Allogeneic hematopoietic stem cell transplantation (alloHCT) represents the only potentially curative treatment in high-risk AML patients, but up to 40% of patients suffer from relapse after alloHCT. Treatment of overt relapse poses a major therapeutic challenge and long-term disease control is achieved only in a minority of patients. In order to avoid post-allograft relapse, maintenance as well as pre-emptive therapy strategies based on MRD-detection have been used. A prerequisite for the implementation of pre-emptive therapy is the accurate identification of patients at risk for imminent relapse. Detection of measurable residual disease (MRD) represents an effective tool for early relapse prediction in the post-transplant setting. However, using established MRD methods such as multicolor flow cytometry or quantitative PCR, sensitive MRD monitoring is only applicable in about half of the patients with AML and advanced MDS undergoing alloHCT. Donor chimerism analysis, in particular when performed on enriched leukemic stem and progenitor cells, e.g. CD34+ cells, is a sensitive method and has emerged as an alternative option in the post alloHCT setting. In this review, we will focus on the current strategies for lineage specific chimerism analysis, results of pre-emptive treatment using this technology as well as future developments in this field.

Av de före detta kriminella som avtjänat sitt straff återfaller hela 40 % i brottslighet inom tre år. Organisationen Krami arbetar för att minska antalet återfall genom att hjälpa målgruppen till sysselsättning. Med avstamp i detta är syftet med vår studie att undersöka hur anställda i Krami ser på sina arbeten med att värna om före detta kriminellas respekt och integritet i individernas process in på arbetsmarknaden och i att undvika återfall. Detta gör vi genom att undersöka hur åtta intervjupersoner A) ser på de före detta kriminellas möjligheter kontra begränsningar på arbetsmarknaden och B) hur dessa intervjupersoner ser på sina möjligheter att arbeta med de tidigare kriminellas värderingar för att motverka återfall i brott. De teorier som används i vår studie är: Värderingsbaserad teori med begreppet värderingar; Social cognitive career theory (SCCT) med begreppen självuppfattning, förväntade resultat och personliga mål; Känsla av sammanhang (KASAM) med begreppen begriplighet, hanterbarhet och meningsfullhet. Utöver ovanstående teorier har begreppen cooling down och pushing up använts. Studiens resultat visar att intervjupersonerna använder sig av cooling down och pushing up med avsikten att öka målgruppens möjligheter på arbetsmarknaden. Intervjupersonerna upplever att de behöver stötta målgruppen i att öka sin känsla av hanterbarhet för att kunna förändra vissa värderingar, vilka intervjupersonerna anser nödvändiga för att öka sina möjligheter på arbetsmarknaden och för att motverka återfall. Samtliga intervjupersoner upplever att det är viktigt att tro på varje enskild individ, och att alla förtjänar en andra chans. / 40 % of convicted criminals relapse to criminal behavior within three years. Krami is an organization working towards dwindling/reducing recoil numbers by providing alternative occupation. The purpose of this study is to investigate how Krami employees perceive their task in shielding ex-convicts’ respect and well being through their journey towards employment as well as dodging any form of criminal relapse. This will be examined by analyzing how eight interviewees A) experience ex-convicts’ opportunities counter the limitation through the labor market, and B) how they evaluate the prospect to work with ex-convict valuation to diminish criminal relapse. The theories used in this study is: Value based theory based on the concept of valuation; Social cognitive career theory (SCCT) with the conceptions of self-efficacy, outcome expectations and personal goals; Sense of coherence (SOC) in the concept of comprehensibility, manageability and meaningfulness. In addition to aforementioned concepts, we have cooling down and pushing up. The results show that the interviewees make use of cooling down and pushing up with the intention to amplify the target audiences prospective as employees. The interviewees experience support requirements from the target audience to gain coping to handle and change certain values i.e. what the interviewees consider to be necessary to enhance employment opportunities and reduce criminal recoil. All interviewees feel that it is important to believe in every solitary individual and that everyone deserves a second chance.

This thesis aims to examine the importance of the organization Process Kedjan regarding youth’s termination of delinquency and drug abuse. It also aims to examine in which extent the organization helps the youths in different ways than authorities, as well as how the organization can function as a complement to authorities. The thesis is designed as a case study and is based on the perspective of the organization’s members. The study was performed by using qualitative interviews with five boys who have received or still are receiving help from the organization. Three of them are still receiving support and two of them are now working in the organization. They are all in the ages between 18 and 25, and has been active in delinquency and drug abuse in the ages between approximately 12 and 20. The theory of age-graded informal social control by Laub and Sampson was applied in the analysis. In the processing of the empirical material it emerged that Process Kedjan has been of great importance for the youths in their desistance of delinquency and drug abuse. Other factors of significance has been: close relationships, daily routines and activities and a sense of guilt for the harm they have caused other human beings. Another finding in the study was that Process Kedjan has qualities that cannot be found in authorities. These qualities are summarized in four different terms: identification, reliance, accessibility and fellowship. By the result we could find that Process Kedjan is an important complement to the authorities work regarding to prevent relapse in delinquency and drug abuse among youths, but collaboration between the organization and different authorities is required to be able to help a youth. The organization has contributed to a better view on authorities among the youths, they now understand the importance of dealing with for instance social services. / Denna uppsats syftar till att undersöka vilken betydelse organisationen Process Kedjan har för ungdomars upphörande av kriminalitet och missbruk. Den syftar även till att undersöka i vilken utsträckning organisationen hjälper ungdomar på andra sätt än myndigheter samt hur organisationen kan fungera som ett komplement till myndigheter. Uppsatsen är utformad som en fallstudie och utgår från medlemmarna i Process Kedjans perspektiv. Empirin har insamlats genom kvalitativa intervjuer med fem unga män som får eller har fått hjälp av organisationen. Tre av dem tar fortfarande emot hjälp och två arbetar numera i organisationen. I analysen tillämpades Laub och Sampsons teori om upphörandeprocesser, vändpunkter och sociala band. Vid bearbetning av det empiriska materialet framkom det att Process Kedjan har varit av stor betydelse för att ungdomarna ska kunna upprätthålla ett liv utan brott och missbruk. Andra viktiga faktorer har varit: nära relationer framför allt med familj, dagliga rutiner och aktiviteter samt en skuldkänsla av att ha orsakat skada hos andra människor. Det framkom också att Process Kedjans verksamhet innehåller delar som inte går att finna hos myndigheter. Dessa har sammanfattats i fyra olika begrepp: identifikation, tillit, tillgänglighet och gemenskap. I resultatet går det att utläsa att Process Kedjan är ett viktigt komplement till det arbete som myndigheter utför angående att förebygga återfall i kriminalitet och missbruk bland ungdomar, men för att kunna hjälpa en ungdom krävs ett samarbete mellan organisationen och olika myndigheter. Med hjälp av stöd från organisationens personal har ungdomarna fått en förändrad syn på myndigheter och ser nu vikten av att ha en kontakt med exempelvis socialtjänsten.

Studies have indicated that relapse is noted as a major problem facing mental health services both nationally and internationally whereby family members caring for mental health care users experience a serious burden. Factors commonly associated with relapse include poor adherence to treatment, substance abuse, co-morbid psychiatric illness, a co-morbid medical and or surgical condition, stressful life events and the treatment setting. Relapse prevention strategies have been identified and they include, empowering people with mental illness to recognize early warning signs of relapse in order to develop appropriate response plans as well as communication and understanding between the mentally ill person, their family, and specialist mental health system and community support services. The researcher was prompted by the problem of relapse faced by mental health services to explore and describe the strengths of families in assisting mental health care users to limit relapse and to formulate guidelines for psychiatric nurses to empower family members caring for mental health care users to limit relapse. A phenomenological design was used in this study and a purposive sampling technique was used to select participants who met the selection criteria. In-depth individual interviews were conducted with 15 family members. All interviews were recorded with an audio recorder after participants gave consent. Data saturation was achieved after 13 participants were interviewed and further two interviews confirmed data saturation. Field notes were written immediately after each interview. Data analysis was done according to Tesch as quoted by Creswell (2007:187) and the researcher and co-analyzer reached consensus on the themes in a meeting. The findings of research resulted in four main categories namely, accepting the condition of a mentally ill family member, having faith in God, involving a mentally ill family member in daily activities and being aware of what aggravates the mentally ill family member. The conclusion that can be made is that “acceptance through education” assisted family members in developing a positive attitude and acceptance of their feelings as well as the condition of their mentally ill family members. A strong spiritual base provides family members with strength and hope in times of adversity and teaches them how to have healthy relationships within the family unit and with others. It is also evident that sharing activities, as the things that all members of the family do together, reinforce and strengthen their togetherness and that if family members can be aware of what aggravates mentally ill family members by communicating well with them, that can bring harmony in families and ultimately limit relapse. Recommendations in this research are made for nursing education, nursing research and psychiatric nursing practice with guidelines for psychiatric nurses to empower families caring for mentally ill family members to use their strengths and contribute to limiting relapse. / MCur, North-West University, Potchefstroom Campus, 2014

Relapse prevention after pain management is a neglected area and Internet-based interventions have the potential to partly fill this gap. A challenge in designing effective relapse prevention program is how to motivate patients to persist throughout the full length of treatment. Following a regular pain management program, 29 participants underwent a 20 week long Internet–based relapse prevention program based on acceptance-oriented CBT. Qualitative analyses showed changes in attitudes towards their pain and body during the course of treatment. Degree of personal commitment in treatment goals seemed to affect gains relating to new perspective on self and future. Therapeutic strategies of defusion and mindfulness seemed to ease perspective changes and persistence to comply. Values interventions are hypothesized to be a plausible therapeutic strategy to engage participants in continuous behavior change. Further studies on non-compliers and drop-outs could enhance understanding of interventions necessary to maintaining motivation. When and how to give therapist support during Internet-based treatment for chronic pain is another area in need of further studies.

Identification of recurrent mutations through next-generation sequencing (NGS) has given us a deeper understanding of the molecular mechanisms involved in chronic lymphocytic leukemia (CLL) development and progression and provided novel means for risk assessment in this clinically heterogeneous disease. In paper I, we screened a population-based cohort of CLL patients (n=364) for TP53, NOTCH1, SF3B1, BIRC3 and MYD88 mutations using Sanger sequencing, and confirmed the negative prognostic impact of TP53, SF3B1 or NOTCH1 aberrations, though at lower frequencies compared to previous studies. In paper II, we assessed the feasibility of targeted NGS using a gene panel including 9 CLL-related genes in a large patient cohort (n=188). We could validate 93% (144/155) of mutations with Sanger sequencing; the remaining were at the detection limit of the latter technique, and technical replication showed a high concordance (77/82 mutations, 94%). In paper III, we performed a longitudinal study of CLL patients (n=41) relapsing after fludarabine, cyclophosphamide and rituximab (FCR) therapy using whole-exome sequencing. In addition to known poor-prognostic mutations (NOTCH1, TP53, ATM, SF3B1, BIRC3, and NFKBIE), we detected mutations in a ribosomal gene, RPS15, in almost 20% of cases (8/41). In extended patient series, RPS15-mutant cases had a poor survival similar to patients with NOTCH1, SF3B1, or 11q aberrations. In vitro studies revealed that RPS15mut cases displayed reduced p53 stabilization compared to cases wildtype for RPS15. In paper IV, we performed RNA-sequencing in CLL patients (n=50) assigned to 3 clinically and biologically distinct subsets carrying stereotyped B-cell receptors (i.e. subsets #1, #2 and #4) and revealed unique gene expression profiles for each subset. Analysis of SF3B1-mutated versus wildtype subset #2 patients revealed a large number of splice variants (n=187) in genes involved in chromatin remodeling and ribosome biogenesis. Taken together, this thesis confirms the prognostic impact of recurrent mutations and provides data supporting implementation of targeted NGS in clinical routine practice. Moreover, we provide evidence for the involvement of novel players, such as RPS15, in disease progression and present transcriptome data highlighting the potential of global approaches for the identification of molecular mechanisms contributing to CLL development within prognostically relevant subgroups.

Nicotine replacement therapy (NRT) is a pharmacotherapy used commonly to help tobacco smokers quit smoking. All forms of NRT are demonstrably efficacious for this indication, and several forms, including transdermal nicotine (TN) are available over-the-counter in the United States. NRT is less efficacious in women than in men, although the specific reasons for this gender difference are unknown. NRT generally, and TN specifically, is thought to work, at least in part, by suppressing withdrawal symptoms in abstinent smokers. While TN-induced withdrawal suppression has been demonstrated, the degree to which this withdrawal suppression is influenced by smokers' gender is uncertain. The purpose of this acute laboratory study is to determine if TN-induced withdrawal suppression is influenced by smokers' gender.One hundred twenty eight overnight-abstinent smokers completed four, double-blind, randomized, 6.5-hour laboratory sessions in which further cigarette abstinence was required. Sessions differed by TN dose (0, 7, 21, or 42 mg). All sessions were double-blind and randomly ordered. Each session included regular assessment of subjective symptoms of nicotine/tobacco withdrawal, subjective effects of transdermal nicotine dose, psychomotor performance, heart rate and plasma nicotine level. Results from this laboratory study revealed clear nicotine dose-related effects for plasma nicotine and heart rate, symptoms of nicotine intoxication (e.g. Nausea, Lightheaded) and suppression of Urges to smoke and Craving. Many DSM IV nicotine/tobacco withdrawal symptoms did not show dose-related suppression (e.g. Irritability/frustration/anger, Anxious, Difficulty concentrating). Importantly, results from this study indicated that there were very few differences between men and women in nicotine-induced suppression of the nicotine/tobacco withdrawal syndrome. Future research addressing this important issue may benefit from focusing on a potential interaction between gender and other effects of TN (i.e., blunting the effects of a concurrently administered cigarette) and/or on other triggers for relapse (i.e., smoking-related stimuli).

Trend of declining crime rates in recent years, on the other hand rising recidivism raises many questions for the existing criminal justice system. High return to prison gives the impression that the purpose of a sentence of custodial sentence lose at the beginning of the third millennium its meaning. The challenge not only for the state apparatus, but the whole society is more than ever becoming reintegration of offenders, which is a predictor of risk of recidivism. The aim of this thesis is therefore description and evaluation aspects of the process of social reintegration, taking into account current possibilities to prevent reoffending. Empirical part extends the intention of re-socialization efforts charting selection of innovative programs in social work with offenders. Theoretical material consists of key concepts weighing the Criminology and Penology, which is completed at the end of work formulating recommendations for social work with offenders as a possible guide changes in the life of each individual offender.

Introduction: Successful treatment of class II Division 1 malocclusion is also implied to the long-term stability of treatment changes and many are the factors that can influence that. Objective: This research aimed to evaluate the long-term stability of the cephalometric changes obtained during Class II malocclusion correction with the MARA (Mandibular Anterior Repositioning Appliance) associated with fixed appliances. Methods: The treatment group comprised 12 patients who were evaluated at three stages: pretreatment (T1), posttreatment (T2) and long-term posttreatment (T3). The mean initial age of the patients was 12.35 years and the mean final age was 15.65 years. The mean age at the long-term posttreatment stage was 22.53 years and the mean long-term posttreatment period was 6.88 years. The control group comprised 12 subjects with normal occlusion and no orthodontic treatment with ages comparable to the treatment group at the posttreatment and long-term posttreatment stages. Intra-treatment group comparison between the three stages was performed with repeated measures analysis of variance (ANOVA), followed by Tukey tests. Intergroup comparison of posttreatment changes and normal growth changes of the treatment group were performed with t tests. Results: reduction of the maxillary protrusion and improvement of the maxillomandibular relationships remained stable during the long-term posttreatment period. Maxillary incisors inclination and overjet presented a tendency to relapse in relation to the control group Conclusions: Despite the different amount of growth potential, the reduction of the maxillary protrusion and maxillomandibular relationship improvement remained stable with no difference from normal occlusion behavior. Palatal inclination of the maxillary incisors and the overjet improvement showed a slight tendency towards relapse when compared to normal occlusion. Therefore, an increase of active retention time could be recommended to prevent that. / Introdução: o tratamento bem-sucedido da má oclusão de classe II Divisão 1 está implícito na estabilidade em longo prazo das correções e muitos são os fatores que podem influenciar esta estabilidade. Objetivos: observando que a terapia com o aparelho MARA (Mandibular Anterior Repositioning Appliance) associado ao aparelho ortodôntico fixo mostrou-se eficaz na correção da Classe II, este trabalho estabeleceu como objetivo avaliar cefalometricamente a estabilidade em longo prazo das correções obtidas durante este tratamento. Materiais e métodos: foram analisadas as alterações durante e após o tratamento através das telerradiografias em norma lateral de 12 pacientes (09 meninos e 03 meninas) nas fases: inicial (T1), final (T2) e pós-tratamento (T3), com idade média inicial de 12,35 anos e 15,65 anos ao final do tratamento. A idade media no estágio de pós tratamento em longo prazo foi de 22,53 e o tempo de acompanhamento pós tratamento foi em media 6,88 anos. As alterações foram comparadas a um Grupo Controle com oclusão normal, não tratados ortodonticamente, com idades compatíveis ao grupo experimental nos estágios final e pós tratamento em longo prazo. Os dados obtidos foram analisados através da análise de variância (ANOVA) para medidas repetidas e o teste de comparações múltiplas de Tukey. As alterações ocorridas no período de póstratamento foram comparadas com as alterações do Grupo Controle durante o período correspondente utilizando o teste t independente. Resultados: Observou-se uma redução da protrusão maxilar, assim como, uma melhora das relações maxilomandibulares, as quais, permaneceram estáveis durante o período de póstratamento. A inclinação dos incisivos superiores e o overjet apresentaram tendência à recidiva em relação ao grupo controle. Conclusões: A redução da protrusão maxilar e melhora da relação maxilomandibular mantiveram-se estáveis, sem diferença estatisticamente significante do comportamento na oclusão normal. A retroinclinação dos incisivos superiores e a melhora do overjet mostraram uma ligeira tendência à recidiva quando comparada ao comportamento da oclusão normal. Portanto, um aumento do tempo de retenção ativo pode ser recomendado para evitar essa recidiva.

Die akute lymphoblastische Leukämie (ALL) ist die häufigste maligne Erkrankung im Kindesalter. Trotz risikoadaptierter Chemotherapie erleiden 25 - 30 % der Kinder mit ALL ein Rezidiv. Im Rezidivfall liegen die Heilungschancen trotz intensivierter Therapie nur bei 35- 40%. In retrospektiven und prospektiven Analysen konnten wir einerseits prognostisch-relevante, genetische Merkmale in den Leukämiezellen von Kindern mit ALL-Rezidiv erstmals identifizieren. Diese leukämiespezifischen Merkmale umfassen sowohl Translokations-assoziierte Fusionsgene (TEL-AML1, BCR-ABL, MLL-Aberrationen, E2A-PBX1), Deletionen von Tumorsuppressorgenen (p15, p16, p18) als auch Mutationen in DNA-Reparaturgenen (NBS1). Zusammen mit der sensitiven molekularen Bestimmung der Kinetik der Leukämiezellreduktion (Reaktion auf die Therapie, (MRD, minimal residual disease)) läßt sich die Prognose der Kinder mit ALL-Rezidiv durch die Verwendung dieser Marker zuverlässiger bewerten. Andererseits zeigen unsere Analysen, dass das Ansprechen auf die Therapie und die Prognose von wirtseigenen Faktoren (medikamenten metabolisierenden Enzyme) und von der Interaktion zwischen Leukämie- und Stromazellen und löslichen Wachstumsfaktoren (Zytokinen) abhängt. Eine adäquatere Behandlung dieser Patientengruppe, die bereits eine intensive Therapie erhalten hat und wesentlich risikoreichere, mit einer hohen Akut- und Spättoxizität behaftete Therapieverfahren einschließt, lässt sich durch die Berücksichtigung dieser Ergebnisse erreichen. Die genetische Typisierung und die sensitive Quantifizierung des molekularen Ansprechens auf die Therapie ergänzen heute die klinischen Determinanten zur Risikostratifizierung der Kinder mit ALL-Rezidiv der derzeitigen Therapieoptimierungsstudie ALL-REZ BFM 2002 (Berlin-Frankfurt-Münster). / Acute lymphoblastic leukemia is the most common malignancy in childhood. Although the prognosis for pediatric ALL with risk-adapted chemotherapy has improved dramatically, 25-30% of the children suffer a relapse. The prognosis for relapsed ALL remains poor (35-40%). In retrospective and prospective studies, we identified prognostic-relevant genetic features in leukemic blasts from children with ALL relapse. These leukemia-specific aberrations include translocation-associated fusion genes (TEL-AML1, BCR-ABL, MLL changes, E2A-PBX1), deletions of tumor suppressor genes (p15, p16, p18) and point mutations in DNA repair genes (NBS1). Together with the sensitive quantitative assessment of the molecular response to therapy (MRD, minimal residual disease), prediction of outcome is now more reliable. Furthermore, response to therapy and, thus, prognosis is significantly dependent on modifying host factors (drug-metabolizing enzymes) and interactions between leukemic and stromal cells as well as soluble growth factors (cytokines). Today, the genetic characterization of leukemic cells as well as the molecular quantification of response to therapy complement prognostic significant clinical determinants allowing a more precise risk stratification of children with ALL relapse in the relapse trial ALL-REZ BFM 2002 of the BFM (Berlin-Frankfurt-Münster) study group.