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Background The risk of bloodstream infections may be increased in hospitalized patients receiving ready-made parenteral nutrition (PN) multichamber bags (MCBs) compared with customized PN; however, as highlighted in recent international guidelines, there are no comparable data relating to home PN (HPN). Methods Data from a prospectively maintained database were analyzed to compare incidence rates of catheter-related bloodstream infections (CRBSIs) between patients receiving customized HPN compared with MCB HPN at a national UK referral center between May 2018 and August 2020. Results Sixty patients with chronic intestinal failure were commenced on MCBs and 45 received customized HPN for a total of 5914 and 7641 catheter days, respectively. No difference in CRBSI incidence was found (0.51/1000 catheter days for MCBs, 0.39/1000 catheter days for customized HPN; incidence rate ratio, 1.29; 95% CI, 0.26-6.37). Eighteen patients were switched from customized HPN to MCB HPN. The study period covered 7401 catheter days receiving customized HPN and 4834 days on MCBs. No significant change was noted in the CRBSI rates following this switch (0.27/1000 catheter days receiving customized HPN vs 0.21/1000 catheter days on MCBs; incidence rate ratio, 1.31; 95% CI, 0.12-14.3). Conclusion The use of MCBs for HPN patients is not associated with an increased risk of CRBSI. This study will inform international guidelines and provide reassurance for the continued, safe use of MCB HPN.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) is a life-saving therapy for patients with chronic intestinal failure but can be associated with a degree of psychological distress. The factors associated with the need for antidepressants (AD) in this cohort have not yet been described.METHODS: The study involved prospective data collection from patients attending HPN clinic at a national intestinal failure referral centre. Patients requiring HPN as a result of active malignancy were excluded. Patients were divided in two groups according to AD usage; demographic, anthropometric, socioeconomic characteristics and IVS regimens were compared between groups.RESULTS: A total of 184 patients were recruited between July 2018 and April 2019, with an overall prevalence of AD use of 41.7%. Daily mean IVS volume was significantly higher among patients taking AD ('AD' group; 2125.48±991.8 ml/day, 'no-AD' group; 1828.54±847.0 ml/day, P = 0.039) with the proportion of patients needing high volume IVS (≥3000ml/day) being three-times higher in the AD group (20.0% vs. 6.1%, P = 0.006). The average energy IVS infusion per day was similar between the two groups. Hypnotic use (25.7% vs. 5.1%, P

International audience; Purpose: Geant4 is a multi-purpose Monte Carlo simulation tool for modeling particle transport in matter. It provides a wide range of settings, which the user may optimize for their specific application. This study investigates GATE/Geant4 parameter settings for proton pencil beam scanning therapy.Methods: GATE8.1/Geant4.10.3.p03 (matching the versions used in GATE-RTion1.0) simulations were performed with a set of prebuilt Geant4 physics lists (QGSP_BIC, QGSP_BIC_EMY, QGSP_BIC_EMZ, QGSP_BIC_HP_EMZ), using 0.1mm-10mm as production cuts on secondary particles (electrons, photons, positrons) and varying the maximum step size of protons (0.1mm, 1mm, none). The results of the simulations were compared to measurement data taken during clinical patient specific quality assurance at The Christie NHS Foundation Trust pencil beam scanning proton therapy facility. Additionally, the influence of simulation settings was quantified in a realistic patient anatomy based on computer tomography (CT) scans.Results: When comparing the different physics lists, only the results (ranges in water) obtained with QGSP_BIC (G4EMStandardPhysics_Option0) depend on the maximum step size. There is clinically negligible difference in the target region when using High Precision neutron models (HP) for dose calculations. The EMZ electromagnetic constructor provides a closer agreement (within 0.35 mm) to measured beam sizes in air, but yields up to 20% longer execution times compared to the EMY electromagnetic constructor (maximum beam size difference 0.79 mm). The impact of this on patient-specific quality assurance simulations is clinically negligible, with a 97% average 2%/2 mm gamma pass rate for both physics lists. However, when considering the CT-based patient model, dose deviations up to 2.4% are observed. Production cuts do not substantially influence dosimetric results in solid water, but lead to dose differences of up to 4.1% in the patient CT. Small (compared to voxel size) production cuts increase execution times by factors of 5 (solid water) and 2 (patient CT).Conclusions: Taking both efficiency and dose accuracy into account and considering voxel sizes with 2 mm linear size, the authors recommend the following Geant4 settings to simulate patient specific quality assurance measurements: No step limiter on proton tracks; production cuts of 1 mm for electrons, photons and positrons (in the phantom and range-shifter) and 10 mm (world); best agreement to measurement data was found for QGSP_BIC_EMZ reference physics list at the cost of 20% increased execution times compared to QGSP_BIC_EMY. For simulations considering the patient CT model, the following settings are recommended: No step limiter on proton tracks; production cuts of 1 mm for electrons, photons and positrons (phantom/range-shifter) and 10 mm (world) if the goal is to achieve sufficient dosimetric accuracy to ensure that a plan is clinically safe; or 0.1 mm (phantom/range-shifter) and 1 mm (world) if higher dosimetric accuracy is needed (increasing execution times by a factor of 2); most accurate results expected for QGSP_BIC_EMZ reference physics list, at the cost of 10-20% increased execution times compared to QGSP_BIC_EMY.

Purpose Herein, we evaluate the use of MRI as a tool for assessing iron oxide nanoparticle (IONP) distribution within IONP perfused organs and vascularized composite allografts (VCAs) (i.e., hindlimbs) prepared for cryopreservation. Methods Magnetic resonance imaging was performed on room-temperature organs and VCAs perfused with IONPs and were assessed at 9.4 T. Quantitative T1 mapping and T 2 ∗ -weighted images were acquired using sweep imaging with Fourier transformation and gradient-echo sequences, respectively. Verification of IONP localization was performed through histological assessment and microcomputer tomography. Results Quantitative imaging was achieved for organs and VCAs perfused with up to 642 mMFe (36 mgFe /mL), which is above previous demonstrations of upper limit detection in agarose (35.7mMFe [2 mgFe /mL]). The stability of IONPs in the perfusate had an effect on the quality of distribution and imaging within organs or VCA. Finally, MRI provided more accurate IONP localization than Prussian blue histological staining in this system, wherein IONPs remain primarily in the vasculature. Conclusion Using MRI, we were able to assess the distribution of IONPs throughout organs and VCAs varying in complexity. Additional studies are necessary to better understand this system and validate the calibration between T1 measurements and IONP concentration.

Oncology drug development increasingly relies on single‐arm clinical trials. External controls (ECs) derived from electronic health record (EHR) databases may provide additional context. Patients from a US‐based oncology EHR database were aligned with patients from randomized controlled trials (RCTs) and trial‐specific eligibility criteria were applied to the EHR dataset. Overall survival (OS) in the EC‐derived control arm was compared with OS in the RCT experimental arm. The primary outcome was OS, defined as time from randomization or treatment initiation (EHR) to death. Cox regression models were used to obtain effect estimates using EHR data. EC‐derived hazard ratio estimates aligned closely with those from the corresponding RCT with one exception. Comparing log HRs among all RCT and EC results gave a Pearson correlation coefficient of 0.86. Properly selected control arms from contemporaneous EHR data could be used to put single‐arm trials of OS in advanced non‐small cell lung cancer into context.

BACKGROUND Home parenteral nutrition (HPN) provides life-sustaining treatment for people with chronic intestinal failure (CIF). Poor quality of life is reported in association with the burden of HPN and the underlying condition leading to intestinal failure (IF). However, levels of negative affect (NA), incorporating anxiety and depression, have not been reported in CIF. This study examined the occurrence and risk factors for NA in a large CIF population using the validated Hospital Anxiety & Depression Scale (HADS) and Multidimensional Scale of Perceived Social Support (MSPSS) questionnaires. METHODS A survey pack including HADS and MSPSS were distributed to patients managed by a specialist IF center. Data from these measures were analyzed against factors including underlying disease, length of time receiving HPN, employment status, and demographics. RESULTS Of 85 patients who completed this study, 56% had clinical levels of anxiety and/or depression. Linear regression analysis confirmed significant correlations between social support and HADS scores, with poorer perceived social support associated with higher levels of NA (-0.26 MSPSS + 33.24; R2 = 0.29; P < .0001). There were also significant associations between unemployment and higher anxiety (P = .004), depression (P = .008), and NA scores (P = .003). By contrast, there were no significant associations between patient age, duration of time receiving parenteral nutrition, pathophysiological mechanisms of CIF, and NA levels. CONCLUSIONS Clinical anxiety and depression are common, affecting more than half of patients with CIF. Patients with poor social networks and those of working age who have ceased employment are particularly vulnerable and should be prioritized for psychological support because of their elevated risk.

Objective To create a high-quality electronic health record (EHR)-derived mortality dataset for retrospective and prospective real-world evidence generation. Data sources/study setting Oncology EHR data, supplemented with external commercial and US Social Security Death Index data, benchmarked to the National Death Index (NDI). Study design We developed a recent, linkable, high-quality mortality variable amalgamated from multiple data sources to supplement EHR data, benchmarked against the highest completeness U.S. mortality data, the NDI. Data quality of the mortality variable version 2.0 is reported here. Principal findings For advanced non-small-cell lung cancer, sensitivity of mortality information improved from 66 percent in EHR structured data to 91 percent in the composite dataset, with high date agreement compared to the NDI. For advanced melanoma, metastatic colorectal cancer, and metastatic breast cancer, sensitivity of the final variable was 85 to 88 percent. Kaplan-Meier survival analyses showed that improving mortality data completeness minimized overestimation of survival relative to NDI-based estimates. Conclusions For EHR-derived data to yield reliable real-world evidence, it needs to be of known and sufficiently high quality. Considering the impact of mortality data completeness on survival endpoints, we highlight the importance of data quality assessment and advocate benchmarking to the NDI.

Melanins are a class of biopolymers that are widespread in nature and have diverse origins, chemical compositions, and functions. Their chemical, electrical, optical, and paramagnetic properties offer opportunities for applications in materials science, particularly for medical and technical uses. This review focuses on the application of analytical techniques to study melanins in multidisciplinary contexts with a view to their use as sustainable resources for advanced biotechnological applications, and how these may facilitate the achievement of the United Nations Sustainable Development Goals., Melanin‐based materials have broad applicability in materials science and engineering for medical and technical applications. This review offers an overview of the techniques used to analyze their chemical, electrical, optical, and paramagnetic properties with a view to their use as sustainable resources for advanced biotechnological applications that may help the achieve the United Nations Sustainable Development Goals.

Objective: Succinate dehydrogenase-deficient leukoencephalopathy is a complex II-related mitochondrial disorder for which the clinical phenotype, neuroimaging pattern, and genetic findings have not been comprehensively reviewed.

To examine the effectiveness of an initial management strategy of watchful waiting for follicular lymphoma (FL) in clinical practice, we compared outcomes for patients diagnosed 2004-2007 in the United States initially managed with watchful waiting with outcomes following initial rituximab monotherapy and chemoimmunotherapy. In total, 1754 stage II-IV patients in the National LymphoCare Study underwent watchful waiting (n = 386), rituximab monotherapy (n = 296) or rituximab plus chemotherapy (n = 1072) as initial management strategy. Female patients and those who received treatment in the Northeast or in an academic setting more commonly underwent watchful waiting versus initial chemoimmunotherapy; whereas patients with grade 3 histology, anaemia, elevated lactate dehydrogenase, extranodal involvement, B symptoms or performance status ≥1 more commonly received chemoimmunotherapy. Although time to new treatment and progression-free survival following first- and second-line therapy were improved with chemoimmunotherapy, and time to chemotherapy was improved with rituximab monotherapy, there were no differences in overall survival between watchful waiting and chemoimmunotherapy or rituximab monotherapy. With 8-year overall survival estimates of 74%, initial management with watchful waiting in the context of sequential therapy remains a viable option for FL patients in the modern era. This trial was registered at www.clinicaltrials.gov (NCT00097565).

The regenerative potential of cardiosphere-derived cells (CDCs) for ischaemic heart disease has been demonstrated in mice, rats, pigs and a recently completed clinical trial. The regenerative potential of CDCs from dog hearts has yet to be tested. Here, we show that canine CDCs can be produced from adult dog hearts. These cells display similar phenotypes in comparison to previously studied CDCs derived from rodents and human beings. Canine CDCs can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition, conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte death. In a doxorubicin-induced mouse model of dilated cardiomyopathy (DCM), intravenous infusion of canine CDCs improves cardiac function and decreases cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the mouse heart and increase capillary density. Out study demonstrates the regenerative potential of canine CDCs in a mouse model of DCM., Journal of Cellular and Molecular Medicine, 19(8), pp.1805-1813; 2015

The catalytic A1 subunit of cholera toxin (CTA1) has a disordered structure at 37°C. An interaction with host factors must therefore place CTA1 in a folded conformation for the modification of its Gsα target which resides in a lipid raft environment. Host ADP-ribosylation factors (ARFs) act as in vitro allosteric activators of CTA1, but the molecular events of this process are not fully characterized. Isotope-edited Fourier transform infrared spectroscopy monitored ARF6-induced structural changes to CTA1, which were correlated to changes in CTA1 activity. We found ARF6 prevents the thermal disordering of structured CTA1 and stimulates the activity of stabilized CTA1 over a range of temperatures. Yet ARF6 alone did not promote the refolding of disordered CTA1 to an active state. Instead, lipid rafts shifted disordered CTA1 to a folded conformation with a basal level of activity that could be further stimulated by ARF6. Thus, ARF alone is unable to activate disordered CTA1 at physiological temperature: additional host factors such as lipid rafts place CTA1 in the folded conformation required for its ARF-mediated activation. Interaction with ARF is required for in vivo toxin activity, as enzymatically active CTA1 mutants that cannot be further stimulated by ARF6 fail to intoxicate cultured cells.

BACKGROUND The authors examined the “real-world” effectiveness of rituximab (R) maintenance therapy (R-maintenance) compared with observation after R-based induction therapy in patients with previously untreated follicular lymphoma (FL) in the United States. METHODS The National LymphoCare Study is a prospective, multicenter, observational study that enrolled > 2700 untreated patients with FL diagnosed from 2004 to 2007 at 265 sites in the United States. Among these, patients who achieved at least stable disease after R-based induction therapy were eligible for the current analysis. Patients who initiated R-maintenance within 215 days of completing induction therapy were categorized as the R-maintenance group, and those who did not initiate therapy during this period were categorized as the observation group. The objective of the current study was to determine the effect of R-maintenance on progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). RESULTS A total of 1439 patients completed R-based induction therapy, 1186 of whom met all inclusion criteria (541 patients received R-maintenance and 645 patients were observed). Characteristics that were found to be predictive of receiving R-maintenance were histology grade (1/2), Ann Arbor stage of disease (III/IV), geographic region (region other than the West), and practice setting (community practice). With a median follow-up of 5.7 years, R-maintenance was associated with superior PFS (hazards ratio [HR], 0.68; 95% confidence interval [95% CI], 0.56-0.84 [P = .0003]) and TTNT (HR, 0.66; 95% CI, 0.52-0.84 [P = .0007]). No significant difference in OS was observed (HR, 0.81; 95% CI, 0.58-1.14 [P = .23]). CONCLUSIONS R-maintenance in patients with FL and at least stable disease after R-based induction therapy provided significantly longer PFS and TTNT in comparison with observation, but no significant difference in OS was observed with 5-years of follow-up. This comparative effectiveness study aligns with the results of randomized trials suggesting that similar outcomes occur with R-maintenance in FL with the treatment variations observed in clinical practice. Cancer 2014;120:1830–1837. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. The authors present what, to their knowledge, is the largest published series to date of prospectively enrolled patients with previously untreated follicular lymphoma in the modern era examining the effectiveness of rituximab maintenance in clinical practice. With > 5 years of follow-up, it was found that, compared with observation, receipt of rituximab maintenance therapy was associated with significantly longer progression-free survival and time to next treatment in previously untreated patients with follicular lymphoma who achieved at least stable disease after rituximab-based induction therapy.

Aspirin is the most commonly prescribed antiplatelet agent worldwide, but evidence supporting its use varies by age and disease process. Despite its frequent use in childhood acute ischemic stroke prevention and management, major knowledge gaps exist about optimal pediatric aspirin use, particularly in this setting, where high-quality clinical trials are urgently needed. This review focuses upon the evidence for aspirin use in childhood acute ischemic stroke, includes a summary of aspirin pharmacology to highlight misconceptions and common clinical situations which may limit its efficacy, and discusses the techniques and potential role of laboratory monitoring of aspirin efficacy in children.

This case report provides an account by a patient (with permission) of chronic factitious disorder and the factors that led to recovery. Such accounts are extremely rare in the literature. This account also throws into sharp focus current controversies in the classification of factitious disorders. Copyright © 2013 John Wiley & Sons, Ltd.

Introduction Pastoral Care (PC) practitioners respond to the spiritual needs of patients and families of all spiritual orientations. The integrated PC service in an acute psychogeriatric inpatient ward at St Vincent's Aged Mental Health Service, Melbourne, Australia, was examined to investigate how PC was being accessed by inpatients. Methods A retrospective medical record file audit was undertaken of patients admitted over a 16-month period from 1 February 2009 to 30 June 30 2010 (n = 202). Results Sixty-eight percent were seen by PC practitioners during their admission. Sixty-six percent received PC assessments, 32% received PC ministry, and 10% received PC ritual or worship interventions. Other interventions (counseling/education, crisis situation, grief/ bereavement counseling) occurred infrequently. Seventy-five percent of Roman Catholic patients received PC compared to 57% of those patients with no religious affiliation. However, the overall association between religious grouping and receiving PC was not significant. Gender, religion, marital status, legal status, country of birth, language spoken, living situation, carer needs, or educational level were not related to PC contact. Whether or not an inpatient received PC assessment was unrelated to diagnostic category. Patients seen by PC were significantly more likely to engage in religious practice, have longer length of stay, and have neuropsychological, social work and occupational therapy assessments. Discussion Results suggest that PC practitioners can help optimize the clinical care of patients by developing a comprehensive understanding of their spiritual and religious needs and providing a more holistic service.

This paper explores and unpacks the nature of the processes shaping regional economic growth in Turkey using an econometric modelling strategy. Economic modelling is an important approach to the analysis and understanding of regional growth and development. Over the decades, there have been a range of attempts to measure and understand the dynamics of regional growth through the modelling of underlying internal and external forces. However, existing empirical research in this field has focussed on regions in economically advanced and technologically innovative economies and comparable studies of less developed and emerging countries and their regions that suffer from poverty, unemployment and regional disparities are far fewer. As a consequence, the broader picture of the dynamics of regional development in less developed countries, particularly its social and political origins and the overall changes in regional inequality, have remained elusive and less clear. However, as globalization deepens and processes such as Europeanization and regionalization facilitate and accelerate the implementation of externally developed policies, less developed and emerging economies have started to adopt the ‘successful’ regional economic planning policies and practices developed and implemented in totally different national contexts. The problem with this issue is that those policy ideas have only partial relevance in the developed country context potentially making them even less relevant in developing economies. To explore this problem, this paper seeks to understand, empirically, the drivers of local and regional development in Turkey and how they can be used to develop a theoretically informed econometric analysis in the context of an emerging market economy. Not only has this form of analysis not been undertaken in Turkey, but the theories of local and regional economic development have had a major impact on the Turkish regional planning process. A set of econometric models is developed to explore the validity of a range of theoretical propositions in explaining the trajectories of regional economic change in Turkey between 2004 and 2008. Growth is calibrated in terms of employment and changing rates of unemployment in the chosen time period in the eighty one provinces of Turkey. The results of the study explain that implications of the current local and regional economic development theories are a Curate’s Egg – good in parts – because these theories are only partially relevant in the Turkish context. JEL codes: R10 Abstract content: Regional growth, emerging economies, Turkey

Aim: To examine the general practitioner (GP) consultation patterns for primary health-care services provided in residential aged care facilities (RACFs) by consultation type. Method: Analyses of service provision and RACF population data for the period 1998-2011. All Medicare-subsidised services provided by GPs across Australia in RACFs were included and categorised by consultation type and by time of service delivery (business or after-hours). Results: Overall service delivery increased from 12118 per 1000 residents in financial year (FY) 1998-99 to 17079 per 1000 residents in FY2010-11, a 41% increase. Since FY2007-08, the rate of brief consultations has grown by an average of 20% each year. Delivery of after-hours consultations also increased. Conclusions: The pattern of GP services provided in RACFs has changed substantially over time. To some extent these changes reflect regulatory adjustments; however, the pattern is at odds with the ever-increasing dependence levels of residents. © 2012 The Authors. Australasian Journal on Ageing © 2012 ACOTA.

Purpose: There are a range of genetic and nongenetic factors influencing the elemental composition of different human tissues. The elemental composition of canceroustissues frequently differs from healthy tissue of the same organ, particularly in high-Z trace element concentrations. For this reason, one could suggest that this may be exploited in diagnostics and perhaps even influence dosimetry. Methods: In this work, for the first time, effective atomic numbers are computed for common cancerous and healthy tissues using a robust, energy-dependent approach between 10 keV and 100 MeV. These are then quantitatively compared within the context of diagnostics and dosimetry. Results: Differences between effective atomic numbers of healthy and diseased tissues are found to be typically less than 10%. Fibrotic tissues and calcifications of the breast exhibit substantial (tens to hundreds of percent) differences to healthy tissue. Expectedly, differences are most pronounced in the photoelectric regime and consequently most relevant for kV imaging/therapy and radionuclides with prominent low-energy peaks. Canceroustissue of the testes and stomach have lower effective atomic numbers than corresponding healthy tissues, while diseased tissues of the other organ sites typically have higher values. Conclusions: As dose calculation approaches improve in accuracy, there may be an argument for the explicit inclusion of pathologies. This is more the case for breast, penile, prostate, nasopharyngeal, and stomach cancer, less so for testicular and kidneycancer. The calculated data suggest dual-energy computed tomography could potentially improve lesion identification in the aforementioned organs (with the exception of testicular cancer), with most import in breast imaging. Ultimately, however, the differences are very small. It is likely that the assumption of a generic “tissue ramp” in planning will be sufficient for the foreseeable future, and that theZ differences do not notably aid lesion detection beyond that already facilitated by differences in mass density.

Purpose: The use of time-resolved four-dimensional computed tomography (4D-CT) in radiotherapy requires strict quality assurance to ensure the accuracy of motion management protocols. The aim of this work was to design and test a phantom capable of large amplitude motion for use in 4D-CT, with particular interest in small lesions typical for stereotactic body radiotherapy. Methods: The phantom of 'see-saw' design is light weight, capable of including various sample materials and compatible with several surrogate marker signal acquisition systems. It is constructed of polymethylmethacrylate (Perspex) and its movement is controlled via a dc motor and drive wheel. It was tested using two CT scanners with different 4D acquisition methods: the Philips Brilliance Big Bore CT (helical scan, pressure belt) and a General Electric Discovery STE PET/CT (axial scan, infrared marker). Amplitudes ranging from 1.5 to 6.0 cm and frequencies of up to 40 cycles per minute were used to study the effect of motion on image quality. Maximum intensity projections (MIPs), as well as average intensity projections (AIPs) of moving objects were investigated and their quality dependence on the number of phase reconstruction bins assessed. Results: CT number discrepancies between moving and stationary objects were found to have no systematicmore » dependence on amplitude, frequency, or specific interphase variability. MIP-delineated amplitudes of motion were found to match physical phantom amplitudes to within 2 mm for all motion scenarios tested. Objects undergoing large amplitude motions (>3.0 cm) were shown to cause artefacts in MIP and AIP projections when ten phase bins were assigned. This problem can be mitigated by increasing the number of phase bins in a 4D-CT scan. Conclusions: The phantom was found to be a suitable tool for evaluating the image quality of 4D-CT motion management technology, as well as providing a quality assurance tool for intercenter/intervendor testing of commercial 4D-CT systems. When imaging objects with large amplitudes, the completeness criterion described here indicates the number of phase bins required to prevent missing data in MIPs and AIPs. This is most relevant for small lesions undergoing large motions.« less

Purpose: Strategies for dose accumulation in deforming anatomy are of interest in radiotherapy. Algorithms exist for the deformation of dose based on patient image sets, though these are sometimes contentious because not all such image calculations are constrained by physical laws. While tumor and organ motion has been a key area of study for a considerable amount of time, deformation is of increasing interest. In this work, we demonstrate a full 3D experimental validation of results from a range of dose deformation algorithms available in the public domain. Methods: We recently developed the first tissue-equivalent, full 3D deformable dosimetric phantom-'DEFGEL.' To assess the accuracy of dose-warping based on deformable image registration (DIR), we have measured doses in undeformed and deformed states of the DEFGEL dosimeter and compared these to planned doses and warped doses. In this way we have directly evaluated the accuracy of dose-warping calculations for 11 different algorithms. We have done this for a range of stereotactic irradiation schemes and types and magnitudes of deformation. Results: The original Horn and Schunck algorithm is shown to be the best performing of the 11 algorithms trialled. Comparing measured and dose-warped calculations for this method, it is found that for amore » 10 Multiplication-Sign 10 mm{sup 2} square field, {gamma}{sub 3%/3mm}= 99.9%; for a 20 Multiplication-Sign 20 mm{sup 2} cross-shaped field, {gamma}{sub 3%/3mm}= 99.1%; and for a multiple dynamic arc (0.413 cm{sup 3} PTV) treatment adapted from a patient treatment plan, {gamma}{sub 3%/3mm}= 95%. In each case, the agreement is comparable to-but consistently {approx}1% less than-comparison between measured and calculated (planned) dose distributions in the absence of deformation. The magnitude of the deformation, as measured by the largest displacement experienced by any voxel in the volume, has the greatest influence on the accuracy of the warped dose distribution. Considering the square field case, the smallest deformation ({approx}9 mm) yields agreement of {gamma}{sub 3%/3mm}= 99.9%, while the most significant deformation ({approx}20 mm) yields agreement of {gamma}{sub 3%/3mm}= 96.7%. Conclusions: We have confirmed that, for a range of mass and density conserving deformations representative of those observable in anatomical targets, DIR-based dose-warping can yield accurate predictions of the dose distribution. Substantial differences can be seen between the results of different algorithms indicating that DIR performance should be scrutinized before application todose-warping. We have demonstrated that the DEFGEL deformable dosimeter can be used to evaluate DIR performance and the accuracy of dose-warping results by direct measurement.« less

Purpose: Interfraction and intrafraction variation in anatomic structures is a significant challenge in contemporary radiotherapy. The objective of this work is to develop a novel tool for deformable structure dosimetry, using a tissue-equivalent deformable gel dosimeter that can reproducibly simulate targets subject to deformation. This will enable direct measurement of integrated doses delivered in different deformation states, and the verification of dose deforming algorithms. Methods: A modified version of the nPAG polymer gel has been used as a deformable 3D dosimeter and phantom to investigate doses delivered to deforming tissue-equivalent geometry. The deformable gel (DEFGEL) dosimeter/phantom is comprised of polymer gel in a latex membrane, moulded (in this case) into a cylindrical geometry, and deformed with an acrylic compressor. Fifteen aluminium fiducial markers (FM) were implanted into DEFGEL phantoms and the reproducibility of deformation was determined via multiple computed tomography (CT) scans in deformed and nondeformed states before and after multiple (up to 150) deformations. Dose was delivered to the DEFGEL phantom in three arrangements: (i) without deformation, (ii) with deformation, and (iii) cumulative exposures with and without deformation, i.e., dose integration. Irradiations included both square field and a stereotactic multiple dynamic arc treatment adapted from a patient plan. Dosesmore » delivered to the DEFGEL phantom were read out using cone beam optical CT. Results: Reproducibility was verified by observation of interscan shifts of FM locations (as determined via CT), measured from an absolute reference point and in terms of inter-FM distance. The majority (76%) of points exhibited zero shift, with others shifting by one pixel size consistent with setup error as confirmed with a control sample. Comparison of dose profiles and 2D isodose distributions from the three arrangements illustrated complex spatial redistribution of dose in all three dimensions occurring as a result of the change in shape of the target between irradiations, even for a relatively simple deformation. Discrepancies of up to 30% of the maximum dose were evident from dose difference maps for three orthogonal planes taken through the isocenter of a stereotactic field. Conclusions: This paper describes the first use of a tissue-equivalent, 3D dose-integrating deformable phantom that yields integrated or redistributed dosimetric information. The proposed methodology readily yields three-dimensional (3D) dosimetric data from radiation delivery to the DEFGEL phantom in deformed and undeformed states. The impacts of deformation on dose distributions were readily seen in the isodose contours and line profiles from the three arrangements. It is demonstrated that the system is potentially capable of reproducibly emulating the physical deformation of an organ, and therefore can be used to evaluate absorbed doses to deformable targets and organs at risk in three dimensions and to validate deformation algorithms applied to dose distributions.« less

Purpose: The most appropriate method of evaluating the effective atomic number necessitates consideration of energy-dependent behavior. Previously, this required quite laborious calculation, which is why many scientists revert to over-simplistic power-law methods. The purpose of this work is to develop user-friendly software for the robust, energy-dependent computation of effective atomic numbers relevant within the context of medical physics, superseding the commonly employed simplistic power law approaches. Method : Visual Basic was used to develop a GUI allowing the straightforward calculation of effective atomic numbers. Photon interaction cross section matrices are constructed for energies spanning 10 keV to 10 GeV and elementsZ = 1–100. Coefficients for composite media are constructed via linear additivity of the fractional constituents and contrasted against the precalculated matrices at each energy, thereby associating an effective atomic number through interpolation of adjacent cross section data. Uncertainties are of the order of 1–2%. Results : Auto-Zeff allows rapid (∼0.6 s) calculation of effective atomic numbers for a range of predefined or user-specified media, allowing estimation of radiological properties and comparison of different media (for instance assessment of water equivalence). The accuracy of Auto-Zeff has been validated against numerous published theoretical and experimental predictions, demonstrating good agreement. The results also show that commonly employed power-law approaches are inaccurate, even in their intended regime of applicability (i.e., photoelectric regime). Furthermore, comparing the effective atomic numbers of composite materials using power-law approaches even in a relative fashion is shown to be inappropriate. Conclusion : Auto-Zeff facilitates easy computation of effective atomic numbers as a function of energy, as well as average and spectral-weighted means. The results are significantly more accurate than normal power-law predictions. The software is freely available to interested readers, who are encouraged to contact the authors.

OBJECTIVE: Alkaptonuria is a genetic disorder of tyrosine metabolism, resulting in elevated circulating concentrations of homogentisic acid. Homogentisic acid is deposited as a polymer, termed ochronotic pigment, in collagenous tissues, especially cartilages of weight-bearing joints, leading to a severe osteoarthropathy. We undertook this study to investigate the initiation and progression of ochronosis from the earliest detection of pigment through complete joint failure. METHODS: Nine joint samples with varying severities of ochronosis were obtained from alkaptonuria patients undergoing surgery and compared to joint samples obtained from osteoarthritis (OA) patients. Samples were analyzed by light and fluorescence microscopy, 3-dimensional scanning electron microscopy (SEM), and the quantitative backscattered electron mode of SEM. Cartilage samples were mechanically tested by compression to determine Young's modulus of pigmented, nonpigmented, and OA cartilage samples. RESULTS: In alkaptonuria samples with the least advanced ochronosis, pigment was observed intracellularly and in the territorial matrix of individual chondrocytes at the boundary of the subchondral bone and calcified cartilage. In more advanced ochronosis, pigmentation was widespread throughout the hyaline cartilage in either granular composition or as blanket pigmentation in which there is complete and homogenous pigmentation of cartilage matrix. Once hyaline cartilage was extensively pigmented, there was aggressive osteoclastic resorption of the subchondral plate. Pigmented cartilage became impacted on less highly mineralized trabeculae and embedded in the marrow space. Pigmented cartilage samples were much stiffer than nonpigmented or OA cartilage as revealed by a significant difference in Young's modulus. CONCLUSION: Using alkaptonuria cartilage specimens with a wide spectrum of pigmentation, we have characterized the progression of ochronosis. Intact cartilage appears to be resistant to pigmentation but becomes susceptible following focal changes in calcified cartilage. Ochronosis spreads throughout the cartilage, altering the mechanical properties. In advanced ochronosis, there is aggressive resorption of the underlying calcified cartilage leading to an extraordinary phenotype in which there is complete loss of the subchondral plate. These findings should contribute to better understanding of cartilage-subchondral interactions in arthropathies.

The World Health Organization (WHO) specifies that attention to the spiritual needs of the elderly with mental health problems is essential to good patient care, yet little evidence-based practice is documented in this field. This paper reviews the literature on the provision of pastoral care services (PCS) to elderly people with mental impairment. Integration of Pastoral Care Practitioners (PCPs) into the multidisciplinary team is rare. Research into mental health clinicians' attitudes to addressing patients' spiritual needs, and the integration of PCPs into multidisciplinary teams in aged mental health are reported and discussed. The contextual needs of PCPs in aged mental health, and options for qualitative and quantitative research are explored. Further research is needed to guide the integration of PCS into multidisciplinary teams in aged persons' mental health services. Copyright © 2011 Blackwell Publishing Asia Pty Ltd.

Progress in research into rare diseases is challenging. This paper discusses strategies to identify individuals with the rare genetic disease alkaptonuria (AKU) within the general population. Strategies used included a questionnaire survey of general practitioners, a dedicated website and patient network contact, targeted family screening and medical conference targeting. Primary care physicians of the UK were targeted by a postal survey that involved mailing 11,151 UK GPs; the response rate was 18.2%. We have identified 75 patients in the UK with AKU by the following means: postal survey (23), targeted family screening (11), patient networks and the website (41). Targeting medical conferences (AKU, rare diseases, rheumatology, clinical biochemistry, orthopaedics, general practitioners) did not lead to new identification in the UK but helped identify overseas cases. We are now aware of 626 patients worldwide including newly identified non-UK people with AKU in the following areas: Slovakia (208), the rest of Europe (including Turkey) (79), North America (including USA and Canada) (110), and the rest of the world (154). A mechanism for identifying individuals with AKU in the general population-not just in the UK but worldwide-has been established. Knowledge of patients with AKU, both in the UK and outside, is often confined to establishing their location in a particular GP practice or association with a particular medical professional. Mere identification, however, does not always lead to full engagement for epidemiological research purposes or targeting treatment since further barriers exist.

Alkaptonuria (AKU) is a rare genetic disease associated with the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in connective tissues up to the deposition of melanin-like pigments (ochronosis). Since little is known on the effects of HGA and its metabolites on articular cells, we carried out a proteomic and redox-proteomic analysis to investigate how HGA and ascorbic acid (ASC) affect the human chondrocytic protein repertoire. We settled up an in vitro model using a human chondrocytic cell line to evaluate the effects of 0.33 mM HGA, alone or combined with ASC. We found that HGA and ASC significantly affect the levels of proteins with specific functions in protein folding, cell organization and, notably, stress response and cell defense. Increased protein carbonyls levels were found either in HGA or ASC treated cells, and evidences produced in this paper support the hypothesis that HGA-induced stress might be mediated by protein oxidation. Our finding can lay the basis towards the settling up of more sophisticated models to study AKU and ochronosis.

This paper argues that the cluster model of local economic growth is model that became a message that is now a mantra. It is an approach that has extended its explanatory reach through the accretion of layers of contingency. The paper suggests seven major limitations that undermine the explanatory power of what is now a mesmeric policy prescription for local economic development. It neglects the imperatives of capitalism, underestimates of the impact of unequal power relations on business relationships, fails to incorporate time, fetishises proximity, treats entrepreneurship simplistically, promotes the chaotic concept of institutional thickness, and is limited by the chaotic concept of social capital. It is concluded that a more nuanced and empirically grounded approach to agglomerated local growth is needed and a set of research questions is suggested.

Contrast fluoroscopy is a valuable tool to examine avian gastrointestinal motility. However, the lack of a standardized examination protocol and reference ranges prevents the objective interpretation of motility disorders and other gastrointestinal abnormalities. Our goals were to evaluate gastrointestinal motility in 20 Hispaniolan Amazon parrots (Amazona ventralis) by contrast fluoroscopy. Each parrot was crop-fed an equal part mixture of barium sulfate and hand-feeding formula and placed in a cardboard box for fluoroscopy. Over a 3-h period, 1.5 minute segments of lateral and ventrodorsal fluoroscopy were recorded every 30 min. The gastric cycle and patterns of intestinal motility were described. The frequency of crop contractions, esophageal boluses, and gastric cycles were determined in lateral and ventrodorsal views. A range of 3.4-6.6 gastric cycles/min was noted on the lateral view and 3.0-6.6 gastric cycles/min on the ventrodorsal view. Circular measurements of the proventriculus diameter, ventriculus width, and length were obtained using the midshaft femoral diameter as a standard reference unit. The upper limits of the reference ranges were 3.6 and 4.7 femoral units for the proventriculus diameter in the lateral and ventrodorsal view, respectively. Two consecutive measurements were obtained and the measurement technique was found to have high reproducibility. In this study, we established a standardized protocol for contrast fluoroscopic examination of the gastrointestinal tract and a reliable measurement method of the proventriculus and ventriculus using femoral units in the Hispaniolan Amazon parrot.

It is argued in the paper that Regional science needs to rethink its theoretical frameworks and research agendas. Globalization and impending recession show starkly how too little attention has been paid to issues of finance and the supply of funds within economies. Too frequently business relationships have been seen as embedded in benign networks, neglecting issues of power, control and exclusion, the role of contracts and their enforcement, and the pursuit of inimitability to maximise rents. Rethinking these issues involves new perspectives to be developed on policy development, including the neglected significance of ‘bureaucratic politics’, and how policy interacts with communities to create outcomes on the ground. The paper seeks to stimulate a debate that is needed to keep Regional Science relevant.

As the knowledge economy develops and intensifies, increasing pressure is being placed on universities to help in local economic capacity building to meet the challenges of globalization. This article explores this expanded university role from the perspective of the provision of policy analysis and advice they can provide. It proposes the use of mixed-methods analysis, combining informed empirical modeling and “intensive” case studies to reveal local economic processes. An analysis of Australia’s regional problems to exemplify this approach highlights the significance of “enterprising human capital” in promoting regional economic growth and suggests a policy prescription that includes enterprising education. In contradistinction, using U.K. evidence, the pitfalls of entrepreneurship education are outlined as it relates to the role of universities in local economic capacity building. The study calls for dialogue to bring about radical rethinking of policy analysis, advice, and the role universities can play in local economic capacity building.

In the economically developed world, over 75 percent of all jobs involve some form of service work. Over the last 30 years, there has been a dramatic growth in business and professional services (BPS) or those firms that provide “creative” intermediate inputs into the activities of client companies. BPS firms have a double impact on regional economic performance: they add value in their own right but also create productivity improvements in client companies. This article explores the development of a BPS-focused regional economic development policy in the West Midlands, United Kingdom. Developing a policy framework for BPS is problematic as the heterogeneous nature of BPS activities means that no single lobbying group exists to represent their interests. The West Midlands has tried to overcome this difficulty by creating subregional networking organizations and, more recently, by developing a policy approach that attempts to enhance the added value BPS firms provide to their clients. This represents a major, but as yet untested, development in policy intervention as it recognizes the complex interactions that occur between BPS firms and their clients.