Effect of Lactobacillus plantarum 299v on symptom relief in patients with IBS – A systematic review

Title: Effect of Lactobacillus plantarum 299v on symptom relief in patients with IBS – A systematic review Author: Madeléne Ingesson & Amanda Wellander Supervisor: Heléne Bertéus Forslund Examiner: Frode Slinde Programme: Programme in dietetics, 180/240 ECTS Type of paper: Bachelor’s thesis in clinical nutrition, 15 hp Date: May 25, 2016 Background: In Sweden the prevalence of IBS is about 13,5 percent. Probiotics have been shown to provide symptom relief, and studies have demonstrated that some patients with IBS have an alternated gut flora. On the market there are several products containing the probiotic strain Lactobacillus plantarum 299v, which is able to establish in the human gastrointestinal tract. Objective: To examine the scientific basis if probiotic supplementation with Lactobacillus plantarum 299v can provide symptom relief in patients with IBS. Search strategy: The databases PubMed, Cochrane, Scopus and snowballing were used. Keywords used in various combinations were, for example, Irritable bowel syndrome, IBS, Probiotics, Lactobacillus plantarum 299v and LP299v. Selection criteria: Inclusion criteria consisted of RCT-human studies in patients aged over 19 with IBS diagnosis and articles written in English or Swedish. Exclusion criteria were patients with other gastrointestinal diseases and an intervention period less than four weeks. Studies not investigating Lactobacillus plantarum 299v separately were also excluded. Data collection and analysis: Literature searches were conducted between March 14, 2016 and March 17, 2016. When searching the databases, four articles were obtained, and another article was discovered by snowballing. The authors controlled the quality of the articles both separate and together using the SBU “Mall för kvalitetsgranskning av randomiserade studier”. One of the articles reviewed were excluded due to low study quality. The scientific basis for the chosen outcome measures abdominal pain, stool frequency and bloating was graded according to the University of Gothenburg template “Underlag för sammanvägd bedömning enligt GRADE”. Main results: Significant improvement regarding abdominal pain was seen in two of four studies. The strength of evidence was graded as moderate (+++). Regarding stool frequency, a significant improvement was seen in one of three studies and the grade of evidence was considered as low (++). Concerning bloating three of four studies showed a significant improvement and the grade of evidence was rated as moderate (+++). Conclusions: There is moderate evidence that Lactobacillus plantarum 299v reduces abdominal pain and bloating, and low evidence for improved stool frequency in patients with IBS. Keywords: IBS, Irritable Bowel Syndrome, Probiotics, Lactobacillus plantarum 299v, LP299Titel: Effekt av Lactobacillus plantarum 299v på symtomlindring hos patienter med IBS – En systematisk översiktsartikel Författare: Madeléne Ingesson & Amanda Wellander Handledare: Heléne Bertéus Forslund Examinator: Frode Slinde Linje: Dietistprogrammet, 180/240 hp Typ av arbete: Självständigt arbete i klinisk nutrition, 15 hp Datum: 2016-05-25 Bakgrund: I Sverige är prevalensen av IBS cirka 13,5 procent. Probiotika har visats kunna ge symtomlindring, och studier har demonsterat förekomst rubbningar i tarmfloran hos patienter med IBS. Ute på marknaden finns flera produkter innehållande probiotikastammen Lactobacillus plantarum 299v vilken har visats kunna etablera sig i människans magtarmkanal. Syfte: Att undersöka det vetenskapliga underlaget för att probiotikasupplementering av Lactobacillus plantarum 299v kan ge symtomlindring hos patienter med IBS. Sökväg: Databaserna PubMed, Cochrane, Scopus samt snowballing användes. Sökord som användes i olika kombinationer var exempelvis Irritable bowel syndrome, IBS, Probiotics, Lactobacillus plantarum 299v samt LP299v. Urvalskriterier: Inklusionskriterierna utgjordes av RCT-humanstudier på patienter över 19 år med IBS-diagnos samt artiklar skrivna på engelska eller svenska. Exklusionskriterierna bestod av patienter med andra gastrointestinala sjukdomar och en interventionstid under fyra veckor. Även studier som ej undersökt Lactobacillus plantarum 299v separat exkluderas. Datainsamling och analys: Litteratursökningarna genomfördes mellan 2016-03-14 och 2016- 03-17. Fyra artiklar erhölls via sökning i databaserna, och ytterligare en artikel upptäcktes genom snowballing. Kvalitetsgranskning av artiklarna skedde både separat och gemensamt författarna emellan med hjälp av SBU:s ”Mall för kvalitetsgranskning av randomiserade studier”. En av de granskade studiernas studiekvalitet bedömdes som låg, varför den exkluderades. Det vetenskapliga underlaget för de valda effektmåtten buksmärta, avföringsfrekvens samt uppblåsthet evidensgraderades enligt Göteborgs universitets mall ”Underlag för sammanvägd bedömning enligt GRADE”. Resultat: Signifikant förbättring gällande buksmärta sågs i två av fyra studier. Evidensstyrkan graderades som måttlig (+++). Angående avföringsfrekvens sågs en signifikant förbättring i en av tre studier och evidensstyrkan bedömdes till låg (++). Gällande uppblåsthet visade tre av fyra studier en signifikant förbättring och evidensstyrkan graderades som måttlig (+++). Slutsats: Det finns måttlig evidensstyrka för att Lactobacillus plantarum 299v ger minskad buksmärta och uppblåsthet samt låg evidens för förbättrad avföringsfrekvens hos patienter med IBS. Keywords: IBS, Irritable Bowel Syndrome, Probiotics, Lactobacillus plantarum 299v, LP299

Radio frequency induced and neoclassical asymmetries and their effects on turbulent impurity transport in a tokamak

Poloidal asymmetries in the impurity density can be generated by radio frequency heating in the core and by neoclassical effects in the edge of tokamak plasmas. In a pedestal case study, using global neoclassical simulations we find that finite orbit width effects can generate significant poloidal variation in the electrostatic potential, which varies on a small radial scale. Gyrokinetic modeling shows that these poloidal asymmetries can be strong enough to significantly modify turbulent impurity peaking. In the pedestal the ExB drift in the radial electric field can give a larger contribution to the poloidal motion of impurities than that of their parallel streaming. Under such circumstances we find that up-down asymmetries can also affect impurity peaking.Comment: Paper for 14th International Workshop on Plasma Edge Theory in Fusion Devices, revised version, submitte

The Politics of Combat : The Political and Strategic Impact of Tactical-Level Subcultures, 1939-1995

This dissertation argues that lower-level military leaders, commanding between a dozen and a few hundred troops, can have a major political and strategic impact. Furthermore, it is argued that the decisions made by these lower-level military leaders are shaped by subcultures, in particular under conditions of stress and uncertainty. The concept of tactical-level subcultures is defined, drawing on existing research from public administration, military psychology, tactical decision-making and management studies, and used as a conceptual framework for the dissertation. Using the conceptual framework, the theory is then presented, stating that the degree of convergence or divergence between these subcultures and the political and strategic policy objectives can be used to predict the likelihood of compliant output, defined as decisions that are in line with the policy objectives, and thus more likely to produce the desired outcome. Eight case studies are employed to illustrate the conceptual framework and theory. The case studies are arranged in four pairs, which are first compared to each other. In the summary of the dissertation, the case pairs are then evaluated as a whole. In the first case pair, German and American submarine warfare is compared by studying the first year of combat operations of each organization, in 1939-1940 and 1941-1942, respectively. In the second case pair, two Israeli armored units fighting on the Golan Heights in 1973 are compared to German independent tank units on the Eastern Front in World War II in 1942-1945. In the third case pair, atrocities committed by the American Charlie Company in Song My in 1968 is compared to the development of the German concentration camp guards (Totenkopfverbände) in 1933-1942. In the fourth and final case pair, the Swedish-Danish-Norwegian peacekeeping battalion Nordbat 2 in Bosnia in 1993-1995 is compared to the Dutch battalion operating in the same country during the same time period. The case studies show that tactical-level subcultures can have a significant impact on the outcomes of war, the conduct of diplomacy, the propensity to commit atrocities and the effectiveness of military units in demanding peacekeeping operations. The dissertation also finds that lower-level military leaders should be regarded as a type of street-level bureaucrats, and that the impact they can have on major political and strategic outcomes has largely been overlooked within political science

Great Powers, Great Perils: A Neorealist Analysis of the Impact of Multipolarity on the Risks of Confrontation, 1890-1911 and 2001-2009

This thesis departs from a neorealist theoretical perspective but adds a rational actor perspective based on game theory. It shares Waltz' assumption of deep anarchy and the need for states to ensure their security but also maintains that actor prospects may be able to cope with the structural incentives in a flexible manner. Two cases of international politics are studied; 1890-1911 and 2001-2009. It is then argued that the historical case can provide a basis for limited probabilistic generalization about the use of hard power in a modern multipolar setting using a methodological approach based on the concept of transferability. The underlying assumption is that the world may be headed for a multipolar world order and that some patterns related to the use of hard power from 1890-1911 were being repeated in 2001-2009. The use of hard power manifests itself in two major ways; warfare and power projection. Multipolarity increases the number of actors that can use these instruments without implicit or explicit approval from another state. The differing actor prospects mean that some great powers are more likely to resort to hard power than others

Model-Based Control of Gasoline Partially Premixed Combustion

Partially Premixed Combustion (PPC) is an internal combustion engine concept that aims to yield low NOx and soot emission levels together with high engine efficiency. PPC belongs to the class of low temperature combustion concepts where the ignition delay is prolonged in order to promote the air-fuel-mixture homogeneity in the combustion chamber at the start of combustion. A more homogeneous combustion process in combination with high exhaust-gas recirculation (EGR) ratios gives lower combustion temperatures and thus decreased NOx and soot formation. The ignition delay is mainly controlled by temperature, gas-mixture composition, fuel type and fuel-injection timing. It has been shown that PPC run on gasoline fuel can provide sufficient ignition delays in conventional compression-ignition engines. The PPC concept differs from conventional direct-injection diesel combustion because of its increased sensitivity to intake conditions, its decreased combustion-phasing controllability and its high pressure-rise rates related to premixed combustion, this puts higher demands on the engine control system. This thesis investigates model predictive control (MPC) of PPC with the use of in-cylinder pressure sensors. Online heat-release analysis is used for the detection of the combustion phasing and the ignition delay that function as combustion-feedback signals. It is shown that the heat-release analysis could be automatically calibrated using nonlinear estimation methods, the heat-release analysis is also a central part of a presented online pressure-prediction method which can be used for combustion-timing optimization. Low-order autoignition models are studied and compared for the purpose of model-based control of the ignition-delay, the results show that simple mathematical models are sufficient when anipulating the intake-manifold conditions. The results also show that the relation between the injection timing and the ignition delay is not completely captured by these types of models when the injection timing is close to top-dead-center. Simultaneous control of the ignition delay and the combustion phasing using a dual-path EGR system, thermal management and fuel injection timings is studied and a control design is presented and evaluated experimentally. Closed-loop control of the pressure-rise rate using a pilot fuel injection is also studied and the multiple fuel-injection properties are characterized experimentally. Experiments show that the main-fuel injection controls the combustion timing and that the pilot-injection fuel could be used to decrease the main fuel injection ignition delay and thus the pressure-rise rate. The controllability of the pressure-rise rate was shown to be higher when the pilot injection was located close to the main-fuel injection. A pressure-rise-rate controller is presented and evaluated experimentally. All experiments presented in this thesis were conducted on a Scania D13 production engine with a modified gas-exchange system, the fuel used was a mixture of 80 % gasoline and 20 % N-heptane (by volume)

Growing up with Dyslexia : Cognitive and Psychosocial Impact, and Salutogenic Factors

The studies in this doctoral thesis report aspects of cognitive and socio emotional development in a group of teenagers and young adults with dyslexia. The 75 subjects, between 14 and 25 years of age, had been diagnosed in the latter half of the 1990s, and the collection of quantitative and qualitative data was performed in 2003-04. Study I investigated the stability of intelligence. Earlier research had shown contradictory results. Participants, who were 12 years old on the average at the first test, were retested after a mean period of 6½ years. There was a significant relative decrease in Verbal IQ, interpreted as an effect of the dyslexic individuals having less experience with reading and writing, and as a consequence, a lag in verbal ability. Performance IQ improved significantly and the tentative interpretation was that of a compensatory process. Dyslexic children might develop a more visual, intuitive and creative way to process information and solve problems, leading to an improvement in non verbal intelligence. Study II involved interviews about school experiences in terms of well being, educational achievement, self esteem, peer relations, and future beliefs. Earlier studies suggest that secondary emotional problems are common. Early on, school was experienced as full of distress and failure for a majority. Peer relations were good for the majority though. With time, problems became more limited to reading and writing activities, interpreted as an effect of compartmentalization of the disability along with suitable choices of school curricula and occupations. Academic self-esteem seemed low and the most optimistic subjects were those who had finished school and were permanently employed. In Study III, the first of its kind in Scandinavia, the purpose was to uncover factors important for a favourable socio-emotional outcome, so called salutogenic factors. The subjects and parents were interviewed. Subjects' global self-worth and sense of coherence were measured. Dyslexia was found to be a risk factor for low global self-worth when associated with poor peer relations and low parental support, typical for a group of "resigned" subjects. External salutogenic factors were; having significant others who believe in the subjects' capacity to cope with the situation, together with good peer and family relations, and having a hobby or being good at sports. Important internal factors were a special talent, the ability to compartmentalize the disability and a personal trait of persistence. The emergence of the latter was discussed

Causes and Contexts - A structural analysis of terrorism past and present

The purpose of this study is to provide a theoretical framework that can be applied to both religious and secular terrorism. It is suggested that terrorism can be divided into two categories; practical and ideological. The first category, terrorists with practical objectives like sovereignty or end to repression, are generated by local conflicts. These local conflicts can also have a global impact, thus inspiring others sharing that ideology or religion to take up terrorism. For this second type of terrorists, ideology comes after the cause as a means to achieve an end. Ideology becomes both the means and the end. The theory is applied to two empirical cases, one being the West German terrorism of 1968-1993, the other being Islamic terrorism 1998-2005. The two cases are compared and the similarities between the two cases despite differences between religious and secular terrorism are used to support the validity of the theory. The findings indicate that secular and religious terrorism share some characteristics which could be used to analyse the emergence of terrorism past and present

Controlled drinking : a viable treatment goal in alcohol use disorder?

Alcohol use disorders (AUD) has one of the largest treatment gaps among psychiatric diagnoses, with a treatment coverage of 10 to 20 %. One of the key contributing factors is the lack of treatments aiming for controlled drinking (CD) instead of abstinence. Although a large number of trials investigated CD as the outcome, there are major limitations to the existing studies, such as small sample sizes, non-adequate control conditions, and heterogenous definitions of CD outcomes. Further, very few studies have investigated clinically relevant predictors of outcomes specifically in CD in sufficiently large sample sizes. Efficacy studies have been the main focus in research on CD and very few studies have investigated patient perspectives on the treatments offered for a CD goal. Lastly, there are few validated clinically relevant measures for the assessment and evaluation of impaired control over alcohol consumption, which is predictive of outcome in treatment for controlled drinking. The primary aim of the thesis was to investigate if a CD goal was viable in a treatment seeking sample of individuals of patients with AUD. This aim was broken down in the four following studies. Study I was a randomized controlled superiority trial including 250 individuals with alcohol use disorder. We hypothesized that Behavioral Self-Control Training (BSCT), a five-session cognitive and behavioral treatment, would be superior to Motivational Enhancement Therapy (MET), which was a four-session treatment based on Motivational Interviewing in reducing weekly alcohol consumption. Linear mixed models were used to analyze primary and secondary outcomes alongside with a Bayes factor analysis for the primary outcome. No differences were identified between groups for the primary outcome of mean weekly alcohol consumption at 26 weeks (primary endpoint). The secondary outcome proportion of weeks with hazardous drinking defined in line with the former Swedish low-risk drinking recommendations of >9/>14 weekly standard drinks was found to be statistically different between groups. Study II was a prospective cohort study, in which we investigated differences at 52 weeks post inclusion between BSCT and MET for both alcohol consumption and related consequences as well as predictors of treatment outcome. Linear and logistic mixed regression models were used for the outcomes at 52 weeks, and linear and logistic regression models for the predictor analyses. BSCT was superior to MET for the change between baseline to 52 weeks for the outcome of CD, which was defined as drinking levels in line with the new low-risk drinking levels of less than10.0 weekly standard drinks per week for both women and men(p=0.048). In the sample altogether, 50.5 % succeeded with a CD level at 52 weeks. A total of 57 % of individuals in BSCT attained a level of CD, as opposed to 43 % in MET, which was a statistically significant difference. The clinical characteristics in individuals with CD levels compared to those not attaining a CD goal showed that there were substantial differences om clinically relevant outcomes, such as quality of life and reduction of risk and harm, favoring those with CD. Further, Study II showed that predictors for obtaining CD and reducing weekly alcohol consumption was a lower baseline alcohol consumption. Predictors of symptom reduction in AUD were lower severity of AUD at baseline and a lower self-rated impaired control over alcohol consumption. Women were also found be significantly more successful in attaining CD, at both 12, and 52 weeks post inclusion. In conclusion, the study suggested that females and receiving BSCT was more favorable for attaining a long-term goal of CD. Baseline levels of AUD, baseline consumption and impaired control were corroborated as predictors of outcome. Study III was a qualitative interview study with the aim to investigate how patients experienced MET as their treatment for AUD and a goal of controlled drinking. Fifteen patients (8/7 female/male) were recruited at the 26-week follow-up. Interview data was analyzed with thematic analysis. Five themes were identified: the therapist conveyed the MI-spirit, the therapist did not guide on how to reach the goal, participants were committed to change before starting treatment, participants were uncertain if treatment was enough to maintain change, and significant others were not wanted in sessions. One conclusion from this study was that there may be a need for modification of the MET manual, to support some patients in attaining a CD goal. The format may need to be prolonged to support patients sense of self-efficacy to change. Lastly, significant others were important for the support of change without necessarily being present in sessions. Study IV was a psychometric study which evaluated the psychometric properties of the Swedish version of the Impaired control scale. We aimed to investigate dimensionality, reliability, convergent and divergent validity, measurement invariance and sensitivity to change for the evaluation of psychometric properties. The analyses of dimensionality by a principal component analysis of Rasch residuals indicated some multidimensionality created by two items (12, 22) (I can stop/ I would be able to stop/ before getting completely drunk). Tests of convergent and divergent validity showed that failed control had the strongest associations to impaired control and alcohol use disorder while the attempted control part was not associated with the construct of impaired control or alcohol use disorder. The conclusion from this study was that the failed control scale was the most valid measure of impaired control, and was sensitive to change when measured again post treatment. This makes the ICS (except the attempted control subscale) suitable as an assessment- and treatment evaluation instrument in AUD treatment of drinking. The main conclusions of the thesis were that CD was a viable goal to the majority of individuals in a sample of treatment-seeking individuals with AUD with a low level of psychiatric comorbidity, one year after receiving psychological treatment aiming for CD. When comparing outcomes on alcohol- and related consequences as well as quality of life, individuals with a CD level showed more favorable outcomes than those who were not at this consumption level. Baseline alcohol consumption was corroborated as a key predictor of outcome in treatment for CD, for the outcomes of CD and mean weekly consumption, while AUD severity and impaired control were corroborated for the prediction of reduction of AUD symptoms. Although not proven to be superior for the primary outcome, there was supporting evidence that patients who received BSCT were shown to attain a CD level in more cases both at 12 weeks and at the one-year follow-up. Further, women were far more successful in attaining a CD goal. In order to increase self-efficacy to change in patients receiving MET, the manual may need modification on how to adapt treatment to a CD goal, as well as delivering MET in more flexible format. Lastly, the Swedish version of the Impaired control scale (except the attempted control subscale) can be used in health care settings and in research for the assessment and evaluation of treatment for CD

Speed control of a peristaltic blood pump

Hemodialysis is today the main treatment used for patients with renal impairment, a serious medical condition. Hemodialysis treatment handles a very delicate system which is why it is of the utmost importance that the dialysis machine has got a reliable safety monitoring system that can detect severe complications during treatment. A new such system is currently under development at Gambro, Lund, which focuses on early detection of venous needle dislodgement(VND). The safety monitoring system determines the heart pulses from the patient on both the venous and arterial side.VND is indicated when no venous heart pulses can be detected. Large pressure disturbances are induced by the rollers on the peristaltic pump which makes it dicult to extract the patient's heart pulses. In order to successfully filter out the large disturbances it is required that the pump has a nearly constant period time. The objective of this thesis was to evaluate the current control system which is a hardware motor speed controller connected in cascade with a software blood flow controller. The project objective was also to find an improved control system for the peristaltic pump which can fulfill the required standard deviation of the relative period time of less than 0.1 %. This was done by first analyzing the pump process in open loop. Results showed that the process had high-frequency disturbances possibly originating from some mechanical unevenness in the motor since the frequency of the disturbances was dependent on the motor speed. It was also found that these disturbances were enhanced by the existing control system. In order to find a new improved control system, a hardware controller similar to the existing controller, was evaluated. With the alternative hardware controller the standard deviations of the relative period times were improved, except at low blood flows (100-150 ml/min). A PI controller was implemented in software using LabView. The PI controller fulfilled the relative period time standard deviation requirement at all blood flows and showed improved performance compared to the original controller. Used together with a feed forward implementation, the performance was further improved