AOA Critical Issues Symposium: So, You Want to Be a Department Leader: Essentials for Success.

ABSTRACT: Most health systems are vertically integrated, and the leaders of orthopaedic surgery departments or service lines must have a comprehensive understanding of their role in the strategic plan of the health system. Orthopaedic surgery departments must be profitable while supporting the tripartite mission of excellence in clinical care, research, and education. This symposium had 4 specific objectives: to discuss how to (1) create synergy between the department or service line and the health system, (2) develop a strategy to enhance financial stability and revenue growth, (3) develop a comprehensive plan to enhance recruitment and retention of a diverse faculty, and (4) consider alternative strategies to foster education and research, even when the health system may be more focused on revenue generation.

A comparison of different approaches for the analysis of 36Cl in graphite samples.

This study compares different approaches for the quantification of the massic activity of 36Cl in graphite samples. All approaches consisted of a combustion step in combination with a trapping solution to collect the volatile elements. Two different resins were used to separate 36Cl from the matrix (CL resin and PS resin). Liquid scintillation counting (LSC), scintillation counting (SC) and tandem inductively coupled plasma mass spectrometry (ICP-MS/MS) were used to quantify 36Cl activity. The chemical yield in all approaches was determined by means of ion chromatography (IC). In addition, the methods were applied to a real activated graphite sample.

Updated guidelines for gene nomenclature in wheat.

KEY MESSAGE: Here, we provide an updated set of guidelines for naming genes in wheat that has been endorsed by the wheat research community. The last decade has seen a proliferation in genomic resources for wheat, including reference- and pan-genome assemblies with gene annotations, which provide new opportunities to detect, characterise, and describe genes that influence traits of interest. The expansion of genetic information has supported growth of the wheat research community and catalysed strong interest in the genes that control agronomically important traits, such as yield, pathogen resistance, grain quality, and abiotic stress tolerance. To accommodate these developments, we present an updated set of guidelines for gene nomenclature in wheat. These guidelines can be used to describe loci identified based on morphological or phenotypic features or to name genes based on sequence information, such as similarity to genes characterised in other species or the biochemical properties of the encoded protein. The updated guidelines provide a flexible system that is not overly prescriptive but provides structure and a common framework for naming genes in wheat, which may be extended to related cereal species. We propose these guidelines be used henceforth by the wheat research community to facilitate integration of data from independent studies and allow broader and more efficient use of text and data mining approaches, which will ultimately help further accelerate wheat research and breeding.

Investigation of a new approach for 36Cl determination in solid samples using plastic scintillators.

This work reports a new approach for the determination of 36Cl in radioactive waste samples from nuclear decommissioning, wherein novel plastic scintillator (PS) materials were used for the concentration of 36Cl prior to the detection with scintillation counting. Different plastic scintillator (PS) materials were tested for their selective absorption and detection of 36Cl activity in solid samples. PS microspheres (PSm), cross-linked PSm (CPSm) and PS resin have been investigated. PS resin was identified as the most suitable material for 36Cl analysis. Pyrolysis and subsequent trapping of the volatile elements in a bubbler was used. The trapping solution was finally loaded onto a cartridge of the PS resin. Scintillation counting and ion chromatography were used to determine the activity concentration and the chemical recovery, respectively.

Validation of efficiency transfer for high-density materials in HPGe spectrometry.

Recycling and conventional reuse of lead materials and structures originating from controlled areas in nuclear facilities rely on historical knowledge and well selected characterization procedures. At the SCK•CEN, one of these procedures involves performing high-resolution gamma-ray spectrometry measurements on several cylindrical shaped test samples (50 mm diameter and approximately 5 mm thickness), obtained during the lead melting campaigns. The high density (11.3 g/cm³) of these samples is a challenge for radionuclide analysis by gamma-ray spectrometry since no such calibration sources nor reference materials are available. We used the efficiency transfer procedure, relying on regular standard sources available in our laboratory, to set up calibrations for this specific counting geometry. The method proves to be fit for purpose.

Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study, a collaborative study carried out in 14 countries.

AIMS: To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries. METHODS: People with diabetes aged 18-65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected. RESULTS: A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (P<0.0001), a lower level of education (P<0.05), doing less exercise (P<0.01), higher levels of diabetes distress (P<0.0001) and a previous diagnosis of major depressive disorder (P<0.0001). The proportion of those with either current major depressive disorder or moderate to severe levels of depressive symptomatology who had a diagnosis or any treatment for their depression recorded in their medical records was extremely low and non-existent in many countries (0-29.6%). CONCLUSIONS: Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes.

Determination of the neutron activation profile of core drill samples by gamma-ray spectrometry.

This paper provides guidance for determining the neutron activation profile of core drill samples taken from the biological shield of nuclear reactors using gamma spectrometry measurements. Thus, it provides guidance for selecting a model of the right form to fit data and using least squares methods for model fitting. The activity profiles of two core samples taken from the biological shield of a nuclear reactor were determined. The effective activation depth and the total activity of core samples along with their uncertainties were computed by Monte Carlo simulation.

Ptychographic coherent diffractive imaging with orthogonal probe relaxation.

Ptychography is a scanning coherent diffractive imaging (CDI) technique that relies upon a high level of stability of the illumination during the course of an experiment. This is particularly an issue for coherent short wavelength sources, where the beam intensity is usually tightly focused on the sample in order to maximize the photon flux density on the illuminated region of the sample and thus a small change in the beam position results in a significant change in illumination of the sample. We present an improved ptychographic method that allows for limited stability of the illumination wavefront and thus significantly improve the reconstruction quality without additional prior knowledge. We have tested our reconstruction method in a proof of concept experiment, where the beam instability of a visible light source was emulated using a piezo driven mirror, and also in a short wavelength microscopy CDI setup using a high harmonic generation source in the extreme ultraviolet range. Our work shows a natural extension of the ptychography method that paves the way to use ptychographic imaging with any limited pointing stability coherent source such as free electron or soft X-ray lasers and improve reconstruction quality of long duration synchrotron experiments.

Helium ion beam milling to create a nano-structured domain wall magnetoresistance spin valve.

We have fabricated and measured single domain wall magnetoresistance devices with sub-20 nm gap widths using a novel combination of electron beam lithography and helium ion beam milling. The measurement wires and external profile of the spin valve are fabricated by electron beam lithography and lift-off. The critical bridge structure is created using helium ion beam milling, enabling the formation of a thinner gap (and so a narrower domain wall) than that which is possible with electron beam techniques alone. Four-point probe resistance measurements and scanning electron microscopy are used to characterize the milled structures and optimize the He ion dose. Successful operation of the device as a spin valve is demonstrated, with a 0.2% resistance change as the external magnetic field is cycled. The helium ion beam milling efficiency as extracted from electrical resistance measurements is 0.044 atoms/ion, about half the theoretical value. The gap in the device is limited to a maximum of 20 nm with this technique due to sub-surface swelling caused by injected ions which can induce catastrophic failure in the device. The fine patterning capabilities of the helium ion microscope milling technique indicate that sub-5 nm constriction widths could be possible.

The oxygenation response to functional stimulation: is there a physiological meaning to the lag between parameters?

To investigate the regulation of the hemodynamic response to functional stimulation, functional near-infrared spectroscopy (fNIRS) has been used, due to its ability to assess the dynamics of oxygenated, deoxygenated and total hemoglobin concentration ([oxy-Hb], [deoxy-Hb] and [tot-Hb]). Concerning the latency of these parameters, recent studies have returned a consistent picture when comparing the oxygenation response in the sensorimotor to the visual system: changes in [oxy-Hb] lead those in [deoxy-Hb] by 1.6+/-0.2 s (mean+/-SD) for the sensorimotor system but not for the visual system (0.1+/-0.3 s). A number of physiological differences between these cortical areas may account for such a discrepancy, however, the methodological properties of transcranial NIRS also have a relevant influence. Here we show that for the motor system the latency between changes in oxy- compared to deoxy-Hb vanishes once efforts are made to reduce the effects of a systemic response accompanying sensorimotor activity. We apply two independent approaches to reduce the systemic response and find a simultaneous change in [oxy-Hb] and [deoxy-Hb] even in response to a motor paradigm. The two approaches are: (i) an experimental paradigm with alternating contralateral and ipsilateral motor performance without interspersed rest periods designed to minimize systemic changes and (ii) a global correction scheme in an experiment, comparing a unilateral motor performance to rest. These data shed some doubt on the alleged fundamental physiological difference between cortical hemodynamic regulation in motor and visual cortex and highlight the relevance to respect contributions of the systemic hemodynamics.

Spine fusion by gene therapy.

Over 250 000 patients each year undergo a spine fusion procedure in the US. This constitutes 50% of all bone graft procedures. Despite best efforts, a large percentage of spine fusions (up to 35%) fail to form a solid bony arthrodesis. This is a significant clinical problem and has led to research in bone formation biology to augment spine fusion rates. Both recombinant and purified osteoinductive cytokines have been studied in pilot and pivotal studies in humans. At this point, recombinant human bone morphogenetic protein-2 has received FDA approved for lumbar interbody application with titanium cages. Despite these successes, limitations of directly applying osteoinductive proteins related to cost and carriers remain to be overcome. Gene therapy for spine fusion and other bone healing applications are being pursued as an alternative strategy. This article will review the state of the art of local gene therapy for bone formation and to highlight specific issues, which must be addressed when pursuing such a program. A critical step in using gene therapy for bone formation is choosing an appropriate osteoinductive gene. In choosing the gene, one must consider the differences in efficacy of the gene as well as the gene availability due to proprietary constraints. The choice of delivery vector is important. Factors such as the potency of the gene and the specific application intended play a role in this decision. Next, the effective dose, transduction time, and gene transfer method must be established. The choice of carrier material to form the scaffold for the new bone formation is another critical step that must be optimized for successful bone formation. Finally, a strategy for in vitro and in vivo testing must be developed to maximize the chances of success in human trials.

Demineralized bone matrix, bone morphogenetic proteins, and animal models of spine fusion: an overview.

Preclinical investigations on the use of bone morphogenetic proteins (BMP) in the spine have yielded promising results. This has led to the preliminary introduction of these growth factors in controlled clinical trials. Initial data made available suggest that these differentiating factors will play a major role in the treatment of spinal disorders in the future. This article reviews key preclinical studies and their results that formed the basis for introduction into clinical trials. Non-primate and non-human primate models of spine fusion with BMP are reviewed objectively, and important issues regarding carrier, dose, and site of implantation are discussed. Finally, exciting new gene therapy research is discussed, with comments made on its applicability for the future.

Do the intervertebral disc cells respond to different levels of hydrostatic pressure?

OBJECTIVE: To test the hypothesis that hydrostatic pressure directly affects the synthesis of collagen and proteoglycan by intervertebral disc cells. DESIGN: By the use of pressure vessels, hydrostatic pressure was applied to intervertebral disc cells cultured in alginate. BACKGROUND: The influence of compression (both hydrostatic and axial) on chondrocyte metabolism was examined in a number of earlier studies. However, in most of these studies, articular cartilage, not intervertebral disc was used, and in none of these was hydrostatic pressure applied to intervertebral disc cells cultured in alginate. METHODS: Fresh cells were harvested from the lumbar intervertebral discs of dogs. Before their suspension in an alginate gel system, the cells were plated and expanded until they reached confluence. Then, by use of the alginate gel system, the cells were exposed (for up to 9 days) to specific values of hydrostatic pressure inside two stainless steel pressure vessels. One vessel was kept at 0.35 MPa and the other at atmospheric pressure (approximately 0.1 MPa). The effects of 0.35 MPa were compared against atmospheric pressure by measuring the incorporation of [3H]-proline and [35S]-sulfate into collagen and proteoglycans, respectively, for the anulus cells and nucleus cells separately, and by determining whether this incorporation was reflected by changes in the levels of mRNA for aggrecan and Types I and II collagen. RESULTS: Proteoglycan synthesis was inhibited at 0.35 MPa as compared to atmospheric pressure for both the nucleus and anulus cells, whereas collagen synthesis was stimulated in the nucleus cells, but inhibited in the anulus cells. The mRNA levels of collagen 1A and collagen 2A decreased in the anulus but showed a differential response in the nucleus (collagen 1A increased, while collagen 2A decreased). The mRNA levels for aggrecan core protein decreased in the anulus and increased in the nucleus. CONCLUSIONS: Hydrostatic pressure directly affects the synthesis of collagen and proteoglycan by the intervertebral disc cells. RELEVANCE: This in vitro study reveals the direct effect of hydrostatic pressure on disc cells, in the absence of other factors. However, circumspection must be applied when comparisons between these results, from in vitro experiments on dog disc cells, are extrapolated and applied to the whole discs of humans.

Anterior lumbar interbody fusion using a barbell-shaped cage: a biomechanical comparison.

There are drawbacks to using threaded cylindrical cages (e.g., limited area for bone ingrowth and metal precluding radiographic visualization of bone healing). To somewhat offset these drawbacks, a barbell-shaped cage has been designed. The central core of the barbell can be wrapped with collagen sheets infiltrated with bone morphogenetic protein. The obvious theoretical advantages of a barbell cage have to be weighed against potential biomechanical disadvantages. Our purpose was to compare the biomechanical properties of an anterior lumbar interbody reconstruction using 18-mm-diameter threaded cylindrical cages, with a reconstruction using barbell cages (18-mm diameter and 6 mm wide at both cylindrical ends, with a round 4-mm-diameter bar joining the two ends). Twelve cadaveric lumbar motion segments were tested. Three L5-S1 segments received two threaded cylindrical cages, and three L5-S1 segments received two barbell cages. Three L3-L4 segments received one threaded cylindrical cage, and three L3-L4 segments received one barbell cage. A series of biomechanical loading sequences were carried out on each motion segment, and stiffness curves were obtained. After the biomechanical testing, an axial compressive load was applied to the motion segments until failure. They were then radiographed and bisected through the disc, and the subsidence (or penetration) of the cage(s) in the cancellous bone of the vertebral bodies was measured. There was no difference in terms of stiffness between the motion segments with the threaded cylindrical cage(s) inserted and those with the barbell cage(s) inserted (p > 0.15). The average values of subsidence was 0.96 mm for the threaded cylindrical cage group and 0.80 mm for the barbell cage group (difference not significant: p = 0.38). The results suggest that a reconstruction using barbell cages is a biomechanically acceptable alternative to one using threaded cylindrical cages.

The value of magnetic resonance imaging of the lumbar spine to predict low-back pain in asymptomatic subjects : a seven-year follow-up study.

BACKGROUND: In 1989, a group of sixty-seven asymptomatic individuals with no history of back pain underwent magnetic resonance imaging of the lumbar spine. Twenty-one subjects (31%) had an identifiable abnormality of a disc or of the spinal canal. In the current study, we investigated whether the findings on the scans of the lumbar spine that had been made in 1989 predicted the development of low-back pain in these asymptomatic subjects. METHODS: A questionnaire concerning the development and duration of low-back pain over a seven-year period was sent to the sixty-seven asymptomatic individuals from the 1989 study. A total of fifty subjects completed and returned the questionnaire. A repeat magnetic resonance scan was made for thirty-one of these subjects. Two neuroradiologists and one orthopaedic spine surgeon interpreted the original and repeat scans in a blinded fashion, independent of clinical information. At each disc level, any radiographic abnormality, including bulging or degeneration of the disc, was identified. Radiographic progression was defined as increasing severity of an abnormality at a specific disc level or the involvement of additional levels. RESULTS: Of the fifty subjects who returned the questionnaire, twenty-nine (58%) had no back pain. Low-back pain developed in twenty-one subjects during the seven-year study period. The 1989 scans of these subjects demonstrated normal findings in twelve, a herniated disc in five, stenosis in three, and moderate disc degeneration in one. Eight individuals had radiating leg pain; four of them had had normal findings on the original scans, two had had spinal stenosis, one had had a disc protrusion, and one had had a disc extrusion. In general, repeat magnetic resonance imaging scans revealed a greater frequency of disc herniation, bulging, degeneration, and spinal stenosis than did the original scans. CONCLUSIONS: The findings on magnetic resonance scans were not predictive of the development or duration of low-back pain. Individuals with the longest duration of low-back pain did not have the greatest degree of anatomical abnormality on the original, 1989 scans. Clinical correlation is essential to determine the importance of abnormalities on magnetic resonance images.

Stimulation of leukotriene synthesis in intact polymorphonuclear cells by the 5-lipoxygenase inhibitor 3-oxo-tirucallic acid.

Commercially available extracts from Boswellia serrata resin used as anti-inflammatory drugs or phytonutrients show paradoxical concentration-dependent potentiating and inhibitory actions on 5-lipoxygenase (5-LO) product synthesis in stimulated PMNs. In our attempt to characterize the stimulating constituents, we identified the tetracyclic triterpene 3-oxo-tirucallic acid (3-oxo-TA), which, in the range from 2.5 to 15 microM, enhanced 5-LO product formation in ionophore-challenged polymorphonuclear cells (PMNs) (e.g., from 1981 +/- 177 to 3042 +/- 208 pmol at 10 microM 3-oxo-TA), and initiated Ca(2+) mobilization, MEK-1/2 phosphorylation, 5-LO translocation, and 5-LO product formation in resting cells (534 +/- 394 pmol/5 x 10(6) PMNs). In cell-free 5-LO assays, 3-oxo-TA acted only inhibitory (IC(50) value of about 3 microM), demonstrating the pivotal role of intact cell structure for its activating property. In 3-oxo-TA-challenged PMNs, the mitogen-activated protein kinase kinase (MEK)-1/2 inhibitor PD098059 abolished 5-LO product formation, along with inhibition of MEK-1/2 phosphorylation and 5-LO translocation. The 3-acetoxy derivative of 3-oxo-TA acted like 3-oxo-TA in intact PMNs, whereas 3-hydroxy-TA barely stimulated MEK phosphorylation in resting cells and showed only inhibition on ionophore-induced 5-LO product synthesis. Steroid-type tetracycles neither induced 5-LO activation nor had enhancing or inhibitory effects. In summary, defined natural tetracyclic triterpenes, which act as inhibitors of the 5-LO in the cell-free assay, initiate 5-LO activation by a MEK-inhibitor sensitive mechanism and potentiate stimulated product synthesis in intact cells. Because TAs contribute significantly to the overall biological effects of B. serrata resin extracts, special precaution for standardization is recommended when using B. serrata preparations as drugs or dietary supplements.

Acetyl-11-keto-beta-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis.

The gum resin extract from Boswellia serrata (H15), an herbal product, was recently shown to have positive therapeutic effects in inflammatory bowel disease (IBD). However, the mechanisms and constituents responsible for these effects are poorly understood. This study examined the effect of the Boswellia extract and its single constituent acetyl-11-keto-beta-boswellic acid (AKBA) on leukocyte-endothelial cell interactions in an experimental model of IBD. Ileitis was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats 24 h apart. Rats also received oral treatment with the Boswellia extract (H15) or AKBA at two different doses (low and high) equivalent to recommendations in human disease over 2 days. Controls received only the carriers NaHCO3 (subcutaneously) and tylose (orally). Effects of treatment were assessed by intravital microscopy in ileal submucosal venules for changes in the number of rolling and adherent leukocytes and by macroscopic and histological scoring. Increased leukocyte-endothelial cell adhesive interactions and severe tissue injury accompanied indomethacin-induced ileitis. Treatment with the Boswellia extract or AKBA resulted in a dose-dependent decrease in rolling (up to 90%) and adherent (up to 98%) leukocytes. High-dose Boswellia extract as well as both low- and high-dose AKBA significantly attenuated tissue injury scores. Oral therapy with the Boswellia extract or AKBA significantly reduces macroscopic and microcirculatory inflammatory features normally associated with indomethacin administration, indicating that the anti-inflammatory actions of the Boswellia extract in IBD may be due in part to boswellic acids such as AKBA.