Spatial patterns in the fruiting bodies of the cellular slime mold Polysphondylium pallidum

During morphogenesis in the slime mold Polysphondylium pallidum cell masses are periodically pinched off from the base of the developing sorogen. These masses round up and differentiate into secondary sorogens, which become radially ordered arrays of secondary fruiting bodies called whorls. Here we describe the morphogenesis of P. pallidum and characterize the spacing of whorls along the central stalk of the fruiting body and the spacing of soro-carps within whorls. We find both are highly regular. We propose that the linear spacing of whorls can be accounted for satisfactorily by a model that views the periodic release of cell masses from the base of the developing sorogen as the consequence of an imbalance between forces that orient amoebae toward the tip of the culminating sorogen, and cohesive forces between randomly moving cells in the basal region of the sorogen, which act as a retarding force. The orderly arrangement of fruiting bodies within whorls can be explained most easily by models that employ short-range activation and lateral inhibition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72498/1/j.1432-0436.1988.tb00200.x.pd

Long term (5 Year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial

<b>Background:</b> Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure. <br></br> <br></br> <b>Methods:</b> Patients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 μg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs) and spirometry data were used to assess long-term safety out to 5 years post-BT. <br></br> <br></br> <b>Results:</b> 45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject) was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group. <br></br><br></br> <b>Conclusions:</b> The absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of FVC and FEV1) over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years

Integrated Front End Circuitry for Microultrasound Capsule Endoscopy

Video capsule endoscopy (VCE) was originally developed to address the limitation of conventional endoscopy in accessing the small bowel as a remote part of the gastrointestinal tract. To further enhance the diagnostic ability of VCE, microultrasound capsule endoscopy is under development for identification of disease at an earlier stage and visualisation of subsurface tissue features. This paper presents an evaluation of two approaches to improve signal to noise ratio (SNR) in rapid prototyped capsule endoscopes. First, noise reduction techniques are applied to the integrated front-end circuits in the prototype capsules. Secondly, multiple types of coded excitation transmission are tested and benchmarked with respect to non-coded transmission. Results are presented for both bench top phantom imaging and in vivo translational trial imaging

Ultrasound capsule endoscopy:sounding out the future

Video capsule endoscopy (VCE) has been of immense benefit in the diagnosis and management of gastrointestinal (GI) disorders since its introduction in 2001. However, it suffers from a number of well recognized deficiencies. Amongst these is the limited capability of white light imaging, which is restricted to analysis of the mucosal surface. Current capsule endoscopes are dependent on visual manifestation of disease and limited in regards to transmural imaging and detection of deeper pathology. Ultrasound capsule endoscopy (USCE) has the potential to overcome surface only imaging and provide transmural scans of the GI tract. The integration of high frequency microultrasound (µUS) into capsule endoscopy would allow high resolution transmural images and provide a means of both qualitative and quantitative assessment of the bowel wall. Quantitative ultrasound (QUS) can provide data in an objective and measurable manner, potentially reducing lengthy interpretation times by incorporation into an automated diagnostic process. The research described here is focused on the development of USCE and other complementary diagnostic and therapeutic modalities. Presently investigations have entered a preclinical phase with laboratory investigations running concurrently

Translational trial outcomes for capsule endoscopy test devices

Current clinical standards in the endoscopic diagnosis of gastrointestinal diseases are primarily based on the use of optical systems. Ultrasound has established diagnostic credibility in the form of endoscopic ultrasound (EUS), however it is limited to examination of the upper gastrointestinal tract (oesophagus, stomach and upper (proximal) small bowel). Access to the remainder of the small bowel is currently limited to optical capsule endoscopes and a limited number of other modalities as these capsules are restricted to visual examination of the surface or mucosa of the gut wall. Ultrasound capsule endoscopy has been proposed to integrate microultrasound imaging capabilities into the existing capsule format and extend examination capabilities beyond the mucosa. To establish the ability of high frequency ultrasound to resolve the histological structure of the gastrointestinal tract, ex vivo scans of pig and human tissue were performed. This was done using 25 and 34 MHz single element, physically focused composite transducers mechanically scanned along the tissue. Tethered prototype devices were then developed with 30 MHz physically focused polyvinylidene fluoride (PVDF) single element transducers embedded for use in initial translational trials in the small bowel of porcine subjects. B-scan images from the ex vivo model validation and the in vivo trials are presented

Developing and testing an internal audit tool of the psychosocial work environment in the oil and gas industry

The objective of this paper is to present and discuss a pilot study for conducting internal psychosocial risk auditing in the oil and gas industry, focusing on offshore units. Psychosocial risk auditing is a proactive method for monitoring the status of psychosocial factors influencing the risk of stress and ill-health in the oil and gas industry. It is a systematic and independent assessment of the status of psychosocial factors and barriers, it reveals non-compliance with requirements and best practice within different relevant levels of the organization, and is suitable as a basis for the development of risk reduction measures. The method comprises performance standards that are linked to the company’s internal organizational requirements related to the psychosocial work environment. A range of different methods and data are used to assess and grade compliance with these standards. The aim of the auditing is to provide transfer of experience between units and the development of best practice while supporting organizational learning in offshore (and onshore) environments

The calcilytic agent NPS 2143 rectifies hypocalcemia in a mouse model with an activating calcium-sensing-receptor (CaSR) mutation:relevance to autosomal dominant hypocalcemia type 1 (ADH1)

Autosomal dominant hypocalcemia type 1 (ADH1) is caused by germline gain-of-function mutations of the calcium-sensing receptor (CaSR) and may lead to symptomatic hypocalcemia, inappropriately low serum parathyroid hormone (PTH) concentrations and hypercalciuria. Negative allosteric CaSR modulators, known as calcilytics, have been shown to normalise the gain-of-function associated with ADH-causing CaSR mutations in vitro and represent a potential targeted therapy for ADH1. However, the effectiveness of calcilytic drugs for the treatment of ADH1-associated hypocalcemia remains to be established. We have investigated NPS 2143, a calcilytic compound, for the treatment of ADH1 by in vitro and in vivo studies involving a mouse model, known as Nuf, which harbors a gain-of-function CaSR mutation, Leu723Gln. Wild-type (Leu723) and Nuf mutant (Gln723) CaSRs were expressed in HEK293 cells and the effect of NPS 2143 on their intracellular calcium responses determined by flow cytometry. NPS 2143 was also administered as a single intraperitoneal bolus to wild-type and Nuf mice and plasma concentrations of calcium and PTH, and urinary calcium excretion measured. In vitro administration of NPS 2143 decreased the intracellular calcium responses of HEK293 cells expressing the mutant Gln723 CaSR in a dose-dependent manner, thereby rectifying the gain-of-function associated with the Nuf mouse CaSR mutation. Intraperitoneal injection of NPS 2143 in Nuf mice led to significant increases in plasma calcium and PTH without elevating urinary calcium excretion. These studies of a mouse model with an activating CaSR mutation demonstrate NPS 2143 to normalize the gain-of-function causing ADH1, and improve the hypocalcemia associated with this disorder

Constraining CP Violating Phases of the MSSM

Possible CP violation in supersymmetric (SUSY) extensions of the Standard Model (SM) is discussed. The consequences of CP violating phases in the gaugino masses, trilinear soft supersymmetry-breaking terms and the `mu' parameter are explored. Utilizing the constraints on these parameters from electron and neutron electric dipole moments, possible CP violating effects in B-physics are shown. A set of measurements from the B-system which would overconstrain the above CP violating phases is illustrated.Comment: 14 pages, 6 figure

Ultrasound mediated delivery of quantum dots from a capsule endoscope to the gastrointestinal wall

Biologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in-vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focussed ultrasound. These findings suggest that the use of focused ultrasound together with microbubbles could play a role in the oral delivery of biologic therapeutics

Ultrasound mediated delivery of quantum dots from a proof of concept capsule endoscope to the gastrointestinal wall

Biologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focused ultrasound during in vivo experiments using porcine models. This study illustrates how such a device could be potentially used for gastrointestinal drug delivery and the challenges to be overcome before focused ultrasound and microbubbles could be used with this device for the oral delivery of biologic therapeutics