Thesis (Ph.D.)--Boston University / The purpose of the present study was to determine whether positive reinforcement, chlorpromazine and secobarbital alter the ability of chronic schizophrenics to maintain sustained attention and whether these affect their psychomotor functioning. Eight male, chronic schizophrenic patients, with an age range of 25-50 and in good physical health, served as the subjects. All subjects had been hospitalized continuously for at least three years. Medication was discontinued for all subjects two months before the study started. In the course of the study, each subject was tested twice under all of the following conditions: no-drug, placebo, chlorpromazine 100 mg, chlorpromazine 200 mg, secobarbital 100 mg, secobarbital 200 mg. The drugs were given once weekly in single doses. A testing day consisted of four sessions: 1/2, 1 1/2, 2 1/2, and 3 1/2 hours post-medication. The different drug conditions were administered according to a modified Latin Square design with each active drug following each other active drug an equal number of times. Half of the trials in each session were reinforced by candy and cigarettes and the other half were not. Two tests were employed: The Continuous Performance Test (CPT), and the Subject Paced Test (SPT). On the CPT, a test of sustained attention, a subject is required to respond, by pulling a lever, to one of twelve letters which are randomly exposed at the rate of 1.10 sec. for a period of .10 second.[TRUNCATED]

Osteoporosis is a skeletal disease characterized with poor bone quality and low bone mineral density. The pathogenesis of osteoporosis is the imbalance of bone resorption and bone formation. Two strategies can be employed to cure osteoporosis. One is to inhibit bone resorption and the other is to stimulate bone formation. Currently, therapeutic drugs approved by FDA are mainly antiresorptive agents. Till now, there is only one bone anabolic agent approved. Obviously, more efforts should be poured into the development of bone anabolic agents. Sclerostin is a key negative regulator of osteoblast Wnt signaling making it a promising therapeutic target for bone anabolic therapy. Anti-sclerostin humanized monoclonal antibody romosozumab, which could effectively promote bone formation, has been accepted by the FDA for the review of biologic license application in 2017. However, there are several concerns about the humanized anti-sclerostin antibody, including immunogenicity, high cost of production and relative low stability. Nucleic acid aptamers are short single stranded oligonucleotides. They can bind to their targets with similar high affinity as antibodies. Moreover, aptamers have some superior advantages compared to antibodies, such as no immunogenicity, easily synthesized, and high stability. Aptamers against sclerostin could be a promising alternative to antibodies in terms of promotion of bone formation and reversal of osteoporosis. In this thesis, 20 rounds of SELEX were performed to select aptamers with high binding affinity and specificity to sclerostin. The inhibition potency of aptamer candidates to the antagonistic effect of sclerostin on Wnt signaling was also evaluated. Low KD and EC50 values of aptamer candidates against sclerostin implied a great potential of sclerostin aptamer being novel agents to promote bone formation. The study establishes the foundation for the next stage of preclinical studies and it will benefit the development of novel bone anabolic agents to reverse osteoporosis.

Abstract Background People with alcohol and other drug (AOD) problems are offered treatment by a variety of organisations in the non-government sector, many of which have religious affiliations. Little is known about the actual treatment offered, and whether the ideology of the organisation has an impact on the choice of treatment provided. Christian churches were amongst the first service-delivery organisations in the Australian AOD sector, and those remaining in the sector appear to have evolved from providing overt Christian-care to providing some evidence-based care in line with the move to best practice under Australia’s National Drug Strategy. It remains to be determined, however, whether the approach to treatment and service provision by religiously-affiliated agencies is influenced by their religious background and orientation. To resolve this gap in knowledge a national survey of non-government AOD agencies was conducted in late 2005–early 2006. Methods Survey participants consisted of all identified non-government AOD agencies in Australia. The operational definition of AOD agencies was in keeping with definitions used in other investigations in the sector. The sample frame was compiled using the most recent directories and databases available. Two questionnaires were posted to 331 agencies throughout Australia. Responses were sought from both the director/coordinator and a staff member working directly with clients. Completed questionnaires were received from 169 (51 per cent) of agencies. A completed questionnaire from both the director/coordinator and an AOD worker was received from 90 of these 169 agencies. Where this was the case, the response from the director/coordinator was taken to be the ‘agency response’. Questions were about the agency’s profile, goals, activities, the respondent’s own view of substance dependence and the respondent’s demographic characteristics. Qualitative methods were also used to gain further information and clarification from key informants, both prior to and after the quantitative survey. Findings There was surprising homogeneity amongst all agencies in their use of the eight treatment orientations studied (12-step, therapeutic community, cognitive behaviour, psychodynamic, rehabilitation, dual diagnosis, medical, and family). Cognitive behaviour therapy was the most popular treatment across all types of agencies in contrast to the 12-step approach which was only a major focus for a small number of agencies. Psychodynamic and therapeutic community orientations were also widely used but family and rehabilitation orientations were amongst the least popular orientations. With the family orientation there was a wide discrepancy between agencies that had family goals but not family activities. In regard to accessing treatment, mothers accompanied by their children and couples were the two groups least likely to be accepted into treatment (44 per cent and 40 per cent respectively did not accept couples). Directors interviewed in this study indicated that not accepting mothers accompanied by their children was due to the cost of providing relevant services. Of the agencies surveyed, 42 per cent were affiliated with a church organisation. Although 85 per cent of church-affiliated agencies indicated that they received some contribution towards policy from a religious organisation, results suggested that there was very little difference between church-affiliated and non-church-affiliated agencies in service delivery. One area of significant difference between church-affiliated and non-church-affiliated agencies was access. Church-affiliated agencies were significantly more likely than non-church-affiliated agencies to not accept couples, Indigenous people, and people referred from the criminal justice system. Church-affiliated agencies were also significantly more likely to take into consideration a prospective client’s motivation to succeed. Across all agencies activities of a spiritual nature (e.g. meditation/prayer, talking with clients about spirituality/religion) were only a major feature for a small number of agencies; although 70 per cent of agencies included developing a client’s spiritual self in their goals. The majority of directors/coordinators indicated that they have a broad set of beliefs about substance use that allows for various social and psychological understandings and treatment responses. Conclusion Overall, there was uniformity in the type of treatment goals and activities offered by the non-government AOD agencies. The findings suggest that churches are becoming indistinguishable from secular organisations in their delivery of AOD services. Where once there may have been faith in religion as a basis of service provision there now appears to be faith in science. This is in the context that the ‘best evidence’ of effective treatments suggests that most treatments are relatively weak predictors of a positive outcome, and that the choice of treatment may not impact on treatment outcomes. The evidence-based medicine movement may have become a form of religion and, in association with a population health approach, is dominating the AOD service delivery sector. Although successful drug treatment programs may well require that the client/patient undergo moral and value changes, these may occur without connection to organised religion. Ideology in the form of religious belief has historically played a central role in treatment choices and it continues to do so in the form of an ideology giving priority to best practice, despite the likelihood that best practice may nevertheless continue to produce poor outcomes.