Change in Low Back Movement Patterns After Neurosurgical Intervention for Lumbar Spondylosis.

OBJECTIVES: The purpose of this study was to assess the use of computer-aided combined movement examination (CME) to measure change in low back movement after neurosurgical intervention for lumbar spondylosis and to use a CME normal reference range (NRR) to compare and contrast movement patterns identified from lumbar disk disease, disk protrusion, and nerve root compression cases. METHODS: A test-retest, cohort observational study was conducted. Computer-aided CME was used to record lumbar range of motion in 18 patients, along with pain, stiffness, disability, and health self-report questionnaires. A minimal clinically important difference of 30% was used to interpret meaningful change in self-reports. z Scores were used to compare CME. Post hoc observation included subgrouping cases into 3 discrete pathologic conditions-disk disease, disk protrusion, and nerve root compression-to report intergroup differences in CME. RESULTS: Self-report data indicated that 11, 7, and 10 patients improved by ≥30% in pain, stiffness, and function, respectively. Three patients experienced clinically significant improvement in health survey. A CME pattern reduced in all directions suggested disk disease. Unilaterally restricted movement in side-flexed or extended directions suggested posterolateral disk protrusion with or without ipsilateral nerve root compression. Bilateral restrictions in extension suggested posterior disk protrusion with or without nerve root compression. In 11 of the 18 cases, CME converged toward the NRR after surgery. CONCLUSION: We described the use of CME to identify atypical lumbar movement relative to an NRR. Data from this short-term postoperative study provide preliminary evidence for CME movement patterns suggestive of disk disease, disk protrusion, and nerve root compression.

Structure-Specific Movement Patterns in Patients With Chronic Low Back Dysfunction Using Lumbar Combined Movement Examination.

OBJECTIVE: A test-retest cohort study was conducted to assess the use of a novel computer-aided, combined movement examination (CME) to measure change in low back movement after pain management intervention in 17 cases of lumbar spondylosis. Additionally we desired to use a CME normal reference range (NRR) to compare and contrast movement patterns identified from 3 specific structural pathologic conditions: intervertebral disc, facet joint, and nerve root compression. METHODS: Computer-aided CME was used before and after intervention, in a cohort study design, to record lumbar range of movement along with pain, disability, and health self-report questionnaires in 17 participants who received image-guided facet, epidural, and/or rhizotomy intervention. In the majority of cases, CME was reassessed after injection together with 2 serial self-reports after an average of 2 and 14 weeks. A minimal clinically important difference of 30% was used to interpret meaningful change in self-reports. A CME NRR (n = 159) was used for comparison with the 17 cases. Post hoc observation included subgrouping cases into 3 discrete pathologic conditions, intervertebral disc, facet dysfunction, and nerve root compression, in order to report intergroup differences in CME movement. RESULTS: Seven of the 17 participants stated that a "combined" movement was their most painful CME direction. Self-report outcome data indicated that 4 participants experienced significant improvement in health survey, 5 improved by ≥30% on low back function, and 8 reported that low back pain was more bothersome than stiffness, 6 of whom achieved the minimal clinically important difference for self-reported pain. Subgrouping of cases into structure-specific groups provided insight to different CME movement patterns. CONCLUSION: The use of CME assists in identifying atypical lumbar movement relative to an age and sex NRR. Data from this study, exemplified by representative case studies, provide preliminary evidence for distinct intervertebral disc, facet joint, and nerve root compression CME movement patterns in cases of chronic lumbar spondylosis.

Effects of the assessment of 4 determinants of structural geometry on QCT- and DXA-derived hip structural analysis measurements in elderly women.

Previously we reported that the corresponding 2-dimensional (2D) structural geometry measures derived from quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) of femoral neck were different. Now, we test the hypothesis that the following 4 measures: areal bone mineral density, W, and 2 new measures, standard deviation (σ) of a normalized mineral mass projection profile distribution and the displacement between centre of mineral mass and geometric centre of mineral mass (δ) of the projection profile allow transformation from one measurement modality to the other with high precision. QCT and DXA scans and hip structural analysis (HSA) performed on 237 women were randomly allocated into cohorts of 118 (cohort A) and 119 (cohort B). Intercepts and gradients from linear regression of the 4 QCT- and DXA-derived measures were obtained from cohort A and used to convert cohort B QCT-derived structural geometry measurements into their DXA equivalent. Corresponding cohort B QCT- and DXA-derived structural geometrical measurements were compared using Bland-Altman plots and regression analysis. Apart from W, comparisons of the 7 nontransformed QCT- and DXA-derived variables were significantly different using paired t-tests. Cross-calibration with the set of 4 base measures resolved the differences in all original variables. These data provide a mechanism for cross-calibrating HSA outcomes acquired using QCT and DXA and demonstrate that a complex 2D digitized structure can be described by 4 variables.

Enzyme-mediated site-specific bioconjugation of metal complexes to proteins: sortase-mediated coupling of copper-64 to a single-chain antibody.

The enzyme-mediated site-specific bioconjugation of a radioactive metal complex to a single-chain antibody using the transpeptidase sortase A is reported. Cage amine sarcophagine ligands that were designed to function as substrates for the sortase A mediated bioconjugation to antibodies were synthesized and enzymatically conjugated to a single-chain variable fragment. The antibody fragment scFv(anti-LIBS) targets ligand-induced binding sites (LIBS) on the glycoprotein receptor GPIIb/IIIa, which is present on activated platelets. The immunoconjugates were radiolabeled with the positron-emitting isotope (64)Cu. The new radiolabeled conjugates were shown to bind selectively to activated platelets. The diagnostic potential of the most promising conjugate was demonstrated in an in vivo model of carotid artery thrombosis using positron emission tomography. This approach gives homogeneous products through site-specific enzyme-mediated conjugation and should be broadly applicable to other metal complexes and proteins.

Diagnostic imaging agents for Alzheimer's disease: copper radiopharmaceuticals that target Aß plaques.

One of the pathological hallmarks of Alzheimer's disease is the presence of amyloid-ß plaques in the brain and the major constituent of these plaques is aggregated amyloid-ß peptide. New thiosemicarbazone-pyridylhydrazine based ligands that incorporate functional groups designed to bind amyloid-ß plaques have been synthesized. The new ligands form stable four coordinate complexes with a positron-emitting radioactive isotope of copper, (64)Cu. Two of the new Cu(II) complexes include a functionalized styrylpyridine group and these complexes bind to amyloid-ß plaques in samples of post-mortem human brain tissue. Strategies to increase brain uptake by functional group manipulation have led to a (64)Cu complex that effectively crosses the blood-brain barrier in wild-type mice. The new complexes described in this manuscript provide insight into strategies to deliver metal complexes to amyloid-ß plaques.

An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits.

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6x10(-8)), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6x10(-13); SOX6, p = 6.4x10(-10)) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation.

Direct in vivo comparison of [18F]PSMA-1007 with [68Ga]Ga-PSMA-11 and [18F]AlF-PSMA-11 in mice bearing PSMA-expressing xenografts.

The aim of this preclinical study was to directly compare [18F]PSMA-1007 with both [68Ga]Ga-PSMA-11 and [18F]AlF-PSMA-11 in mice bearing PSMA-positive tumor xenografts. Uptake was assessed by PET/CT at 1, 2 and 4 h post-injection, and by ex vivo measurement after 4 h. [18F]PSMA-1007 demonstrated the highest tumor uptake of the three tracers. The high uptake in bone for mice injected with [18F]AlF-PSMA-11 suggested rapid in vivo decomposition. This was confirmed by an in vitro plasma stability study.

A comparative study between corresponding structural geometric variables using 2 commonly implemented hip structural analysis algorithms applied to dual-energy X-ray absorptiometry images.

Hip structural analysis (HSA) has been developed over 20 yr, applied extensively in research, and has demonstrated useful outcomes associating bone structural geometry with bone fragility (research-HSA or r-HSA). In 2007, Hologic Inc. (Bedford, MA) incorporated HSA with some modifications as an option for Hologic dual-energy X-ray absorptiometry (DXA) scanners (clinical HSA or c-HSA). This brought HSA from the research environment into the clinical environment. This article reports a comparison of r-HSA and c-HSA implementations using DXA scans from a group of 191 females. Bland-Altman plots at the narrow-neck (NN) HSA region indicated higher r-HSA areal bone mineral density (mean difference: 0.27 g/cm(2); 21.7% [of mean]); cross-sectional area (0.63 cm(2); 18.7%); cross-sectional moment of inertia (0.26 cm(4); 11.1%), and section modulus (0.22 cm(3); 14.5%) compared with c-HSA. The converse was observed for NN subperiosteal width (-0.09 cm; 3.1%). High linear correlations (r(2) > 0.81) were found between r-HSA and c-HSA NN structural geometric outcomes, with the exception of neck shaft angle (r(2) > 0.47). As differences were significant (p < 0.001), slopes and intercepts are provided to enable linear transformations from r-HSA to corresponding c-HSA structural geometric data.

Geometric indices of bone strength are associated with physical activity and dietary calcium intake in healthy older women.

UNLABELLED: A population-based study on 1008 postmenopausal women identified that the 24% of women achieving high levels of PA and CI had 3.4-4.4% higher femoral bone strength in axial compression and 1.7-5.2% in bending than those achieving low levels, indicating that lifestyle factors influence bone strength in the proximal femur. INTRODUCTION: Extensive research has shown that increased physical activity (PA) and calcium intake (CI) decrease the rate of bone loss; however, there is little research on how these lifestyle variables affect bone geometry. This study was designed to investigate the effects of modifiable lifestyle variables, habitual PA and dietary CI, on femoral geometry in older women. MATERIALS AND METHODS: Femoral geometry, habitual PA, and dietary CI were measured in a population-based sample of 1008 women (median age+/-interquartile range, 75+/-4years) enrolled in a randomized controlled trial (RCT) of calcium supplementation. Baseline PA and CI were assessed by validated questionnaires, and 1-year DXA scans (Hologic 4500A) were analyzed using the hip structural analysis technique. Section modulus (Z), an index of bending strength, cross-sectional area (CSA), an index of axial compression strength, subperiosteal width (SPW), and centroid position, the position of the center of mass, were measured at the femoral neck (NN), intertrochanter (IT), and femoral shaft (FS) sites. These data were divided into tertiles of PA and CI, and the results were compared using analysis of covariance (ANCOVA), with corrections for age, height, weight, and treatment (calcium/placebo). RESULTS AND CONCLUSIONS: PA showed a significant dose-response effect on CSA all hip sites (p<0.03) and Z at the narrow neck and intertrochanter sites (p<0.02). For CI, there was a dose-response effect for centroid position at the intertrochanter (p=0.03). These effects were additive, such that the women (n=240) with PA in excess of 65.5 kcal/day and CI in excess of 1039 mg/day had significantly greater CSA (NN, 4.4%; IT, 4.3%; FS, 3.4%) and Z (NN, 3.9%; IT, 5.2%). These data show a favorable association between PA and aspects of bone structural geometry consistent with better bone strength. Association between CI and bone structure was only evident in 1 of 15 variables tested. However, there was evidence that there may be additive effects, whereby women with high levels of PA and CI in excess of 1039 mg/day had significantly greater CSA (NN, 0.4%; FS, 2.1%) and Z (IT, 3.0%) than women with high PA but low CI. These data show that current public health guidelines for PA and dietary CI are not inappropriate where bone structure is the health component of interest.

Change of sagittal spinal alignment and its association with pain and function after lumbar surgery augmented with an interspinous implant.

BACKGROUND: Interspinous spacer/implants like the Device for Intervertebral Assisted Motion (DIAM™) are controversially yet commonly used in the surgical treatment of lumbar degenerative pathologies. Criticism is based on ill-defined indications, lack of superiority over decompression, and a poorly understood mechanical effect. Yet, continued use by surgeons implies their perceived clinical merit. We examined radiographic spinal alignment for 12 months, and pain and function for 24 months, after DIAM-augmented surgery to improve the understanding of the mechanical effect relating to clinical outcomes in patients. METHODS: We undertook a single-surgeon prospective, longitudinal study of 40 patients (20 F, 20 M) who received DIAM-augmented surgery in treatment of their symptomatic lumbar degenerative condition. Outcomes measured included sagittal spinal alignment (lumbar lordosis, sacral inclination, primary (PDA), supradjacent (SDA) disc angles, and regional sagittal balance (RSB; standing lateral radiographs), and back and leg pain (visual analogue scale; VAS) and function (Oswestry Disability Index; ODI). Responders were identified as those with clinically meaningful improvement to pain (>20%) and function (>15%) at 24 months postoperatively; features of sagittal spinal alignment between responders and non-responders were examined. RESULTS: Sagittal alignment was unchanged at 12 months. At 6 weeks postoperatively, PDA (mean (SD)) reduced by 2.2° (4.0°; p < 0.01) and more-so in back pain non-responders (3.8° (3.2°)) than responders (0.7° (4.4°); p < 0.05). Positive preoperative RSB in responders (26.7Rmm (42.3Rmm); Rmm is a system-relative measure) decreased at 6 weeks (by 3.1Rmm (9.1Rmm)). Non-responders had a negative RSB preoperatively (-1.0Rmm (32.0Rmm)) and increased at 6 weeks (11.2Rmm (15.5Rmm); p < 0.05). Clinically meaningful improvement for the whole cohort for back pain and function were observed to 24 months (back pain: 25.0% (28.0); function: 15.4% (17.6); both p < 0.0001). CONCLUSIONS: Unaltered sagittal alignment at 12 months was not related to symptoms after DIAM-augmented lumbar surgery. Subtle early flattening at the index disc angle was not maintained. Preoperative and early post-operative sagittal alignment may indicate response after DIAM-augmented surgery for mixed lumbar pathologies. Further investigation toward defining indications and patient suitability is warranted.

An MRI investigation of intervertebral disc deformation in response to torsion.

BACKGROUND: The nucleus pulposus deforms towards an area of least compression in response to offset loading, however, there is a lack of data reporting the deformation patterns of nuclear material in rotated positions of the lumbar spine. Our purpose was to assess a novel methodology using MRI to track nuclear deformation in response to flexion and extension positions, and the combined positions of flexion with left rotation and extension with left rotation, at L1-2 and L4-5. METHODS: Three asymptomatic female subjects, mean age 27 years, underwent T2 weighted MRI sequences in flexed, extended, and left rotated positions combined with flexion and extension. A pixel profile technique was employed to determine direction and magnitude of nuclear deformation. RESULTS: In 5 of 6 discs examined, deformation of the nucleus occurred anteriorly in extension and posteriorly in flexion. Left rotation resulted in migration of nuclear material to the right in 9 of 12 discs. Of the three discs that demonstrated a right nuclear migration, two occurred at L4-5 and one at L1-2. INTERPRETATION: This methodology demonstrated that nucleus pulposus deformation can be measured reliably in various positions achieved within the confines of the MRI. The consistent migration of nuclear material following sagittal plane movement and the less consistent response to rotation positions suggest other asymmetrical loading on the intervertebral disc may accompany rotation.

In vivo short-term precision of hip structure analysis variables in comparison with bone mineral density using paired dual-energy X-ray absorptiometry scans from multi-center clinical trials.

Hip structural analysis (HSA) is a technique for extracting strength-related structural dimensions of bone cross-sections from two-dimensional hip scan images acquired by dual energy X-ray absorptiometry (DXA) scanners. Heretofore the precision of the method has not been thoroughly tested in the clinical setting. Using paired scans from two large clinical trials involving a range of different DXA machines, this study reports the first precision analysis of HSA variables, in comparison with that of conventional bone mineral density (BMD) on the same scans. A key HSA variable, section modulus (Z), biomechanically indicative of bone strength during bending, had a short-term precision percentage coefficient of variation (CV%) in the femoral neck of 3.4-10.1%, depending on the manufacturer or model of the DXA equipment. Cross-sectional area (CSA), a determinant of bone strength during axial loading and closely aligned with conventional DXA bone mineral content, had a range of CV% from 2.8% to 7.9%. Poorer precision was associated with inadequate inclusion of the femoral shaft or femoral head in the DXA-scanned hip region. Precision of HSA-derived BMD varied between 2.4% and 6.4%. Precision of DXA manufacturer-derived BMD varied between 1.9% and 3.4%, arising from the larger analysis region of interest (ROI). The precision of HSA variables was not generally dependent on magnitude, subject height, weight, or conventional femoral neck densitometric variables. The generally poorer precision of key HSA variables in comparison with conventional DXA-derived BMD highlights the critical roles played by correct limb repositioning and choice of an adequate and appropriately positioned ROI.

Epidemiology of ductal carcinoma in situ in Western Australia: implications for surgical margins and management.

BACKGROUND: In 2010, the Australian Institute of Health and Welfare published a report examining the characteristics of Australian women diagnosed with ductal carcinoma in situ (DCIS). This study identified the characteristics of women who were diagnosed with DCIS in Western Australia (WA) 1996-2005, and built on a national study by determining the rate of second operation and breast cancer events (BCE) in WA. METHODS: A retrospective analysis of data from the WA Cancer Registry and the Hospital Morbidity Database was undertaken. The main outcome measures were histological characteristics, second operation rate, breast cancer events. RESULTS: A total of 1356 cases of DCIS were diagnosed in WA between 1996 and 2005, with a minimum 5-year follow-up. The age-standardised incidence rate in 2005 was 15.4 per 100,000 women. 72 % of patients received breast-conserving therapy for primary treatment, 18 % of patients requiring a second operation to obtain adequate margins and 35 % of patients received postoperative radiotherapy. 17.3 % of cases had a subsequent BCE, with the 5- and 10-year probabilities being 4.36 and 8.27 %, respectively. A BCE was significantly associated with age (p < 0.001), no second operation (p < 0.001) and no radiotherapy (p = 0.049 recurrence, p = 0.043 invasion). CONCLUSION: This study supports the need to ensure adequate margins during primary surgery for DCIS is obtained to reduce the need for a second operation or the risk of a subsequent BCE. The consideration of mastectomy versus radiotherapy should be made in conjunction with the identified risk factors, specifically age and whether a second operation was performed.

Bifunctional (64)Cu-labelled macrobicyclic cage amine isothiocyanates for immuno-positron emission tomography.

New macrobicyclic cage amine or "sarcophagine" (sar) bifunctional chelators have been synthesised that form copper complexes of exceptional in vivo stability and incorporate isothiocyanate (-NCS) functional groups for conjugation to an antibody. The chelators were synthesised from the methyl-capped complex [Mg(II)(CH3)(NH2)sar](2+). Coordination of Mg(II) within the cavity of the cage amine ligand protects the secondary amine atoms from reacting with the -NCS functional groups. Two different [Mg(II)(NCS-sar)](2+) derivatives were conjugated to the HER2/neu-targeting antibody trastuzumab and the progress of the reaction monitored by electrospray mass spectrometry. The Mg(II) ion was removed from the immunoconjugates under mild conditions (0.1 M citrate buffer, pH 6). Labelling of the (CH3)(p-NCS-Ph)sar-trastuzumab conjugate with (64)Cu(II), a radioisotope suitable for positron emission tomography (PET), was fast (∼5 min) and easily performed at room temperature with high radiochemical purity (>95%). Biodistribution and PET imaging studies in vivo showed that (64)Cu-labelled (CH3)(p-NCS-Ph)sar-trastuzumab maintained high stability under physiological conditions with high and selective uptake in a HER2-positive cancer cell line. The stability of the copper complex and the 12.7 h half-life of the radioisotope allows clear visualisation of tumours out to 48 h.

Engineering poly(ethylene glycol) particles for improved biodistribution.

We report the engineering of poly(ethylene glycol) (PEG) hydrogel particles using a mesoporous silica (MS) templating method via tuning the PEG molecular weight, particle size, and the presence or absence of the template and investigate the cell association and biodistribution of these particles. An ex vivo assay based on human whole blood that is more sensitive and relevant than traditional cell-line based assays for predicting in vivo circulation behavior is introduced. The association of MS@PEG particles (template present) with granulocytes and monocytes is higher compared with PEG particles (template absent). Increasing the PEG molecular weight (from 10 to 40 kDa) or decreasing the PEG particle size (from 1400 to 150 nm) reduces phagocytic blood cell association of the PEG particles. Mice biodistribution studies show that the PEG particles exhibit extended circulation times (>12 h) compared with the MS@PEG particles and that the retention of smaller PEG particles (150 nm) in blood, when compared with larger PEG particles (>400 nm), is increased at least 4-fold at 12 h after injection. Our findings highlight the influence of unique aspects of polymer hydrogel particles on biological interactions. The reported PEG hydrogel particles represent a new class of polymer carriers with potential biomedical applications.

Lifestyle influences on 9-year changes in BMD in young women.

UNLABELLED: The effects of dietary calcium intake and physical activity on longitudinal changes in BMD over a mean of 9.4 years were examined in 62 healthy young women. Proximal femur BMD declined, lumbar spine BMD increased, and physical activity was associated with BMD change at intertrochanter and total hip sites. INTRODUCTION: Maximizing premenopausal BMD is an important strategy for the prevention of osteoporosis and resultant fractures later in life. MATERIALS AND METHODS: Young women who previously participated in a placebo-controlled 2-year calcium intervention study at a mean age of 18.5 +/- 0.3 years were remeasured at 27.8 +/- 1.0 years of age. DXA (Hologic QDR 1000W) was used to measure changes in BMD, and lifestyle factors were ascertained by questionnaire. RESULTS AND CONCLUSIONS: Early decline in BMD at the neck of femur (-3.3%/decade) and the converse gain in BMD at the lumbar spine (+4.3%/decade) and intertrochanter (+1.9%/decade) suggest site-specific changes in BMD in young premenopausal women. No effect of previous calcium supplementation was seen on current BMD or changes in BMD (p > 0.10). Lifestyle predictors of change in BMD were determined using hierarchical regression analysis after forced correction for the covariates baseline BMD and previous calcium supplementation. Physical activity was positively associated with change in BMD at total hip and intertrochanter sites (beta-coefficients, beta = 0.26 and 0.26 respectively; p < 0.05). Calcium intake was negatively associated with change in BMD at the lumbar spine (beta = -0.27, p < 0.05). Parity was negatively associated with change in BMD at all sites (beta = -0.40 to -0.26, p < 0.05). These data show that BMD is already declining at the proximal femur in these healthy young women. Physical activity assists in maintenance of BMD at some sites and thus may contribute to lifelong fracture prevention. There was no positive association between calcium intake and change in BMD.

Impact of the analysis of a bone density reference range on determination of the T-score.

There are uncertainties concerning the optimal threshold value of bone mineral density (BMD) for the diagnosis of osteoporosis using dual-energy X-ray absorptiometry (DXA). The most widely accepted clinical criteria are based on T- and Z-scores, derived statistically from an age-dependent BMD reference range that includes healthy young adults. This study has compared different analyses of BMD data of healthy, nonfractured, adult white females aged 18-90 years, consisting of 953 studied with DXA in the L1-L4 spine and 1018 measured at the hip. Four regression curves were applied to each reference data set; mean peak BMD (PBMD(R)) and the age-independent standard deviation (SD(R)) were calculated. These data, plus derived T-score thresholds, were compared with equivalent values (PBMD(YN), SD(YN)) determined from BMDs of a subgroup of young normals. Choice of regression curve caused a variation of 0.044 g/cm(2) in spinal PBMD(R) and 0.015-0.022 g/cm(2) in the hip. The variation in calculated SD(R) between the regressions was minimal (maximum variation, 0.03 SD unit in the spine). A split-linear model was chosen as the best overall fit for both the spine and the hip on the basis of goodness-of-fit and biological plausibility. PBMD(R) and PBMD(YN) varied by less than 1% at the spine or hip. Although the difference between SD(R) and SD(YN) was < or =7% for the hip sites, SD(R) was 0.022 g/cm(2) > SD(YN) for the spine (17% difference). At each hip site, BMD T-score thresholds, derived from regression analysis of the entire reference range (T(R)) or from young normals only (T(YN)), were not significantly different; however, equivalent spinal values differed by 0.062 g/cm(2) for T = -2.5. The percentage of the Australian female population (AFP) aged 50 yr or older and classified as osteoporotic, using population census data and the split-line-based T-score threshold of T(R) = -2.5, was 23% for spinal BMD and 17% for the total hip. For T(YN) = -2.5, the values were 36% (spine) and 17% (total hip). The hip BMDs of this study were greater than those of NHANES III in the third, seventh and eighth decades by as much as 0.6 SD. This produced a difference of 0.049-0.077 g/cm(2) for T(YN) = -2.5 between the two reference ranges.

Comparison of pencil-beam and fan-beam DXA systems.

Patients attending a routine bone densitometry clinic were scanned on two different densitometers on the same day using a pencil-beam (Hologic QDR1000W) and fan-beam (Hologic QDR4500W) machine. Subjects were scanned at the lumbar spine site and or the proximal femur. The differences in bone mineral density (BMD) between the fan-beam and pencil-beam (QDR4500W-QDR1000W) were determined for all pairs of scans. The mean difference in BMD was also calculated to see if there was a systematic bias between the machines. The mean difference in BMD was -8 mg/cm2 and 25 mg/cm2 at the spine and total hip, respectively. The individual differences in BMD between the two machines were examined to assess if they were significantly greater than measurement error. The percentage of scans classified as significantly different was calculated for the difference in BMD before and after adjusting for the mean difference in BMD. The percentage of individuals classified as significantly different ranged from 17.1-45.0% before adjustment, at the spine and total hip, respectively, and 16.1-22.6% after adjustment. From a clinical perspective, this degree of misclassification is probably unacceptable. These results suggest that scans obtained from a QDR4500W fan-beam system and QDR1000W pencil-beam system should not be compared, with or without adjustment for systematic bias.

Intraoperative assessment of margins in breast conserving therapy: a systematic review.

Approximately one quarter of patients undergoing breast conserving therapy for breast cancer will require a second operation to achieve adequate clearance of the margins. A number of techniques to assess margins intraoperatively have been reported. This systematic review examines current intraoperative methods for assessing margin status. The final pathology status, statistical measures including accuracy of tumour margin assessment, average time impact on the procedure and second operation rate, were used as criteria for comparison between studies. Although pathological methods, such as frozen section and imprint cytology performed well, they added on average 20-30 min to operation times. An ultrasound probe allows accurate examination of the margins and delivers results in a timely manner, yet it has a limited role with DCIS where calcification is present and in multifocal cancer. Further research is required in other intraoperative margin assessment techniques, such as mammography, radiofrequency spectroscopy and optical coherence tomography.

Excitation functions of (nat)Zn(p,x) nuclear reactions with proton beam energy below 18 MeV.

We measured the excitation functions of (nat)Zn (p,x) reactions up to 17.6MeV, using the stacked-foils activation technique. High-purity natural zinc (and copper) foils were irradiated with proton beams generated by an 18MeV isochronous cyclotron. Activated foils were measured using high-purity Ge gamma spectroscopy to quantify the radionuclides (61)Cu, (66)Ga, (67)Ga, and (65)Zn produced from the reactions. Thick-target integral yields were also deduced from the measured excitation functions of the produced radioisotopes. These results were compared with the published literature and were found to be in good agreement with most reports, particularly those most recently compiled.