Mothers of children with congenital heart defects: the effects of ethnicity and education on perceptions, attitudes and feelings; (Implications for social work practice)

Thesis (M.S.)--Boston University, 196

Association of Chronic Pain With Participation in Motor Skill Activities in Children With Cerebral Palsy

Many children with cerebral palsy (CP) experience the secondary condition of pain, which is problematic because children with CP face barriers to participation in motor skill activities.1,2 Motor performance in activities of daily living among children with CP is markedly lower than that among their age-matched peers.3 Because of the potential effect of pain on children with CP, we sought to examine the association between pain and activities requiring motor skill performance (ie, difficulty dressing or bathing and participation in sport) among a nationally representative sample of US children with CP

Expert agreement confirms that negative changes in hand and foot radiographs are a surrogate for repair in patients with rheumatoid arthritis

The objective of the present study was to test the hypothesis that experts recognize repair of erosions and, if so, to determine which, if any, morphologic features permitted them to recognize the repair. We also tested whether scoring by a standard method detected repair. Seven experienced readers of radiographs in rheumatoid arthritis were presented with 64 sets of single joints-of-interest at two time points, randomized and blinded for the correct sequence. The readers assessed which joint was better, and recorded whether any of six specific features were seen. Two independent readers, experienced in scoring by the van der Heijde-modified Sharp method who were not on the expert panel, then scored the complete films that included the joint-of-interest. The panel agreed very well on which of two joints was better, and, even though they did not know the true sequence, the panel accurately assigned a sequence slightly better than chance alone (58%) but worse than their agreement on which image was 'better or worse' (78%). The readers therefore indirectly assigned repair by choosing the second film as the best. Putative repair features were seen in cases of both repair and progression, and were not discriminatory. Similar results were obtained when the experts were presented with the entire hand or foot containing the joint-of-interest. In the third repair exercise, two independent readers who scored whole hands and feet using a standard method found a mean negative score in 22/60 joints-of-interest. All 22 joints were also scored as repair by the panel. Repair was detected reliably by a majority of the panel on viewing paired images based on a better/worse decision and assigning sequence in a set of images that were blinded for sequence by an independent project manager. In this test set of images, repair was manifested by a reduction in the size of erosion in many cases. Size was one feature that aided the experts to detect repair but cannot be the only one; the experts had to find other features to determine whether a smaller erosion was the first in a sequence of radiographs in a patient with progressive damage or was the second film in a patient exhibiting repair. The change in size of erosion was also picked up by independent readers applying the van der Heijde-modified Sharp scoring method and was reflected in their scores

Additional conference abstracts

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43490/1/11111_2005_Article_BF02208413.pd

Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation

While the catalog of mammalian transcripts and their expression levels in different cell types and disease states is rapidly expanding, our understanding of transcript function lags behind. We present a robust technology enabling systematic investigation of the cellular consequences of repressing or inducing individual transcripts. We identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%–99% knockdown with minimal off-target effects, and activators (CRISPRa) to endogenous genes via endonuclease-deficient Cas9. Together they enable modulation of gene expression over a ∼1,000-fold range. Using these rules, we construct genome-scale CRISPRi and CRISPRa libraries, each of which we validate with two pooled screens. Growth-based screens identify essential genes, tumor suppressors, and regulators of differentiation. Screens for sensitivity to a cholera-diphtheria toxin provide broad insights into the mechanisms of pathogen entry, retrotranslocation and toxicity. Our results establish CRISPRi and CRISPRa as powerful tools that provide rich and complementary information for mapping complex pathways

Direct measurement of antiferromagnetic domain fluctuations

Measurements of magnetic noise emanating from ferromagnets due to domain motion were first carried out nearly 100 years ago and have underpinned much science and technology. Antiferromagnets, which carry no net external magnetic dipole moment, yet have a periodic arrangement of the electron spins extending over macroscopic distances, should also display magnetic noise, but this must be sampled at spatial wavelengths of order several interatomic spacings, rather than the macroscopic scales characteristic of ferromagnets. Here we present the first direct measurement of the fluctuations in the nanometre-scale spin- (charge-) density wave superstructure associated with antiferromagnetism in elemental Chromium. The technique used is X-ray Photon Correlation Spectroscopy, where coherent x-ray diffraction produces a speckle pattern that serves as a "fingerprint" of a particular magnetic domain configuration. The temporal evolution of the patterns corresponds to domain walls advancing and retreating over micron distances. While the domain wall motion is thermally activated at temperatures above 100K, it is not so at lower temperatures, and indeed has a rate which saturates at a finite value - consistent with quantum fluctuations - on cooling below 40K. Our work is important because it provides an important new measurement tool for antiferromagnetic domain engineering as well as revealing a fundamental new fact about spin dynamics in the simplest antiferromagnet.Comment: 19 pages, 4 figure

Complications of intertrochanteric rotational osteotomy

Intertrochanteric anterior rotational osteotomy is a recently developed surgical procedure to treat osteonecrosis of the femoral head. We reviewed the radiographic findings in four cases to acquaint radiologists with the usual appearance of the procedure and to assess surgical complications. In all cases, immediate postoperative radiographs showed rotation of the necrotic portion of the femoral head anteriorly so that it was no longer weight-bearing. Clinical and radiologic follow-up ranged from 12 to 30 months. In this time, three patients developed complications, including nonunion of the osteotomy, further osteonecrosis with collapse of the femoral head, and worsening pain in the absence of progressive radiologic change.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46773/1/256_2004_Article_BF00357901.pd

Transdiagnostic risk of mental disorders in offspring of affected parents:a meta-analysis of family high-risk and registry studies

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I2 statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.</p

Effect of Different Stellar Galactic Environments on Planetary Discs I: The Solar Neighbourhood and the Birth Cloud of the Sun

We have computed trajectories, distances and times of closest approaches to the Sun by stars in the Solar neighbourhood with known position, radial velocity and proper motions. For this purpose we have used a full potential model of the Galaxy that reproduces the local z-force, the Oort constants, the local escape velocity, and the rotation curve of the Galaxy. From our sample we constructed initial conditions, within observational uncertainties, with a Monte Carlo scheme for the twelve most suspicious candidates because of their small tangential motion. We find that the star Gliese 710 will have the closest approach to the Sun, with a distance of approximately 0.34 pc at 1.36 Myr in the future. We show that the effect of a flyby with the characteristics of Gliese 710 on a 100 AU test particle disk representing the Solar system is negligible. However, since there is a lack of 6D data for a large percentage of stars in the Solar neighbourhood, closer approaches may exist. We calculate parameters of passing stars that would cause noticeable effects on the Solar disk. Regarding the birth cloud of the Sun, we performed experiments to reproduce roughly the observed orbital parameters such as eccentricities and inclinations of the Kuiper Belt. It is known now that in Galactic environments, such as stellar formation regions, the stellar densities of new born stars, are high enough to produce close encounters within 200 AU. Moreover, in these Galactic environments, the velocity dispersion is relatively low, typically approximately 1-3 km s-1.We find that with a velocity dispersion of approximately 1 km s-1 and an approach distance of about 150 AU, typical of these regions, we obtain approximately the eccentricities and inclinations seen in the current Solar system. Simple analytical calculations of stellar encounters effects on the Oort cloud are presented.Comment: Accepted 2011 August 2 by MNRAS (Monthly Notices of the Royal Astronomical Society Main Journal). Received 2011 June 27; in original form 2010 June 10 The paper contains 10 figures and 5 table

Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years

Ankylosing spondylitis (AS) is a chronic rheumatic disease associated with spinal inflammation that subsequently leads to progression of structural damage and loss of function. The fully human anti-tumor necrosis factor (anti-TNF) antibody adalimumab reduces the signs and symptoms and improves overall quality of life in patients with active AS; these benefits have been maintained through 2 years of treatment. Our objective was to compare the progression of structural damage in the spine in patients with AS treated with adalimumab for up to 2 years versus patients who had not received TNF antagonist therapy. Radiographs from patients with AS who received adalimumab 40 mg every other week subcutaneously were pooled from the Adalimumab Trial Evaluating Long-Term Efficacy and Safety for Ankylosing Spondylitis (ATLAS) study and a Canadian AS study (M03-606). Radiographic progression from baseline to 2 years in the spine of adalimumab-treated patients from these two studies (adalimumab cohort, n = 307) was compared with an historic anti-TNF-naïve cohort (Outcome in AS International Study [OASIS], n = 169) using the modified Stoke AS Spine Score (mSASSS) method. mSASSS results were not significantly different between the adalimumab cohort and the OASIS cohort, based on baseline and 2-year radiographs. Mean changes in mSASSS from baseline to 2 years were 0.9 for the OASIS cohort and 0.8 for the adalimumab cohort (P = 0.771), indicating similar radiographic progression in both groups. When results for patients in the OASIS cohort who met the baseline disease activity criteria for the ATLAS and Canadian studies (OASIS-Eligible cohort) were analyzed, there was no significant difference in mean change in mSASSS from baseline to 2 years between OASIS-Eligible patients and adalimumab-treated patients; the mean changes in mSASSS were 0.9 for the OASIS-Eligible cohort and 0.8 for the adalimumab cohort (P = 0.744). Two years of treatment with adalimumab did not slow radiographic progression in patients with AS, as assessed by the mSASSS scoring system, when compared with radiographic data from patients naïve to TNF antagonist therap