Breast cancer diagnosis and treatment wait times in specialized diagnostic units compared with usual care: a population-based study.

Background: Breast assessment sites (bass) were developed to provide expedited and coordinated care for patients being evaluated for breast cancer (bca) in Ontario. We compared the diagnostic and treatment intervals for patients diagnosed at a bas and for those diagnosed through a usual care (uc) route. Methods: This population-based, cross-sectional study of patients diagnosed with bca in Ontario during 2007-2015 used linked administrative data. "Diagnostic interval" was the time from the earliest cancer-related health care encounter before diagnosis to diagnosis; "treatment interval" was the time from diagnosis to treatment. Diagnosis at a bas was determined from the patient's biopsy and mammography institutions. Interval lengths for the bas and uc groups were compared using multivariable quantile regression, stratified by detection method. Results: The diagnostic interval was shorter for patients who were bas-diagnosed than for those who were uc-diagnosed, with adjusted median differences of -4.0 days [95% confidence interval (ci): -3.2 days to -4.9 days] for symptomatic patients and -5.4 days (95% ci: -4.7 days to -6.1 days) for screen-detected patients. That association was modified by stage at diagnosis, with larger differences in patients with early-stage cancers. In contrast, the treatment interval was longer in patients who were bas-diagnosed than in those who were uc-diagnosed, with adjusted median differences of 4.2 days (95% ci: 3.8 days to 4.7 days) for symptomatic patients and 4.2 days (95% ci: 3.7 days to 4.8 days) for screen-detected patients. Conclusions: Diagnosis of bca through a bas was associated with a shorter diagnostic interval, but a longer treatment interval. Although efficiencies in the diagnostic interval might help to reduce distress experienced by patients, the longer treatment intervals for patients who are bas-diagnosed remain a cause for concern.

Play in Elephants: Wellbeing, Welfare or Distraction?

We explore elephant play behaviour since (a) play has been proposed to represent a potential welfare indicator; and (b) play has been associated with long-term survival in the wild. We categorised play into four types, and investigate both social (gentle, escalated-contact) and non-social (lone-locomotor, exploratory-object) play from observations made on wild (Asian N = 101; African N = 130) and captive (Asian N = 8; African N = 7) elephant calves ranging in age from birth to five years. Social play was the most frequent type of play among immature elephants, accounting for an average of 3%-9% of active time. Non-social play accounted for an additional 1%-11% of time. The most time spent in play was seen in captive Asian calves, particularly at the ages of 1-6 months, while wild African calves spent the least time in play overall, even though they had the greatest number and most diverse range of play partners available. We assessed calf energetics using time spent suckling, resting, moving and independent feeding. Time spent playing was unrelated to time spent suckling but negatively associated with time spent independently feeding. There were no associations with time spent moving or resting. Maternal energy via lactation was unrelated to play early in life, but energy acquired independently may constrain or enable play. Play, while a potential indicator of compromised welfare for many species when absent, can act as a highly stimulating activity for captive elephants in the absence of other forms of arousal.

Selective Sensory Axon Reinnervation and TRPV1 Activation.

Current strategies to enhance regeneration of peripheral neurons involve broad activation of sensory, autonomic, and motor axons. Peripheral neuron regeneration is limited in persons with damage or disease of peripheral axons. Here, we provide evidence that subtoxic activation of TRPV1 channels in sensory neurons is associated with activation of growth and subtle changes in skin reinnervation. We identify a bidirectional, dose-related impact of capsaicin, a TRPV1 agonist, on sensory neurons and their axons with rises in their outgrowth plasticity at low doses and toxic neurodegeneration at high doses. Moreover, its impact on growth added to that of preconditioning. Neither outcome was observed in TRPV1 null neurons. We confirmed that low dose activation was associated with rises in neuronal calcium, as well as rises in TRPV1 mRNA transcripts. In mice with a sciatic nerve crush followed by a single application of capsaicin directly to the injury site, there was no impact on motor or myelinated axon recovery but there was evidence of better recovery of thermal sensation toward baseline with hyperalgesia. Moreover, skin reinnervation by epidermal axons approached contralateral levels. TRPV1 null mice displayed loss of thermal sensation during later recovery. In sensory axons innervating the pinna of the ear, local capsaicin rendered early axon loss followed by later hyperinnervation. Taken together, TRPV1 activation alters the regenerative behavior of adult neurons and their axons both in vitro and during epidermal reinnervation in vivo. The findings identify a selective manipulation that augments cutaneous innervation by thermosensitive axons.

Electrical stimulation as a conditioning strategy for promoting and accelerating peripheral nerve regeneration.

The delivery of a nerve insult (a "conditioning lesion") prior to a subsequent test lesion increases the number of regenerating axons and accelerates the speed of regeneration from the test site. A major barrier to clinical translation is the lack of an ethically acceptable and clinically feasible method of conditioning that does not further damage the nerve. Conditioning electrical stimulation (CES), a non-injurious intervention, has previously been shown to improve neurite outgrowth in vitro. In this study, we examined whether CES upregulates regeneration-associated gene (RAG) expression and promotes nerve regeneration in vivo, similar to a traditional nerve crush conditioning lesion (CCL). Adult rats were divided into four cohorts based on conditioning treatment to the common peroneal (fibular) nerve: i) CES (1h, 20Hz); ii) CCL (10s crush); iii) sham CES (1h, 0Hz); or iv) naïve (unconditioned). Immunofluorescence and qRT-PCR revealed significant RAG upregulation in the dorsal root ganglia of both CES and CCL animals, evident at 3-14days post-conditioning. To mimic a clinical microsurgical nerve repair, all cohorts underwent a common peroneal nerve cut and coaptation one week following conditioning. Both CES and CCL animals increased the length of nerve regeneration (3.8-fold) as well as the total number of regenerating axons (2.2-fold), compared to the sham and naïve-conditioned animals (p<0.001). These data support CES as a non-injurious conditioning paradigm that is comparable to a traditional CCL and is therefore a novel means to potentially enhance peripheral nerve repair in the clinical setting.

The decrease in population bone lead levels in Canada between 1993 and 2010 as assessed by in vivo XRF.

Objective and Approach: A study, conducted in Toronto, Canada, between 2009 and 2011, measured the bone lead concentrations of volunteers aged 1-82 years using in vivo x-ray fluorescence (XRF) technology. MAIN RESULTS: Bone lead levels were lower compared to Ontario in vivo XRF studies from the early 1990s. In adults, the slope of tibia lead content versus age was reduced by 36-56%, i.e. bone lead levels for a given age group were approximately half compared to the same age group 17 years prior. Further, bone lead levels of individuals fell over that time period. In 2010, an average person aged 57 years had a bone lead level approximately 1/3 less than their bone lead level age 40 years in 1993. Using this data, the half-lives of lead in the tibia were estimated as 7-26 years. Tibia lead levels were found to be low in children. The reduction in bone tibia content in children was not significant (p = 0.07), but using data from additional north eastern US studies, there is evidence that childhood tibia stores are lower than in the 1990s. SIGNIFICANCE: In vivo XRF analysis shows that there has been a reduction in the level of lead in bone in Canada over the last two decades. Public health measures have been very successful in reducing ongoing exposure to lead and in reducing bone lead stores.

Association between the time to surgery and survival among patients with colon cancer: A population-based study.

Factors associated with time-to-surgery (TTS) and survival in colon cancer has not been well studied. Cancer Care Ontario recommends surgery within 42 days of diagnosis and that 90% of patients meet this benchmark. We describe factors associated with TTS and survival in routine clinical practice. METHODS: Retrospective population-based cohort study of patients receiving elective colonic resection after diagnosis of colon cancer in Ontario, Canada from 2002 to 2008 followed until 2012. Factors associated with TTS were identified using multivariate log-binomial and Quantile regression at 42 days and 90th percentiles. The association between TTS and cancer-specific (CSS) and overall survival (OS) were examined using multivariate Cox regression. RESULTS: 4326 patients; median age 71 years and 52% male. Median TTS was 24 days (IQR 14-37); at the 90th percentile 56 days. Factors associated with TTS ≥ 42 days and >90th percentile included older age, co-morbid illness, surgeon volume, and stage I disease (P < 0.05 for all). In patients whose TTS was either at 42 days or 90th percentile, those ≥80 years old waited two weeks longer than those <60 years, individuals with co-morbid illness waited 10 days longer than without co-morbidity, and patients with stage I disease waited 10 days longer than those with stage IV disease (P < 0.05 for all). Delay in TTS > 42 days or >90th percentile was not associated with OS or CSS. CONCLUSION: Age, co-morbidity, and stage of cancer are associated with TTS. There was no association between TTS and CSS or OS.

The reproductive advantages of a long life: longevity and senescence in wild female African elephants.

Long-lived species such as elephants, whales and primates exhibit extended post-fertile survival compared to species with shorter lifespans but data on age-related fecundity and survival are limited to few species or populations. We assess relationships between longevity, reproductive onset, reproductive rate and age for 834 longitudinally monitored wild female African elephants in Amboseli, Kenya. The mean known age at first reproduction was 13.8 years; only 5 % commenced reproduction by 10 years. Early reproducers (<12.5 years) had higher age-specific fertility rates than did females who commenced reproduction late (15+ years) with no differences in survival between these groups. Age-specific reproductive rates of females dying before 40 years were reduced by comparison to same-aged survivors, illustrating a mortality filter and reproductive advantages of a long life. Overall, 95 % of fertility was completed before 50, and 95 % of mortality experienced by age 65, with a mean life expectancy of 41 years for females who survived to the minimum age at first birth (9 years). Elephant females have a relatively long period (c. 16 years) of viability after 95 % completed fertility, although reproduction does not entirely cease until they are over 65. We found no evidence of increased investment among females aged over 40 in terms of delay to next birth or calf mortality. The presence of a mother reproducing simultaneously with her daughter was associated with higher rates of daughter reproduction suggesting advantages from maternal (and grandmaternal) co-residence during reproduction.

Abnormal error processing in depressive states: a translational examination in humans and rats.

Depression has been associated with poor performance following errors, but the clinical implications, response to treatment and neurobiological mechanisms of this post-error behavioral adjustment abnormality remain unclear. To fill this gap in knowledge, we tested depressed patients in a partial hospital setting before and after treatment (cognitive behavior therapy combined with medication) using a flanker task. To evaluate the translational relevance of this metric in rodents, we performed a secondary analysis on existing data from rats tested in the 5-choice serial reaction time task after treatment with corticotropin-releasing factor (CRF), a stress peptide that produces depressive-like signs in rodent models relevant to depression. In addition, to examine the effect of treatment on post-error behavior in rodents, we examined a second cohort of rodents treated with JDTic, a kappa-opioid receptor antagonist that produces antidepressant-like effects in laboratory animals. In depressed patients, baseline post-error accuracy was lower than post-correct accuracy, and, as expected, post-error accuracy improved with treatment. Moreover, baseline post-error accuracy predicted attentional control and rumination (but not depressive symptoms) after treatment. In rats, CRF significantly degraded post-error accuracy, but not post-correct accuracy, and this effect was attenuated by JDTic. Our findings demonstrate deficits in post-error accuracy in depressed patients, as well as a rodent model relevant to depression. These deficits respond to intervention in both species. Although post-error behavior predicted treatment-related changes in attentional control and rumination, a relationship to depressive symptoms remains to be demonstrated.

Predicting pneumococcal community-acquired pneumonia in the emergency department: evaluation of clinical parameters.

The aim of this study was to quantify the value of clinical predictors available in the emergency department (ED) in predicting Streptococcus pneumoniae as the cause of community-acquired pneumonia (CAP). A prospective, observational, cohort study of patients with CAP presenting in the ED was performed. Pneumococcal aetiology of CAP was based on either bacteraemia, or S. pneumoniae being cultured from sputum, or urinary immunochromatographic assay positivity, or positivity of a novel serotype-specific urinary antigen detection test. Multivariate logistic regression was used to identify independent predictors and various cut-off values of probability scores were used to evaluate the usefulness of the model. Three hundred and twenty-eight (31.0%) of 1057 patients with CAP had pneumococcal CAP. Nine independent predictors for pneumococcal pneumonia were identified, but the clinical utility of this prediction model was disappointing, because of low positive predictive values or a small yield. Clinical criteria have insufficient diagnostic capacity to predict pneumococcal CAP. Rapid antigen detection tests are needed to diagnose S. pneumoniae at the time of hospital admission.

Demographic variables for wild Asian elephants using longitudinal observations.

Detailed demographic data on wild Asian elephants have been difficult to collect due to habitat characteristics of much of the species' remaining range. Such data, however, are critical for understanding and modeling population processes in this endangered species. We present data from six years of an ongoing study of Asian elephants (Elephas maximus) in Uda Walawe National Park, Sri Lanka. This relatively undisturbed population numbering over one thousand elephants is individually monitored, providing cohort-based information on mortality and reproduction. Reproduction was seasonal, such that most births occurred during the long inter-monsoon dry season and peaked in May. During the study, the average age at first reproduction was 13.4 years and the 50(th) percentile inter-birth interval was approximately 6 years. Birth sex ratios did not deviate significantly from parity. Fecundity was relatively stable throughout the observed reproductive life of an individual (ages 11-60), averaging between 0.13-0.17 female offspring per individual per year. Mortalities and injuries based on carcasses and disappearances showed that males were significantly more likely than females to be killed or injured through anthropogenic activity. Overall, however, most observed injuries did not appear to be fatal. This population exhibits higher fecundity and density relative to published estimates on other Asian elephant populations, possibly enhanced by present range constriction. Understanding the factors responsible for these demographic dynamics can shed insight on the future needs of this elephant population, with probable parallels to other populations in similar settings.

Nerve growth factor acts through the TrkA receptor to protect sensory neurons from the damaging effects of the HIV-1 viral protein, Vpr.

Distal sensory polyneuropathy (DSP) with associated neuropathic pain is the most common neurological disorder affecting patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Viral protein R (Vpr) is a neurotoxic protein encoded by HIV-1 and secreted by infected macrophages. Vpr reduces neuronal viability, increases cytosolic calcium and membrane excitability of cultured dorsal root ganglion (DRG) sensory neurons, and is associated with mechanical allodynia in vivo. A clinical trial with HIV/AIDS patients demonstrated that nerve growth factor (NGF) reduced the severity of DSP-associated neuropathic pain, a problem linked to damage to small diameter, potentially NGF-responsive fibers. Herein, the actions of NGF were investigated in our Vpr model of DSP and we demonstrated that NGF significantly protected sensory neurons from the effects of Vpr. Footpads of immunodeficient Vpr transgenic (vpr/RAG1(-/-)) mice displayed allodynia (p<0.05), diminished epidermalinnervation (p<0.01) and reduced NGF mRNA expression (p<0.001) compared to immunodeficient (wildtype/RAG1(-/-)) littermate control mice. Compartmented cultures confirmed recombinant Vpr exposure to the DRG neuronal perikarya decreased distal neurite extension (p<0.01), whereas NGF exposure at these distal axons protected the DRG neurons from the Vpr-induced effect on their cell bodies. NGF prevented Vpr-induced attenuation of the phosphorylated glycogen synthase-3 axon extension pathway and tropomyosin-related kinase A (TrkA) receptor expression in DRG neurons (p<0.05) and it directly counteracted the cytosolic calcium burst caused by Vpr exposure to DRG neurons (p<0.01). TrkA receptor agonist indicated that NGFacted through the TrkA receptor to block the Vpr-mediated decrease in axon outgrowth in neonatal and adult rat and fetal human DRG neurons (p<0.05). Similarly, inhibiting the lower affinity NGF receptor, p75, blocked Vpr's effect on DRG neurons. Overall, NGF/TrkA signaling or p75 receptor inhibition protects somatic sensory neurons exposed to Vpr, thus laying the groundwork for potential therapeutic options for HIV/AIDS patients suffering from DSP.

Enduring consequences of early experiences: 40 year effects on survival and success among African elephants (Loxodonta africana).

Growth from conception to reproductive onset in African elephants (Loxodonta africana) provides insights into phenotypic plasticity, individual adaptive plastic responses and facultative maternal investment. Using growth for 867 and life histories for 2652 elephants over 40 years, we demonstrate that maternal inexperience plus drought in early life result in reduced growth rates for sons and higher mortality for both sexes. Slow growth during early lactation was associated with smaller adult size, later age at first reproduction, reduced lifetime survival and consequently limited reproductive output. These enduring effects of trading slow early growth against immediate survival were apparent over the very long term; delayed downstream consequences were unexpected for a species with a maximum longevity of 70+ years and unpredictable environmental experiences.

Vertebral fracture prevalence in a referral population of 750 Canadian men and women.

AIM: To establish the prevalence of vertebral fracture (VF) in a representative sample of 750 Canadians and to examine the relationships between VF prevalence and bone mineral density (BMD) at the spine and proximal femur. MATERIALS AND METHODS: X-ray-based dual-photon absorptiometry (DXA) was used to perform measurements of lumbar spine BMD, proximal femur BMD, and VF assessment (VFA). RESULTS: Two hundred and fifty-nine VFs were identified in 156 patients and the prevalence of unknown or unsuspected VF was 18.7%. For premenopausal women and for men, there was no difference in BMD at either the spine or the hip whether or not there was at least one VF. For postmenopausal women, BMD of the total region of the proximal femur was statistically lower (p < 0.001) in women with at least one VF whereas spine BMD only tended to be less (0.10 > p > 0.05). Proximal femur BMD was lower for postmenopausal women with more VF, while spine BMD was virtually unchanged as the number of VF increased. Neither spine nor hip BMD was lower for men with more VF. A strong association was observed in postmenopausal women between an age-dependent increase in VF prevalence and a reduction in femoral BMD. Such an association was not present in men. CONCLUSION: VFs are common, are often independent of either spine or hip BMD, and frequently go unnoticed. Therefore, VFA should be part of a routine assessment of fracture risk.

The feasibility of in vivo quantification of bone-fluorine in humans by delayed neutron activation analysis: a pilot study.

Fluorine (F) plays an important role in dental health and bone formation. Many studies have shown that excess fluoride (F(-)) can result in dental or skeletal fluorosis, while other studies have indicated that a proper dosage of fluoride may have a protective effect on bone fracture incidence. Fluorine is stored almost completely in the skeleton making bone an ideal site for measurement to assess long-term exposure. This paper outlines a feasibility study of a technique to measure bone-fluorine non-invasively in the human hand using in vivo neutron activation analysis (IVNAA) via the (19)F(n,γ)(20)F reaction. Irradiations were performed using the Tandetron accelerator at McMaster University. Eight NaI(Tl) detectors arranged in a 4π geometry were employed for delayed counting of the emitted 1.63 MeV gamma ray. The short 11 s half-life of (20)F presents a difficult and unique practical challenge in terms of patient irradiation and subsequent detection. We have employed two simultaneous timing methods to determine the fluorine sensitivity by eliminating the interference of the 1.64 MeV gamma ray from the (37)Cl(n,γ)(38)Cl reaction. The timing method consisted of three counting periods: an initial 30 s (sum of three 10 s periods) count period for F, followed by a 120 s decay period, and a subsequent 300 s count period to obtain information pertaining to Ca and Cl. The phantom minimum detectable limit (M(DL)) determined by this method was 0.96 mg F/g Ca. The M(DL) was improved by dividing the initial timing period into three equal segments (10 s each) and combining the results using inverse variance weighting. This resulted in a phantom M(DL) of 0.66 mg F/g Ca. These detection limits are comparable to ex vivo results for various bones in the adult skeleton reported in the literature. Dosimetry was performed for these irradiation conditions. The equivalent dose for each phantom measurement was determined to be 30 mSv. The effective dose was however low, 35 µSv, which is comparable to other clinical diagnostic tools. The M(DL), relatively low radiation dose and non-invasiveness indicate the suitability of this method for routine in vivo analysis of bone-fluorine content. This prompted us to perform a trial study in human subjects. A preliminary human study on 34 participants was completed, with 33 of the 34 measurements proving to be successful. The in vivo M(DL) based on the improved timing method was determined to be 0.69 mg F/g Ca for the 33 successful human measurements. In our opinion, this technique has been demonstrated to be a suitable method for in vivo assessment of fluorine bone-burden.

Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines.

SUMMARY: We compared the distribution of vertebral fractures in adults and children and found that fractures occurred in different locations in the two age groups. This likely relates to the different shape of the immature spine. INTRODUCTION: We hypothesized that the anatomical distribution of vertebral fractures (VF) would be different in children compared to adults. METHODS: We compared the distribution of VF defined using the Genant semi-quantitative method (GSQ method) in adults (N = 221; 545 fractures) and in children early in the course of glucocorticoid therapy (N = 44; 94 fractures). RESULTS: The average age in the adult cohort was 62.9 years (standard deviation (SD), 13.4 years), 26% was male, the mean lumbar spine Z-score was -1.0 (SD, 1.5), and the corresponding T-score was -2.4 (SD, 1.4). The pediatric cohort median age was 7.7 years (range, 2.1-16.6 years), the mean lumbar spine Z-score was -1.7 (SD, 1.5), 52% was male, and disease categories were acute lymphoblastic leukemia (66%), rheumatological conditions (21%), and nephrotic syndrome (14%). The VF distribution was biphasic in both populations, but the peaks differed in location. In adults, the peaks were at T7/T8 and at T12/L1. In children, the focus was higher in the thoracic spine, at T6/T7, and lower in the lumbar spine, at L1/L2. When children were assessed in two age-defined sub-groups, a biphasic VF distribution was seen in both, but the upward shift of the thoracic focus to T6 was observed only in the older group, with the highest rates of fracture present between ages 7 and 10 years. CONCLUSIONS: These results suggest that the anatomical distribution of VF differs between children and adults, perhaps relating to the different shape of the immature spine, notably the changing ratio of kyphosis to lordosis.

Functional enrichment analysis with structural variants: pitfalls and strategies.

Interpreting the phenotypic consequences of human structural variation remains challenging. Functional enrichment analysis, which can identify functional enrichments among genes affected by structural variants, is providing significant biological insights into the genotype-phenotype relationship. In this review, we discuss the different approaches and choices in the application of this technique to human structural variation. We consider the importance of choosing the right background distribution for detection, the significance of the gene selection criteria, the effects of tissue-specific gene length biases and discuss sources of functional annotations with a focus on Gene Ontology and mouse phenotypic resources. Throughout this review, we highlight potential sources of significant bias that are of particular concern to the analysis of structural variants, and illustrate the importance of examining the expectations upon which enrichment analysis techniques depend.

Cortical and trabecular bone at the radius and tibia in postmenopausal breast cancer patients: a Peripheral Quantitative Computed Tomography (pQCT) study.

Bone morbidity associated with antineoplastic treatment is a significant health concern for postmenopausal breast cancer patients. Trials have demonstrated that adjuvant therapy with an Aromatase Inhibitor is associated with an increase in musculoskeletal disorders and bone fractures. The objective of this study was to utilize Peripheral Quantitative Computed Tomography (pQCT) to assess in vivo trabecular and cortical volumetric bone at peripheral skeletal sites in healthy postmenopausal women and breast cancer patients prescribed Anastrozole. Fifty-eight women were recruited for this study: 27 breast cancer patients and 31 healthy control participants. pQCT measurements were taken at distal and diaphyseal sites of the radius and tibia using a Stratec XCT-2000 pQCT scanner. Bone measurement values for total density and total content at the 4% radius; total and cortical content as well as cortical density at the 20% radius; total density at the 4% tibia; and cortical density at the 38% tibia were found to be significantly lower in breast cancer patients. Moreover, the duration of time on Anastrozole showed a significant negative correlation with the following measurements: total content at the 4% radius (r=-0.36, p<0.01); total content (r=-0.33, p<0.05), cortical content (r=-0.34, p<0.05) and cortical density (r=-0.44, p<0.01) at the 20% radius; as well as cortical density (r=-0.39, p<0.01) and cortical content (r=-0.27, p<0.05) at the 38% tibia. Overall, the breast cancer patients demonstrated significantly lower values for volumetric bone density and content at the radius and tibia compared with healthy postmenopausal women. Furthermore, this novel study found adverse effects from Anastrozole treatment primarily in cortical bone.

Quantitative analysis of subchondral sclerosis of the tibia by bone texture parameters in knee radiographs: site-specific relationships with joint space width.

OBJECTIVES: To determine the ability of radiographic bone texture (BTX) parameters to quantify subchondral tibia sclerosis and to examine clinical relevance for assessing osteoarthritis (OA) progression. We examined the relationship between BTX parameters and each of (1) location-specific joint space width (JSW) [JSW(x)] and minimum JSW (mJSW) of the affected compartment, and (2) knee alignment (KA) angle in knee radiographs of participants undergoing total knee arthroplasty (TKA). DESIGN: Digitized fixed-flexion knee radiographs were analyzed for run-length and topological BTX parameters in a subchondral region using an algorithm. Medial JSW(x) was computed at x=0.200, 0.225, 0.250 and 0.275 according to a coordinate system defined by anatomic landmarks. mJSW was determined for medial and lateral compartment lesions. KA angles were determined from radiographs using an anatomic landmark-guided algorithm. JSW measures and the magnitude of knee malalignment were each correlated with BTX parameters. Reproducibility of BTX parameters was measured by root-mean square coefficients of variation (RMSCV%). RESULTS: Run-length BTX parameters were highly reproducible (RMSCV%<1%) while topological parameters showed poorer reproducibility (>5%). In TKA participants (17 women, 13 men; age: 66+/-9 years; body mass index (BMI): 31+/-6 kg m(-2); WOMAC: 41.5+/-16.1; Kellgren-Lawrence score mode: 4), reduced trabecular spacing (Tb.Sp) and increased free ends (FE) were correlated with decreased JSW after accounting for BMI, gender and knee malalignment. These relationships were dependent on site of JSW measurement. CONCLUSION: High reproducibility in quantifying bone sclerosis using Tb.Sp and its significant relationship with JSW demonstrated potential for assessing OA progression. Increased trabecular FE and reduced porosity observed with smaller JSW suggest collapsing subchondral bone or trabecular plate perforation in advanced knee OA.

Accounting for body size deviations when reporting bone mineral density variables in children.

UNLABELLED: In a child, bone mineral density (BMD) may differ from an age-expected normal value, not only because of the presence of disease, but also because of deviations of height or weight from population averages. Appropriate adjustment for body size deviations simplifies interpretation of BMD measurements. INTRODUCTION: For children, a bone mineral density (BMD) measurement is normally expressed as a Z score. Interpretation is complicated when weight or height distinctly differ from age-matched children. We develop a procedure to allow for the influence of body size deviations upon measured BMD. METHODS: We examined the relation between body size deviation and spine, hip and whole body BMD deviation in 179 normal children (91 girls). Expressions were developed that allowed derivation of an expected BMD based on age, gender and body size deviation. The difference between measured and expected BMD was expressed as a HAW score (Height-, Age-, Weight-adjusted score). RESULTS: In a second independent sample of 26 normal children (14 girls), measured spine, total femur and whole body BMD all fell within the same single normal range after accounting for age, gender and body size deviations. When traditional Z scores and HAW scores were compared in 154 children, 17.5% showed differences of more than 1 unit and such differences were associated with height and weight deviations. CONCLUSION: For almost 1 in 5 children, body size deviations influence BMD to an extent that could alter clinical management.