Error and uncertainty of adult age estimation of the pubic symphysis in an Australian sub-population using computed tomography

After attending this presentation, attendees will gain awareness of: (1) the error and uncertainty associated with the application of the Suchey-Brooks (S-B) method of age estimation of the pubic symphysis to a contemporary Australian population; (2) the implications of sexual dimorphism and bilateral asymmetry of the pubic symphysis through preliminary geometric morphometric assessment; and (3) the value of three-dimensional (3D) autopsy data acquisition for creating forensic anthropological standards. This presentation will impact the forensic science community by demonstrating that, in the absence of demographically sound skeletal collections, post-mortem autopsy data provides an exciting platform for the construction of large contemporary ‘virtual osteological libraries’ for which forensic anthropological research can be conducted on Australian individuals. More specifically, this study assesses the applicability and accuracy of the S-B method to a contemporary adult population in Queensland, Australia, and using a geometric morphometric approach, provides an insight to the age-related degeneration of the pubic symphysis. Despite the prominent use of the Suchey-Brooks (1990) method of age estimation in forensic anthropological practice, it is subject to intrinsic limitations, with reports of differential inter-population error rates between geographical locations1-4. Australian forensic anthropology is constrained by a paucity of population specific standards due to a lack of repositories of documented skeletons. Consequently, in Australian casework proceedings, standards constructed from predominately American reference samples are applied to establish a biological profile. In the global era of terrorism and natural disasters, more specific population standards are required to improve the efficiency of medico-legal death investigation in Queensland. The sample comprises multi-slice computed tomography (MSCT) scans of the pubic symphysis (slice thickness: 0.5mm, overlap: 0.1mm) on 195 individuals of caucasian ethnicity aged 15-70 years. Volume rendering reconstruction of the symphyseal surface was conducted in Amira® (v.4.1) and quantitative analyses in Rapidform® XOS. The sample was divided into ten-year age sub-sets (eg. 15-24) with a final sub-set of 65-70 years. Error with respect to the method’s assigned means were analysed on the basis of bias (directionality of error), inaccuracy (magnitude of error) and percentage correct classification of left and right symphyseal surfaces. Morphometric variables including surface area, circumference, maximum height and width of the symphyseal surface and micro-architectural assessment of cortical and trabecular bone composition were quantified using novel automated engineering software capabilities. The results of this study demonstrated correct age classification utilizing the mean and standard deviations of each phase of the S-B method of 80.02% and 86.18% in Australian males and females, respectively. Application of the S-B method resulted in positive biases and mean inaccuracies of 7.24 (±6.56) years for individuals less than 55 years of age, compared to negative biases and mean inaccuracies of 5.89 (±3.90) years for individuals greater than 55 years of age. Statistically significant differences between chronological and S-B mean age were demonstrated in 83.33% and 50% of the six age subsets in males and females, respectively. Asymmetry of the pubic symphysis was a frequent phenomenon with 53.33% of the Queensland population exhibiting statistically significant (χ2 - p<0.01) differential phase classification of left and right surfaces of the same individual. Directionality was found in bilateral asymmetry, with the right symphyseal faces being slightly older on average and providing more accurate estimates using the S-B method5. Morphometric analysis verified these findings, with the left surface exhibiting significantly greater circumference and surface area than the right (p<0.05). Morphometric analysis demonstrated an increase in maximum height and width of the surface with age, with most significant changes (p<0.05) occurring between the 25-34 and 55-64 year age subsets. These differences may be attributed to hormonal components linked to menopause in females and a reduction in testosterone in males. Micro-architectural analysis demonstrated degradation of cortical composition with age, with differential bone resorption between the medial, ventral and dorsal surfaces of the pubic symphysis. This study recommends that the S-B method be applied with caution in medico-legal death investigations of unknown skeletal remains in Queensland. Age estimation will always be accompanied by error; therefore this study demonstrates the potential for quantitative morphometric modelling of age related changes of the pubic symphysis as a tool for methodological refinement, providing a rigor and robust assessment to remove the subjectivity associated with current pelvic aging methods.

Estimating the burden of malignant neoplasm on village residents in a mountainous area [山区农村居民恶性肿瘤疾病负担的估计]

Objective To make a comprehensive estimation of the burden of malignant neoplasm on village residents in Linqu County by the means of DALY (Disability-adjusted life year). Methods DALYs, YLLs and YLDs were calculated following the procedures developed for the Global Burden of Disease (GBD) study to ensure comparability, based on the cancer registration data of Linqu villages during 1998-2004, in order to measure the burden of various caners. Results All cancers were responsible for 20.00 DALYs for every thousand population in Linqu County (24.82 for men and 14.96 for women). 92.5% of the losses were due to premature death and 7.5% to disability. 31.5% of the DALYs happened among 45-59 age group. The top 10 cancers for DALYs were stomach cancer, lung cancer, liver cancer, oesophagus cancer, leukemia,colon/rectum cancer, brain cancer, pancreas cancer, breast cancer and bone cancer in turn. Only stomach cancer, lung cancer and liver cancer together account for 69.3% of total DALYs due to malignant neoplasm. The burden of malignant neoplasm was on rising recent years. Conclusions The burden of disease of malignant neoplasm is mainly because of premature death. Stomach cancer, lung cancer and liver cancer lead to heavier burden than the global and national levels. Abstract in Chinese 目的 应用伤残调整寿命年(DALY)对临朐县农村恶性肿瘤疾病负担进行评价. 方法 以1998～2004年临朐县农村肿瘤登记资料为基础,利用全球疾病负担研究中使用的专门公式计算恶性肿瘤的YLLs、YLDs和DALYs,以此评价各类恶性肿瘤的疾病负担. 结果 临朐农村每千人每年因恶性肿瘤造成20.0个DALYs损失(男性24.82,女性14.96),其中92.5%为早死所致,7.5%因残疾所致;恶性肿瘤主要导致45～59岁人群的DALYs损失,占31.5%;恶性肿瘤疾病负担前10位依次为胃癌、肺癌、肝癌、食道癌、白血病、肠癌、脑癌、胰腺癌、乳腺癌和骨癌,其中仅胃癌、肺癌和肝癌三大肿瘤DALYs就占全部肿瘤的69.3%;临朐县农村恶性肿瘤疾病负担有进一步上升的趋势. 结论 恶性肿瘤疾病负担主要由早死所致,胃癌、肺癌、肝癌等主要癌症疾病负担高于全球和中国区水平.

Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer

INTRODUCTION: Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. METHODS: Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m/10 min without routine steroid premedication) or paclitaxel (225 mg/m/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. RESULTS: A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade ≥3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). CONCLUSION: PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient. © 2008International Association for the Study of Lung Cancer.

Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2 : prognostic factors and treatment selection based on two large randomized clinical trials

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival imes were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy. © 2009 by the International Association for the Study of Lung Cancer.

Combination therapy with gefitinib and rofecoxib in patients with platinum-pretreated relapsed non-small-cell lung cancer

Purpose: In non-small-cell lung cancer (NSCLC), the epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) play major roles in tumorigenesis. This phase I/II study evaluated combined therapy with the EGFR tyrosine kinase inhibitor (TKI) gefitinib and the COX-2 inhibitor rofecoxib in platinum-pretreated, relapsed, metastatic NSCLC (n = 45). Patients and Methods: Gefitinib 250 mg/d was combined with rofecoxib (dose escalated from 12.5 to 25 to 50 mg/d through three cohorts, each n = 6). Because the rofecoxib maximum-tolerated dose was not reached, the 50 mg/d cohort was expanded for efficacy evaluation (n = 33). Results: Among the 42 assessable patients, there was one complete response (CR) and two partial responses (PRs) and 12 patients with stable disease (SD); disease control rate was 35.7% (95% CI, 21.6% to 52.0%). Median time to tumor progression was 55 days (95% CI, 47 to 70 days), and median survival was 144 days (95% CI, 103 to 190 days). In a pilot study, matrix-assisted laser desorption/ionization (MALDI) proteomics analysis of baseline serum samples could distinguish patients with an objective response from those with SD or progressive disease (PD), and those with disease control (CR, PR, and SD) from those with PD. The regimen was generally well tolerated, with predictable toxicities including skin rash and diarrhea. Conclusion: Gefitinib combined with rofecoxib provided disease control equivalent to that expected with single-agent gefitinib and was generally well tolerated. Baseline serum proteomics may help identify those patients most likely to benefit from EGFR TKIs. © 2007 by American Society of Clinical Oncology.

Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer

Background: The Lung Cancer Cetuximab Study is an open-label, randomized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone, in patients with advanced EGFR-expressing, non-small-cell lung cancer (NSCLC). End points of the study are activity, safety and pharmacokinetics. Patients and methods: Following randomization, for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m2, day 1) and vinorelbine (25 mg/m2 on days 1 and 8) alone or following cetuximab treatment (initial dose 400 mg/m, followed by 250 mg/m2 weekly thereafter). Results: Eighty-six patients were randomly allocated to the study (43 per arm). Confirmed response rates were 28% in the cisplatin/vinorelbine arm (A) and 35% in the cetuximab plus cisplatin/vinorelbine arm (B). Median progression-free survival (PFS) was 4.6 months in arm A and 5.0 months in arm B, with PFS rates at 12 months of 0% and 15%, respectively. Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0% and 16%, respectively. The cetuximab combination was well tolerated. Conclusion: In the first-line treatment of advanced NSCLC, the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone. © 2007 European Society for Medical Oncology.

Urban traffic state estimation: Fusing point and zone based data

Loop detectors are the oldest and widely used traffic data source. On urban arterials, they are mainly installed for signal control. Recently state of the art Bluetooth MAC Scanners (BMS) has significantly captured the interest of stakeholders for exploiting it for area wide traffic monitoring. Loop detectors provide flow- a fundamental traffic parameter; whereas BMS provides individual vehicle travel time between BMS stations. Hence, these two data sources complement each other, and if integrated should increase the accuracy and reliability of the traffic state estimation. This paper proposed a model that integrates loops and BMS data for seamless travel time and density estimation for urban signalised network. The proposed model is validated using both real and simulated data and the results indicate that the accuracy of the proposed model is over 90%.

The effect of very small air gaps on small field dosimetry

The purpose of this study was to investigate the effect of very small air gaps (less than 1 mm) on the dosimetry of small photon fields used for stereotactic treatments. Measurements were performed with optically stimulated luminescent dosimeters (OSLDs) for 6 MV photons on a Varian 21iX linear accelerator with a Brainlab lMLC attachment for square field sizes down to 6 mm 9 6 mm. Monte Carlo simulations were performed using EGSnrc C++ user code cavity. It was found that the Monte Carlo model used in this study accurately simulated the OSLD measurements on the linear accelerator. For the 6 mm field size, the 0.5 mm air gap upstream to the active area of the OSLD caused a 5.3 % dose reduction relative to a Monte Carlo simulation with no air gap...

Road infrastructure vulnerability to groundwater table variation due to sea level rise

This study was conducted to assess the vulnerability of coastal road infrastructures due to climate change induced sea level rise and extreme weather conditions through the estimation of road subgrade strength reduction as a result of changes in soil moisture content. The study area located in the Gold Coast, Australia highlighted that the risk is significant. In wet seasons or areas with wet condition, the groundwater table is already high, so even a small change in the groundwater table can raise the risk of inundation; particularly, in areas with existing shallow groundwater. The predicted risk of a high groundwater table on road infrastructure is a long-term hazard. Therefore, there is time to undertake some management plans to decrease the possible risks, for instance, some deep root plants could be planted along the roads with a high level of risk, to decrease the groundwater table elevation.

Small firms, the paid maternity leave debate in Australia and the business case

Purpose The purpose of this paper is to examine the management of maternity leave in small firms and particularly to explore the perceived costs and benefits of paid maternity leave (PML). PML is a universal right in some countries (i.e. the UK), but not in Australia where most private sector female employees only have access to 12 months unpaid maternity leave. It also aims to explore how the business case for (or against) PML is constructed in small firms. Design/methodology/approach The study was limited to smaller firms operating in the business services sector in the same regional area. Semi‐structured interviews were conducted with eight employers and female employees in six of these firms. Analysis by theme was undertaken within and across interview transcripts. Findings Not one of these small firm employers offered PML and the cost of doing so was not considered to outweigh the benefits already realised through the (legislated) unpaid maternity leave scheme. In these firms maternity leave was managed in an informal way with notions of flexibility – give and take – characterising what happens. Originality/value The paper addresses the lack of research on access to family‐related leave policies in small firms. Employer and employee views of the issue are drawn upon, the latter not often being heard. The paper contributes to understanding the construction of the business case for a specific issue in smaller firms and human resource management from a resource‐based view more generally in smaller firms.

Q-RARA : a rapid and rigorous method for researching small, primary health care organisations

Understanding the organisational processes driving quality primary care is crucial to the maintaining and improving practice. Qualitative methods are increasingly popular in health services research, but this area is dominated by interview studies. Multiple qualitative methods are rarely used in a systematically integrated fashion. We developed a method to study small primary health care organizations using rapid appraisal and qualitative mixed methods: Q-RARA – Qualitative Rapid Appraisal, Rigorous Analysis

Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany [Berufliche und außerberufliche Risikofaktoren für das Harnblasenkarzinom in einem ehemaligen Industriegebiet der neuen Bundesländer]

Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1-2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis. [Article in German]

Temporal Characterization of Ossification of the Crania in Australian Subadults: New standards for Age Estimation using Computed Tomography

After attending this presentation, attendees will gain awareness of the ontogeny of cranial maturation, specifically: (1) the fusion timings of primary ossification centers in the basicranium; and (2) the temporal pattern of closure of the anterior fontanelle, to develop new population-specific age standards for medicolegal death investigation of Australian subadults. This presentation will impact the forensic science community by demonstrating the potential of a contemporary forensic subadult Computed Tomography (CT) database of cranial scans and population data, to recalibrate existing standards for age estimation and quantify growth and development of Australian children. This research welcomes a study design applicable to all countries faced with paucity in skeletal repositories. Accurate assessment of age-at-death of skeletal remains represents a key element in forensic anthropology methodology. In Australian casework, age standards derived from American reference samples are applied in light of scarcity in documented Australian skeletal collections. Currently practitioners rely on antiquated standards, such as the Scheuer and Black1 compilation for age estimation, despite implications of secular trends and population variation. Skeletal maturation standards are population specific and should not be extrapolated from one population to another, while secular changes in skeletal dimensions and accelerated maturation underscore the importance of establishing modern standards to estimate age in modern subadults. Despite CT imaging becoming the gold standard for skeletal analysis in Australia, practitioners caution the application of forensic age standards derived from macroscopic inspection to a CT medium, suggesting a need for revised methodologies. Multi-slice CT scans of subadult crania and cervical vertebrae 1 and 2 were acquired from 350 Australian individuals (males: n=193, females: n=157) aged birth to 12 years. The CT database, projected at 920 individuals upon completion (January 2014), comprises thin-slice DICOM data (resolution: 0.5/0.3mm) of patients scanned since 2010 at major Brisbane Childrens Hospitals. DICOM datasets were subject to manual segmentation, followed by the construction of multi-planar and volume rendering cranial models, for subsequent scoring. The union of primary ossification centers of the occipital bone were scored as open, partially closed or completely closed; while the fontanelles, and vertebrae were scored in accordance with two stages. Transition analysis was applied to elucidate age at transition between union states for each center, and robust age parameters established using Bayesian statistics. In comparison to reported literature, closure of the fontanelles and contiguous sutures in Australian infants occur earlier than reported, with the anterior fontanelle transitioning from open to closed at 16.7±1.1 months. The metopic suture is closed prior to 10 weeks post-partum and completely obliterated by 6 months of age, independent of sex. Utilizing reverse engineering capabilities, an alternate method for infant age estimation based on quantification of fontanelle area and non-linear regression with variance component modeling will be presented. Closure models indicate that the greatest rate of change in anterior fontanelle area occurs prior to 5 months of age. This study complements the work of Scheuer and Black1, providing more specific age intervals for union and temporal maturity of each primary ossification center of the occipital bone. For example, dominant fusion of the sutura intra-occipitalis posterior occurs before 9 months of age, followed by persistence of a hyaline cartilage tongue posterior to the foramen magnum until 2.5 years; with obliteration at 2.9±0.1 years. Recalibrated age parameters for the atlas and axis are presented, with the anterior arch of the atlas appearing at 2.9 months in females and 6.3 months in males; while dentoneural, dentocentral and neurocentral junctions of the axis transitioned from non-union to union at 2.1±0.1 years in females and 3.7±0.1 years in males. These results are an exemplar of significant sexual dimorphism in maturation (p<0.05), with girls exhibiting union earlier than boys, justifying the need for segregated sex standards for age estimation. Studies such as this are imperative for providing updated standards for Australian forensic and pediatric practice and provide an insight into skeletal development of this population. During this presentation, the utility of novel regression models for age estimation of infants will be discussed, with emphasis on three-dimensional modeling capabilities of complex structures such as fontanelles, for the development of new age estimation methods.

Utility of assessing nerve morphology in central cornea versus whorl area for diagnosing diabetic peripheral neuropathy

Purpose To compare small nerve fiber damage in the central cornea and whorl area in participants with diabetic peripheral neuropathy (DPN) and to examine the accuracy of evaluating these 2 anatomical sites for the diagnosis of DPN. Methods A cohort of 187 participants (107 with type 1 diabetes and 80 controls) was enrolled. The neuropathy disability score (NDS) was used for the identification of DPN. The corneal nerve fiber length at the central cornea (CNFLcenter) and whorl (CNFLwhorl) was quantified using corneal confocal microscopy and a fully automated morphometric technique and compared according to the DPN status. Receiver operating characteristic analyses were used to compare the accuracy of the 2 corneal locations for the diagnosis of DPN. Results CNFLcenter and CNFLwhorl were able to differentiate all 3 groups (diabetic participants with and without DPN and controls) (P < 0.001). There was a weak but significant linear relationship for CNFLcenter and CNFLwhorl versus NDS (P < 0.001); however, the corneal location x NDS interaction was not statistically significant (P = 0.17). The area under the receiver operating characteristic curve was similar for CNFLcenter and CNFLwhorl (0.76 and 0.77, respectively, P = 0.98). The sensitivity and specificity of the cutoff points were 0.9 and 0.5 for CNFLcenter and 0.8 and 0.6 for CNFLwhorl. Conclusions Small nerve fiber pathology is comparable at the central and whorl anatomical sites of the cornea. Quantification of CNFL from the corneal center is as accurate as CNFL quantification of the whorl area for the diagnosis of DPN.

Real-time wind speed estimation and compensation for improved flight

This paper presents the development and experimental validation of a prototype system for online estimation and compensation of wind disturbances onboard small Rotorcraft unmanned aerial systems (RUAS). The proposed approach consists of integrating a small pitot-static system onboard the vehicle and using simple but effective algorithms for estimating the wind speed in real time. The baseline flight controller has been augmented with a feed-forward term to compensate for these wind disturbances, thereby improving the flight performance of small RUAS in windy conditions. The paper also investigates the use of online airspeed measurements in a closed-loop for controlling the RUAS forward motion without the aid of a global positioning system (GPS). The results of more than 80 flights with a RUAS confirm the validity of our approach.