Classification and treatment of proximal humerus fractures: inter-observer reliability and agreement across imaging modalities and experience

<p>Abstract</p> <p>Summary</p> <p>Proximal humerus fractures (PHF) are common injuries, but previous studies have documented poor inter-observer reliability in fracture classification. This disparity has been attributed to multiple variables including poor imaging studies and inadequate surgeon experience. The purpose of this study is to evaluate whether inter-observer agreement can be improved with the application of multiple imaging modalities including X-ray, CT, and 3D CT reconstructions, stratified by physician experience, for both classification and treatment of PHFs.</p> <p>Methods</p> <p>Inter-observer agreement was measured for classification and treatment of PHFs. A total of sixteen fractures were imaged by plain X-ray (scapular AP and lateral), CT scan, and 3D CT reconstruction, yielding 48 randomized image sets. The observers consisted of 16 orthopaedic surgeons (4 upper extremity specialists, 4 general orthopedists, 4 senior residents, 4 junior residents), who were asked to classify each image set using the Neer system, and recommend treatment from four pre-selected choices. The results were evaluated by kappa reliability coefficients for inter-observer agreement between all imaging modalities and sub-divided by: fracture type and observer experience.</p> <p>Results</p> <p>All kappa values ranged from "slight" to "moderate" (k = .03 to .57) agreement. For overall classification and treatment, no advanced imaging modality had significantly higher scores than X-ray. However, when sub-divided by experience, 3D reconstruction and CT scan both had significantly higher agreement on classification than X-ray, among upper extremity specialists. Agreement on treatment among upper extremity specialists was best with CT scan. No other experience sub-division had significantly different kappa scores. When sub-divided by fracture type, CT scan and 3D reconstruction had higher scores than X-ray for classification only in 4-part fractures. Agreement on treatment of 4 part fractures was best with CT scan. No other fracture type sub-division had significantly different kappa scores.</p> <p>Conclusions</p> <p>Although 3D reconstruction showed a slight improvement in the inter-observer agreement for fracture classification among specialized upper extremity surgeons compared to all imaging modalities, fracture types, and surgeon experience; overall all imaging modalities continue to yield low inter-observer agreement for both classification and treatment regardless of physician experience.</p

Vertebral Body Stapling versus Bracing for Patients with High-Risk Moderate Idiopathic Scoliosis.

Purpose. We report a comparison study of vertebral body stapling (VBS) versus a matched bracing cohort for immature patients with moderate (25 to 44°) idiopathic scoliosis (IS). Methods. 42 of 49 consecutive patients (86%) with IS were treated with VBS and followed for a minimum of 2 years. They were compared to 121 braced patients meeting identical inclusion criteria. 52 patients (66 curves) were matched according to age at start of treatment (10.6 years versus 11.1 years, resp. [P = 0.07]) and gender. Results. For thoracic curves 25-34°, VBS had a success rate (defined as curve progressio

Spitzer Space Telescope Measurements of Dust Reverberation Lags in the Seyfert 1 Galaxy NGC 6418

We present results from a fifteen-month campaign of high-cadence (~ 3 days) mid-infrared Spitzer and optical (B and V ) monitoring of the Seyfert 1 galaxy NGC 6418, with the objective of determining the characteristic size of the dusty torus in this active galactic nucleus (AGN). We find that the 3.6 $\mu$m and 4.5 $\mu$m flux variations lag behind those of the optical continuum by $37.2^{+2.4}_{-2.2}$ days and $47.1^{+3.1}_{-3.1}$ days, respectively. We report a cross-correlation time lag between the 4.5 $\mu$m and 3.6 $\mu$m flux of $13.9^{+0.5}_{-0.1}$ days. The lags indicate that the dust emitting at 3.6 $\mu$m and 4.5 $\mu$m is located at a distance of approximately 1 light-month (~ 0.03 pc) from the source of the AGN UV-optical continuum. The reverberation radii are consistent with the inferred lower limit to the sublimation radius for pure graphite grains at 1800 K, but smaller by a factor of ~ 2 than the corresponding lower limit for silicate grains; this is similar to what has been found for near-infrared (K-band) lags in other AGN. The 3.6 and 4.5 $\mu$m reverberation radii fall above the K-band $\tau \propto L^{0.5}$ size-luminosity relationship by factors $\lesssim 2.7$ and $\lesssim 3.4$, respectively, while the 4.5 $\mu$m reverberation radius is only 27% larger than the 3.6 $\mu$m radius. This is broadly consistent with clumpy torus models, in which individual optically thick clouds emit strongly over a broad wavelength range.Comment: 13 pages, 9 figure

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge

SNPs associated with testosterone levels influence human facial morphology

Many factors influence human facial morphology, including genetics, age, nutrition, biomechanical forces, and endocrine factors. Moreover, facial features clearly differ between males and females, and these differences are driven primarily by the influence of sex hormones during growth and development. Specific genetic variants are known to influence circulating sex hormone levels in humans, which we hypothesize, in turn, affect facial features. In this study, we investigated the effects of testosterone-related genetic variants on facial morphology. We tested 32 genetic variants across 22 candidate genes related to levels of testosterone, sex hormone-binding globulin (SHGB) and dehydroepiandrosterone sulfate (DHEAS) in three cohorts of healthy individuals for which 3D facial surface images were available (Pittsburgh 3DFN, Penn State and ALSPAC cohorts; total n = 7418). Facial shape was described using a recently developed extension of the dense-surface correspondence approach, in which the 3D facial surface was partitioned into a set of 63 hierarchically organized modules. Each variant was tested against each of the facial surface modules in a multivariate genetic association-testing framework and meta-analyzed. Additionally, the association between these candidate SNPs and five facial ratios was investigated in the Pittsburgh 3DFN cohort. Two significant associations involving intronic variants of SHBG were found: both rs12150660 (p = 1.07E-07) and rs1799941 (p = 6.15E-06) showed an effect on mandible shape. Rs8023580 (an intronic variant of NR2F2-AS1) showed an association with the total and upper facial width to height ratios (p = 9.61E-04 and p = 7.35E-04, respectively). These results indicate that testosterone-related genetic variants affect normal-range facial morphology, and in particular, facial features known to exhibit strong sexual dimorphism in humans

Six NSCL/P loci show associations with normal-range craniofacial variation

Objectives: Orofacial clefting is one of the most prevalent craniofacial malformations. Previous research has demonstrated that unaffected relatives of patients with non-syndromic cleft lip with/without cleft palate (NSCL/P) show distinctive facial features, which can be an expression of underlying NSCL/P susceptibility genes. These results support the hypothesis that genes involved in the occurrence of a cleft also play a role in normal craniofacial development. In this study, we investigated the influence of genetic variants associated with NSCL/P on normal-range variation in facial shape. Methods: A literature review of genome wide association studies (GWAS) investigating the genetic etiology of NSCL/P was performed, resulting in a list of 75 single nucleotide polymorphisms (SNPs) located in 38 genetic loci. Genotype data were available for 65 of these selected SNPs in three datasets with a combined sample size of 7,418 participants of European ancestry, whose 3D facial images were also available. The effect of each SNP was tested using a multivariate canonical correlation analysis (CCA) against 63 hierarchically-constructed facial segments in each of the three datasets and meta-analyzed. This allowed for the investigation of associations between SNPs known to be involved in NSCL/P and normal-range facial shape variations in a global-to-local perspective, without preselecting specific facial shape features or characteristics. Results: Six NSCL/P SNPs showed significant associations with variation in normal-range facial morphology. rs6740960 showed significant effects in the chin area (p = 3.71 × 10−28). This SNP lies in a non-coding area. Another SNP, rs227731 near the NOG gene, showed a significant effect in the philtrum area (p = 1.96 × 10−16). Three SNPs showed significant effects on the shape of the nose. rs742071 (p = 8.71 × 10−14), rs34246903 (p = 6.87 × 10−12), and rs10512248 (p = 8.4 × 10−9). Respectively, these SNPs are annotated to PAX7, MSX1, and PTCH1. Finally, rs7590268, an intron variant of THADA, showed an effect in the shape of the supraorbital ridge (p = 3.84 × 10−7). Conclusions: This study provides additional evidence NSCL/P-associated genetic variants influence normal-range craniofacial morphology, with significant effects observed for the chin, the nose, the supraorbital ridges and the philtrum area