Brief Report: A Preliminary Study of the Relationship between Repetitive Behaviors and Concurrent Executive Function Demands in Children with Autism Spectrum Disorder

Journal of Autism and Developmental Disorders - The present study evaluated the hypothesis that the strength of the relationship between executive function (EF) and repetitive behaviors and...     

Characterization of noise sources for two generations of computed radiography systems using powder and crystalline photostimulable phosphors

The performances of two generations of computed radiography (CR) were tested and compared in terms of resolution and noise characteristics. The main aim was to characterize and quantify the noise sources in the images. The systems tested were (1) Agfa CR 25.0, a flying spot reader with powder phosphor image plates (MD 40.0); and (2) the Agfa DX-S, a line-scanning CR reader with needle crystal phosphor image plates (HD 5.0). For both systems, the standard metrics of presampled modulation transfer function (MTF), normalized noise power spectra (NNPS) and detective quantum efficiency (DQE) were measured using standard radiation quality RQA5 as defined by the International Electrotechnical Commission. The various noise sources contributing to the NNPS were separated by using knowledge of their relationship with air kerma, MTF, absorption efficiency and antialiasing filters. The DX-S MTF was superior compared with the CR 25.0. The maximum difference in MTF between the DX-S scan and CR 25.0 subscan directions was 0.13 at 1.3 mm(-1). For a nominal detector air kerma of 4 microGy, the peak DQE of the DX-S was 43 (+/-3)%, which was over double that of the CR 25.0 of 18 (+/-2)%. The additive electronic noise was negligible on the CR 25.0 but calculated to be constant 3.4 x 10(-7) (+/-0.4 x 10(-7)) mm2 at 3.9 microGy on the DX-S. The DX-S has improved image quality compared with a traditional flying spot reader. The separation of the noise sources indicates that the improvements in DQE of the DX-S are due not only to the higher quantum, efficiency and MTF, but also the lower structure, secondary quantum, and excess noise.     

TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions

TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Thus, TDP-43 defines a novel class of neurodegenerative diseases called TDP-43 proteinopathies. We performed ubiquitin and TDP-43 immunohistochemistry on 193 cases of familial and sporadic FTLD with or without MND. On selected cases, immunoelectron microscopy and biochemistry were performed. Clinically defined frontotemporal dementias (FTDs) included four groups: 1) familial FTD with mutations in progranulin (n = 36), valosin-containing protein (n = 5), charged multivesicular body protein 2B (n = 4), and linked to chromosome 9p (n = 7); 2) familial cases of FTD with unknown gene association (n = 29); 3) sporadic FTD (n = 72); and 4) familial and sporadic FTD with MND (n = 40). Our studies confirm that the spectrum of TDP-43 proteinopathies includes most cases of sporadic and familial FTLD-U with and without MND and expand this disease spectrum to include reported families with FTD linked to chromosome 9p but not FTD with charged multivesicular body protein 2B mutations. Thus, despite significant clinical, genetic, and neuropathological heterogeneity of FTLD-U, TDP-43 is a common pathological substrate underlying a large subset of these disorders, thereby implicating TDP-43 in novel and unifying mechanisms of FTLD pathogenesis.     

Assessing exclusionary power of a paternity test involving a pair of alleged grandparents

BACKGROUND: The power of a genetic test battery to exclude a pair of individuals as grandparents is an important consideration for parentage testing laboratories. However, a reliable method to calculate such a statistic with short-tandem repeat (STR) genetic markers has not been presented. STUDY DESIGN AND METHODS: Two formulae describing the random grandparents not excluded (RGPNE) statistic at a single genetic locus were derived: RGPNE = a(4 - 6a + 4a(2)- a(3)) when the paternal obligate allele (POA) is defined and RGPNE = 2[(a + b)(2 - a - b)][1 - (a + b)(2 - a - b)] + [(a + b)(2 - a - b)] when the POA is ambiguous. A minimum number of genetic markers required to yield cumulative RGPNE values of not greater than 0.01 was calculated with weighted average allele frequencies of the CODIS STR loci. RGPNE data for actual grandparentage cases are also presented to empirically examine the exclusionary power of routine casework. RESULTS: A comparison of RGPNE and random man not excluded (RMNE) values demonstrates the increased difficulty involved in excluding two individuals as grandparents compared to excluding a single alleged parent. A minimum of 12 STR markers is necessary to achieve RGPNE values of not greater than 0.01 when the mother is tested; more than 25 markers are required without the mother. Cumulative RGPNE values for each of 22 nonexclusionary grandparentage cases were not more than 0.01 but were significantly weaker when calculated without data from the mother. CONCLUSION: Calculation of the RGPNE provides a simple means to help minimize the potential of false inclusions in grandparentage analyses. This study also underscores the importance of testing the mother when examining the parents of an unavailable alleged father (AF).     

Task-Specific Perturbation Training Improves the Recovery Stepping Responses by Women With Knee Osteoarthritis Following Laboratory-Induced Trips

Trip-specific training improves the kinematics of trip-specific compensatory stepping response (CSR) in the laboratory and reduces prospectively measured trip-related fall-rate of middle age and older women. We examined whether one session of trip-specific perturbation training could improve recovery step kinematics in women with knee osteoarthritis (OA), a condition known to increase fall risk. Seventeen women with self-reported symptomatic knee OA (age 61.1 ± 7.7 years, body mass index [BMI] 29.7 ± 5.9 kg/m²) and 22 control women (age 59.5 ± 6.8 years, BMI 28.4 ± 6.2 kg/m²) completed a brief training protocol consisting of 20 trials of treadmill-delivered trip-specific perturbations. We assessed pre- and post-training recovery step length and trunk kinematics at the instant of recovery step completion. Repeated-measures analysis of variance was used to determine the significance of between-group differences following the training protocol, and to evaluate the significance of within-group pre-to-post changes in the variables of interest. The group by training interaction effects for step length (p = 0.466), trunk flexion angle (p = 0.751), and trunk angular velocity (p = 0.413) were not significant and the pre-to-post changes in step length were not significant (p = 0.286). However, pre-to-post trunk flexion angle improved by 26% and 34% in the OA and control groups, respectively (p < 0.001) and trunk flexion angular velocity decreased by 193% in the OA group and by 32% in the control group, respectively (p < 0.001), often reflecting a transition to the direction of extension. The results suggest that trip-specific training can improve CSR kinematics in women with knee OA. It is important to determine, the effectiveness of trip-specific training in decreasing trip-specific fall-rate by women with knee OA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:663–669, 2020     

Meta-Analysis of Associations Between Hypothalamic-Pituitary-Adrenal Axis Genes and Risk of Posttraumatic Stress Disorder

The hypothalamic-pituitary-adrenal (HPA) axis has been of interest in attempts to identify genetic vulnerability for posttraumatic stress disorder (PTSD). Although numerous HPA-axis genes have been implicated in candidate gene studies, the findings are mixed and interpretation is limited by study design and methodological inconsistencies. To address these inconsistencies in the PTSD candidate gene literature, we conducted meta-analyses of HPA-related genes from both a traditional single nucleotide polymorphism (SNP)–level analysis and a gene-level analysis, using novel methods aggregating markers in the same gene. Database searches (PubMed and PsycINFO) identified 24 unique articles examining six HPA-axis genes in PTSD; analyses were conducted on four genes (ADCYAP1R1, CRHR1, FKBP5, NR3C1) that met study eligibility criteria (original research, human subjects, main effect association study of selected genes, PTSD as an outcome, trauma-exposed control group) and had sufficient data and number of studies for use in meta-analysis, within 20 unique articles. Findings from SNP-level analyses indicated that two variants (rs9296158 in FKBP5 and rs258747 in NR3C1) were nominally associated with PTSD, ps = .001 and .001, respectively, following multiple testing correction. At the gene level, significant relations between PTSD and both NR3C1 and FKBP5 were detected and robust to sensitivity analyses. Although study limitations exist (e.g., varied outcomes, inability to test moderators), taken together, these results provide support for FKBP5 and NR3C1 in risk for PTSD. Overall, this work highlights the utility of meta-analyses in resolving discrepancies in the literature and the value of adopting gene-level approaches to investigate the etiology of PTSD.     

Effectiveness of newspaper advertising for patient recruitment into a clinical trial

Aims

To measure the impact of newspaper advertising across Scotland on patient interest, and subsequent recruitment into the Standard Care vs. Celecoxib Outcome Trial (SCOT), a clinical trial investigating the cardiovascular safety of non-steroidal anti-inflammatory drugs in patients with osteoarthritis or rheumatoid arthritis.

Methods

Newspaper advertisements about the SCOT trial were placed sequentially in regional and national Scottish newspapers. The number of phone calls as a result of exposure to the advertisements and ongoing study recruitment rates were recorded before, during and after the advertising campaign. To enroll in SCOT individuals had to be registered with a participating GP practice.

Results

The total cost for the advertising campaign was £46 250 and 320 phone calls were received as a result of individuals responding to the newspaper advertisements. One hundred and seventy-two individuals were identified as possibly suitable to be included in the study. However only 36 were registered at participating GP practices, 17 completed a screening visit and 15 finally were randomized into the study. The average cost per respondent individual was £144 and the average cost per randomized patient was £3083. Analysis of recruitment rate trends showed that there was no impact of the newspaper advertising campaign on increasing recruitment into SCOT.

Conclusions

Advertisements placed in local and national newspapers were not an effective recruitment strategy for the SCOT trial. The advertisements attracted relatively small numbers of respondents, many of whom did not meet study inclusion criteria or were not registered at a participating GP practice.     

Timing of corticosteroid treatment. Effect of lung lymph dynamics in air injury in awake sheep

In paired experiments, we studied the effects of high-dose methylprednisolone on the acute pulmonary injury caused by 4 h of venous air embolization in 19 chronically instrumented, unanesthetized sheep with lung lymph fistulas. We compared the effect of methylprednisolone (30 mg/kg intravenous bolus) given before embolization, early (1 H) in the course of embolization, late (3 h) in the course of embolization, or after embolization (at the beginning of the recovery period). We measured pulmonary hemodynamics and lymph dynamics. In six sheep we also fixed lung tissue for semiquantitative histology, and in some we measured leukocyte concentrations in blood and in pulmonary lymph. Methylprednisolone did not significantly affect pulmonary hemodynamics but it largely prevented lung injury when it was given before embolization. It also lessened the degree of lung injury when it was given during embolization, although this effect became less marked as treatment was delayed. Methylprednisolone had no effect on lung injury when given after embolization was completed (4 h). We found fewer leukocytes attached to air emboli and fewer endothelial cell gaps in the lungs of sheep given methylprednisolone as prophylaxis. Leukocyte counts were lower in lung lymph and higher in the circulating blood of methylprednisolone-treated sheep. We conclude that methylprednisolone has a preventive effect on air embolism lung injury, such that its effect is greater when given earlier during the development of injury.     

Antiphospholipid antibodies and HLA associations in primary Sj?gren's syndrome.

Blood samples from 65 patients with primary Sjögren''s syndrome were evaluated for the presence of antiphospholipid antibodies. Increased levels of antiphospholipid antibodies were found in 13 of 65 (20%) of patients. These antiphospholipid antibodies were predominantly of the IgA isotype, in contrast with the IgG isotype antiphospholipid antibodies found in patients with systemic lupus erythematosus (SLE). The presence of IgA antiphospholipid antibodies in the patients with primary Sjögren''s syndrome was not significantly associated with arterial or vascular thrombosis, nor peripheral or central nervous system vasculitis. There was no association with laboratory determined features such as lupus anticoagulant or false positive results of the Venereal Disease Research Laboratory (VDRL) test. Oligonucleotide specific DNA amplification and hybridisation with allele specific probes was used to examine the HLA-D antigens occurring in this group of patients with primary Sjögren''s syndrome. Of 13 patients with antiphospholipid antibodies, seven had the genotype HLA-DR2/DR3. However, compared with the whole group of 65 patients with Sjögren''s syndrome, no increased occurrence of haplotype DR2 or DR3 was noted. These results suggest that gene interaction between DR2 and DR3 may play a part in the production of antiphospholipid antibodies in patients with Sjögren''s syndrome. In contrast with patients with SLE, the IgA antiphospholipid antibodies in patients with Sjögren''s syndrome are not risk factors for thrombosis or vasculitis. The presence of IgA antiphospholipid antibodies in patients with Sjögren''s syndrome probably reflects its production at mucosal sites of inflammation and the absence of vasculopathy may be due to the inability of IgA antibodies to activate complement.