A mass spectrometer for isotope analysis

Thesis (M.A.)--Boston University, 1949. This item was digitized by the Internet Archive

Physiological and Behavioral Differences in Sensory Processing: A Comparison of Children with Autism Spectrum Disorder and Sensory Modulation Disorder

A high incidence of sensory processing difficulties exists in children with Autism Spectrum Disorder (ASD) and children with Sensory Modulation Disorder (SMD). This is the first study to directly compare and contrast these clinical disorders. Sympathetic nervous system markers of arousal and reactivity were utilized in a laboratory paradigm that administered a series of sensory challenges across five sensory domains. The Short Sensory Profile, a standardized parent-report measure, provided a measure of sensory-related behaviors. Physiological arousal and sensory reactivity were lower in children with ASD whereas reactivity after each sensory stimulus was higher in SMD, particularly to the first stimulus in each sensory domain. Both clinical groups had significantly more sensory-related behaviors than typically developing children, with contrasting profiles. The ASD group had more taste/smell sensitivity and sensory under-responsivity while the SMD group had more atypical sensory seeking behavior. This study provides preliminary evidence distinguishing sympathetic nervous system functions and sensory-related behaviors in Autism Spectrum Disorder and Sensory Modulation Disorder. Differentiating the physiology and sensory symptoms in clinical groups is essential to the provision of appropriate interventions

Parasympathetic functions in children with sensory processing disorder.

The overall goal of this study was to determine if parasympathetic nervous system (PsNS) activity is a significant biomarker of sensory processing difficulties in children. Several studies have demonstrated that PsNS activity is an important regulator of reactivity in children, and thus, it is of interest to study whether PsNS activity is related to sensory reactivity in children who have a type of condition associated with sensory processing disorders termed sensory modulation dysfunction (SMD). If so, this will have important implications for understanding the mechanisms underlying sensory processing problems of children and for developing intervention strategies to address them. The primary aims of this project were: (1) to evaluate PsNS activity in children with SMD compared to typically developing (TYP) children, and (2) to determine if PsNS activity is a significant predictor of sensory behaviors and adaptive functions among children with SMD. We examine PsNS activity during the Sensory Challenge Protocol; which includes baseline, the administration of eight sequential stimuli in five sensory domains, recovery, and also evaluate response to a prolonged auditory stimulus. As a secondary aim we examined whether subgroups of children with specific physiological and behavioral sensory reactivity profiles can be identified. Results indicate that as a total group the children with severe SMD demonstrated a trend for low baseline PsNS activity, compared to TYP children, suggesting this may be a biomarker for SMD. In addition, children with SMD as a total group demonstrated significantly poorer adaptive behavior in the communication and daily living subdomains and in the overall Adaptive Behavior Composite of the Vineland than TYP children. Using latent class analysis, the subjects were grouped by severity and the severe SMD group had significantly lower PsNS activity at baseline, tones and prolonged auditory. These results provide preliminary evidence that children who demonstrate severe SMD may have physiological activity that is different from children without SMD, and that these physiological and behavioral manifestations of SMD may affect a child\u27s ability to engage in everyday social, communication, and daily living skills

Goal attainment scaling as a measure of meaningful outcomes for children with sensory integration disorders.

Goal attainment scaling (GAS) is a methodology that shows promise for application to intervention effectiveness research and program evaluation in occupational therapy (Dreiling & Bundy, 2003; King et al., 1999; Lannin, 2003; Mitchell & Cusick, 1998). This article identifies the recent and current applications of GAS to occupational therapy for children with sensory integration dysfunction, as well as the process, usefulness, and problems of application of the GAS methodology to this population. The advantages and disadvantages of using GAS in single-site and multisite research with this population is explored, as well as the potential solutions and future programs that will strengthen the use of GAS as a measure of treatment effectiveness, both in current clinical practice and in much-needed larger, multisite research studies

Controlled release of ethanehydroxy diphosphonate from polyurethane reservoirs to inhibit calcification of bovine pericardium used in bioprosthetic heart valves

Calcification (CALC) of bioprosthetic heart valves (BHVs) fabricated from either glutaraldehyde-pretreated bovine pericardial tissue or porcine aortic valves is the most frequent cause of clinical failure of these devices. Previous studies have demonstrated that calcification is inhibited by diphosphonate compounds released into the vicinity of bioprosthetic tissue implanted subcutaneously in rats. Controlled release of the anticalcification agent ethanehydroxy diphosphonate (EHDP), as a 1:1 mixture of Na2 EHDP and CaEHDP from cylindrical polyurethane (PU) reservoirs (o.d. = 0.36 cm i.d. = 0.33 cm, length = 4 cm) fabricated by solvent casting was assessed in vitro and in vivo. The diffusivity (D), determined independently using standard diffusion cells, for ionic EHDP diffusion across the PU membrane was 1.2 x 10 cm2/s. Volume influx of buffer into the reservoirs in vitro was observed experimentally to reach a maximum at 7.8 days (288 +/- 44 [mu]l) with a biexponential decline to 147 +/- 6 [mu]l at 70 days. The cumulative EHDP released in vitro after 70 days was 4.2 +/- 0.6% (4.8 +/- 0.7 mg) compared to 15.7 +/- 3.2% (18.1 +/- 3.7 mg) in vivo (subcutaneously in 3 week-old, male, CD rats) over 21 days. The release rate of EHDP from the reservoirs was not a zero-order process. Reservoir administration of EHDP effectively inhibited pericardial BHV-CALC in 21-day subdermal explants (Ca2+ = 4.5 +/- 1.4 [mu]g Ca2+/mg tissue; control, Ca2+ = 120 +/- 13 [mu]g Ca2+/mg tissue) without diphosphonate-related untoward effects at a dose of approx. 3 mg/kg per day.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28671/1/0000488.pd

Fidelity in sensory integration intervention research.

OBJECTIVE: We sought to assess validity of sensory integration outcomes research in relation to fidelity (faithfulness of intervention to underlying therapeutic principles). METHOD: We identified core sensory integration intervention elements through expert review and nominal group process. Elements were classified into structural (e.g., equipment used, therapist training) and therapeutic process categories. We analyzed 34 sensory integration intervention studies for consistency of intervention descriptions with these elements. RESULTS: Most studies described structural elements related to therapeutic equipment and interveners\u27 profession. Of the 10 process elements, only 1 (presentation of sensory opportunities) was addressed in all studies. Most studies described fewer than half of the process elements. Intervention descriptions in 35% of the studies were inconsistent with one process element, therapist-child collaboration. CONCLUSION: Validity of sensory integration outcomes studies is threatened by weak fidelity in regard to therapeutic process. Inferences regarding sensory integration effectiveness cannot be drawn with confidence until fidelity is adequately addressed in outcomes research

Controlled release of 1-hydroxyethylidene diphosphonate: in vitro assessment and effects on bioprosthetic calcification in sheep tricuspid valve replacements

Calcification (CALC) is the most frequent cause of the clinical failure of bioprosthetic valves (BHV's). Controlled-release (paravalvar) administration of the anticalcification agent ethanehydroxydiphosphonate (EHDP), as either Na2EHDP or in combination (1:1) with the less soluble CaEHDP, from a silicone rubber matrix (20% w/w EHDP) was studied both in vitro and in vivo for the prevention of BHV CALC. Seventeen sheep (6-7 months old, male, Suffolk) underwent tricuspid valve replacement using Hancock I, 25 mm porcine aortic bioprostheses. BHV explant evaluation after 16-20 weeks revealed that two of the 7 control BHV were calcified (139 +/- 20.8 [mu]gCa2+/mg of tissue), while none of the 9 BHV retrieved from animals receiving controlled release EHDP demonstrated CALC (4.41 +/- 1.09 [mu]g Ca2+/mg of tissue). No adverse effects of EHDP on bone or calcium metabolism were noted. The cumulative percent of EHDP released per electron microprobe analysis was 40.4% +/- 9.68 (Na, CaEHDP) to 79.0% +/- 4.82 (Na2EHDP) in vivo compared to 35.7% +/- 7.72 and 78.6 +/- 11.1 in vitro, respectively. Assessment of the Young's modulus (Y) using thermomechanical analysis (TMA) revealed a 1.5-fold (Silastic Q7-4840) to 9.5-fold (Silastic 382) increase in Y following drug loading. The Y for explanted, Silastic Q7-4840 polymer matrices ranged from 2.84 x 104 to 5.57 x 105 dyne/cm2. In vitro osmotic related matrix swelling of the Na2EHDP loaded, unsealed matrices (20% w/w) after 75 days was minimized to a 35.8% increase in weight due to coincorporation of CaEHDP with Na2EHDP in a 1:1 ratio and was further reduced (22.2% increase in weight) by sealing 76% of the releasing surface, compared to Na2EHDP matrices which demonstrated a 414% and 141% increase in weight, respectively.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27902/1/0000322.pd

Association Between Smoking and Molecular Subtypes of Colorectal Cancer

Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking. Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutation, KRAS mutation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. A multinomial logistic regression analysis was used to assess the association between smoking and risk of CRC subtypes by molecular characteristics, adjusting for age, sex, and study. All statistical tests were 2-sided and adjusted for Bonferroni correction. Results: Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (P-trend <.001). The associations differed statistically significantly between all molecular subtypes, which was the most statistically significant for CIMP and BRAF. Compared with never-smokers, smokers in the fourth quartile of pack-years had a 90% higher risk of CIMP-positive CRC (odds ratio = 1.90, 95% confidence interval = 1.60 to 2.26) but only 35% higher risk for CIMP-negative CRC (odds ratio = 1.35, 95% confidence interval = 1.22 to 1.49; P-difference = 2.1 x 10(-6)). The association was also stronger in tumors that were CIMP positive, MSI high, or KRAS wild type when combined (P-difference <.001). Conclusion: Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. Heavier smokers had particularly higher risk of CRC subtypes that were CIMP positive and MSI high in combination, suggesting that smoking may be involved in the development of colorectal tumors via the serrated pathway

Polymorphisms of genes coding for ghrelin and its receptor in relation to colorectal cancer risk: a two-step gene-wide case-control study

<p>Abstract</p> <p>Background</p> <p>Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also indicates a role of ghrelin in cancer development.</p> <p>Methods</p> <p>We conducted a case-control study to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with colorectal cancer risk. Pairwise tagging was used to select the 11 polymorphisms included in the study. The selected polymorphisms were genotyped in 680 cases and 593 controls from the Czech Republic.</p> <p>Results</p> <p>We found two SNPs associated with lower risk of colorectal cancer, namely SNPs rs27647 and rs35683. We replicated the two hits, in additional 569 cases and 726 controls from Germany.</p> <p>Conclusion</p> <p>A joint analysis of the two populations indicated that the T allele of rs27647 SNP exerted a protective borderline effect (P_trend= 0.004).</p

Transforming medical professionalism to fit changing health needs

<p>Abstract</p> <p>Background</p> <p>The professional organization of medical work no longer reflects the changing health needs caused by the growing number of complex and chronically ill patients. Key stakeholders enforce coordination and remove power from the medical professions in order allow for these changes. However, it may also be necessary to initiate basic changes to way in which the medical professionals work in order to adapt to the changing health needs.</p> <p>Discussion</p> <p>Medical leaders, supported by health policy makers, can consciously activate the self-regulatory capacity of medical professionalism in order to transform the medical profession and the related professional processes of care so that it can adapt to the changing health needs. In doing so, they would open up additional routes to the improvement of the health services system and to health improvement. This involves three consecutive steps: (1) defining and categorizing the health needs of the population; (2) reorganizing the specialty domains around the needs of population groups; (3) reorganizing the specialty domains by eliminating work that could be done by less educated personnel or by the patients themselves. We suggest seven strategies that are required in order to achieve this transformation.</p> <p>Summary</p> <p>Changing medical professionalism to fit the changing health needs will not be easy. It will need strong leadership. But, if the medical world does not embark on this endeavour, good doctoring will become merely a bureaucratic and/or marketing exercise that obscures the ultimate goal of medicine which is to optimize the health of both individuals and the entire population.</p