Multiple Levels of Heuristic Reasoning Processes in Scientific Model Construction.

Science historians have recognized the importance of heuristic reasoning strategies for constructing theories, but their extent and degree of organization are still poorly understood. This paper first consolidates a set of important heuristic strategies for constructing scientific models from three books, including studies in the history of genetics and electromagnetism, and an expert think-aloud study in the field of mechanics. The books focus on qualitative reasoning strategies (processes) involved in creative model construction, scientific breakthroughs, and conceptual change. Twenty four processes are examined, most of which are field-general, but all are heuristic in not being guaranteed to work. An organizing framework is then proposed as a four-level hierarchy of nested reasoning processes and subprocesses at different size and time scales, including: Level (L4) Several longer-time-scale Major Modeling Modes, such as Model Evolution and Model Competition; the former mode utilizes: (L3) Modeling Cycle Phases of Model Generation, Evaluation, and Modification under Constraints; which can utilize: (L2) Thirteen Tactical Heuristic Processes, e.g., Analogy, Infer new model feature (e.g., by running the model), etc.; many of which selectively utilize: (L1) Grounded Imagistic Processes, namely Mental Simulations and Structural Transformations. Incomplete serial ordering in the framework gives it an intermediate degree of organization that is neither anarchistic nor fully algorithmic. Its organizational structure is hypothesized to promote a difficult balance between divergent and convergent processes as it alternates between them in modeling cycles with increasingly constrained modifications. Videotaped think-aloud protocols that include depictive gestures and other imagery indicators indicate that the processes in L1 above can be imagistic. From neurological evidence that imagery uses many of the same brain regions as actual perception and action, it is argued that these expert reasoning processes are grounded in the sense of utilizing the perceptual and motor systems, and interconnections to and possible benefits for reasoning processes at higher levels are examined. The discussion examines whether this grounding and the various forms of organization in the framework may begin to explain how processes that are only sometimes useful and not guaranteed to work can combine successfully to achieve innovative scientific model construction.

3D assessment of mandibular skeletal effects produced by the Herbst appliance.

BACKGROUND: A functional appliance is commonly used to optimize the development of the facial skeleton in the treatment of Class II malocclusion. Recent three-dimensional(3D) image-based analysis offers numerous advantages in quantitative measurement and visualization in orthodontics. The aim of this study was to localize in 3D the skeletal effect produced by the Herbst appliance on the mandible using the geometric morphometric technique. METHODS: Twenty patients treated with a Herbst appliance and subsequent fixed appliances were included. Cone-beam computed tomography (CBCT) images were taken before treatment (T1), 8 weeks after Herbst appliance removal (T2), and after subsequent fixed appliance treatment (T3). Spatially dense morphometric techniques were used to establish the corresponding points of the mandible. The mandibular morphological changes from T1-T2, T2-T3, and T1-T3 were calculated for each patient by superimposing two mandibular models at two time points with robust Procrustes superimposition. These changes were then compared to the morphological changes estimated from normative mandibular growth curves over the same period. The proportion of cases exceeding the growth expression for controls was compared to a normal population using a one tailed binomial test. RESULTS: Approximately 1.5-2 mm greater condylar changes and 0.5 mm greater changes in the chin occurred from Tl to T2. This effect lasted until the completion of treatment (T1-T3), but there was no obvious skeletal effect during the orthodontic phase (T2-T3). Approximately 40-50% of the patient sample exceeded condylar growth by > 1.5 mm compared to untreated controls (p < .05). However, changes at the chin were not statistically significant. CONCLUSIONS: The principal skeletal effect of Herbst appliance treatment was additional increase in condylar length for about half of the sample. This inconsistency may relate to the degree of mandibular growth suppression associated with a specific malocclusion.

The use of µCT and fractal dimension for fracture prediction in osteoporotic individuals.

Osteoporosis (OP) is a widespread condition with commonly associated fracture sites at the hip, vertebra and wrist. This study examines the effects of age and osteoporosis on bone quality by comparing the efficacy of using parameters which indicate bone quality (both traditional clinical parameters such as bone mineral density (BMD), as well as apparent Young's modulus determined by finite element analysis, among others) to predict fracture. Non-fracture samples were collected from the femoral heads of 83 donors (44 males, 39 females), and fracture samples were obtained from the femoral heads of 17 donors (female). Microarchitectural parameters (Bone Volume/Total Volume [BV/TV], Bone Surface/Bone Volume [BS/BV], Tissue Mineral Density [TMD, etc.]) were measured from µCT of each sample as well as 2D and 3D fractal dimension (D2D and D3D respectively). A cube was cropped from µCT images and an isotropic hexahedral element was assigned to each voxel. Finite element analysis was used to calculate the Young's modulus for each sample. Overall, values for microarchitectural characteristics, fractal dimension measurements and Young's Modulus were consistent with values within literature. Significant correlations are observed between age and BV/TV for non-fracture males and females, as well as between age and volumetric BMD (vBMD) for the same groups. Significant differences are present between age-matched non-fracture and fracture females for BV/TV, BS/BV, vBMD, TMD, D2D, D3D, (p < 0.01 for all). Properties which are not age dependent are significantly different between age-matched non-fracture and fracture specimens, indicating OP is a disease, and not just an accelerated aging process.

Quantification of age-related changes in midsagittal facial profile using Fourier analysis: A longitudinal study on Japanese adult males.

OBJECTIVES: The aim of the present study was to use Fourier analysis to quantify and study age-related changes in midsagittal facial profile. MATERIALS AND METHODS: Midsagittal facial profiles were extracted as lists of x and y coordinates from 125 pairs of 3D facial scans captured at an average of 10.5 years apart for adult Japanese males aged 23-52 years. These were categorized into three 10-year-long age groups. Files of x and y coordinates underwent Fourier analysis at 30 harmonic levels. Paired t-tests were used to determine statistical significance of differences across corresponding harmonic coefficients. Mean harmonic coefficients were used to construct mean pre and post ageing profiles for each age group for qualitative comparisons. RESULTS: Full detail of facial profile was described by the first 20 harmonics. With increasing age, there was a trend of longitudinal changes involving more midsagittal shape features with increased magnitudes. However, all changes were lower than 1 mm. CONCLUSIONS: Fourier analysis is a useful morphometric approach to quantify age-related midsagittal facial changes. The small variations in the study groups prompt for testing Fourier analysis on the elderly and on other parasagittal and transverse facial features.

Quantification of mandibular sexual dimorphism during adolescence.

The present study investigates how sexual dimorphism in the human mandible develops in three-dimensionally during adolescence. A cross-sectional sample of mandibular meshes of 268 males and 386 females, aged between 8.5 and 19.5 years of age, were derived from cone beam computed tomography and were analysed using geometric morphometric methods. Growth trajectories of the mandible in males and females were modelled separately using a recently developed non-linear kernel regression framework. Growth rate and direction at a dense array of points all over the mandibular surface were visualized within each group and compared between groups. We found that mandibular sexual dimorphism already exists at 9 years of age, but this is mostly in size not in shape. The differential growth rate and duration between the sexes during pubertal growth largely explained by adult sexual dimorphism: the growth direction in both males and females is similar but the male mandible changed more quickly and over a longer period than the female mandible, where the growth rate peaked and declined earlier. This results in increasing dimorphism in form, which is evident in both size and shape. The development of dimorphic features, concentrated in the chin and ramus, were further visualized. The dense morphometric approach provides detailed three-dimensional quantitative assessment of the development of sexual dimorphism of the mandible.

Marker-based watershed transform method for fully automatic mandibular segmentation from CBCT images.

OBJECTIVES:: To propose a reliable and practical method for automatically segmenting the mandible from CBCT images. METHODS:: The marker-based watershed transform is a region-growing approach that dilates or "floods" predefined markers onto a height map whose ridges denote object boundaries. We applied this method to segment the mandible from the rest of the CBCT image. The height map was generated to enhance the sharp decreases of intensity at the mandible/tissue border and suppress noise by computing the intensity gradient image of the CBCT itself. Two sets of markers, "mandible" and "background" were automatically placed inside and outside the mandible, respectively in a novel image using image registration. The watershed transform flooded the gradient image by dilating the markers simultaneously until colliding at watershed lines, estimating the mandible boundary. CBCT images of 20 adolescent subjects were chosen as test cases. Segmentation accuracy of the proposed method was evaluated by measuring overlap (Dice similarity coefficient) and boundary agreement against a well-accepted interactive segmentation method described in the literature. RESULTS:: The Dice similarity coefficient was 0.97 ± 0.01 (mean ± SD), indicating almost complete overlap between the automatically and the interactively segmented mandibles. Boundary deviations were predominantly under 1 mm for most of the mandibular surfaces. The errors were mostly from bones around partially erupted wisdom teeth, the condyles and the dental enamels, which had minimal impact on the overall morphology of the mandible. CONCLUSIONS:: The marker-based watershed transform method produces segmentation accuracy comparable to the well-accepted interactive segmentation approach.

Virtual trial to evaluate the robustness of cementless femoral stems to patient and surgical variation.

Primary stability is essential for the success of cementless femoral stems. In this study, patient specific finite element (FE) models were used to assess changes in primary stability due to variability in patient anatomy, bone properties and stem alignment for two commonly used cementless femoral stems, Corail® and Summit® (DePuy Synthes, Warsaw, USA). Computed-tomography images of the femur were obtained for 8 males and 8 females. An automated algorithm was used to determine the stem position and size which minimized the endo-cortical space, and then span the plausible surgical envelope of implant positions constrained by the endo-cortical boundary. A total of 1952 models were generated and ran, each with a unique alignment scenario. Peak hip contact and muscle forces for stair climbing were scaled to the donor's body weight and applied to the model. The primary stability was assessed by comparing the implant micromotion and peri-prosthetic strains to thresholds (150 µm and 7000 µÎµ, respectively) above which fibrous tissue differentiation and bone damage are expected to prevail. Despite the wide range of implant positions included, FE prediction were mostly below the thresholds (medians: Corail®: 20-74 µm and 1150-2884 µÎµ, Summit®: 25-111 µm and 860-3010 µÎµ), but sensitivity of micromotion and interfacial strains varied across femora, with the majority being sensitive (p < 0.0029) to average bone mineral density, cranio-caudal angle, post-implantation anteversion angle and lateral offset of the femur. The results confirm the relationship between implant position and primary stability was highly dependent on the patient and the stem design used.

Age-Related Changes in Femoral Head Trabecular Microarchitecture.

Osteoporosis is a prevalent bone condition, characterised by low bone mineral density and increased fracture risk. Currently, the gold standard for identifying osteoporosis and increased fracture risk is through quantification of bone mineral density using dual energy X-ray absorption. However, many studies have shown that bone strength, and consequently the probability of fracture, is a combination of both bone mass and bone 'quality' (architecture and material chemistry). Although the microarchitecture of both non-fracture and osteoporotic bone has been previously investigated, many of the osteoporotic studies are constrained by factors such as limited sample number, use of ovariectomised animal models, and lack of male and female discrimination. This study reports significant differences in bone quality with respect to the microarchitecture between fractured and non-fractured human femur specimens. Micro-computed tomography was utilised to investigate the microarchitecture of femoral head trabecular bone from a relatively large cohort of non-fracture and fracture human donors. Various microarchitectural parameters have been determined for both groups, providing an understanding of the differences between fracture and non -fracture material. The microarchitecture of non-fracture and fracture bone tissue is shown to be significantly different for many parameters. Differences between sexes also exist, suggesting differences in remodelling between males and females in the fracture group. The results from this study will, in the future, be applied to develop a fracture model which encompasses bone density, architecture and material chemical properties for both female and male tissues.

Evaluating the primary stability of standard vs lateralised cementless femoral stems - A finite element study using a diverse patient cohort.

BACKGROUND: Restoring the original femoral offset is desirable for total hip replacements as it preserves the original muscle lever arm and soft tissue tensions. This can be achieved through lateralised stems, however, the effect of variation in the hip centre offset on the primary stability remains unclear. METHODS: Finite element analysis was used to compare the primary stability of lateralised and standard designs for a cementless femoral stem (Corail®) across a representative cohort of male and female femora (N = 31 femora; age from 50 to 80 years old). Each femur model was implanted with three designs of the Corail® stem, each designed to achieve a different degree of lateralisation. An automated algorithm was used to select the size and position that achieve maximum metaphyseal fit for each of the designs. Joint contact and muscle forces simulating the peak forces during level gait and stair climbing were scaled to the body mass of each subject. FINDINGS: The study found that differences in restoring the native femoral offset introduce marginal differences in micromotion (differences in peak micromotion <21 µm), for most cases. Nonetheless, significant reduction in the interfacial strains (>3000 µÎµ) was achieved for some subjects when lateralized stems were used. INTERPRETATION: Findings of this study suggest that, with the appropriate size and alignment, the standard offset design is likely to be sufficient for primary stability, in most cases. Nonetheless, appropriate use of lateralised stems has the potential reduce the risk of peri-prosthetic bone damage. This highlights the importance of appropriate implant selection during the surgical planning stage.

Modal analysis of nanoindentation data, confirming that reduced bone turnover may cause increased tissue mineralization/elasticity.

It is widely believed that the activities of bone cells at the tissue scale not only govern the size of the vascular pore spaces (and hence, the amount of bone tissue available for actually carrying the loads), but also the characteristics of the extracellular bone matrix itself. In this context, increased mechanical stimulation (in mediolateral regions of human femora, as compared to anteroposterior regions) may lead to increased bone turnover, lower bone matrix mineralization, and therefore lower tissue modulus. On the other hand, resorption-only processes (in endosteal versus periosteal regions) may have the opposite effect. A modal analysis of nanoindentation data obtained on femurs from the Melbourne Femur Research Collection (MFRC) indeed confirms that bone is stiffer in endosteal regions compared to periosteal regions (E̅endost = 29.34 ± 0.75 GPa >E̅periost = 24.67 ± 1.63 GPa), most likely due to the aging-related increase in resorption modeling on endosteal surfaces resulting in trabecularization of cortical bone. The results also show that bone is stiffer along the anteroposterior direction compared the mediolateral direction (E̅anteropost = 28.89 ± 1.08 GPa >E̅mediolat = 26.03 ± 2.31 GPa), the former being aligned with the neutral bending axis of the femur and, thus, undergoing more resorption modeling and consequently being more mineralized.

Modelling 3D craniofacial growth trajectories for population comparison and classification illustrated using sex-differences.

Many disorders present with characteristic abnormalities of the craniofacial complex. Precise descriptions of how and when these abnormalities emerge and change during childhood and adolescence can inform our understanding of their underlying pathology and facilitate diagnosis from craniofacial shape. In this paper we develop a framework for analysing how anatomical differences between populations emerge and change over time, and for binary group classification that adapts to the age of each participant. As a proxy for a disease-control comparison we use a database of 3D photographs of normally developing boys and girls to examine emerging sex-differences. Essentially we define 3D craniofacial 'growth curves' for each sex. Differences in the forehead, upper lip, chin and nose emerge primarily from different growth rates between the groups, whereas differences in the buccal region involve different growth directions. Differences in the forehead, buccal region and chin are evident before puberty, challenging the view that sex differences result from pubertal hormone levels. Classification accuracy was best for older children. This paper represents a significant methodological advance for the study of facial differences between growing populations and comprehensively describes developing craniofacial sex differences.

Estimating age and synthesising growth in children and adolescents using 3D facial prototypes.

3D facial images are becoming increasingly common. They provide more information about facial form than their 2D counterparts and will be useful in future forensic applications. These include age estimation and predicting changes in appearance of missing persons (synthetic growth). We present a framework for both age estimation and synthetic growth of children and adolescents from 3D photographs. Age estimation accuracy was substantially better than for existing approaches (mean absolute error=1.19 years). Our synthetically 'grown' images were compared to actual longitudinal images of the same cases. On average 75% of the head overall and 85% of the face were predicted correctly to within three millimetres. We find that our approach is most suitable for ageing children from late childhood into adolescence. The work can be improved in the future by modelling skin colouring and taking account of other factors that influence face shape such as BMI.

Influence of collars on the primary stability of cementless femoral stems: A finite element study using a diverse patient cohort.

For cementless femoral stems, there is debate as to whether a collar enhances primary stability and load transfer compared to collarless designs. Finite Element (FE) analysis has the potential to compare stem designs within the same cohort, allowing for subtle performance differences to be identified, if present. Subject-specific FE models of intact and implanted femora were run for a diverse cohort (21 males, 20 females; BMI 16.4-41.2 kg/m2 , age 50-80 yrs). Collared and collarless versions of Corail® (DePuy Synthes, Warsaw, IN) were sized and positioned using an automated algorithm that aligns the femoral/stem axes, preserves the head-center location, and maximizes metaphyseal fit. Joint contact and muscle forces simulating peak forces in level gait and stair climbing and were scaled to the body mass and applied to each subject. Three failure scenarios were assessed: Potential for peri-prosthetic fibrous tissue formation (stem micromotion), potential for peri-prosthetic bone damage (equivalent strains), and calcar bone remodeling (changes in strain-energy density). Comparisons were performed using paired t-tests. Only subtle differences were found (mean 90th percentile micromotion: Collared = 86 µm, collarless = 92.5 µm, mean 90th percentile interface strains: Collared = 733 µÏµ, collarless = 767 µÏµ, and similar remodeling stimuli were predicted). The slight differences observed were small in comparison with the inter-patient variability. Statement of clinical significance: Our results suggest that the presence/absence of a collar is unlikely to substantially alter the bone-implant biomechanics nor the initial mechanical environment. Hence, a collar is likely to have minimal clinical impact. Analysis using different femoral stem designs is recommended before generalising these findings. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1185-1195, 2018.

Immunohistochemistry of Five Molecular Markers for Typing and Management of Ameloblastomas: A Retrospective Analysis of 40 Cases.

PURPOSE: The aims of this study are to elucidate if molecular markers can be used to differentiate between the two main types of ameloblastoma (unicystic and solid/multicystic), and to determine whether a biologically 'less-aggressive' subtype exists. METHODS: A retrospective analysis of 33 solid/multicystic ameloblastomas and six unicystic ameloblastomas was completed using immunohistochemistry for five molecular markers: P16, P53, MMP-9, Survivin, and Ki-67. Tumors were graded as either negative or positive (mild, moderate, strong), and the results were related to both ameloblastoma subtypes and outcomes following treatment. RESULTS: Unicystic ameloblastomas were more likely to test strongly positive for P53 than solid/multicystic ameloblastomas (p < 0.05), whereas the latter were more likely to be negative for Survivin (p < 0.05). Solid/multicystic and Type 3 unicystic ameloblastomas that were positive for P16, but also negative for MMP-9 and Survivin, were less likely to recur than all other tumors (p < 0.05). The proliferation index of an ameloblastic carcinoma (11 %) was shown to be higher than benign ameloblastomas (4.5 %). CONCLUSIONS: Immunohistochemistry can be valuable in lesions where histological sub-typing of an ameloblastoma is unclear. A biologically 'less-aggressive' subtype may exist, and hence further research into this area is required.

Three-dimensional reconstruction of Haversian systems in human cortical bone using synchrotron radiation-based micro-CT: morphology and quantification of branching and transverse connections across age.

This study uses synchrotron radiation-based micro-computed tomography (CT) scans to reconstruct three-dimensional networks of Haversian systems in human cortical bone in order to observe and analyse interconnectivity of Haversian systems and the development of total Haversian networks across different ages. A better knowledge of how Haversian systems interact with each other is essential to improve understanding of remodeling mechanisms and bone maintenance; however, previous methodological approaches (e.g. serial sections) did not reveal enough detail to follow the specific morphology of Haversian branching, for example. Accordingly, the aim of the present study was to identify the morphological diversity of branching patterns and transverse connections, and to understand how they change with age. Two types of branching morphologies were identified: lateral branching, resulting in small osteon branches bifurcating off of larger Haversian canals; and dichotomous branching, the formation of two new osteonal branches from one. The reconstructions in this study also suggest that Haversian systems frequently target previously existing systems as a path for their course, resulting in a cross-sectional morphology frequently referred to as 'type II osteons'. Transverse connections were diverse in their course from linear to oblique to curvy. Quantitative assessment of age-related trends indicates that while in younger human individuals transverse connections were most common, in older individuals more evidence of connections resulting from Haversian systems growing inside previously existing systems was found. Despite these changes in morphological characteristics, a relatively constant degree of overall interconnectivity is maintained throughout life. Altogether, the present study reveals important details about Haversian systems and their relation to each other that can be used towards a better understanding of cortical bone remodeling as well as a more accurate interpretation of morphological variants of osteons in cross-sectional microscopy. Permitting visibility of reversal lines, synchrotron radiation-based micro-CT is a valuable tool for the reconstruction of Haversian systems, and future analyses have the potential to further improve understanding of various important aspects of bone growth, maintenance and health.

Does 3D orientation account for variation in osteon morphology assessed by 2D histology?

The primary microstructural unit of cortical bone, the secondary osteon or Haversian system, is widely assumed to have a cylindrical shape. It is generally accepted that osteons are roughly circular in cross-section and deviations from circularity have been attributed to deviations from longitudinal orientation. To our knowledge this idealized geometric relationship, which assumes osteons are perfect cylinders, has not been rigorously explored. As such, we sought to explore two research questions: (i) Does the orientation of osteons in 3D explain variation in shapes visualized in 2D? (ii) Can differences in osteon 3D orientation explain previously reported age-related differences observed in their 2D cross-sectional shape (e.g. more circular shape and decreased area with age)? To address these questions we utilized a combination of 2D histology to identify osteon shape and superimposed micro-computed tomography data to assess osteon orientation in 3D based upon the osteonal canal. Shape was assessed by the inverse of Aspect Ratio (On.AspR(-1), based on a fitted ellipse) - which ranged from 0 (infinitely elongated shape) to 1 (perfectly circular). A sample (n = 27) of human female anterior femoral cortical bone samples from across the human lifespan (20-87 years) were included in the analysis, which involved 1418 osteons. The overall mean measure of On.AspR(-1) was 0.703 (1.42 Aspect Ratio). Mean osteon orientation was 79.1° (90° being longitudinal). While we anticipated a positive relation between orientation and On.AspR(-1), we found the opposite - a weak negative correlation (with more oblique 3D osteon alignment, the 2D shape became more circular as reflected by increased On.AspR(-1)). When analysis of covariance was performed with age and orientation as covariates, the negative relation with orientation was replaced by a significant relation with age alone. This relation with age accounted for 41% of the variation of On.AspR(-1). The results revealed that osteons, on average, are not circular in cross-section and that 3D orientation cannot account for deviation from circular shape. Osteons thus are strictly speaking not cylinders, as they tend to have elliptical cross-sections. We observed that osteons did become less elliptical in cross-section with age independent of orientation - suggesting this is a real change in morphology.

Hospitalization rates and utilization among patients with giant cell arteritis: A population-based study from 1987 to 2012.

BACKGROUND: Patients with giant cell arteritis (GCA) may experience serious vascular and visual complications. It is unknown, however, to what extent the difficulties of the disease may lead to hospitalization. The goal of this study is to discern whether patients with GCA are at greater risk for all-cause hospitalizations when compared to the general population. METHODS: This retrospective, population-based cohort study utilized patients with large vessel or visual involvement who were diagnosed with GCA (as defined by the 1990 ACR criteria) between 1/1/1950 and 12/31/2009, and a reference cohort of patients without GCA matched on age, sex, and calendar year. Each patients' medical record was examined for hospitalizations from 1987 through 2012. For this analysis, follow-up began with the latter of index date or 1/1/1987 and ended at the earlier of death, emigration from Olmsted County, or 12/31/2012. Discharge diagnoses were grouped together using the Clinical Classifications Software (CCS) for ICD-9-CM from Healthcare Cost and Utilization Project (HCUP). Data were analyzed using person-year methods and rate ratios comparing GCA to non-GCA. RESULTS: The GCA cohort consists of 199 patients with a mean age of 76.2 (79.9% female) and follow-up of 8.2 years. The non-GCA cohort is comprised of 194 patients with a mean age of 75.7 (78.9% female) and follow-up of 8.6 years. The patients with GCA had 816 hospitalizations and the non-GCA patients had 737 hospitalizations. GCA patients proved to be at a marginally greater risk for all causes of hospitalization [rate ratio (RR) = 1.13; 95% confidence interval (CI): 1.02-1.25]; however, the rate of hospitalization for patients with and without GCA decreased significantly from 1987 to 2012. Two specific discharge categories are of interest. First, transient cerebral ischemia is a greater risk of hospitalization for patients with GCA who had 16 hospitalizations compared to patients without GCA who only had 5 hospitalizations (RR = 3.06; 95% CI: 1.27-9.47). Second, patients with GCA (21 hospitalizations) are at greater risk of hospitalization for syncope than patients without GCA (5 hospitalizations) (RR = 3.98; 95% CI: 1.72-12.14). CONCLUSION: In this first ever analysis of all-cause hospitalizations in a population-based cohort, patients with GCA appear to be at a marginally greater risk for hospitalization than patients without GCA, although the rate of hospitalization for GCA patients decreased from 1987 to 2012. Patients with GCA are at increased risk of hospitalization for both transient cerebral ischemia and syncope.

Normal variation in cortical osteocyte lacunar parameters in healthy young males.

The most abundant cell in bone, osteocytes form an interconnected system upon which the regulation of healthy bone relies. Although the complete nature of the role of osteocytes has yet to be defined, they are generally accepted to play a part in the sensing of load and the initiation of damage repair. A previous study conducted by our group identified variation of up to 30% in osteocyte lacunar density and morphological parameters between regions of a single cross-section of human femoral shaft; that study, however, was limited to a single individual. The aim of the current study was to determine whether this pattern consistently occurs in healthy young male femora. Anterior, posterior, medial and lateral blocks were prepared from the proximal femoral shaft of seven males and synchrotron radiation micro-CT imaged. Average lacunar densities (± SD) from the anterior, posterior, medial and lateral regions were 23 394 ± 1705, 30 180 ± 4860, 35 946 ± 5990 and 29 678 ± 6081 lacunae per mm(3) of bone tissue, respectively. These values were significantly different between the anterior and both the medial and posterior regions (P < 0.05). The density of the combined anterior and posterior regions was also significantly lower (P = 0.006) than the density of the combined medial and lateral regions. Although no difference was found in predominant orientation, shape differences were found; with the combined anterior-posterior regions having lacunae that were significantly more elongated and less flat than the combined medial-lateral values (P < 0.001). As expected, in this larger study, there was a dramatic difference in lacunar density between the medial and anterior region (up to ~ 54%). The study clearly demonstrates that the high variation seen in osteocyte lacunar density as well as other lacunar parameters, noted in a number of biomechanical, age and pathology studies, are well within the range of normal variation; however, the reasons for and consequences of this variation remain unclear. Lacunar parameters including abundance and shape are being increasingly incorporated into computational modeling of bone biology and this paper represents a more comprehensive description of normal healthy lacunae.