Onset of Antarctic Circumpolar Current 30 million years ago as Tasmanian Gateway aligned with westerlies.

Earth's mightiest ocean current, the Antarctic Circumpolar Current (ACC), regulates the exchange of heat and carbon between the ocean and the atmosphere, and influences vertical ocean structure, deep-water production and the global distribution of nutrients and chemical tracers. The eastward-flowing ACC occupies a unique circumglobal pathway in the Southern Ocean that was enabled by the tectonic opening of key oceanic gateways during the break-up of Gondwana (for example, by the opening of the Tasmanian Gateway, which connects the Indian and Pacific oceans). Although the ACC is a key component of Earth's present and past climate system, the timing of the appearance of diagnostic features of the ACC (for example, low zonal gradients in water-mass tracer fields) is poorly known and represents a fundamental gap in our understanding of Earth history. Here we show, using geophysically determined positions of continent-ocean boundaries, that the deep Tasmanian Gateway opened 33.5 ± 1.5 million years ago (the errors indicate uncertainty in the boundary positions). Following this opening, sediments from Indian and Pacific cores recorded Pacific-type neodymium isotope ratios, revealing deep westward flow equivalent to the present-day Antarctic Slope Current. We observe onset of the ACC at around 30 million years ago, when Southern Ocean neodymium isotopes record a permanent shift to modern Indian-Atlantic ratios. Our reconstructions of ocean circulation show that massive reorganization and homogenization of Southern Ocean water masses coincided with migration of the northern margin of the Tasmanian Gateway into the mid-latitude westerly wind band, which we reconstruct at 64° S, near to the northern margin. Onset of the ACC about 30 million years ago coincided with major changes in global ocean circulation and probably contributed to the lower atmospheric carbon dioxide levels that appear after this time.

Anaemia in elective orthopaedic surgery - Royal Adelaide Hospital, Australia.

BACKGROUND: An anaemia clinic was established to improve the preoperative management of elective orthopaedic patients scheduled for arthroplasty. This paper is a report on the first 100 patients assessed. AIM: To assess the incidence and causes of anaemia in patients on a waiting list for elective arthroplasty in a public hospital and to assess the impact of anaemia detection in this patient population. METHODS: Patients attending an Anaemia Clinic for elective orthopaedic surgical patients, during March 2010 to June 2013 were studied. Outcome measures included change in haemoglobin preoperative results and perioperative transfusion rates by preoperative haemoglobin. RESULTS: Seventeen per cent of patients scheduled for elective surgery were found to be anaemic. Of the 100 patients who attended, approximately half were found to be iron deficient and the remainder had anaemia of chronic disease. Serum ferritin <30 µg/L alone did not identify iron deficiency in 80% of patients with iron deficiency. Patients with iron deficient anaemia were able to be treated, in all cases, to achieve a significant increase in preoperative haemoglobin. The general unavailability of erythropoietin limited effective intervention for the non-iron-deficient anaemic patients. Seven patients had their surgery cancelled because of the screening programme. CONCLUSIONS: Half of the anaemic patients in a joint replacement screening clinic were iron deficient, and treatment was effective in improving the pre-operative haemoglobin and reducing perioperative transfusion rates. This screening process should improve patient outcome. Another important finding in this group of patients is that ferritin levels cannot be reliably used as the sole indicator in the diagnosis of iron deficiency anaemia in this group of patients undergoing elective arthroplasty.

Th17 cells induce a distinct graft rejection response that does not require IL-17A.

IL-17A-producing helper T (Th17) cells have been implicated in the pathogenesis of autoimmune disease, inflammatory bowel disease and graft rejection, however the mechanisms by which they cause tissue damage remain ill-defined. We examined what damage Th17 cell lines could inflict on allogeneic skin grafts in the absence of other adaptive lymphocytes. CD4(+) Th17 cell lines were generated from two TCR transgenic mouse strains, A1(M).RAG1(-/-) and Marilyn, each monospecific for the male antigen Dby. After prolonged in vitro culture in polarizing conditions, Th17 lines produced high levels of IL-17A with inherently variable levels of interferon gamma (IFNγ) and these cells were able to maintain IL-17A expression following adoptive transfer into lymphopenic mice. When transferred into lymphopenic recipients of male skin grafts, Th17 lines elicited a damaging reaction within the graft associated with pathological findings of epidermal hyperplasia and neutrophil infiltration. Th17 cells could be found in the grafted skins and spleens of recipients and maintained their polarized phenotype both in vivo and after ex vivo restimulation. Antibody-mediated neutralization of IL-17A or IFNγ did not interfere with Th17-induced pathology, nor did it prevent neutrophil infiltration. In conclusion, tissue damage by Th17 cells does not require IL-17A.

Reduced femoral component subsidence with improved impaction grafting at revision hip arthroplasty.

BACKGROUND: Despite stem subsidence being a major complication of femoral impaction bone grafting in cemented revision hip arthroplasty, few studies have distinguished subsidence at the prosthesis-cement interface from that at the cement-bone interface. It is unknown how technique developments intended to improve the procedure influence stability of the stem. QUESTIONS/PURPOSES: We used a sensitive technique to measure subsidence of a cemented polished collarless double-taper stem at each interface after femoral impaction grafting and compared subsidence, radiographic loosening, complications, and reoperations over three series of hips defined by technique developments. PATIENTS AND METHODS: Three series were defined: Series 1 (n = 23, irradiated allograft), Series 2 (n = 12, double-washed, size-profiled graft, nonirradiated bone, long stems as required), and Series 3 (n = 21, modular tamps). Stem subsidence was analyzed with Ein Bild Röntgen Analyse software. Radiographic loosening, complications, and reoperations were also determined. RESULTS: The median subsidence at 12 months for Series 1, 2, and 3 were 2.1, 0.5, and 0.7 mm at the prosthesis-cement interface and 1.3, 0.1, and 0.1 mm at the cement-bone interface. There were two postoperative Vancouver B periprosthetic fractures in Series 1, four hips were revised for loosening in Series 1, and there were no fractures or loosening in Series 2 and 3 at minimum 2 years' followup. There were no surviving hips radiographically classified as possibly or probably loose. CONCLUSIONS: Evolution in techniques of femoral impaction grafting in this study were associated with reduced subsidence of the stem at both the prosthesis-cement interface and cement-bone interface when compared to the original series. Concurrent with reduced stem subsidence was the absence of periprosthetic fracture, radiographic loosening, and complications requiring rerevision.

Probing the Ecology and Climate of the Eocene Southern Ocean With Sand Tiger Sharks Striatolamia macrota.

Many explanations for Eocene climate change focus on the Southern Ocean-where tectonics influenced oceanic gateways, ocean circulation reduced heat transport, and greenhouse gas declines prompted glaciation. To date, few studies focus on marine vertebrates at high latitudes to discern paleoecological and paleoenvironmental impacts of this climate transition. The Tertiary Eocene La Meseta (TELM) Formation has a rich fossil assemblage to characterize these impacts; Striatolamia macrota, an extinct (†) sand tiger shark, is abundant throughout the La Meseta Formation. Body size is often tracked to characterize and integrate across multiple ecological dimensions. †S. macrota body size distributions indicate limited changes during TELMs 2-5 based on anterior tooth crown height (n = 450, mean = 19.6 ± 6.4 mm). Similarly, environmental conditions remained stable through this period based on δ18OPO4 values from tooth enameloid (n = 42; 21.5 ± 1.6‰), which corresponds to a mean temperature of 22.0 ± 4.0°C. Our preliminary ε Nd (n = 4) results indicate an early Drake Passage opening with Pacific inputs during TELM 2-3 (45-43 Ma) based on single unit variation with an overall radiogenic trend. Two possible hypotheses to explain these observations are (1) †S. macrota modified its migration behavior to ameliorate environmental changes related to the Drake Passage opening, or (2) the local climate change was small and gateway opening had little impact. While we cannot rule out an ecological explanation, a comparison with climate model results suggests that increased CO2 produces warm conditions that also parsimoniously explain the observations.

Surgical anatomy for pelvic external fixation.

Pelvic external fixators have a high rate of reported complications, most of which relate to pin placement. In this descriptive study, we analyzed the morphology of the ilium in cadaveric specimens and compared these with the measures obtained from normal human pelvic computer tomograph scans, and how these related to each of the three basic configurations of pin positioning for the external fixation of a pelvis: anterosuperior (Slätis type), anteroinferior (supra-acetabular), and subcristal. The irregular shape and size of the iliac wing and the abdominal wall overlying the pin's insertion site could hinder accurate placement of anterosuperior pins. Potential disadvantages of the use of anteroinferior pins was found related to the deep location of the anterior inferior iliac spine, interference with the hip flexion area, risk of hip joint penetration, and the variable obliquity of the ilium. As subcristal pins are positioned between two superficial bony landmarks of the iliac crest, our findings suggest that they are more likely to have a correct placement and avoid complications.

Risk analysis of patients with an osteolytic acetabular defect after total hip arthroplasty using subject-specific finite-element modelling.

AIMS: Osteolysis, secondary to local and systemic physiological effects, is a major challenge in total hip arthroplasty (THA). While osteolytic defects are commonly observed in long-term follow-up, how such lesions alter the distribution of stress is unclear. The aim of this study was to quantitatively describe the biomechanical implication of such lesions by performing subject-specific finite-element (FE) analysis on patients with osteolysis after THA. PATIENTS AND METHODS: A total of 22 hemipelvis FE models were constructed in order to assess the transfer of load in 11 patients with osteolysis around the acetabular component of a THA during slow walking and a fall onto the side. There were nine men and two women. Their mean age was 69 years (55 to 81) at final follow-up. Changes in peak stress values and loads to fracture in the presence of the osteolytic defects were measured. RESULTS: The von Mises stresses were increased in models of those with and those without defects for both loading scenarios. Although some regions showed increases in stress values of up to 100%, there was only a moderate 11.2% increase in von Mises stress in the series as a whole. The site of fracture changed in some models with lowering of the load to fracture by 500 N. The most common site of fracture was the pubic ramus. This was more frequent in models with larger defects. CONCLUSION: We conclude that cancellous defects cause increases in stress within cortical structures. However, these are likely to lead to a modest decrease in the load to fracture if the defect is large (> 20cm3) or if the patient is small with thin cortical structures and low bone mineral density. Cite this article: Bone Joint J 2018;100-B:1455-62.

The gene defective in X-linked lymphoproliferative disease controls T cell dependent immune surveillance against Epstein-Barr virus.

Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the past two years. The gene that is aberrant in the condition - SH2D1A/SAP, which encodes SAP (signaling lymphocytic activation molecule [SLAM]-associated protein) - was cloned, the crystal structure of its product was solved and insights into the signaling mechanisms of this small SH2-domain-containing protein via the cell surface receptors SLAM and 2B4 have been provided. SAP mutation, and not Epstein-Barr virus infection per se, may be critical for XLP.

Revision total hip replacement using cemented collarless double-taper femoral components.

We investigated 219 revisions of total hip replacement (THR) in 211 patients using a collarless double-taper cemented femoral component. The mean age of the patients was 72 years (30 to 90). The 137 long and 82 standard length stems were analysed separately. The mean follow-up was six years (2 to 18), and no patient was lost to follow-up. Survival of the long stems to re-revision for aseptic loosening at nine years was 98% (95% confidence interval (CI) 94 to 100), and for the standard stems was 93% (95% CI 85 to 100). At five years, one long stem was definitely loose radiologically and one standard stem was probably loose. Pre-operative femoral bone deficiency did not influence the results for the long stems, and corrective femoral osteotomy was avoided, as were significant subsidence, major stress shielding and persistent thigh pain. Because of these reliable results, cemented long collarless double-taper femoral components are recommended for routine revision THR in older patients.

Proximal translation of > 1 mm within the first two years of revision total hip arthroplasty correctly predicts whether or not an acetabular component is loose in 80% of cases: a case-control study with confirmed intra-operative outcomes.

AIMS: The purpose of this study was to determine the sensitivity, specificity and predictive values of previously reported thresholds of proximal translation and sagittal rotation of cementless acetabular components used for revision total hip arthroplasty (THA) at various times during early follow-up. PATIENTS AND METHODS: Migration of cementless acetabular components was measured retrospectively in 84 patients (94 components) using Ein-Bild-Rontgen-Analyse (EBRA-Cup) in two groups of patients. In Group A, components were recorded as not being loose intra-operatively at re-revision THA (52 components/48 patients) and Group B components were recorded to be loose at re-revision (42 components/36 patients). RESULTS: The mean proximal translation and sagittal rotation were significantly higher in Group B than in Group A from three months onwards (p < 0.02). Proximal translation > 1.0 mm within 24 months had a positive predictive value (PPV) of 90% and a specificity of 94%, but a sensitivity of 64%. Proximal translation > 1.0 mm within the first 24 months correctly identified 76 of 94 (81%) of components to be either loose or not loose. However, ten components in Group B (24%) did not migrate proximally above 1.0 mm within the first 60 months. CONCLUSION: The high PPV of EBRA-Cup measurements of proximal translation (90%) shows that this can be used in early follow-up to identify patients at risk of aseptic loosening. The absence of proximal translation within the first 60 months indicates a component is not likely to be loose at re-revision THA although it does not exclude late aseptic loosening as a cause of failure. Cite this article: Bone Joint J 2017;99-B:465-74.

The diagnostic performance of radiographic criteria to detect aseptic acetabular component loosening after revision total hip arthroplasty.

AIMS: This study aimed to determine the diagnostic performance of radiographic criteria to detect aseptic acetabular loosening after revision total hip arthroplasty (THA). Secondary aims were to determine the predictive values of different thresholds of migration and to determine the predictive values of radiolucency criteria. PATIENTS AND METHODS: Acetabular component migration to re-revision was measured retrospectively using Ein-Bild-Rontgen-Analyse (EBRA-Cup) and manual measurements (Sutherland method) in two groups: Group A, 52 components (48 patients) found not loose at re-revision and Group B, 42 components (36 patients) found loose at re-revision between 1980 and 2015. The presence and extent of radiolucent lines was also assessed. RESULTS: Using EBRA, both proximal translation and sagittal rotation were excellent diagnostic tests for detecting aseptic loosening. The area under the receiver operating characteristic (ROC) curves was 0.94 and 0.93, respectively. The thresholds of 2.5 mm proximal translation or 2° sagittal rotation (EBRA) in combination with radiolucency criteria had a sensitivity of 93% and specificity of 88% to detect aseptic loosening. The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of radiolucency criteria were 41%, 100%, 100% and 68% respectively. Manual measurements of both proximal translation and sagittal rotation were very good diagnostic tests. The area under the ROC curve was 0.86 and 0.92 respectively. However, manual measurements had a decreased specificity compared with EBRA. Radiolucency criteria had a poor sensitivity and NPV of 41% and 68% respectively. CONCLUSION: This study shows that EBRA and manual migration measurements can be used as accurate diagnostic tools to detect aseptic loosening of cementless acetabular components used at revision THA. Radiolucency criteria should not be used in isolation to exclude loosening of cementless acetabular components used at revision THA given their poor sensitivity and NPV. Cite this article: Bone Joint J 2017;99-B:458-64.

Head-neck taper corrosion in hip arthroplasty.

Modularity at the head-neck junction of the femoral component in THA became popular as a design feature with advantages of decreasing implant inventory and allowing adjustment of leg length, offset, and soft tissue balancing through different head options. The introduction of a new modular interface to femoral stems that were previously monoblock, or nonmodular, comes with the potential for corrosion at the taper junction through mechanically assisted crevice corrosion. The incidence of revision hip arthroplasty is on the rise and along with improved wear properties of polyethylene and ceramic, use of larger femoral head sizes is becoming increasingly popular. Taper corrosion appears to be related to all of its geometric parameters, material combinations, and femoral head size. This review article discusses the pathogenesis, risk factors, clinical assessment, and management of taper corrosion at the head-neck junction.

Revision total hip arthroplasty using cemented collarless double-taper femoral components at a mean follow-up of 13 years (8 to 20): an update.

The outcome of 219 revision total hip arthroplasties (THAs) in 98 male and 121 female patients, using 137 long length and 82 standard length cemented collarless double-taper femoral stems in 211 patients, with a mean age of 72 years (30 to 90) and mean follow-up of six years (two to 18) have been described previously. We have extended the follow-up to a mean of 13 years (8 to 20) in this cohort of patients in which the pre-operative bone deficiency Paprosky grading was IIIA or worse in 79% and 73% of femurs with long and standard stems, respectively. For the long stem revision group, survival to re-revision for aseptic loosening at 14 years was 97% (95% confidence interval (CI) 91 to 100) and in patients aged > 70 years, survival was 100%. Two patients (two revisions) were lost to follow-up and 86 patients with 88 revisions had died. Worst-case analysis for survival to re-revision for aseptic loosening at 14 years was 95% (95% CI 89 to 100) and 99% (95% CI 96 to 100) for patients aged > 70 years. One additional long stem was classified as loose radiographically but not revised. For the standard stem revision group, survival to re-revision for aseptic loosening at 14 years was 91% (95% CI 83 to 99). No patients were lost to follow-up and 49 patients with 51 hips had died. No additional stems were classified as loose radiographically. Femoral revision using a cemented collarless double-taper stem, particularly with a long length stem, and in patients aged > 70 years, continues to yield excellent results up to 20 years post-operatively, including in hips with considerable femoral metaphyseal bone loss.

Intra-operative deviation in limb alignment occurring at implantation in total knee arthroplasty.

BACKGROUND: Long-term survival of knee replacement depends on accurate alignment. Despite improvements in cut accuracy mal-alignment of 3° or more is still seen. All methods share common implantation techniques. This study examines the effect of implantation on overall limb alignment relating it to cut alignment and trial alignment. METHODS: A retrospective review of navigated primary knee replacements was undertaken (n=113). Overall coronal limb alignments for the aggregated cuts, trial and final implanted components were examined. RESULTS: All 113 knees had coronal aggregated cut alignment within 2° of neutral (range: 2° varus to 2° valgus). With trial components 99 knees (88%) had an overall coronal limb alignment within 2° of neutral (range: 3° varus to 4° valgus). After final implantation 106 knees (94%) were within 2° of neutral (range: 4° varus to 4° valgus). Forty eight knees (42%) showed no alignment deviation occurring between trial and the final implanted prostheses and 16 knees (14%) shoed a deviation of 2° or more. There was a correlation of both aggregated cut (r=0.284, p=0.002) and trial (r=0.794, p<0.001) with final alignment. There was no significant difference between the final alignment and the aggregated cut alignment(mean difference=-0.15°, p=0.254) or trial alignment (mean difference -0.13°, p=0.155). CONCLUSIONS: Even when the aggregated alignment produced by the bone cuts is accurate, inaccuracy in final alignment can result from the implantation process. It may be productive for surgeons to concentrate on the implantation process to improve alignment and reduce outliers.

Synovial macrophage response to aluminium oxide ceramic and cobalt-chrome alloy wear particles in rats.

The tissue response to intra-articular injection into rat knees of similar concentrations of sterile cobalt-chrome (Co-Cr) alloy and aluminium oxide (AL2O3) ceramic prosthesis wear particles was assessed at 1, 4 and 13 wk. A semiquantitative method of histological assessment showed a correlation between the numbers of particles and macrophage response in the tissues, and a difference in the response to different concentrations of Co-Cr particles. At 1 wk, the macrophage response to Co-Cr particles was significantly greater (p less than or equal to 0.01) than that to AL2O3 particles but no difference was detected at 4 and 13 wk. The difference may be due to necrosis of macrophages induced by Co-Cr particles.

Macrophage colony-stimulating factor and interleukin-6 release by periprosthetic cells stimulates osteoclast formation and bone resorption.

Periprosthetic bone loss is an important contributory factor for aseptic loosening of total joint replacements. It has recently been shown that osteoclast precursor cells are present in the wear particle-associated macrophage infiltrate found in the membrane surrounding loose implants and that these cells are capable of differentiating into osteoclastic bone-resorbing cells. Long-term co-culture of arthroplasty-derived macrophages and the rat osteoblast-like cell line, UMR-106, in the presence of 1,25(OH)2D3 results in the formation of numerous multinucleated cells that are positive for tartrate-resistant acid phosphatase and vitronectin receptor and capable of extensive lacunar bone resorption. The aim of this study was to determine the effect of cytokines/growth factors, known to be present in the arthroplasty membrane, on this process of osteoclast differentiation. During osteoclast formation, increased levels of macrophage colony-stimulating factor, interleukin-6, and to a lesser extent, interleukin-1beta, but not tumour necrosis factor alpha, were detected in the co-culture supernatants. Addition of neutralising antibodies to human interleukin-1beta or tumour necrosis factor alpha to the co-culture system did not inhibit osteoclast formation. In contrast, co-cultures to which neutralising antibodies to human macrophage colony-stimulating factor or interleukin-6 were added contained fewer cells positive for tartrate-resistant acid phosphatase and vitronectin receptor and formed significantly fewer resorption pits. Time-course studies showed that macrophage colony-stimulating factor and interleukin-6 increase osteoclast formation mainly in the early stages of osteoclast differentiation. These results indicate that the release of macrophage colony-stimulating factor and interleukin-6 by activated cells in the arthroplasty membrane is likely to contribute to pathological bone resorption associated with aseptic loosening by stimulating differentiation of mononuclear phagocyte osteoclast precursors into mature bone-resorbing cells.

A method for production and characterization of metal prosthesis wear particles.

The wear of joint prostheses generates wear particles that produce an inflammatory response in the surrounding tissues and may contribute to bone resorption resulting in prosthetic loosening. Although the effects of particles produced from prosthetic materials have been studied extensively in vitro and in vivo, little attention has been paid to the standardisation of methods for the generation and characterization of these particles. This paper describes a reproducible method for generation of metal particles by the abrasive shaking of joint replacement components. Particular attention was given to the production of metal particles that closely resembled particles found around solid and loose human prostheses. To achieve this, particle size, size distribution, chemical composition, and shape were characterized. Particles that were 0.5-3.0 microns in diameter were isolated by differential sedimentation, and the distribution of particle sizes was determined with use of a Coulter Multisizer. Chemical composition was measured by atomic absorption spectrophotometry, and transmission electron microscopy was used to characterize particle shape. The techniques were shown to be reproducible, since there was little variation between batches over a lengthy time period. These or similar methods of particle production and characterization should be an essential part of future in vitro and in vivo studies of wear particles.

A rat model of resorption of bone at the cement-bone interface in the presence of polyethylene wear particles.

Resorption of bone and the formation of a membrane at the interface between acrylic cement and bone were induced by particles of high-density polyethylene that were similar in size to those that are present in the tissues surrounding a human joint prosthesis. A non-weight-bearing plug of methylmethacrylate was inserted through the knee joint into the distal part of the femur of the rat. The plug rapidly became surrounded by a shell of bone. After repeated injections of particles of high-density polyethylene into the knee joint, resorption of bone occurred at this stable interface. No resorption of bone occurred after the opposite knee was injected with a control preparation that did not contain particles. The resorption of bone that occurred around the plug after the injection of particles of polyethylene took place in the absence of mechanical causes for loosening and in the absence of infection.

Wagner resurfacing hip arthroplasty. The results of one hundred consecutive arthroplasties after eight to ten years.

In a prospective study of 100 consecutive Wagner resurfacing hip arthroplasties in ninety-three patients, the outcomes for all hips were determined for an eight to ten-year follow-up period. By survivorship analysis, the rate of survival of the arthroplasty was calculated to be 70 per cent at five years, but only 40 per cent at eight years. The major cause of failure was aseptic loosening of the acetabular or femoral component, or both. Fracture of the neck of the femur occurred in three hips. Although the medium-term results (at fifty-six to eighty-three months) were better than those in most comparable studies of resurfacing arthroplasty, the poor long-term results (at ninety-one to 118 months) show that meaningful studies of new prosthetic designs must continue for at least eight years, and, if at all possible, must include 100 per cent follow-up. The survival curve for the resurfacing arthroplasties in this study can serve as the basis for comparison of the early, medium, and long-term results of future designs of resurfacing hip prostheses.

The technetium phosphate bone scan in the diagnosis of osteomyelitis in childhood.

We reviewed the technetium phosphate scans of 280 patients who had been referred with a clinical diagnosis of osteomyelitis in order to establish the diagnostic accuracy of this procedure. Strict criteria were established to define two subgroups: one of patients with proved osteomyelitis and one of patients who definitely did not have osteomyelitis. The scan correctly identified osteomyelitis at fifty-five of sixty-two sites, and was correctly negative in seventy-four of seventy-nine patients without osteomyelitis. The scan correctly distinguished all cases of cellulitis or soft-tissue abscess from osteomyelitis, but identified osteomyelitis in eight of thirty-nine patients with septic arthritis. The phosphate bone scan maintained this accuracy through any duration of symptoms, and performed almost equally well at all skeletal sites and in all age groups.