phase was terminated after a mean duration of 3.9 years. After that, the study participants continued to visit the study clinics for the annual examinations, for a mean of 3 years. The intervention group showed significantly greater improvement in each intervention goal. After 1 and 3 years, mean weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 kg and 0.9 kg in the control group. Cardiovascular risk factors improved more in the intervention group. After a mean follow-up of 3.2 years, the risk of diabetes was reduced by 58% in the intervention group compared with the control group. The reduction in the incidence of diabetes was directly associated with achieved lifestyle goals. Furthermore, those who consumed moderate-fat, high-fibre diet achieved the largest weight reduction and, even after adjustment for weight reduction, the lowest diabetes risk during the intervention period. After discontinuation of the counselling, the differences in lifestyle variables between the groups still remained favourable for the intervention group. During the post-intervention follow-up period of 3 years, the risk of diabetes was still 36% lower among the former intervention group participants, compared with the former control group participants. To develop a simple screening tool to identify individuals who are at high risk of type 2 diabetes, follow-up data of two population-based cohorts of 35-64 year old men and women was used. The National FINRISK Study 1987 cohort (model development data) included 4435 subjects, with 182 new drug-treated cases of diabetes identified during ten years, and the FINRISK Study 1992 cohort (model validation data) included 4615 subjects, with 67 new cases of drug-treated diabetes during five years, ascertained using the Social Insurance Institution's Drug register. Baseline age, body mass index, waist circumference, history of antihypertensive drug treatment and high blood glucose, physical activity and daily consumption of fruits, berries or vegetables were selected into the risk score as categorical variables. In the 1987 cohort the optimal cut-off point of the risk score identified 78% of those who got diabetes during the follow-up (= sensitivity of the test) and 77% of those who remained free of diabetes (= specificity of the test). In the 1992 cohort the risk score performed equally well. The final Finnish Diabetes Risk Score (FINDRISC) form includes, in addition to the predictors of the model, a question about family history of diabetes and the age category of over 64 years. When applied to the DPS population, the baseline FINDRISC value was associated with diabetes risk among the control group participants only, indicating that the intensive lifestyle intervention given to the intervention group participants abolished the diabetes risk associated with baseline risk factors. In conclusion, the intensive lifestyle intervention produced long-term beneficial changes in diet, physical activity, body weight, and cardiovascular risk factors, and reduced diabetes risk. Furthermore, the effects of the intervention were sustained after the intervention was discontinued. The FINDRISC proved to be a simple, fast, inexpensive, non-invasive, and reliable tool to identify individuals at high risk of type 2 diabetes. The use of FINDRISC to identify high-risk subjects, followed by lifestyle intervention, provides a feasible scheme in preventing type 2 diabetes, which could be implemented in the primary health care system.

Musculoskeletal disorders and psychosocial factors at work : Effects of a participatory ergonomics intervention in a cluster randomized controlled trial

This study examined the efficacy of a participatory ergonomics intervention in preventing musculoskeletal disorders (MSDs) and changing unsatisfactory psychosocial working conditions among municipal kitchen workers. The occurrence of multiple-site musculoskeletal pain (MSP) and associations between MSP and psychosocial factors at work over time were studied secondarily. A cluster randomized controlled trial was conducted during 2002-2005 in 119 municipal kitchens with 504 workers. The kitchens were randomized to an intervention (n = 59) and control (n = 60) group. The intervention lasted 11 to 14 months. The workers identified strenuous work tasks and sought solutions for decreasing physical and mental workload. The main outcomes were the occurrence of and trouble caused by musculoskeletal pain in seven anatomical sites, local musculoskeletal fatigue after work, and musculoskeletal sick leaves. Psychosocial factors at work (job control, skill discretion, co-worker relationships, supervisor support, mental strenuousness of work, hurry, job satisfaction) and mental stress were studied as intermediate outcomes of the intervention. Questionnaire data were collected at three months intervals during the intervention and the one-year post-intervention follow-up. Response rates varied between 92 % and 99 %. In total, 402 ergonomic changes were implemented. In the control group, 80 changes were spontaneously implemented within normal activity. The intervention did not reduce perceived physical workload and no systematic differences in any health outcomes were found between the intervention and control groups during the intervention or during the one-year follow-up. The results suggest that the intervention as studied in the present trial was not more effective in reducing perceived physical workload or preventing MSDs compared with no such intervention. Little previous evidence of the effectiveness of ergonomics interventions in preventing MSDs exists. The effects on psychosocial factors at work were adverse, especially in the two of the participating cities where re-organization of foodservices timed simultaneously with the intervention. If organizational reforms at workplace are expected to occur, the execution of other workplace interventions at the same time should be avoided. The co-occurrence of musculoskeletal pain at several sites is observed to be more common than pain at single anatomical sites. However, the risk factors of MSP are largely unknown. This study showed that at baseline, 73 % of the women reported pain in at least two, 36 % in four or more, and 10 % in six to seven sites. The seven pain symptoms occurred in over 80 different combinations. When co-occurrence of pain was studied in three larger anatomical areas (neck/low back, upper limbs, lower limbs), concurrent pain in all three areas was the most common combination (36 %). The 3-month prevalence of MSP (≥ 3 of seven sites) varied between 50 % and 61 % during the two-year follow-up period. Psychosocial factors at work and mental stress were strong predictors for MSP over time and, vice versa, MSP predicted psychosocial factors at work and mental stress. The reciprocality of the relationships implies either two mutually dependent processes in time, or some shared common underlying factor(s).

Folates in rye: Determination and enhancement by food processing

The average daily intake of folate, one of the B vitamins, falls below recommendations among the Finnish population. Bread and cereals are the main sources of folate, rye being the most significant single source. Processing is a prerequisite for the consumption of whole grain rye; however, little is known about the effect of processing on folates. Moreover, data on the bioavailability of endogenous cereal folates are scarce. The aim of this study was to examine the variation in as well as the effect of fermentation, germination, and thermal processes on folate contents in rye. Bioavailability of endogenous rye folates was investigated in a four-week human intervention study. One of the objectives throughout the work was to optimise and evaluate analytical methods for determining folate contents in cereals. Affinity chromatographic purification followed by high-performance liquid chromatography (HPLC) was a suitable method for analysing cereal products for folate vitamers, and microbiological assay with Lactobacillus rhamnosus reliably quantified the total folate. However, HPLC gave approximately 30% lower results than the microbiological assay. The folate content of rye was high and could be further increased by targeted processing. The vitamer distribution of whole grain rye was characterised by a large proportion of formylated vitamers followed by 5-methyltetrahydrofolate. In sourdough fermentation of rye, the studied yeasts synthesized and lactic acid bacteria mainly depleted folate. Two endogenous bacteria isolated from rye flour were found to produce folate during fermentation. Inclusion of baker s yeast in sourdough fermentation raised the folate level so that the bread could contain more folate than the flour it was made of. Germination markedly increased the folate content of rye, with particularly high folate concentrations in hypocotylar roots. Thermal treatments caused significant folate losses but the preceding germination compensated well for the losses. In the bioavailability study, moderate amounts of endogenous folates in the form of different rye products and orange juice incorporated in the diet improved the folate status among healthy adults. Endogenous folates from rye and orange juice showed similar bioavailability to folic acid from fortified white bread. In brief, it was shown that the folate content of rye can be enhanced manifold by optimising and combining food processing techniques. This offers some practical means to increase the daily intake of folate in a bioavailable form.

Defining Adequate Vitamin D Intake : Cross-sectional and Intervention Studies

D-vitamiini ylläpitää normaalia luun kasvua ja uudistumista koko elämän ajan. Suomessa, kuten monissa muissakin länsimaissa, väestön D-vitamiinitilanne on riittämätön – talvisin osalla jopa puutteellinen. Tässä väitöskirjassa on tutkittu, lisääkö D-vitamiini luumassan kertymistä kasvuiässä, ja ylläpitäkö D-vitamiini luuston tasapainoista aineenvaihduntaa aikuisiällä. Nämä vaikutukset saattavat ehkäisi osteoporoosin kehittymistä eri ikäkausina. Väitöskirjatyössä tutkittiin erisuuruisten D-vitamiinilisäysten vaikutuksia kolmessa eri ikäryhmässä, jotka olivat 11-12 -vuotiaat tytöt (N=228), 21-49 -vuotiaat miehet (N=54) ja 65-85 -vuotiaat naiset (N=52). Tutkittavat satunnaistettiin ryhmiin, jotka nauttivat joko lumevalmistetta tai 5-20 µg D3-vitamiinia vitamiinilisänä. Tutkimukset olivat kaksoissokkoutettuja. Tutkimuksen aikana tutkittavilta otettiin paastoveri- ja virtsanäytteitä. Lisäksi he täyttivät tutkimuslomakkeen taustatietojen kartoittamiseksi sekä frekvenssikyselylomakkeen kalsiumin ja D-vitamiinin saannin selvittämiseksi. Tyttöjen luunmineraalitiheys (BMD) mitattiin DXA–laitteella ja miesten volumetrinen luuntiheys pQCT-menetelmällä. Näytteistä määritettiin mm. seerumin 25-hydroksi-D-vitamiinin (=S-25-OHD), lisäkilpirauhashormonin (=S-PTH) ja luun aineenvaihduntaa kuvaavien merkkiaineiden pitoisuuksia. Murrosikäisten tyttöjen poikkileikkaustutkimuksessa S-25-OHD- ja luun muodostusmerkkiaineen pitoisuudet vaihtelivat kuukausien välillä; suurimmat pitoisuudet mitattiin syyskuussa ja pienimmät maaliskuussa, mikä kuvastaa vuodenaikaisvaihtelua. Vastaava vaihtelu havaittiin lannerangan ja reisiluun BMD:ssä. D-vitamiinilisäyksellä oli myönteinen vaikutus tyttöjen luumassan lisääntymiseen. Suurin D-vitamiinilisä (10 µg/vrk) lisäsi luumassaa 17.2% enemmän reisiluussa ja 12.5% enemmän lannerangassa verrattuna lumevalmistetta nauttivien tyttöjen vastaaviin tuloksiin, mutta tulos riippui hoitomyöntyvyydestä. D-vitamiinin vaikutus luustoon välittyi vähentyneen luun hajotuksen kautta. Tutkimustuloksiin perustuen riittävä D-vitamiinin saanti murrosikäisille tytöille on 15 µg/vrk. D-vitamiinilisän vaikutus 65-85 -vuotiaiden naisten S-25-OHD-pitoisuuteen vakioitui kuudessa viikossa annoksen ollessa 5-20 µg/vrk. Näillä D-vitamiiniannoksilla ei saavutettu tavoiteltavaa S-25-OHD-pitoisuutta, joka on 80 nmol/l. Arvioimme, että 60 nmol/l -pitoisuuden, jota esiintyy kesäisin tämän ikäryhmän suomalaisilla, tämän ikäryhmän naiset saavuttaisivat 24 µg:n päivittäisellä D-vitamiinin saannilla. Terveillä miehillä havaittiin vuodenaikaisvaihtelu S-25-OHD- ja S-PTH-pitoisuudessa sekä luun hajotusta kuvaavassa merkkiainepitoisuudessa. Toisaalta vaihtelua ei havaittu radiuksen volumetrisessä luuntiheydessä eikä luun muodostusmerkkiaineen pitoisuudessa. Vuodenaikaisvaihtelu estettiin 17 µg:n päivittäisellä D-vitamiinin saannilla, mutta tämän ei havaittu vaikuttavan radiuksen luuntiheyteen kuusi kuukautta kestävän tutkimuksen aikana. Yhteenvetona todetaan, että D-vitamiinin saanti on edelleenkin riittämätöntä tutkimusten kohderyhmillä. Tämä näkyy S-25-OHD- ja PTH-pitoisuuden sekä luunaineenvaihduntaa kuvaavien merkkiaineiden vuodenaikaisvaihteluna, mikä on haitallista luuston hyvinvoinnille. D-vitamiinin saantia tulisi lisätä, jotta vähintäänkin riittävä D-vitamiinitilanne (S-25-OHD>50 nmol/l) tai mahdollisesti jopa tavoiteltava D-vitaminitilanne (S-25-OHD≥80 nmol/l) saavutettaisiin. Jotta D-vitamiinin saannin lisääminen olisi kaikissa ikäryhmissä mahdollista, on suunniteltava nykyistä enemmän D-vitamiinilla täydennettyjä elintarvikkeita.

Co-Signaling by Neurotrophic Factors and the Extracellular Matrix for Axonal Growth and Neuronal Survival

Neurotrophic factors (NTFs) and the extracellular matrix (ECM) are important regulators of axonal growth and neuronal survival in mammalian nervous system. Understanding of the mechanisms of this regulation is crucial for the development of posttraumatic therapies and drug intervention in the injured nervous system. NTFs act as soluble, target-derived extracellular regulatory molecules for a wide range of physiological functions including axonal guidance and the regulation of programmed cell death in the nervous system. The ECM determines cell adhesion and regulates multiple physiological functions via short range cell-matrix interactions. The present work focuses on the mechanisms of the action of NTFs and the ECM on axonal growth and survival of cultured sensory neurons from dorsal root ganglia (DRG). We first examined signaling mechanisms of the action of the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) on axonal growth. GDNF, neurturin (NRTN) and artemin (ART) but not persephin (PSPN) promoted axonal initiation in cultured DRG neurons from young adult mice. This effect required Src family kinase (SFK) activity. In neurons from GFRalpha2-deficient mice, NRTN did not significantly promote axonal initiation. GDNF and NRTN induced extensive lamellipodia formation on neuronal somata and growth cones. This study suggested that GDNF, NRTN and ARTN may serve as stimulators of nerve regeneration under posttraumatic conditions. Consequently we studied the convergence of signaling pathways induced by NTFs and the ECM molecule laminin in the intracellular signaling network that regulates axonal growth. We demonstrated that co-stimulation of DRG neurons with NTFs (GDNF, NRTN or nerve growth factor (NGF)) and laminin leads to axonal growth that requires activation of SFKs. A different, SFK-independent signaling pathway evoked axonal growth on laminin in the absence of the NTFs. In contrast, axonal branching was regulated by SFKs both in the presence and in the absence of NGF. We proposed and experimentally verified a Boolean model of the signaling network triggered by NTFs and laminin. Our results put forward an approach for predictable, Boolean logics-driven pharmacological manipulation of a complex signaling network. Finally we found that N-syndecan, the receptor for the ECM component HB-GAM was required for the survival of neonatal sensory neurons in vitro. We demonstrated massive cell death of cultured DRG neurons from mice deficient in the N-syndecan gene as compared to wild type controls. Importantly, this cell death could not be prevented by NGF the neurotrophin which activates multiple anti-apoptotic cascades in DRG neurons. The survival deficit was observed during first postnatal week. By contrast, DRG neurons from young adult N-syndecan knock-out mice exhibited normal survival. This study identifies a completely new syndecan-dependent type of signaling that regulates cell death in neurons.

Psychosocial processes of health behaviour change in a lifestyle intervention : Influences of gender, socioeconomic status and personality

Background: The onset of many chronic diseases such as type 2 diabetes can be delayed or prevented by changes in diet, physical activity and obesity. Known predictors of successful behaviour change include psychosocial factors such as selfefficacy, action and coping planning, and social support. However, gender and socioeconomic differences in these psychosocial mechanisms underlying health behaviour change have not been examined, despite well-documented sociodemographic differences in lifestyle-related mortality and morbidity. Additionally, although stable personality traits (such as dispositional optimism or pessimism and gender-role orientation: agency and communion) are related to health and health behaviour, to date they have rarely been studied in the context of health behaviour interventions. These personality traits might contribute to health behaviour change independently of the more modifiable domain-specific psychosocial factors, or indirectly through them, or moderated by them. The aims were to examine in an intervention setting: (1) whether changes (during the three-month intervention) in psychological determinants (self-efficacy beliefs, action planning and coping planning) predict changes in exercise and diet behaviours over three months and 12 months, (2) the universality assumption of behaviour change theories, i.e. whether preintervention levels and changes in psychosocial determinants are similar among genders and socioeconomic groups, and whether they predict changes in behaviour in a similar way in these groups, (3) whether the personality traits optimism, pessimism, agency and communion predict changes in abdominal obesity, and the nature of their interplay with modifiable and domain-specific psychosocial factors (self-efficacy and social support). Methods: Finnish men and women (N = 385) aged 50 65 years who were at an increased risk for type 2 diabetes were recruited from health care centres to participate in the GOod Ageing in Lahti Region (GOAL) Lifestyle Implementation Trial. The programme aimed to improve participants lifestyle (physical activity, eating) and decrease their overweight. The measurements of self-efficacy, planning, social support and dispositional optimism/pessimism were conducted pre-intervention at baseline (T1) and after the intensive phase of the intervention at three months (T2), and the measurements of exercise at T1, T2 and 12 months (T3) and healthy eating at T1 and T3. Waist circumference, an indicator of abdominal obesity, was measured at T1 and at oneyear (T3) and three-year (T4) follow-ups. Agency and communion were measured at T4 with the Personal Attributes Questionnaire (PAQ). Results: (1) Increases in self-efficacy and planning were associated with three-month increases in exercise (Study I). Moreover, both the post-intervention level and three-month increases (during the intervention) in self-efficacy in dealing with barriers predicted the 12-month increase in exercise, and a high postintervention level of coping plans predicted the 12-month decrease in dietary fat (Study II). One- and three-year waist circumference reductions were predicted by the initial three-month increase in self-efficacy (Studies III, IV). (2) Post-intervention at three months, women had formed more action plans for changing their exercise routines and received less social support for behaviour change than men had. The effects of adoption self-efficacy were similar but change in planning played a less significant role among men (Study I). Examining the effects of socioeconomic status (SES), psychosocial determinants at baseline and their changes during the intervention yielded largely similar results. Exercise barriers self-efficacy was enhanced slightly less among those with low SES. Psychosocial determinants predicted behaviour similarly across all SES groups (Study II). (3) Dispositional optimism and pessimism were unrelated to waist circumference change, directly or indirectly, and they did not influence changes in self-efficacy (Study III). Agency predicted 12-month waist circumference reduction among women. High communion coupled with high social support was associated with waist circumference reduction. However, the only significant predictor of three-year waist circumference reduction was an increase in health-related self-efficacy during the intervention (Study IV). Conclusions: Interventions should focus on improving participants self-efficacy early on in the intervention as well as prompting action and coping planning for health behaviour change. Such changes are likely to be similarly effective among intervention participants regardless of gender and educational level. Agentic orientation may operate via helping women to be less affected by the demands of the self-sacrificing female role and enabling them to assertively focus on their own goals. The earlier mixed results regarding the role of social support in behaviour change may be in part explained by personality traits such as communion.

The British Intervention in South Russia 1918-1920

Soon after the Bolshevik Revolution of 1917, a three-year civil war broke out in Russia. As in many other civil wars, foreign powers intervened in the conflict. Britain played a leading role in this intervention and had a significant effect on the course of the war. Without this intervention on the White side, the superiority of numbers in manpower and weaponry of the Bolsheviks would have quickly overwhelmed their opponents. The aim of this dissertation is to explain the nature and role of the British intervention on the southern, and most decisive, front of the Civil War. The political decision making in London is studied as a background, but the focus of the dissertation is on the actual implementation of the British policy in Russia. The British military mission arrived in South Russia in late 1918, and started to provide General Denikin s White army with ample supplies. General Denikin would have not been able to build his army of more than 200,000 men or to make his operation against Moscow without the British matériel. The British mission also organized the training and equipping of the Russian troops with British weapons. This made the material aid much more effective. Many of the British instructors took part in fighting the Bolsheviks despite the orders of their government. The study is based on primary sources produced by British departments of state and members of the British mission and military units in South Russia. Primary sources from the Whites, including the personal collections of several key figures of the White movement and official records of the Armed Forces of South Russia are also used to give a balanced picture of the course of events. It is possible to draw some general conclusions from the White movement and reasons for their defeat from the study of the British intervention. In purely material terms the British aid placed Denikin s army in a far more favourable position than the Bolsheviks in 1919, but other military defects in the White army were numerous. The White commanders were unimaginative, their military thinking was obsolete, and they were incapable of organizing the logistics of their army. There were also fundamental defects in the morale of the White troops. In addition to all political mistakes of Denikin s movement and a general inability to adjust to the complex situation in Revolutionary Russia, the Whites suffered a clear military defeat. In South Russia the Whites were defeated not because of the lack of British aid, but rather in spite of it.

Lower Gastrointestinal Microbiota in Health and Irritable Bowel Syndrome : Characterisation and Effect of Probiotic Intervention

The human gastrointestinal (GI) microbiota is a complex ecosystem that lives in symbiosis with its host. The growing awareness of the importance of the microbiota to the host as well as the development of culture-free laboratory techniques and computational methods has enormously expanded our knowledge of this microbial community. Irritable bowel syndrome (IBS) is a common functional bowel disorder affecting up to a fifth of the Western population. To date, IBS diagnosis has been based on GI symptoms and the exclusion of organic diseases. The GI microbiota has been found to be altered in this syndrome and probiotics can alleviate the symptoms, although clear links between the symptoms and the microbiota have not been demonstrated. The aim of the present work was to characterise IBS related alterations in the intestinal microbiota, their relation to IBS symptoms and their responsiveness to probiotic theraphy. In this thesis research, the healthy human microbiota was characterised by cloning and sequencing 16S rRNA genes from a faecal microbial community DNA pool that was first profiled and fractionated according to its guanine and cytosine content (%G+C). The most noticeable finding was that the high G+C Gram-positive bacteria (the phylum Actinobacteria) were more abundant compared to a corresponding library constructed from the unfractionated DNA pool sample. Previous molecular analyses of the gut microbiota have also shown comparatively low amounts of high G+C bacteria. Furthermore, the %G+C profiling approach was applied to a sample constructed of faecal DNA from diarrhea-predominant IBS (IBS-D) subjects. The phylogenetic microbial community comparison performed for healthy and IBS-D sequence libraries revealed that the IBS-D sample was rich in representatives of the phyla Firmicutes and Proteobacteria whereas Actinobacteria and Bacteroidetes were abundant in the healthy subjects. The family Lachnospiraceae within the Firmicutes was especially prevalent in the IBS-D sample. Moreover, associations of the GI microbiota with intestinal symptoms and the quality of life (QOL) were investigated, as well as the effect of probiotics on these factors. The microbial targets that were analysed with the quantitative real-time polymerase chain reaction (qPCR) in this study were phylotypes (species definition according to 16S rRNA gene sequence similarity) previously associated with either health or IBS. With a set of samples, the presence or abundance of a phylotype that had 94% 16S rRNA gene sequence similarity to Ruminococcus torques (R. torques 94%) was shown to be associated with the severity of IBS symptoms. The qPCR analyses for selected phylotypes were also applied to samples from a six-month probiotic intervention with a mixture of Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99. The intervention had been previously reported to alleviate IBS symptoms, but no associations with the analysed microbiota representatives were shown. However, with the phylotype-specific assays applied here, the abundance of the R. torques 94% -phylotype was shown to be lowered in the probiotic-receiving group during the probiotic supplementation, whereas a Clostridium thermosuccinogenes 85% phylotype, previously associated with a healthy microbiota, was found to be increased compared to the placebo group. To conclude, with the combination of methods applied, higher abundance of Actinobacteria was detected in the healthy gut than found in previous studies, and significant phylum-level microbiota alterations could be shown in IBS-D. Thus, the results of this study provide a detailed overview of the human GI microbiota in healthy subjects and in subjects with IBS. Furthermore, the IBS symptoms were linked to a particular clostridial phylotype, and probiotic supplementation was demonstrated to alter the GI microbiota towards a healthier state with regard to this and an additional bacterial phylotype. For the first time, distinct phylotype-level alterations in the microbiota were linked to IBS symptoms and shown to respond to probiotic therapy.