Background: Social Role Valorisation (SRV) is a social science meta-theory about social devaluation. its innovative technologies are designed to promote valorisation (norinalisation). SRV had a major impact on learning disability services in the 1980's but has had limited exposure in mental health. Its effect on policy is evident however. SRV has developed reliable, valid ecological assessments of normalisation in service enviromnents. Life-style Planning operationalises normalisation goals for individuals. Its reliability and validity are unknown. Life-style Planning has two goal domains designed to ensure universal basic needs are met and address unique individual needs arising from primary disabilities. SRV also identifies revalorisation needs, to compensate for prior devaluation. In a previous study an instrument designed to assess universal basic and unique individual needs was standardised on a representative population of people with severe and enduring mental illness. Aims: To validate the goal domains of the assessment instrument and develop an understanding of the user perspective on SRV and revalorisation. Design and participants: Factor analysis was used to explore the underlying structure of the assessment instrument. In a second, qualitative study, "expert" mental health user/survivors were interviewed and their transcripts analysed using Interpretative Phenomenological Analysis. Results: The instrument's factor structure matched its design intentions and supported the validity of its goal domains. The qualitative results compared favourably with similar studies from the user, empowerment and recovery literatures. Participants painted a graphic picture of devaluation and revalorisation and illuminated what is required to promote "psychological revalorisation"'. This took the form of a return from a false identification of themselves, based on the internalisation of ignorance and social prejudice stemming from societal fear and blame, to a new identification with a class of proud and empowered mentally ill people. Implications. The discussion considers revalorising adaptations to psychological therapies for people with significant devaluation histories.

Breast cancer is the most common cancer in the UK and Basal-like breast cancer (a highly aggressive subtype) accounts for approximately 8-22% of all cases depending on ethnicity. Unlike most human malignancies and indeed other PAM50 breast cancer subtypes, the vast majority of Basal-like tumours are positive for wild type p16. This p16 signature is associated with a particularly poor prognosis and p16-positive Basal-like breast cancer remains the most clinically challenging subtype and is the focus of this project. Pro-senescence therapies are gaining momentum as attractive strategies for the treatment of those breast cancers with current unmet clinical need. To identify targets for pro-senescence therapy in p16-positive Basal-like breast cancer, a genome‐wide siRNA screen and two subsequent validation screens using two p16-positive cancer cell lines were performed. Screening revealed 20 siRNAs that induced senescence within both cancer cell lines. Strikingly, 11 of these 20 siRNAs targeted ribosomal proteins, implicating disrupted ribosomal biosynthesis in senescence activation in p16-positive Basal-like breast cancer. Importantly, subsequent experiments in normal human mammary epithelial cells established that specific ribosomal protein knockdown is well tolerated by normal cells. Analysis of the METABRIC data set showed a high degree of ribosomal dysregulation in Basal-like tumours and revealed that all 11 ribosomal hits identified were frequently overexpressed in p16-positive Basal-like breast cancers. Kaplan Meier analysis confirmed that elevated expression of six of the 11 ribosomal proteins correlates with a reduced overall survival in these women, further supporting a role for these proteins as drivers of disease. These six ribosomal hits, associated with the poorest patient survival, were prioritised for further validation. Senescence induction was found to be highly stable, and associated with dramatic changes to nucleolar morphology, reminiscent of the nucleolar signature observed upon premature senescence induction in normal human mammary epithelial cells. In addition, siRNA rescue experiments indicated that senescence initiation is dependent on p16 and p21 expression and is accompanied by p16 nuclear translocation and p21 degradation. Further, ribosomal protein silencing in MDA-MB-231 cells (p16-null Basal-like breast cancer cell line) resulted in a 'death-like' phenotype, partially dependent on p21 expression suggesting that, within a cancer context, ribosomal protein silencing may induce a differential response depending on the status of p16. In conclusion, it is proposed that these six ribosomal candidates may form the basis of a novel pro-senescence therapy for p16-positive Basal-like breast cancer. They may also represent novel prognostic biomarkers for this disease subset and may help to improve disease stratification and future directed personalised therapies.

The rise of antimicrobial resistance (AMR) has culminated in the most pressing problem in modern medicine. The situation is most acute with regards to the management of multi- drug resistant Gram-negative infections (MDRGNB) with common infections increasingly untreatable due to rapidly dwindling therapeutic options. A solution to the problem of AMR is unlikely to be easily found, but revisiting and re-purposing existing antimicrobials is a viable approach in the medium term. This study investigated the use of unorthodox antimicrobial combination therapies for the treatment of MDRGNB, with particular focus on agents of last resort. A systematic review of clinical studies highlighted the potential for polymyxin (colistin) combination therapies (e.g. colistin-rifampicin, colistin-carbapenems), although this could not be supported in a formal meta-analysis. A systematic approach for screening MDRAB for susceptibility to novel colistin combinations using multiple methods was employed and uncovered a number that were more potent than those previously identfied. The most potent combination that was consistently identified was colistin when combined with fusidic acid, despite this drug having no useful activity against MDRGNB on its own. The combination was further evaluated in static time-kill assays against a range of Gram-negative pathogens with defined resistance mechanisms, including to polymyxins and using invertebrate (Galleria mellonella) and murine models of MDRGNB infection. Colistin and fusidic acid combination therapy was subsequently used to successfully treat a case of ventilator-associated pneumonia due to MDR A. baumannii. This work highlights how older drugs can be re-purposed to tackle the problem of AMR using a precision medicine approach. Further studies to elucidate the mechanism of action of the colistin- fusidic acid combination and a formal clinical trial are warranted to investigate the potential utility of this combination in the treatment of MDRGNB with the expressed goal of bridging the current antimicrobial development gap.

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Autologous Bone Marrow Transplantation (ABMT) provides a way to rescue the hematopoietic system in patients receiving high dose chemotherapy. Solid tumors like lung and breast cancer are the targets for new therapies that involve high dose chemotherapy with AMBT due to their growth and pathologic characteristics. Reinfusion of bone marrow with metastatic neoplastic cells could also seed viable tumor cells, and thus be a reason for treatment failure, restricting high-dose chemotherapy with bone marrow support to patients whose marrow is morphologically free of tumor cells. The use magnetic beads for physical separation of tumor from normal cells and the use of a toxin delivered by a monoclonal antibody are examined as two purging methods for treatment. The use of magnetic beads conjugated with specific antibodies (SM1, LAM2 and LS1) against tumor antigens to purge 2-3 logs of Small Cell Lung Cancer (SCLC) contamination from bone marrow is demonstrated. Optimal performance calls for short double exposure to anti-tumor cell-antigen monoclonal antibodies, followed by exposure to magnetic beads coated with antibodies specific for the monoclonal anti-SCLC antibodies, maintaining a bead-to-cell ratio of 10:1 to 100:1. Specific toxin delivery to three breast cancer cell lines (ZR-75, BT20 and MCF7) expressing the DF3 antigen was demonstrated by the use of DF3 immunotoxin (DF3-IT). The optimal concentration of the DF3-IT immunotoxin for highest tumor kill was shown to be 1x1Q-9 M, but this caused a loss of bone marrow progenitor cell colonies of about 30%. Both methods are limited chiefly by the level of antigen expression in the target tumor cells. The purging efficiency could be improved by targeting a wider range of antigens or by inducing higher levels of antigen expression. From the clinical perspective, the advantages and need for purging involved bone marrow to bring about substantially improved curative strategies remains a question still unanswered. / 2031-01-01

Acupuncture has been used for thousands of years to treat a wide range of diseases, but the mechanisms involved in the process have remained a mystery. The present study measures EEG responses to stimulation of a specific acupuncture point, GB37 (Guang Ming), with two different types of manual needle stimulation. Previous studies stimulated for a maximum of 2 minutes. The present study reflects the normal acupuncture treatment time of 20 minutes, with EEG recordings during and for 10 minutes prior to and after stimulation. Our results show no changes in the global spatial and temporal properties of EEG during and shortly after acupuncture treatment of acupoint GB37. The second part of this study examines the global protein expression of glutamic acid decarboxylase (GAD) knockout mice. GAD is the rate-limiting enzyme in the synthesis of GABA, the major inhibitory neurotransmitter in the brain. The protein content of wild type, hetero-, and homozygous GAD knockout mice brains were determined using a LC-MS-based gel-free shotgun profiling of complex protein mixtures. The data was analyzed using the Raculovic algorithm to determine the proteins differences. A short list of 32 proteins was determined with four that have been shown to be significant proteins that influence cell survival and excitotoxicity in the brain and have potential relationships with GABA. These proteins include VATPase, Glutamine synthetase, Beta-synuclein, and Micortuble associated protein (MAP). The proteomics results provide a preliminary best guess list of proteins influencing GAD and GABA production. / by Michael L. Marshall. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

The term ‘restitution narrative’ describes the hope we all have when illness or accidental impairment befalls us to be returned to a pre-morbid condition of health as soon as possible, and in modern Western society we expect the miracle of restitutions to be mediated by medical science. Medicine is still unable to cure a wide range of illness and disability. For these people the restitution narrative fails. This study attempts to create space between health and illness, the space of the failed patient, within which to explore the iatrogenic and disabling effects on bodies and minds living in a society that has come to expect not to suffer when illness or disability is incurable and chronic. Through the medium of a purpose built website, people who are chronically ill and disabled discussed the ‘wicked issues’ that make lives already challenged unnecessarily difficult. Application of the findings of research in psychobiology is applied to speculate whether health may be worsened by being a failed patient in a culture for which health has become the ultimate good. Ideas of social fuzziology are brought into play to help imagine ways in which the dualities of health and illness, normal and abnormal, are broken down and the normalizing ideologies of medicine resisted. / Doctor of Philosophy (PhD)

<p><em>Bakgrund</em>: Primär dysmenorré, svår menstruationssmärta utan sjukdomsrelaterad bakomliggande orsak, är det vanligaste gynekologiska besväret för unga kvinnor. Idag fokuseras behandlingen av menstruationssmärta på läkemedel. Det har dock visats att kvinnor även använder sig av ickefarmakologiska metoder för att lindra sin smärta. Syftet med denna litteraturöversikt var att undersöka om det finns evidens för att följande ickefarmakologiska behandlingsmetoder kan lindra primär dysmenorré: akupunktur, akupressur, kostvanor och kostterapi, massage, transkutan elektrisk nervstimulering (TENS), värme samt örtterapi.</p><p><em>Metod</em>: Sökningar genomfördes i databaserna AMED, CINAHL, Cochrane Library samt Pubmed. På grund av få artikelträffar och låg kvalitet hos artiklarna exkluderades massage och värme. Totalt inkluderades 18 engelskspråkiga artiklar, publicerade mellan år 1999-2009, vilka redovisade resultat från sammanlagt 92 studier. Sammanlagt 23 studier undersökte akupunktur, 11 undersökte akupressur, 46 undersökte örtterapi, 3 undersökte kostterapi och kostvanor samt 9 undersökte TENS. Kvalitetsgranskning genomfördes enligt en mall från Forsberg & Wengström (2008).</p><p><em>Resultat</em>: Det finns evidens för att akupressur, TENS och örtterapi lindrar primär dysmenorré. Vilka specifika akupunkter och örter som har en smärtlindande effekt är dock oklart. Sjuksköterskan kan ge råd till patienter med primär dysmenorré att prova TENS för att lindra sina menstruationssmärtor.</p> / <p><em>Background</em>: Primary dysmenorrhea, menstrual pain without disease-related underlying reason, is the most common gynaecological discomfort for young women. Today the treatment regime for menstrual pain is focused on pharmacologic treatments. However, it has been observed that women also use non-pharmacologic methods to ease their pain. The objective for this literature review was to determine if there is evidence for the following non- pharmacologic treatment-methods to ease primary dysmenorrhea: acupuncture, acupressure, dietary habits and dietary therapies, massage, transcutaneous electrical nerve stimulation (TENS), heat and herbal therapy.</p><p><em>Method</em>: Searches were performed in databases AMED, CINAHL, Cochrane Library and PubMed. Because of a small number of search-results and low quality of the articles massage and heat was excluded. A total of 18 English-speaking articles published between 1999-2009 were identified. They reviewed results from 92 studies. Altogether 23 studies reviewed acupuncture, 11 acupressure, 46 herbal therapy, 3 dietary therapies and dietary habits and 9 TENS. Quality assessment was performed according to a template from Forsberg & Wengström (2008).</p><p><em>Results</em>: There is evidence that acupressure, TENS and herbal therapy ease primary dysmenorrhea. Which specific acupoints and herbs that are pain relieving could not be concluded. The nurse can give advice to patients with primary dysmenorrhea to test TENS to ease their menstrual pain.</p>

Bakgrund: Primär dysmenorré, svår menstruationssmärta utan sjukdomsrelaterad bakomliggande orsak, är det vanligaste gynekologiska besväret för unga kvinnor. Idag fokuseras behandlingen av menstruationssmärta på läkemedel. Det har dock visats att kvinnor även använder sig av ickefarmakologiska metoder för att lindra sin smärta. Syftet med denna litteraturöversikt var att undersöka om det finns evidens för att följande ickefarmakologiska behandlingsmetoder kan lindra primär dysmenorré: akupunktur, akupressur, kostvanor och kostterapi, massage, transkutan elektrisk nervstimulering (TENS), värme samt örtterapi. Metod: Sökningar genomfördes i databaserna AMED, CINAHL, Cochrane Library samt Pubmed. På grund av få artikelträffar och låg kvalitet hos artiklarna exkluderades massage och värme. Totalt inkluderades 18 engelskspråkiga artiklar, publicerade mellan år 1999-2009, vilka redovisade resultat från sammanlagt 92 studier. Sammanlagt 23 studier undersökte akupunktur, 11 undersökte akupressur, 46 undersökte örtterapi, 3 undersökte kostterapi och kostvanor samt 9 undersökte TENS. Kvalitetsgranskning genomfördes enligt en mall från Forsberg &amp; Wengström (2008). Resultat: Det finns evidens för att akupressur, TENS och örtterapi lindrar primär dysmenorré. Vilka specifika akupunkter och örter som har en smärtlindande effekt är dock oklart. Sjuksköterskan kan ge råd till patienter med primär dysmenorré att prova TENS för att lindra sina menstruationssmärtor. / Background: Primary dysmenorrhea, menstrual pain without disease-related underlying reason, is the most common gynaecological discomfort for young women. Today the treatment regime for menstrual pain is focused on pharmacologic treatments. However, it has been observed that women also use non-pharmacologic methods to ease their pain. The objective for this literature review was to determine if there is evidence for the following non- pharmacologic treatment-methods to ease primary dysmenorrhea: acupuncture, acupressure, dietary habits and dietary therapies, massage, transcutaneous electrical nerve stimulation (TENS), heat and herbal therapy. Method: Searches were performed in databases AMED, CINAHL, Cochrane Library and PubMed. Because of a small number of search-results and low quality of the articles massage and heat was excluded. A total of 18 English-speaking articles published between 1999-2009 were identified. They reviewed results from 92 studies. Altogether 23 studies reviewed acupuncture, 11 acupressure, 46 herbal therapy, 3 dietary therapies and dietary habits and 9 TENS. Quality assessment was performed according to a template from Forsberg &amp; Wengström (2008). Results: There is evidence that acupressure, TENS and herbal therapy ease primary dysmenorrhea. Which specific acupoints and herbs that are pain relieving could not be concluded. The nurse can give advice to patients with primary dysmenorrhea to test TENS to ease their menstrual pain.

Purpose: Little is known about the use of complementary and alternative medicine (CAM), including traditional Chinese medicine (TCM) in ethnic populations with cancer living in Canada. The purpose of this study was to assess the prevalence and predictors of TCM/CAM use in newly diagnosed Chinese cancer patients who were starting cancer treatments. <p>Patients and Methods: A consecutive sample of newly diagnosed Chinese cancer patients treated at the British Columbia Cancer Agency over a four month period was surveyed. During admission, the study questionnaire was distributed along with other registration forms and anonymously returned in well-labeled boxes. A bilingual Chinese interpreter was available to answer any questions potential participants might have had. The 15-item questionnaire focused on TCM/CAM use, socio-demographics, and medical and cultural factors. <p>Results: Ninety-one patients completed the questionnaire. The majority of respondents (90%) were born outside of Canada and 64% completed the questionnaire in Chinese. TCM/CAM was used by 44% of respondents. Herbal remedies, vitamins/minerals, and prayer were the most commonly used therapies. In the bivariate analysis, factors predicting TCM/CAM use were prior TCM/CAM use (p < 0.001), having received chemo/radiotherapy (p = 0.021), female sex (p = 0.015), immigrant status (p = 0.040), and reporting a non-official language most frequently used at home (p = 0.018). Following multivariate analysis, it was found that prior CAM use (p < 0.001), lower income (p = 0.043), and immigrant status (p = 0.030) were associated with TCM/CAM use. <p>Conclusion: TCM/CAM use in newly diagnosed Chinese cancer patients is very common and results are comparable to previous studies in other populations. Healthcare practitioners must become aware of the widespread use of CAM and engage discussions about CAM use with their patients, especially those of a specific ethno-cultural group who may be less acculturated to Western society.

Purpose: Little is known about the use of complementary and alternative medicine (CAM), including traditional Chinese medicine (TCM) in ethnic populations with cancer living in Canada. The purpose of this study was to assess the prevalence and predictors of TCM/CAM use in newly diagnosed Chinese cancer patients who were starting cancer treatments. <p>Patients and Methods: A consecutive sample of newly diagnosed Chinese cancer patients treated at the British Columbia Cancer Agency over a four month period was surveyed. During admission, the study questionnaire was distributed along with other registration forms and anonymously returned in well-labeled boxes. A bilingual Chinese interpreter was available to answer any questions potential participants might have had. The 15-item questionnaire focused on TCM/CAM use, socio-demographics, and medical and cultural factors. <p>Results: Ninety-one patients completed the questionnaire. The majority of respondents (90%) were born outside of Canada and 64% completed the questionnaire in Chinese. TCM/CAM was used by 44% of respondents. Herbal remedies, vitamins/minerals, and prayer were the most commonly used therapies. In the bivariate analysis, factors predicting TCM/CAM use were prior TCM/CAM use (p < 0.001), having received chemo/radiotherapy (p = 0.021), female sex (p = 0.015), immigrant status (p = 0.040), and reporting a non-official language most frequently used at home (p = 0.018). Following multivariate analysis, it was found that prior CAM use (p < 0.001), lower income (p = 0.043), and immigrant status (p = 0.030) were associated with TCM/CAM use. <p>Conclusion: TCM/CAM use in newly diagnosed Chinese cancer patients is very common and results are comparable to previous studies in other populations. Healthcare practitioners must become aware of the widespread use of CAM and engage discussions about CAM use with their patients, especially those of a specific ethno-cultural group who may be less acculturated to Western society.