Background: Digital workstations with high-resolution monitors are replacing standard radiographs for image evaluation and interpretation. Radiographic angles in the foot have been evaluated for ...interobserver and intraobserver reliability with plain films, but use of digital workstations has not been validated. Because the 1-2 intermetatarsal (IM) and hallux valgus (HV) angles help determine the most appropriate bunion procedure, the reliability of these measurements is important. Methods: The HV and 1-2 IM angles were evaluated on preoperative radiographs of 25 patients who subsequently underwent bunion procedures. A standardized technique using a film marker and goniometer on plain film was compared with use of a mouse and computerized angle measurement software at a digital workstation. Three foot and ankle surgeons conducted these measurements at various intervals. Completion of three readings of each radiograph in each format by each observer totaled 1,800 measurements. Results: Computerized measurement gave better overall reliability. For the HV angle, inter-observer agreement (measurements within 2 degrees) improved from 66% with plain films to 81% with the digital workstation (p < 0.001). Intraobserver agreement increased from 72% to 80%. The 1-2 IM angle was similarly reliable with both methods for inter- and intraobserver agreement. Conclusions: This study validates the use of computer-assisted angle measurement on digital radiographs for assessment of HV and 1-2 IM angles. Computerized measurement may result in more reliable readings because it eliminates the error inherent with use of a goniometer and facilitates adjustment of radiographic lines on the computer to ensure correct alignment.
Total ankle arthroplasty (TAA) typically involves an anterior approach to the ankle that has been shown to have a risk for wound healing problems. We explored the possibility of using oxygen ...tensiometry as a predictor of incision healing problems in patients undergoing TAA.
The study included 25 patients who underwent TAA with the Scandinavian Total Ankle Replacement (STAR) system at our institution during a three-year period. Transcutaneous oxygen measurements of both ankles were obtained postoperatively to determine whether the results of transcutaneous oxygen tensiometry correlated with wound healing problems. Patients with wound healing problems were compared with those who had an uneventful incision healing.
Seven patients (28%) had wound healing problems after TAA, and five patients (20%) had early wound erythema. Wound healing problems included delayed healing in five patients and dehiscence in two patients. Three patients had transcutaneous oxygen tension of less than 40 mmHg (a threshold for impaired skin oxygenation) on the operative side, of whom one had healing difficulty whereas two did not. When the threshold was extended to 50 mmHg, seven patients (28%) had low readings, two having wound healing problems. There was no significant difference with respect to oxygen measurements between patients with and without wound healing problems (p=0.3).
Oxygen tensiometry is not thought to be useful for predicting patients at risk for postoperative wound healing complications after TAA, suggesting that, if adequate pulses are present before surgery, the trauma of using excessive superficial traction on the skin during surgery is more responsible for wound healing problems than the underlying blood supply.
Abstract
Genome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene ...identification and a strict focus on bone mineral density (BMD). Here, we use Diversity Outbred (DO) mice to directly address these limitations by performing a systems genetics analysis of 55 complex skeletal phenotypes. We apply a network approach to cortical bone RNA-seq data to discover 66 genes likely to be causal for human BMD GWAS associations, including the genes
SERTAD4
and
GLT8D2
. We also perform GWAS in the DO for a wide-range of bone traits and identify
Qsox1
as a gene influencing cortical bone accrual and bone strength. In this work, we advance our understanding of the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics.
Parametrized motion planning algorithms have high degrees of universality and flexibility, as they are designed to work under a variety of external conditions, which are viewed as parameters and form ...part of the input of the underlying motion planning problem. In this paper, we analyze the parameterized motion planning problem for the motion of many distinct points in the plane, moving without collision and avoiding multiple distinct obstacles with a priori unknown positions. This complements our prior work arXiv:2009.06023, where parameterized motion planning algorithms were introduced, and the obstacle-avoiding collision-free motion planning problem in three-dimensional space was fully investigated. The planar case requires different algebraic and topological tools than its spatial analog.
In this paper we introduce and study a new concept of parametrised topological complexity, a topological invariant motivated by the motion planning problem of robotics. In the parametrised setting, a ...motion planning algorithm has high degree of universality and flexibility, it can function under a variety of external conditions (such as positions of the obstacles etc). We explicitly compute the parameterised topological complexity of obstacle-avoiding collision-free motion of many particles (robots) in 3-dimensional space. Our results show that the parameterised topological complexity can be significantly higher than the standard (nonparametrised) invariant.
Abstract
The persistence and roles of memory T cells with effector capability have been questioned. We analyzed human memory CD4+ T cells from peripheral blood defined by their expression of ...chemokine receptors CCR5 and CCR2, the principal subsets being CCR5−CCR2−, CCR5+CCR2−, and CCR5+CCR2+. CCR2+ cells co-expressed the most chemokine receptor types (up to six) and migrated to the greatest number of chemokines, followed by CCR5+CCR2− cells. Numbers of T cell receptor gene excision circles were CCR5−CCR2− > CCR5+CCR2− > CCR5+CCR2+. The CCR2+ cells were those most readily activated through TCR but showed reduced proliferative potential, were enriched in cells responding to a remote immunogen, secreted high levels of effector cytokines, and were resistant to apoptosis. By contrast, the CCR5+CCR2− population was enriched in recently activated/cycling cells and Treg, and was more susceptible to apoptosis. The data suggest that patterns of CCR5 and CCR2 expression separate effector- vs. memory-cell enriched CD4+ subsets, and that CCR2 marks highly differentiated, long-lived memory cells with effector capabilities. The data also suggest co-ordination among a memory cell’s position on a unidirectional pathway of differentiation, ability to be recruited into tissue, and threshold for activation/effector function, with the most chemokine-responsive cells being best equipped as first responders in a recall response.
Summary
Background
Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma ...exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome‐wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response.
Objective
We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings.
Methods
A meta‐analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10−6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations.
Results
A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10−6). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10−3) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10−3). Additionally, the reported association of the L3MBTL4‐ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified.
Conclusions and clinical relevance
This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.
Neutrophils use immunoglobulins to clear antigen, but their role in immunoglobulin production is unknown. Here we identified neutrophils around the marginal zone (MZ) of the spleen, a B cell area ...specialized in T cell-independent immunoglobulin responses to circulating antigen. Neutrophils colonized peri-MZ areas after postnatal mucosal colonization by microbes and enhanced their B cell-helper function after receiving reprogramming signals, including interleukin 10 (IL-10), from splenic sinusoidal endothelial cells. Splenic neutrophils induced immunoglobulin class switching, somatic hypermutation and antibody production by activating MZ B cells through a mechanism that involved the cytokines BAFF, APRIL and IL-21. Neutropenic patients had fewer and hypomutated MZ B cells and a lower abundance of preimmune immunoglobulins to T cell-independent antigens, which indicates that neutrophils generate an innate layer of antimicrobial immunoglobulin defense by interacting with MZ B cells.
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