33,373 research outputs found

    A systematic review of the role of bisphosphonates in metastatic disease

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    Objectives: To identify evidence for the role of bisphosphonates in malignancy for the treatment of hypercalcaemia, prevention of skeletal morbidity and use in the adjuvant setting. To perform an economic review of current literature and model the cost effectiveness of bisphosphonates in the treatment of hypercalcaemia and prevention of skeletal morbidity Data sources: Electronic databases (1966-June 2001). Cochrane register. Pharmaceutical companies. Experts in the field. Handsearching of abstracts and leading oncology journals (1999-2001). Review methods: Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. Overall event rates were pooled in a meta-analysis, odds ratios ( OR) were given with 95% confidence intervals (CI). Where data could not be combined, studies were reported individually and proportions compared using chi- squared analysis. Cost and cost-effectiveness were assessed by a decision analytic model comparing different bisphosphonate regimens for the treatment of hypercalcaemia; Markov models were employed to evaluate the use of bisphosphonates to prevent skeletal-related events (SRE) in patients with breast cancer and multiple myeloma. Results: For acute hypercalcaemia of malignancy, bisphosphonates normalised serum calcium in >70% of patients within 2-6 days. Pamidronate was more effective than control, etidronate, mithramycin and low-dose clodronate, but equal to high dose clodronate, in achieving normocalcaemia. Pamidronate prolongs ( doubles) the median time to relapse compared with clodronate or etidronate. For prevention of skeletal morbidity, bisphosphonates compared with placebo, significantly reduced the OR for fractures (OR [95% CI], vertebral, 0.69 [0.57-0.84], non-vertebral, 0.65 [0.54-0.79], combined, 0.65 [0.55-0.78]) radiotherapy 0.67 [0.57-0.79] and hypercalcaemia 0.54 [0.36-0.81] but not orthopaedic surgery 0.70 [0.46-1.05] or spinal cord compression 0.71 [0.47-1.08]. However, reduction in orthopaedic surgery was significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was pound250 and pound1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. Conclusions: High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting

    Ventricular Entrapment Due To Isolated Intraventricular Aspergillus Infection

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    Introduction: Intraventricular aspergillus infections are a rare manifestation of fungal infections of the central nervous system (CNS). Intraventricular aspergillus infections have most commonly been identified in immunocompromised patients. Spread to the central nervous system is thought to occur hematogenously (usually from pulmonary infection) or directly from the paranasal sinuses. Clinical diagnosis is difficult, as symptoms are nonspecific, but imaging can be used to create a more accurate differential. This case report describes the rare diagnosis of an intraventricular aspergillus infection in an immunocompromised patient presenting with ventricular entrapment and demonstrates the role of imaging in making the diagnosis. Case Report: We present the case of a 59-year-old male with a history of renal transplant on immunosuppressive therapy, presenting with a two-week history of right-sided weakness and speech difficulty. Of note, patient was diagnosed with acute invasive pulmonary aspergillosis during a prior admission this year and had just completed a 12-week course of antifungal therapy. CT of the head at that time demonstrated only slight asymmetry of the ventricles without definite intracranial lesion. Initial non-contrast CT of the head demonstrated a complex cystic mass within the left lateral ventricle with asymmetric ventricular enlargement. CT of the head with contrast demonstrated a complex lesion within the left ventricle with peripheral enhancement and enlargement of the ventricle. MRI demonstrated a cystic lesion within the left lateral ventricle with a hyperintense FLAIR component anteriorly with restricted diffusion. Post-contrast MRI showed enhancement at the periphery of the complex lesion. There was also entrapment of the left lateral ventricle. After placement of an external ventricular drain for hydrocephalus, surgical biopsy of the lesion demonstrated numerous uniform, septate, fungal hyphae with rare acute angle branching consistent with aspergillus. Throughout the admission, there had been slow, but progressive, decline in neurological function. The patient has been continued on antifungal therapy pending improvement in neurological function. Conclusion: Isolated intraventricular aspergillus infection is a rare manifestation of CNS fungal infection, most commonly seen in immunocompromised patients. Given the nonspecific clinical symptoms of this diagnosis, imaging can localize and narrow the vast differential for these CNS lesions. Patients that have been diagnosed as such require immediate, long-term, and systemic antifungal therapy. With the mortality rate of patients with intraventricular aspergillus infections being highly dependent on accurate and immediate diagnosis, recognizing key imaging features can aid in improving current poor outcomes.https://scholarlycommons.henryford.com/merf2020caserpt/1097/thumbnail.jp

    Toughening and stiffening of starch food extrudates through the addition of cellulose fibres and minerals

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    Pet food, one of the largest type of commercial packaged foods, continuously sets new challenges, amongst them the possibility to enhance palatability via adjusting product composition. This will optimise texture perception across consumer groups of diverse chewing capabilities, as well as improve food oral breakdown efficiency with further impact on metabolic health and nutrient bioavailability in the digestive process. Our aim is to pioneer new methods of controlling texture by answering longstanding questions such as the impact of nutrients on the mechanical properties of foods. The impact of cellulose fibres and minerals on the fracture toughness and stiffness properties of starch food extrudates is investigated for the first time through employing tensile tests and two fracture toughness tests namely Essential Work of Fracture (EWF) and cutting, on four different compositions. Fibres alone are found to increase stiffness (stiffening) and toughness (toughening) whereas minerals decrease stiffness (softening) with a minor influence on toughness. Interestingly, fibres and minerals combined maximise toughening at 28% compared to pure starch, due to the synergistic effect of fibre-matrix de-bonding and fibre breakage mechanisms at the crack tip. These new results indicate that texture can be significantly altered through the addition of minerals and short fibres. Such information is critical in the design of products that need to satisfy both nutritional and textural criteria

    Overexpression of connexin 43 using a retroviral vector improves electrical coupling of skeletal myoblasts with cardiac myocytes in vitro.

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    BACKGROUND: Organ transplantation is presently often the only available option to repair a damaged heart. As heart donors are scarce, engineering of cardiac grafts from autologous skeletal myoblasts is a promising novel therapeutic strategy. The functionality of skeletal muscle cells in the heart milieu is, however, limited because of their inability to integrate electrically and mechanically into the myocardium. Therefore, in pursuit of improved cardiac integration of skeletal muscle grafts we sought to modify primary skeletal myoblasts by overexpression of the main gap-junctional protein connexin 43 and to study electrical coupling of connexin 43 overexpressing myoblasts to cardiac myocytes in vitro. METHODS: To create an efficient means for overexpression of connexin 43 in skeletal myoblasts we constructed a bicistronic retroviral vector MLV-CX43-EGFP expressing the human connexin 43 cDNA and the marker EGFP gene. This vector was employed to transduce primary rat skeletal myoblasts in optimised conditions involving a concomitant use of the retrovirus immobilising protein RetroNectin and the polycation transduction enhancer Transfectam. The EGFP-positive transduced cells were then enriched by flow cytometry. RESULTS: More than four-fold overexpression of connexin 43 in the transduced skeletal myoblasts, compared with non-transduced cells, was shown by Western blotting. Functionality of the overexpressed connexin 43 was demonstrated by microinjection of a fluorescent dye showing enhanced gap-junctional intercellular transfer in connexin 43 transduced myoblasts compared with transfer in non-transduced myoblasts. Rat cardiac myocytes were cultured in multielectrode array culture dishes together with connexin 43/EGFP transduced skeletal myoblasts, control non-transduced skeletal myoblasts or alone. Extracellular field action potential activation rates in the co-cultures of connexin 43 transduced skeletal myoblasts with cardiac myocytes were significantly higher than in the co-cultures of non-transduced skeletal myoblasts with cardiac myocytes and similar to the rates in pure cultures of cardiac myocytes. CONCLUSION: The observed elevated field action potential activation rate in the co-cultures of cardiac myocytes with connexin 43 transduced skeletal myoblasts indicates enhanced cell-to-cell electrical coupling due to overexpression of connexin 43 in skeletal myoblasts. This study suggests that retroviral connexin 43 transduction can be employed to augment engineering of the electrocompetent cardiac grafts from patients own skeletal myoblasts

    Synthesis and Cell Adhesive Properties of Linear and Cyclic RGD Functionalized Polynorbornene Thin Films

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    Described herein is the efficient synthesis and evaluation of bioactive arginine-glycine-aspartic acid (RGD) functionalized polynorbornene-based materials for cell adhesion and spreading. Polynorbornenes containing either linear or cyclic RGD peptides were synthesized by ring-opening metathesis polymerization (ROMP) using the well-defined ruthenium initiator [(H_(2)IMes)(pyr)_(2)(Cl)_(2)Ru═CHPh]. The random copolymerization of three separate norbornene monomers allowed for the incorporation of water-soluble polyethylene glycol (PEG) moieties, RGD cell recognition motifs, and primary amines for postpolymerization cross-linking. Following polymer synthesis, thin-film hydrogels were formed by cross-linking with bis(sulfosuccinimidyl) suberate (BS^3), and the ability of these materials to support human umbilical vein endothelial cell (HUVEC) adhesion and spreading was evaluated and quantified. When compared to control polymers containing either no peptide or a scrambled RDG peptide, polymers with linear or cyclic RGD at varying concentrations displayed excellent cell adhesive properties in both serum-supplemented and serum-free media. Polymers with cyclic RGD side chains maintained cell adhesion and exhibited comparable integrin binding at a 100-fold lower concentration than those carrying linear RGD peptides. The precise control of monomer incorporation enabled by ROMP allows for quantification of the impact of RGD structure and concentration on cell adhesion and spreading. The results presented here will serve to guide future efforts for the design of RGD functionalized materials with applications in surgery, tissue engineering, and regenerative medicine

    Peristaltic Transport of a Rheological Fluid: Model for Movement of Food Bolus Through Esophagus

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    Fluid mechanical peristaltic transport through esophagus has been of concern in the paper. A mathematical model has been developed with an aim to study the peristaltic transport of a rheological fluid for arbitrary wave shapes and tube lengths. The Ostwald-de Waele power law of viscous fluid is considered here to depict the non-Newtonian behaviour of the fluid. The model is formulated and analyzed with the specific aim of exploring some important information concerning the movement of food bolus through the esophagus. The analysis has been carried out by using lubrication theory. The study is particularly suitable for cases where the Reynolds number is small. The esophagus is treated as a circular tube through which the transport of food bolus takes places by periodic contraction of the esophageal wall. Variation of different variables concerned with the transport phenomena such as pressure, flow velocity, particle trajectory and reflux are investigated for a single wave as well as for a train of periodic peristaltic waves. Locally variable pressure is seen to be highly sensitive to the flow index `n'. The study clearly shows that continuous fluid transport for Newtonian/rheological fluids by wave train propagation is much more effective than widely spaced single wave propagation in the case of peristaltic movement of food bolus in the esophagus.Comment: Accepted for publication in Applied Mathematics and Mechanics (AMM), Springe

    Numerical Investigation of Second Mode Attenuation over Carbon/Carbon Surfaces on a Sharp Slender Cone

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    We have carried out axisymmetric numerical simulations of a spatially developing hypersonic boundary layer over a sharp 7^{\circ{}}-half-angle cone at M=7.5M_\infty=7.5 inspired by the experimental investigations by Wagner (2015). Simulations are first performed with impermeable (or solid) walls with a one-time broadband pulse excitation applied upstream to determine the most convectively-amplified frequencies resulting in the range 260kHz -- 400kHz, consistent with experimental observations of second-mode instability waves. Subsequently, we introduce harmonic disturbances via continuous periodic suction and blowing at 270kHz and 350kHz. For each of these forcing frequencies complex impedance boundary conditions (IBC), modeling the acoustic response of two different carbon/carbon (C/C) ultrasonically absorptive porous surfaces, are applied at the wall. The IBCs are derived as an output of a pore-scale aeroacoustic analysis -- the inverse Helmholtz Solver (iHS) -- which is able to return the broadband real and imaginary components of the surface-averaged impedance. The introduction of the IBCs in all cases leads to a significant attenuation of the harmonically-forced second-mode wave. In particular, we observe a higher attenuation rate of the introduced waves with frequency of 350kHz in comparison with 270kHz, and, along with the iHS impedance results, we establish that the C/C surfaces absorb acoustic energy more effectively at higher frequencies.Comment: AIAA-SciTech 201

    Evaluation of two mobile health apps in the context of smoking cessation: qualitative study of cognitive behavioral therapy (CBT) versus non-CBT-based digital solutions.

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    BACKGROUND: Mobile health (mHealth) apps can offer users numerous benefits, representing a feasible and acceptable means of administering health interventions such as cognitive behavioral therapy (CBT). CBT is commonly used in the treatment of mental health conditions, where it has a strong evidence base, suggesting that it represents an effective method to elicit health behavior change. More importantly, CBT has proved to be effective in smoking cessation, in the context of smoking-related costs to the National Health Service (NHS) having been estimated to be as high as £2.6bn in 2015. Although the evidence base for computerized CBT in mental health is strong, there is limited literature on its use in smoking cessation. This, combined with the cost-effectiveness of mHealth interventions, advocates a need for research into the effectiveness of CBT-based smoking cessation apps. OBJECTIVE: The objective of this study was, first, to explore participants' perceptions of 2 mHealth apps, a CBT-based app, Quit Genius, and a non-CBT-based app, NHS Smokefree, over a variety of themes. Second, the study aimed to investigate the perceptions and health behavior of users of each app with respect to smoking cessation. METHODS: A qualitative short-term longitudinal study was conducted, using a sample of 29 smokers allocated to one of the 2 apps, Quit Genius or Smokefree. Each user underwent 2 one-to-one semistructured interviews, 1 week apart. Thematic analysis was carried out, and important themes were identified. Descriptive statistics regarding participants' perceptions and health behavior in relation to smoking cessation are also provided. RESULTS: The thematic analysis resulted in five higher themes and several subthemes. Participants were generally more positive about Quit Genius's features, as well as about its design and information engagement and quality. Quit Genius users reported increased motivation to quit smoking, as well as greater willingness to continue using their allocated app after 1 week. Moreover, these participants demonstrated preliminary changes in their smoking behavior, although this was in the context of our limited sample, not yet allowing for the finding to be generalizable. CONCLUSIONS: Our findings underscore the use of CBT in the context of mHealth apps as a feasible and potentially effective smoking cessation tool. mHealth apps must be well developed, preferably with an underlying behavioral change mechanism, to promote positive health behavior change. Digital CBT has the potential to become a powerful tool in overcoming current health care challenges. The present results should be replicated in a wider sample using the apps for a longer period so as to allow for generalizability. Further research is also needed to focus on the effect of greater personalization on behavioral change and on understanding the psychological barriers to the adoption of new mHealth solutions

    Fluctuation of Conductance Peak Spacings in Large Semiconductor Quantum Dots

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    Fluctuation of Coulomb blockade peak spacings in large two-dimensional semiconductor quantum dots are studied within a model based on the electrostatics of several electron islands among which there are random inductive and capacitive couplings. Each island can accommodate electrons on quantum orbitals whose energies depend also on an external magnetic field. In contrast with a single island quantum dot, where the spacing distribution is close to Gaussian, here the distribution has a peak at small spacing value. The fluctuations are mainly due to charging effects. The model can explain the occasional occurrence of couples or even triples of closely spaced Coulomb blockade peaks, as well as the qualitative behavior of peak positions with the applied magnetic field.Comment: 13 pages, 4 figures, accepted for publication in PR

    Heavy Flavour Baryons in Hyper Central Model

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    Heavy flavor baryons containing single and double charm (beauty) quarks with light flavor combinations are studied using the hyper central description of the three-body problem. The confinement potential is assumed as hyper central coulomb plus power potential with power index υ\upsilon. The ground state masses of the heavy flavor, JP=1/2+J^P={1/2}^+ and 3/2+{3/2}^+ baryons are computed for different power index, ν \nu starting from 0.5 to 2.0. The predicted masses are found to attain a saturated value in each case of quark combinations beyond the power index ν=1.0\nu=1.0.Comment: 10 pages, 4 figure
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