Design and implementation of an instrumented ulnar head prosthesis to measure loads in vitro

The development of a novel instrumented implant for ulnar head replacement is presented in this study. This implant was instrumented with strain gauges to quantify bending moments about the anatomic axes of the distal ulna, and subsequently the distal radioulnar joint (DRUJ) reaction force magnitude. The implant was surgically inserted in seven cadaveric upper extremities, which were subsequently mounted in a custom joint simulator. Simulated active unresisted pronation and supination motion trials were conducted using computer-controlled pneumatic actuators to simulate forearm musculature. Passive (unloaded) trials were also conducted. The reaction force across the DRUJ ranged from 2 to 10 N in magnitude during this unresisted motion. Increased bending moment magnitudes were measured when the forearm was positioned in supination compared to pronation. The magnitude of joint bending moments showed a consistent pattern with forearm position, regardless of simulated active or passive rotation, or supination and pronation motion trials. This result illustrates that the primary influence on joint load is likely the position and contact with the radial articulation. This study of DRUJ loading should be useful for biomechanical modeling, implant design considerations and improved knowledge of articular mechanics.     

A comparison of bone strain measurements at anatomically relevant sites using surface gauges versus strain gauged bone staples

Instrumented bone staples were first introduced as an alternative to surface-mounted strain gauges for use in human in vivo bone strain measurements because their fixation to bone is secure and requires not only minimally invasive surgery. Bench-top bone bending models have shown that the output from strain gauged bone staples compares favorably to that of traditional mounted gauges. However their within- and across-subject performance at sites typically instrumented in vivo has never been examined. This study used seven human cadaver lower extremities with an age range of 23-81 years old and a dynamic gait simulator to examine and compare axial strains in the mid tibial diaphysis and on the dorsal surface of the second metatarsal as measured simultaneously with strain gauged bone staples and with traditional surface-mounted gauges. Rosette configurations were used at the tibial site for deriving principal compression and tension, and shear strains. Axial outputs from the two gauge types demonstrated strong linear relationships for the tibia (r(2)=0.78-0.94) and the second metatarsal (r(2)=0.96-0.99), but coefficients (slopes) for the relationship were variable (range 7-20), across subjects and across sites. The apparent low reliability of strain gauged staples may be explained by the fact that both strain gauged staples and surface strain gauges are inexact to some degree, do not measure strains from exactly the same areas and strain gauged staples reflect surface strains as well as deformations within the cortex. There were no relationships for the principal tibia compression, tension or shear strain measurements derived from the two rosette gauge types, reflecting the very different anatomical areas measured by each of the constructs in this study. Strain gauged bone staples may be most useful in comparing relative axial intra-subject differences between activities, but inter-subject variability may require larger sample sizes to detect differences between populations.     

Development and testing of a modular strain measurement clip

A novel, multi-use, low-stiffness and low-cost transducer for measuring in vitro strains has been developed and tested. Currently available strain measurement methods are either too expensive, too complicated or too inflexible for multi-use strain measurement. The stainless-steel modular strain measurement clip introduced here was instrumented with four 350 Omega axial strain gauges in a full Wheatstone bridge configuration to take advantage of commonly available strain gauge amplifier equipment. Adjustable extension arms were designed to allow greater application versatility. The clip was calibrated and produced a linear response (R(2)>0.99) over a minimum of 1.04 mm at high amplifier gain. With reduced amplifier settings, testing showed a linear response over a range of 30.5 mm (R(2)>0.99). Clip stiffness was 0.6N/mm of extension arm tip displacement for minimal instrumentation artifact. A validation test was conducted through a comparison of strain clips, surface-mounted strain gauges and theoretical strain in an aluminium rod subjected to axial tensile loading. The two measurement techniques were used to determine the modulus of elasticity of the aluminium rod. Results were within 6% of the known modulus of elasticity for aluminium. A comparative biomechanical test was also performed on an equine third metacarpal specimen. The traditional bonded strain gauging method produced similar results as the new strain clip, but failed to measure ultimate strains since all strain gauges failed prior to specimen failure. Further investigations into the multiple uses of the clip are underway and recommendations for future versions of the clip are given.     

Joint contact stresses calculated for acetabular dysplasia patients using discrete element analysis are significantly influenced by the applied gait pattern

Gait modifications in acetabular dysplasia patients may influence cartilage contact stress patterns within the hip joint, with serious implications for clinical outcomes and the risk of developing osteoarthritis. The objective of this study was to understand how the gait pattern used to load computational models of dysplastic hips influences computed joint mechanics. Three-dimensional pre- and post-operative hip models of thirty patients previously treated for hip dysplasia with periacetabular osteotomy (PAO) were developed for performing discrete element analysis (DEA). Using DEA, contact stress patterns were calculated for each pre- and post-operative hip model when loaded with an instrumented total hip, a dysplastic, a matched control, and a normal gait pattern. DEA models loaded with the dysplastic and matched control gait patterns had significantly higher (p = 0.012 and p < 0.001) average pre-operative maximum contact stress than models loaded with the normal gait. Models loaded with the dysplastic and matched control gait patterns had nearly significantly higher (p = 0.051) and significantly higher (p = 0.008) average pre-operative contact stress, respectively, than models loaded with the instrumented hip gait. Following PAO, the average maximum contact stress for DEA models loaded with the dysplastic and matched control patterns decreased, which was significantly different (p < 0.001) from observed increases in maximum contact stress calculated when utilizing the instrumented hip and normal gait patterns. The correlation between change in DEA-computed maximum contact stress and the change in radiographic measurements of lateral center-edge angle were greatest (R² = 0.330) when utilizing the dysplastic gait pattern. These results indicate that utilizing a dysplastic gait pattern to load DEA models may be a crucial element to capturing contact stress patterns most representative of this patient population.     

Radiomics analysis of EPID measurements for patient positioning error detection in thyroid associated ophthalmopathy radiotherapy

PurposeElectronic portal imaging detector (EPID)-based patient positioning verification is an important component of safe radiotherapy treatment delivery. In computer simulation studies, learning-based approaches have proven to be superior to conventional gamma analysis in the detection of positioning errors. To approximate a clinical scenario, the detectability of positioning errors via EPID measurements was assessed using radiomics analysis for patients with thyroid-associated ophthalmopathy.MethodsTreatment plans of 40 patients with thyroid-associated ophthalmopathy were delivered to a solid anthropomorphic head phantom. To simulate positioning errors, combinations of 0-, 2-, and 4-mm translation errors in the left–right (LR), superior-inferior (SI), and anterior-posterior (AP) directions were introduced to the phantom. The positioning errors-induced dose differences between measured portal dose images were used to predict the magnitude and direction of positioning errors. The detectability of positioning errors was assessed via radiomics analysis of the dose differences. Three classification models—support vector machine (SVM), k-nearest neighbors (KNN), and XGBoost—were used for the detection of positioning errors (positioning errors larger or smaller than 3 mm in an arbitrary direction) and direction classification (positioning errors larger or smaller than 3 mm in a specific direction). The receiver operating characteristic curve and the area under the ROC curve (AUC) were used to evaluate the performance of classification models.ResultsFor the detection of positioning errors, the AUC values of SVM, KNN, and XGBoost models were all above 0.90. For LR, SI, and AP direction classification, the highest AUC values were 0.76, 0.91, and 0.80, respectively.ConclusionsCombined radiomics and machine learning approaches are capable of detecting the magnitude and direction of positioning errors from EPID measurements. This study is a further step toward machine learning-based positioning error detection during treatment delivery with EPID measurements.     

Nucleosome Positioning,Nucleosome Spacing and the Nucleosome Code

Abstract

Nucleosome positioning has been the subject of intense study for many years. The properties of micrococcal nuclease, the enzyme central to these studies, are discussed. The various methods used to determine nucleosome positions in vitro and in vivo are reviewed critically. These include the traditional low resolution method of indirect end-labelling, high resolution methods such as primer extension, monomer extension and nucleosome sequencing, and the high throughput methods for genome-wide analysis (microarray hybridisation and parallel sequencing). It is established that low resolution mapping yields an averaged chromatin structure, whereas high resolution mapping reveals the weighted superposition of all the chromatin states in a cell population. Mapping studies suggest that yeast DNA contains information specifying the positions of nucleosomes and that this code is made use of by the cell. It is proposed that the positioning code facilitates nucleosome spacing by encoding information for multiple alternative overlapping nucleosomal arrays. Such a code might facilitate the shunting of nucleosomes from one array to another by ATP-dependent chromatin remodelling machines.     

Incision Planning in Thyroid Compartment Surgery: Getting it Perfect

ObjectiveThis study evaluated changes in thyroid compartment incision site locations with patient positioning to define a reliable method for placing the scar in the optimal vertical location.MethodsThe optimal incision location was marked with the patient sitting upright before surgery. The distance from the sternal notch to this mark was measured with the patient in the upright, supine, and final surgical positions.ResultsComplete data were available for 104 procedures. The mean distances from the sternal notch to the incision site were 4.8, 21.5, and 31.9 mm in the sitting, supine, and surgical positions, respectively. Each of these distances were significantly different from one another (P < .0001) and were independent of patient age, sex, body mass index (BMI), or height.ConclusionsCutaneous cervical landmarks migrate significantly during patient positioning. Marking the thyroid compartment incision site while the patient is in an upright position results in a more predictable final scar location. (Endocr Pract. 2015;21:107-114)     

Painting a Perspective on the Landscape of Nucleosome Positioning

Abstract

DNA sequence influences the position of nucleosomes and chromatin architecture. The extent to which underlying DNA sequence affects nucleosome positioning is currently a topic of considerable discussion and active experimentation. To contribute to the discussion, I will outline a few of the methods, data and arguments that I find compelling and believe will ultimately resolve the question of what positions nucleosomes. Basically, I will give a portrait of my current perspective on what influences the landscape of nucleosome positioning and chromatin architecture.     

Cervical spine posteroanterior stiffness differs with neck position

PurposeSpinal stiffness is commonly considered when treating patients with neck pain, but there are few studies reporting the objective measurement of cervical spine stiffness or the possible kinesiological factors that may affect its quantification. The aim of this study was to determine if the position of the neck affects cervical spine stiffness.MethodsAn instrumented stiffness assessment device measured posteroanterior cervical spine stiffness at C4 of 25 prone-lying asymptomatic subjects in three neck positions in randomised order: maximal flexion, maximal extension, and neutral. The device applied five standardised mechanical oscillatory pressures while measuring the applied force and concurrent displacement, defining stiffness as the slope of the linear portion of the force–displacement curve. Repeated measures analysis of variance with Bonferroni-adjusted post hoc comparisons determined whether stiffness differed between neck positions.ResultsThere was a significant difference in cervical spine stiffness between different neck positions (F_(1.6,38.0) = 16.6, P < 0.001). Stiffness was least in extension with a mean of 3.09 N/mm (95% CI 2.59, 3.58) followed by neutral (3.94, 95% CI 3.49, 4.39), and then flexion (4.32, 95% CI 3.96, 4.69).ConclusionWhen assessing cervical spine stiffness, neck position should be standardised to ensure maximal reliability and utility of stiffness judgments.     

Structure-based Analysis of DNA Sequence Patterns Guiding Nucleosome Positioning in vitro

Abstract

Recent studies of genome-wide nucleosomal organization suggest that the DNA sequence is one of the major determinants of nucleosome positioning. Although the search for underlying patterns encoded in nucleosomal DNA has been going on for about 30 years, our knowledge of these patterns still remains limited. Based on our evaluations of DNA deformation energy, we developed new scoring functions to predict nucleosome positioning. There are three principal differences between our approach and earlier studies: (i) we assume that the length of nucleosomal DNA varies from 146 to 147 bp; (ii) we consider the anisotropic flexibility of pyrimidine-purine (YR) dimeric steps in the context of their neighbors (e.g., YYRR versus RYRY); (iii) we postulate that alternating AT-rich and GC-rich motifs reflect sequence-dependent interactions between histone arginines and DNA in the minor groove. Using these functions, we analyzed 20 nucleosome positions mapped in vitro at single nucleotide resolution (including clones 601, 603, 605, the pGUB plasmid, chicken β-globin and three 5S rDNA genes). We predicted 15 of the 20 positions with 1-bp precision, and two positions with 2-bp precision. The predicted position of the ‘601’ nucleosome (i.e., the optimum of the computed score) deviates from the experimentally determined unique position by no more than 1 bp—an accuracy exceeding that of earlier predictions.

Our analysis reveals a clear heterogeneity of the nucleosomal sequences which can be divided into two groups based on the positioning ‘rules’ they follow. The sequences of one group are enriched by highly deformable YR/YYRR motifs at the minor-groove bending sites SHL ±3.5 and ±5.5, which is similar to the α-satellite sequence used in most crystallized nucleosomes. Apparently, the positioning of these nucleosomes is determined by the interactions between histones H2A/H2B and the terminal parts of nucleosomal DNA. In the other group (that includes the ‘601’ clone) the same YR/YYRR motifs occur predominantly at the sites SHL ±1.5. The interaction between the H3/H4 tetramer and the central part of the nucleosomal DNA is likely to be responsible for the positioning of nucleosomes of this group, and the DNA trajectory in these nucleosomes may differ in detail from the published structures.

Thus, from the stereochemical perspective, the in vitro nucleosomes studied here follow either an X-ray-like pattern (with strong deformations in the terminal parts of nucleosomal DNA), or an alternative pattern (with the deformations occurring predominantly in the central part of the nucleosomal DNA). The results presented here may be useful for genome-wide classification of nucleosomes, linking together structural and thermodynamic characteristics of nucleosomes with the underlying DNA sequence patterns guiding their positions.     

TCT、HPV检测在宫颈锥切术后复发中的预测价值

目的:评估薄层液基细胞学检查(thinprep cytologic test,TCT)和人乳头瘤病毒(human papillomavirus,HPV)检测在宫颈锥切术后复发中的预测价值。方法:随访531例病理诊断为子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ-Ⅲ级接受宫颈锥切术的患者,分别于术后3、6个月及术后每6-12月随访1次,以TCT及HPV检测作为随访的检测指标,若二者有一项异常,行阴道镜下活组织检查,病理证实存在子颈上皮内瘤变Ⅰ-Ⅲ级者视为复发。采用敏感度、特异度、阳性预测值、阴性预测值表示TCT、HPV检测性能。结果:531例患者中10%(54例)的患者出现不同级别的病变复发。TCT在术后预测病变复发的灵敏度77%,特异度72%;HPV在术后预测病变复发的灵敏度95%,特异度60%,TCT联合HPV预测病变复发的灵敏度100%,特异性80%。术后HPV负荷量100 RLU/PC者较HPV负荷量100 RLU/PC者而言术后病变复发的风险增高,差别有统计学意义(P0.01),术后HPV负荷量100 RLU/PC是锥切术后病变复发的高危因素。结论:使用细胞学联合HPV检测是有效的预测宫颈锥切术后病变复发的方法,术后高HPV负荷量与病变复发相关,并可对术后复发高风险人群进行分流,临床需严密随访。     

The DNA Sequence-dependence of Nucleosome Positioning in vivo and in vitro

Abstract

The contribution of histone-DNA interactions to nucleosome positioning in vivo is currently a matter of debate. We argue here that certain nucleosome positions, often in promoter regions, in yeast may be, at least in part, specified by the DNA sequence. In contrast other positions may be poorly specified. Positioning thus has both statistical and DNA-determined components. We further argue that the relative affinity of the octamer for different DNA sequences can vary and therefore the interaction of histones with the DNA is a ‘tunable’ property.     

Effect of patient positioning on carbon-ion therapy planned dose distribution to pancreatic tumors and organs at risk

PurposePancreatic tumor treatment dose distribution variations associated with supine and prone patient positioning were evaluated.MethodsA total of 33 patients with pancreatic tumors who underwent CT in the supine and prone positions were analyzed retrospectively. Gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OARs) (duodenum and stomach) were contoured. The prescribed dose of 55.2 Gy (RBE) was planned from four beam angles (0°, 90°, 180°, and 270°). Patient collimator and compensating boli were designed for each field. Dose distributions were calculated for each field in the supine and prone positions. To improve dose distribution, patient positioning was selected from supine or prone for each beam field.ResultsCompared with conventional beam angle and patient positioning, D2cc of 1st-2nd portion of duodenum (D1-D2), 3rd-4th portion of duodenum (D3-D4), and stomach could be reduced to a maximum of 6.4 Gy (RBE), 3.5 Gy (RBE), and 4.5 Gy (RBE) by selection of patient positioning. V10 of D1-D2, D3-D4, and stomach could be reduced to a maximum of 7.2 cc, 11.3 cc, and 11.5 cc, respectively. D95 of GTV and PTV were improved to a maximum of 6.9% and 3.7% of the prescribed dose, respectively.ConclusionsOptimization of patient positioning for each beam angle in treatment planning has the potential to reduce OARs dose maintaining tumor dose in pancreatic treatment.     

Accelerometry-based variables in professional soccer players: comparisons between periods of the season and playing positions

The aim of this study was to provide reference data of variation in external training loads for weekly periods within the annual season. Specifically, we aimed to compare the weekly acute load, monotony, and training strain of accelerometry-based measures across a professional soccer season (pre-season, first and second halves of the season) according to players’ positions. Nineteen professional players were monitored daily for 45 weeks using an 18-Hz global positioning system to obtain measures of high metabolic load distance (HMLD), impacts, and high intensity accelerations and decelerations. Workload indices of acute load, training monotony, and training strain were calculated weekly for each of the measures. The HMLD had greater training strain values in the pre-season than in the first (p ≤ 0.001; d = 0.793) and second halves of the season (p ≤ 0.001; d = 0.858). Comparisons between playing positions showed that midfielders had the highest weekly acute load of HMLD (6901 arbitrary units [AU]), while central defenders had the lowest (4986 AU). The pre-season period was associated with the highest acute and strain load of HMLD and number of impacts, with a progressive decrease seen during the season. In conclusion, coaches should consider paying greater attention to variations in HMLD and impacts between periods of the season and between players to individualize training accordingly.     

Strain and micromotion in intact and resurfaced composite femurs: Experimental and numerical investigations

Understanding the load transfer within a resurfaced femur is necessary to determine the influence of mechanical factors on potential failure mechanisms such as early femoral neck fractures and stress shielding. In this study, an attempt has been made to measure the stem-bone micromotion and implant cup-bone relative displacements (along medial-lateral and anterior-posterior direction), in addition to surface strains at different locations and orientations on the proximal femur and to compare these measurements with those predicted by equivalent FE models. The loading and the support conditions of the experiment were closely replicated in the FE models. A new experimental set-up has been developed, with specially designed fixtures and load application mechanism, which can effectively impose bending and deflection of the tested femurs, almost in any direction. High correlation coefficient (0.92–0.95), low standard error of the estimate (170–379 με) and low percentage error in regression slope (12.8–17.5%), suggested good agreement between the numerical and measured strains. The effect of strain shielding was observed in two (out of eight) strain gauges located on the posterior side. A pronounced strain increase occurred in strain gauges located on the anterior head and neck regions after implantation. Experimentally measured stem-bone micromotion and implant cup-bone relative displacements (0–13.7 μm) were small and similar in trends predicted by the FE models (0–25 μm). Despite quantitative deviations in the measured and numerical results, it appears that the FE model can be used as a valid predictor of the actual strain and stem-bone micromotion.     

Novel Pedicle Screw and Plate System Provides Superior Stability in Unilateral Fixation for Minimally Invasive Transforaminal Lumbar Interbody Fusion: An In Vitro Biomechanical Study

Purpose

This study aims to compare the biomechanical properties of the novel pedicle screw and plate system with the traditional rod system in asymmetrical posterior stabilization for minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). We compared the immediate stabilizing effects of fusion segment and the strain distribution on the vertebral body.

Methods

Seven fresh calf lumbar spines (L3-L6) were tested. Flexion/extension, lateral bending, and axial rotation were induced by pure moments of ± 5.0 Nm and the range of motion (ROM) was recorded. Strain gauges were instrumented at L4 and L5 vertebral body to record the strain distribution under flexion and lateral bending (LB). After intact kinematic analysis, a right sided TLIF was performed at L4-L5. Then each specimen was tested for the following constructs: unilateral pedicle screw and rod (UR); unilateral pedicle screw and plate (UP); UR and transfacet pedicle screw (TFS); UP and TFS; UP and UR.

Results

All instrumented constructs significantly reduced ROM in all motion compared with the intact specimen, except the UR construct in axial rotation. Unilateral fixation (UR or UP) reduced ROM less compared with the bilateral fixation (UP/UR+TFS, UP+UR). The plate system resulted in more reduction in ROM compared with the rod system, especially in axial rotation. UP construct provided more stability in axial rotation compared with UR construct. The strain distribution on the left and right side of L4 vertebral body was significantly different from UR and UR+TFS construct under flexion motion. The strain distribution on L4 vertebral body was significantly influenced by different fixation constructs.

Conclusions

The novel plate could provide sufficient segmental stability in axial rotation. The UR construct exhibits weak stability and asymmetrical strain distribution in fusion segment, while the UP construct is a good alternative choice for unilateral posterior fixation of MI-TLIF.     

Effects of seating load magnitude and load orientation on seating mechanics in 5°40′ mixed-alloy modular taper junctions

BackgroundMechanically-assisted crevice corrosion of modular tapers continues to be a concern in total joint replacements. Surgical factors that may affect taper seating mechanics include seating load magnitude and load orientation. Seating mechanics is defined as the seating load versus displacement behavior. In this study, mixed-alloy (CoCrMo/Ti-6Al-4V) modular head-neck 5°40′ taper junctions were seated over a range of axially-oriented loads and off-axis orientations, capturing load-displacement during seating. The goals of the study were to assess the effects of seating load magnitude and load orientation on seating mechanics and correlate those findings with the taper pull-off load.MethodsA testing fixture measured head-neck seating displacement as the load was quasistatically applied. Motion was captured using two non-contact differential variable reluctance transducers which were mounted to the neck targeting the head. Seating experiments ranged from 1000 N to 8000 N. Load orientation ranged from 0° to 20° at 4000 N.ResultsSeating load-displacement behavior at different seating loads showed a consistent characteristic behavior. Testing demonstrated increased seating displacement with seating load. Pull-off loads increased with seating load and were approximately 44% of the seating load across the range of seating loads investigated. Seating load orientation up to 20° had no significant effect on seating displacement and taper pull-off load.ConclusionIncreased seating load magnitude increased seating displacement, work of seating and pull-off loads in mixed-alloy 5°40′ head-neck tapers. Altering load orientation up to 20° off-axis had no significant effect. Direct measurements of seating mechanics provides insights into the locking of taper junctions.     

Normal pelvic strain pattern in vitro

Four cadaver pelves were dissected of soft tissue and each of the eight hemipelves instrumented with ten rosette strain gauges. Static loading was conducted to simulate single leg stance, and applied through the intact hip joint. The medial portion of the pelvis was under tension directed vertically and the lateral ilium was in compression. This strain pattern is consistent with bending applied to the ilium from the action of the abductor and joint reaction forces.