Functional movement disorders:Exploring lived experiences and psychological interventions.

This thesis examines issues related to functional movement disorders (FMD) and consists of three papers: a literature review, a research paper and a critical appraisal of the research process. The scoping literature review explored the characteristics of psychological interventions for FMD in research studies in the last 20 years. It found that FMD was conceptualised differently across the studies and interventions employed various techniques to target different assumed FMD mechanisms. The review identified that although psychological wellbeing, co-morbid physical symptoms and quality of life are important factors influencing and influenced by FMD, they are often not monitored in research studies. Acceptability of the interventions has also not been measured despite preliminary evidence of their low uptake and high dissatisfaction with psychological explanations of FMD. A number of recommendations have been made for future studies to improve design and evaluation of psychological interventions for this population. The research paper explored lived experiences of people with FMD. Ten semi-structured interviews were analysed using Interpretative Phenomenological Analysis. Three superordinate themes were generated: (1) The tug of war with the secret agent within: the power struggle with symptoms; (2) Navigating risks of disclosing the diagnosis: stigma and self-preservation (3) Pursuing hope, knowledge and treatments against helplessness and passivity. The findings indicate that people with FMD may face many internal and interpersonal battles whilst trying to maintain hope, a sense of control and identity. A sense of oppression, loss of control and stigma were explained in the context of discriminatory power distribution in the society and healthcare settings. Recommendations for research and clinical practice focus on facilitating patients’ empowerment and access to adequate treatments in FMD-informed services. The critical appraisal discusses the studies’ finding in the context of interpersonal and systemic power dynamics and reflects on the research process from critical theory perspective

White matter microstructure associations to amyloid burden in adults with Down syndrome

INTRODUCTION: Individuals with Down syndrome (DS) are at an increased risk of developing Alzheimer\u27s Disease (AD). One of the early underlying mechanisms in AD pathology is the accumulation of amyloid protein plaques, which are deposited in extracellular gray matter and signify the first stage in the cascade of neurodegenerative events. AD-related neurodegeneration is also evidenced as microstructural changes in white matter. In this work, we explored the correlation of white matter microstructure with amyloid load to assess amyloid-related neurodegeneration in a cohort of adults with DS. METHODS: In this study of 96 adults with DS, the relation of white matter microstructure using diffusion tensor imaging (DTI) and amyloid plaque burden using [ RESULTS: TBSS of the DTI maps showed widespread age-by-amyloid interaction with both fractional anisotropy (FA) and mean diffusivity (MD). Further, diffuse negative association of FA and positive association of MD with amyloid were observed. DISCUSSION: These findings are consistent with the white matter microstructural changes associated with AD disease progression in late onset AD in non-DS populations

Delay of polarization event increases the number of Cdx2-positive blastomeres in mouse embryo

AbstractDuring preimplantation mouse embryo development expression of Cdx2 is induced in outer cells, which are the trophectoderm (TE) precursors. The mechanism of Cdx2 upregulation in these cells remains unclear. However, it has been suggested that the cell position and polarization may play a crucial role in this process. In order to elucidate the role of these two parameters in the formation of TE we analyzed the expression pattern of Cdx2 in the embryos in which either the position of cells and the time of polarization or only the position of cells was experimentally disrupted. Such embryos developed from the blastomeres that were isolated from 8-cell embryos either before or after the compaction, i.e. before or after the cell polarization took place. We found that in the embryos developed from polar blastomeres originated from the 8-cell compacted embryo, the experimentally imposed outer position was not sufficient to induce the Cdx2 in these blastomeres which in the intact embryo would form the inner cells. However, when the polarization at the 8-cell stage was disrupted, the embryos developed from such an unpolarized blastomeres showed the increased number of cells expressing Cdx2. We found that in such experimentally obtained embryos the polarization was delayed until the 16-cell stage. These results suggest that the main factor responsible for upregulation of Cdx2 expression in outer blastomeres, i.e. TE precursors, is their polarity

From UML specification into FPGA implementation

In the paper a method of using the Unified Modeling Language for specification of digital systems, especially logic controllers, is presented. The proposed method is based mainly on the UML state machine diagrams and uses Hierarchical Concurrent Finite State Machines (HCFSMs) as a temporary model. The paper shows a way to transform the UML diagrams, expressed in XML language, to the form that is acceptable by reconfigurable FPGAs (Field Programmable Gate Arrays). The UML specification is used to generate an effective program in Hardware Description Languages (HDLs), especially Verilog

Chimerism in Myeloid Malignancies following Stem Cell Transplantation Using FluBu4 with and without Busulfan Pharmacokinetics versus BuCy

In the era of precision medicine, the impact of personalized dosing of busulfan is not clear. We undertook a retrospective analysis of 78 patients with myeloid malignancies who received fludarabine and busulfan (FluBu4) with or without measuring Bu pharmacokinetics (Bu PK) and those who received busulfan with cyclophosphamide (BuCy). Fifty-five patients received FluBu4, of whom 21 had Bu PK measured, and 23 patients received BuCy. Total donor cell chimerism showed that the percentage of patients maintaining 100% donor chimerism on day 100 was 66.7%, 38.2%, and 73.9% in the FluBu4 with PK, FluBu4 with no PK, and BuCy, respectively (P = .001). Patients who had decreasing donor chimerism by day 100 were 23.8%, 52.9%, and 26.1% in the FluBu4 with PK, FluBu4 with no PK, and BuCy, respectively (P = .04). Bu PK group had fewer patients with less than 95% donor chimerism on day 30, which was not statistically significant, 5% (FluBu4 PK), 31% (FluBu4 with no PK), and 21% (BuCy) (P = .18). Survival distributions were not statistically significant (P = .11). Thus, personalized drug dosing can impact donor chimerism in myeloid malignancies. This will need to be examined in larger retrospective multicenter studies and prospective clinical trials

White matter microstructure associations with episodic memory in adults with Down syndrome: a tract-based spatial statistics study.

BACKGROUND: Nearly all persons with Down syndrome will show pathology of Alzheimer's disease in their 40s. There is a critical need for studies to identify early biomarkers of these various pathological changes of Alzheimer's disease in the Down syndrome population and understand the relationship of these biomarkers to cognitive symptoms in order to inform clinical trials. Although Alzheimer's disease is often considered a disease of gray matter, white matter degeneration has been documented during the preclinical stage of Alzheimer's disease. The current study examined the association between diffusion tensor imaging (DTI) measures of white matter microstructure and episodic memory performance in 52 adults with Down syndrome. METHODS: Seventy (N = 70) participants (M = 40.13, SD = 7.77 years) received baseline scans as part of the Neurodegeneration in Aging Down Syndrome (NiAD) study at two imaging facilities (36 at the University of Wisconsin-Madison [UW-Madison] and 34 at the University of Pittsburgh Medical Center [UPMC]). All participants had genetically confirmed trisomy 21. Fifty-two (N = 52) participants remained after QC. The DTI measures, fractional anisotropy (FA) and mean diffusivity (MD), were calculated for each participant. A combined measure of episodic memory was generated by summing the z-scores of (1) Free and Cued Recall test and (2) Rivermead Behavioural Memory Test for Children Picture Recognition. The DTI data were projected onto a population-derived FA skeleton and tract-based spatial statistics analysis was conducted using the FSL tool PALM to calculate Pearson's r values between FA and MD with episodic memory. RESULTS: A positive correlation of episodic memory with FA and a negative correlation of episodic memory and MD in the major association white matter tracts were observed. Results were significant (p < 0.05) after correction for chronological age, imaging site, and premorbid cognitive ability. CONCLUSION: These findings suggest that white matter degeneration may be implicated in early episodic memory declines prior to the onset of dementia in adults with Down syndrome. Further, our findings suggest a coupling of episodic memory and white matter microstructure independent of chronological age

Reducing Superfluous Opioid Prescribing Practices After Brain Surgery: It Is Time to Talk About Drugs

BACKGROUND: Opioids are prescribed routinely after cranial surgery despite a paucity of evidence regarding the optimal quantity needed. Overprescribing may adversely contribute to opioid abuse, chronic use, and diversion. OBJECTIVE: To evaluate the effectiveness of a system-wide campaign to reduce opioid prescribing excess while maintaining adequate analgesia. METHODS: A retrospective cohort study of patients undergoing a craniotomy for tumor resection with home disposition before and after a 2-mo educational intervention was completed. The educational initiative was composed of directed didactic seminars targeting senior staff, residents, and advanced practice providers. Opioid prescribing patterns were then assessed for patients discharged before and after the intervention period. RESULTS: A total of 203 patients were discharged home following a craniotomy for tumor resection during the study period: 98 who underwent surgery prior to the educational interventions compared to 105 patients treated post-intervention. Following a 2-mo educational period, the quantity of opioids prescribed decreased by 52% (median morphine milligram equivalent per day [interquartile range], 32.1 [16.1, 64.3] vs 15.4 [0, 32.9], P \u3c .001). Refill requests also decreased by 56% (17% vs 8%, P = .027) despite both groups having similar baseline characteristics. There was no increase in pain scores at outpatient follow-up (1.23 vs 0.85, P = .105). CONCLUSION: A dramatic reduction in opioids prescribed was achieved without affecting refill requests, patient satisfaction, or perceived analgesia. The use of targeted didactic education to safely improve opioid prescribing following intracranial surgery uniquely highlights the ability of simple, evidence-based interventions to impact clinical decision making, lessen potential patient harm, and address national public health concerns

A Matched Cohort Analysis of Drain Usage in Elective Anterior Cervical Discectomy and Fusion: A Michigan Spine Surgery Improvement Collaborative (MSSIC) Study

STUDY DESIGN: This is a retrospective, cohort analysis of multi-institutional database. OBJECTIVE: This study was designed to analyze the impact of drain use following elective anterior cervical discectomy and fusion (ACDF) surgeries. SUMMARY OF BACKGROUND DATA: After ACDF, a drain is often placed to prevent postoperative hematoma. However, there has been no high quality evidence to support its use with ACDF despite the theoretical benefits and risks of drain placement. METHODS: The Michigan Spine Surgery Improvement Collaborative database was queried to identify all patients undergoing elective ACDF between February 2014 and October 2019. Cases were divided into two cohorts based on drain use. Propensity-score matching was utilized to adjust for inherent differences between the two cohorts. Measured outcomes included surgical site hematoma, length of stay, surgical site infection, dysphagia, home discharge, readmission within 30 days, and unplanned reoperation. RESULTS: We identified 7943 patients during the study period. Propensity-score matching yielded 3206 pairs. On univariate analysis of matched cohorts, there were no differences in rate of postoperative hematoma requiring either return to OR or readmission. We noted patients with drains had a higher rate of dysphagia (4.6% vs. 6.3%; P = 0.003) and had longer hospital stay (P \u3c 0.001). On multivariate analysis, drain use was associated with significantly increased length of stay (relative risk 1.23, 95% confidence interval [CI] 1.13-1.34; P \u3c 0.001). There were no significant differences in other outcomes measured. CONCLUSION: Our analysis demonstrated that drain use is associated with significant longer hospital stay.Level of Evidence: 3

White matter microstructure associations to amyloid burden in adults with Down syndrome.

INTRODUCTION: Individuals with Down syndrome (DS) are at an increased risk of developing Alzheimer's Disease (AD). One of the early underlying mechanisms in AD pathology is the accumulation of amyloid protein plaques, which are deposited in extracellular gray matter and signify the first stage in the cascade of neurodegenerative events. AD-related neurodegeneration is also evidenced as microstructural changes in white matter. In this work, we explored the correlation of white matter microstructure with amyloid load to assess amyloid-related neurodegeneration in a cohort of adults with DS. METHODS: In this study of 96 adults with DS, the relation of white matter microstructure using diffusion tensor imaging (DTI) and amyloid plaque burden using [11C]PiB PET were examined. The amyloid load (AβL) derived from [11C]PiB was used as a global measure of amyloid burden. AβL and DTI measures were compared using tract-based spatial statistics (TBSS) and corrected for imaging site and chronological age. RESULTS: TBSS of the DTI maps showed widespread age-by-amyloid interaction with both fractional anisotropy (FA) and mean diffusivity (MD). Further, diffuse negative association of FA and positive association of MD with amyloid were observed. DISCUSSION: These findings are consistent with the white matter microstructural changes associated with AD disease progression in late onset AD in non-DS populations

The Effect of Per Pupil Expenditure on ACT Scores

The average state expenditure on education has increased by almost one hundred percent from 1995 to 2008. Regression results using state level data from the U.S. Census Bureau, National Center of Education Statistics, and the ACT show that a state’s total expenditure does not have a significant effect on average composite ACT scores when controlling for race, median household income, the percentage of population living in poverty, and the pupil per teacher ratio for each state. Although the results do not show a correlation between education expenditure and ACT scores, the results show that the poverty level does have a significant negative effect on test scores. This suggests that more research be done on the effects of socioeconomic status on academic performance