Uptake and incorporation of Al, Cr, V, Zn and Mo in hematite: Competition, synergies and influence on structural properties.

This study investigated multiple (di-, tri- and tetra-)incorporation of selected minor and trace elements (Al3+, Cr3+, V3-5+, Zn2+, Mo6+ and As5+) into hematite. The purpose was to improve understanding of how hematite may control trace element mobility in the environment, and how physical and chemical properties of hematite are impacted by multi-element incorporation at x/Fe molar ratios of up to 10%. Simultaneous structural incorporation of Al±Cr±V±Zn into hematite was achieved, with both synergistic and antagonistic effects occurring between certain element combinations. Cr+Al had synergistic effects on their co-incorporation, while V negatively affected Al incorporation, and both V and Zn negatively affected Cr incorporation. In contrast, Mo was minimally associated with hematite, and As prevented hematite formation completely. X-ray diffraction indicated contraction and expansion of the hematite unit-cell upon substitution was related to the ionic radius of the substituting element in single-element samples, while V predominantly controlled the direction of deviation in multi-element samples. X-ray absorption near-edge structure spectroscopy indicated V was present as a mixture of V3+-V5+, with a higher average V oxidation state associated with multi-element samples. Results provide new insights into trace element geochemistry within hematite, and highlight the importance of multi-element studies to better understand natural and anthropogenic systems.

Therapeutic assessment of N-formyl-methionyl-leucyl-phenylalanine (fMLP) in reducing periprosthetic joint infection.

Despite many preventive measures, including prophylactic antibiotics, periprosthetic joint infection (PJI) remains a devastating complication following arthroplasty, leading to pain, suffering, morbidity and substantial economic burden. Humans have a powerful innate immune system that can effectively control infections, if alerted quickly. Unfortunately, pathogens use many mechanisms to dampen innate immune responses. The study hypothesis was that immunomodulators that can jumpstart and direct innate immune responses (particularly neutrophils) at the surgical site of implant placement would boost immune responses and reduce PJI, even in the absence of antibiotics. To test this hypothesis, N-formyl-methionyl-leucyl-phenylalanine (fMLP) (a potent chemoattractant for phagocytic leukocytes including neutrophils) was used in a mouse model of PJI with Staphylococcus aureus (S. aureus). Mice receiving intramedullary femoral implants were divided into three groups: i) implant alone; ii) implant + S. aureus; iii) implant + fMLP + S. aureus. fMLP treatment reduced S. aureus infection levels by ~ 2-Log orders at day 3. Moreover, fMLP therapy reduced infection-induced peri-implant periosteal reaction, focal cortical loss and areas of inflammatory infiltrate in mice distal femora at day 10. Finally, fMLP treatment reduced pain behaviour and increased weight-bearing at the implant leg in infected mice at day 10. Data indicated that fMLP therapy is a promising novel approach for reducing PJI, if administered locally at surgical sites. Future work will be toward further enhancement and optimisation of an fMLP-based therapeutic approach through combination with antibiotics and/or implant coating with fMLP.

Quantitative SPECT imaging and biodistribution point to molecular weight independent tumor uptake for some long-circulating polymer nanocarriers.

Polymeric nanocarriers are promising entities for cancer diagnosis and therapy. The aim of such nanocarriers is to selectively accumulate in cancerous tissue that is difficult to visualize or treat. The passive accumulation of a nanocarrier in a tumor through extravasation is often attributed to the enhanced permeation and retention (EPR) effect and the size and shape of the nanocarrier. However, the tumor microenvironment is very heterogeneous and the intratumoral pressure is usually high, leading to different opinions about how the EPR of nanocarriers through the irregular vasculature of a tumor leads to accumulation. In order to investigate this topic, we studied methods for the determination of pharmacokinetic parameters, biodistribution and the tumor uptake of nanocarriers. More specifically, we used non-invasive quantitative Single-Photon Emission Computed Tomography/Computed Tomography (qSPECT/CT) imaging of hyperbranched polyglycerols (HPGs) to explore the specific biodistribution and tumor uptake of six model nanocarriers in Rag2m mice. We were interested to see if a distinct molecular weight (MW) of nanocarriers (HPG 25, 50, 100, 200, 300, 500 kDa) is favoured by the tumor. To trace the model nanocarriers, HPGs were covalently linked to the strong chelator desferrioxamine (DFO), and radiolabeled with the gamma emitter 67Ga (EC = 100%, E γ = 185 keV (21.4%), 300 keV (16.6%), half-life = 3.26 d). Without the need for blood collection, but instead using qSPECT/CT imaging inside the heart, the blood circulation half-lives of the 67Ga labeled HPGs were determined and increased from 9.9 ± 2.9 to 47.8 ± 7.9 hours with increasing polymer MW. Total tumor accumulation correlated positively with the circulation time of the HPGs. Comparing the tumor-to-blood ratio dynamically revealed how blood and tumor concentrations of the nanocarrier change over time and when equilibrium is reached. The time of equilibrium is size-dependent and increases with molecular weight. Furthermore, the data indicate that for larger MWs, nanocarrier uptake and retention by the tumor is size independent. Further studies are necessary to advance our understanding of the interplay between MW and nanoparticle accumulation in tumors.

Strategic planning in an academic radiation medicine program.

BACKGROUND: In this paper, we report on the process of strategic planning in the Radiation Medicine Program (rmp) at the Princess Margaret Cancer Centre. The rmp conducted a strategic planning exercise to ensure that program priorities reflect the current health care environment, enable nimble responses to the increasing burden of cancer, and guide program operations until 2020. METHODS: Data collection was guided by a project charter that outlined the project goal and the roles and responsibilities of all participants. The process was managed by a multidisciplinary steering committee under the guidance of an external consultant and consisted of reviewing strategic planning documents from close collaborators and institutional partners, conducting interviews with key stakeholders, deploying a program-wide survey, facilitating an anonymous and confidential e-mail feedback box, and collecting information from group deliberations. RESULTS: The process of strategic planning took place from December 2014 to December 2015. Mission and vision statements were developed, and core values were defined. A final document, Strategic Roadmap to 2020, was established to guide programmatic pursuits during the ensuing 5 years, and an implementation plan was developed to guide the first year of operations. CONCLUSIONS: The strategic planning process provided an opportunity to mobilize staff talents and identify environmental opportunities, and helped to enable more effective use of resources in a rapidly changing health care environment. The process was valuable in allowing staff to consider and discuss the future, and in identifying strategic issues of the greatest importance to the program. Academic programs with similar mandates might find our report useful in guiding similar processes in their own organizations.

Characterization of degenerative human facet joints and facet joint capsular tissues.

OBJECTIVE: Lumbar facet joint degeneration (FJD) may be an important cause of low back pain (LBP) and sciatica. The goal of this study was to characterize cellular alterations of inflammatory factor expression and neovascularization in human degenerative facet joint capsular (FJC) tissue. These alterations in FJC tissues in pain stimulation were also assessed. DESIGN: FJs were obtained from consented patients undergoing spinal reconstruction surgery and cadaveric donors with no history of back pain. Histological analyses of the FJs were performed. Cytokine antibody array and quantitative real-time polymerase chain reaction (qPCR) were used to determine the production of inflammatory cytokines, and western blotting analyses (WB) were used to assay for cartilage-degrading enzymes and pain mediators. Ex vivo rat dorsal root ganglion (DRG) co-culture with human FJC tissues was also performed. RESULTS: Increased neovascularization, inflammatory cell infiltration, and pain-related axonal-promoting factors were observed in degenerative FJCs surgically obtained from symptomatic subjects. Increased VEGF, (NGF/TrkA), and sensory neuronal distribution were also detected in degenerative FJC tissues from subjects with LBP. qPCR and WB results demonstrated highly upregulated inflammatory cytokines, pain mediators, and cartilage-degrading enzymes in degenerative FJCs. Results from ex vivo co-culture of the DRG and FJC tissue demonstrated that degenerative FJCs increased the expression of inflammatory pain molecules in the sensory neurons. CONCLUSION: Degenerative FJCs possess greatly increased inflammatory and angiogenic features, suggesting that these factors play an important role in the progression of FJD and serve as a link between joint degeneration and neurological stimulation of afferent pain fibers.

Pharmacologic augmentation of implant fixation in osteopenic bone.

Osteoporosis presents a challenge for successful implant fixation due to an impaired healing response. Preclinical studies have consistently reported reduced osseointegration capability in trabecular bone. Although clinical studies of implant success in dentistry have not found a negative effect due to osteoporosis, low bone mass is a significant risk factor for implant migration in orthopedics. Pharmacologic treatment options that limit bone resorption or upregulate formation have been studied preclinically. While, both treatment options improve implant fixation, direct comparisons to-date have found anti-catabolic more effective than anabolic treatments for establishing implant fixation, but combination approaches are better than either treatment alone. Clinically, anti-catabolic treatments, particularly bisphosphonates have been shown to increase the longevity of implants, while limited clinical evidence on the effects of anabolic treatment exists. Preclinical experiments are needed to determine the effects of osteoporosis and subsequent treatment on the long-term maintenance of fixation and recovery after bone loss.

Comparison of 3-D stereoscopic MR imaging with pre and post lesion recording in pallidotomy.

OBJECTIVES: A quantitative on-line analysis of electrical activity in the pallidum of Parkinsonian patients has been developed to determine the focal point of lesioning. Additional recordings are made after the lesioning, to assess residual neural activity. A 3-D volume stereoscopic image system is proposed to display the complex anatomy and to superimpose the electrophysiological data into this system. The purpose of this study is to understand the complex pathophysiology in real-time anatomic/image space and determine the location and effect of lesioning residual energy sites. MATERIAL AND METHODS: Thirty patients undergoing 41 pallidotomies are presented. Neuronal activity from the pallidum is recorded using a semi-microelectrode. Based on this activity, lesioning is performed. Post-lesion recordings are made to determine the necessity of additional lesioning. 3-D volume MR images are acquired pre and postoperatively and compared for accuracy of lesion sites. A 3-D stereoscopic image system has been developed to depict basal ganglia geometry in the last 5 patients. Electrophysiological data are superimposed on this image system to show the surgeon the virtual position of the electrode tip. RESULTS: A stereoscopic 3-D volume MR image system has been developed. This system more efficiently and accurately visualizes and records the coordinates of high neural activity in the pallidum and post lesion residual activity. Post-lesion power analysis was carried out in 30 patients. Additional lesions were indicated in 8 and different trajectories in 6. CONCLUSION: Real-time visualization of neural recording, both pre and post-lesioning during pallidotomy, facilitates the surgeon's understanding of the spatiotemporal relationships of pathophysiological properties within the globus pallidus.

Quantitative on-line analysis of physiological data for lesion placement in pallidotomy.

A computerized method of determining the focal point of electrical activity in the pallidum of parkinsonian patients was developed using on-line quantitative physiological data analysis. Thirty patients in a series of 70 were studied in depth. Neuronal activity was recorded from the pallidum using a semi-microelectrode. The signal is inspected visually while its average power, characteristic frequency and complexity are computed. The target locus was indicated by the highest level of global activity in the vicinity of the electrode (signal power maximum), maximal signal complexity and minimal characteristic frequency. Most often, the vertical coordinate required correction. The postoperative clinical and imaging results have indicated the effectiveness of this method.

Electrophysiological recordings in pallidotomy localized to 3D stereoscopic imaging.

A quantitative on-line analysis of electrical activity in the pallidum of Parkinsonian patients has been developed to determine the focal point of lesioning. A 3D volume image system has been developed to display basal ganglia anatomy and coregister the electrophysiological data within the globus pallidus. Thirty patients undergoing 41 pallidotomies are presented. Neuronal activity from the pallidum is recorded using a semi-microelectrode. Based on this activity, lesioning is performed. Postlesion recordings are made to determine the necessity of additional lesioning. A stereoscopic 3D volume MR image system has been developed that along with on-line signal processing allows visualization of high neural activity in the pallidum and postlesion residual activity.

Evaluation of a semi-automated reticulocyte counting method using the Coulter STKS-2A blood cell counter.

Reticulocyte counting was assessed on the Coulter STKS-2A automated blood cell counter. Using a two step procedure, blood samples were first incubated with the supravital stain new methylene blue. An acidic reagent was then added to clear the haemoglobin and any stained RNA was preserved within the cell. The cells were then analysed by measurement of volume, conductivity and light scatter (VCS). The results of 123 samples analysed on the STKS-2A were compared with those from a Toa Sysmex R-1000 reticulocyte counter. One hundred and seven samples gave no review flags and reticulocyte counts ranging from 0.5% to 22.8%, resulting in a correlation coefficient of 0.93 for the methods. Between run imprecision studies gave CVs ranging from 5.3% for a reticulocyte count of 8.7% to a CV of 16.3% for a 0.34% count. Stability studies showed insignificant changes over 72 h storage. These findings confirm that VCS technology can be adapted to provide precise and accurate routine reticulocyte analysis.

Inaccuracy of the 'derived' fibrinogen measurement.

The 'derived' fibrinogen method is commonly used for the measurement of plasma fibrinogen. This method is not a direct quantitation of plasma fibrinogen, but an estimation of the fibrinogen concentration from the clotting curve of the prothrombin time on automated photo-optical coagulometers. An increasing number of laboratories are now routinely using this method to cope with increasing demands for fibrinogen testing. To study the suitability of this method for routine laboratory use a total of 58 samples, 20 healthy normals and 38 from other patient groups were tested by the 'derived' and Clauss fibrinogen methods on the ACL 300R. The results clearly demonstrated that 'derived' fibrinogen assay values were significantly higher than the Clauss measurements. The discrepancy between 'derived' and Clauss fibrinogen levels was greater in certain patient groups, e.g. patients receiving oral anticoagulants, than in normal controls. Some patients with documented hypodysfibrinogenaemia with low fibrinogen levels by Clauss assay gave normal 'derived' fibrinogen values. Although the 'derived' fibrinogen assay is rapid, economical and easily available to laboratories with suitable instruments, this study shows that it lacks standardization and is inaccurate compared with the Clauss assay.

Chloroplast Structure and Starch Grain Accumulation in Leaves That Received Different Red and Far-Red Levels during Development.

An important step in understanding influence of growth environment on carbon metabolism in plants is to gain a better understanding of effects of light quality on the photosynthetic system. Electron microscopy was used to study chloroplast ultrastructure in developing and fully expanded leaves of tobacco (Nicotiana tabacum L. cv Burley 21). Brief exposures to red or far-red light at the end of each day during growth under controlled environments influenced granum size, granum number and starch grain accumulation in chloroplasts, and the concentration of sugars in leaf lamina. Far-red-treated leaves had chloroplasts with more but smaller grana than did red-treated leaves. Red light at the end of the photosynthetic period resulted in more and larger starch grains in the chloroplasts and a lower concentration of sugars in leaves. Chloroplast ultrastructure and starch grain accumulation patterns that were initiated in the expanding leaves were also evident in the fully expanded leaves that received the treatment during development. It appears that the phytochrome system in the developing leaves sensed the light environment and initiated events which influenced chloroplast development and partitioning of photosynthate to adapt the plant for better survival under those environmental conditions.

Arteriovenous malformation in chronic gastrointestinal bleeding.

Arteriovenous malformations of the gastrointestinal tract are uncommon and treatment is problematic because routine barium contrast studies and endoscopy fail to demonstrate the lesion. Diagnosis is by selective mesenteric arteriography, demonstrating a characteristic vascular tuft and very early venous phase. Two cases of arteriovenous malformation are presented and 47 other reported cases are reviewed. Forty-five per cent were found in the cecum; 37, or 80%, involved the distal ileum, cecum ascending colon, or hepatic flexure. Seventy-five per cent of all patients fall into the 50--80 year age range. The literature reveals a recurring pattern of chronic gastrointestinal blood loss, anemia, and delay (even negative abdominal explorations) before the diagnosis is finally made. A more aggressive approach to chronic gastrointestinal bleeding is suggested through the use of selective mesenteric arteriography.

Optimizing test performance of moderately and severely mentally retarded adolescents and adults.

This study provided further evidence for the validity of a learning potential assessment procedure with institutionalized moderately and severely retarded adolescents and adults. Significant positive correlations were obtained between psychometric and learning scores, attendants' and teachers' ratings of ability, and the posttraining scores on the modified Kohs Extended Learning Potential procedure. In addition, performance on this test-train-test procedure was compared with a train-within-test format for two different tasks: training embedded within the administration of the Leiter International Performance Scale and a formboard version of Raven's Coloured Progressive Matrices. The students responded equally to the two formats. Stanford-Binet IQs were least predictive of performance on the three learning potential measures and were unrelated to teachers' and attendants' ratings of ability. The implications of these data were discussed with particular attention to the potential advantages of the train-within-test model.