Industry perceptions of barriers to commercialization of regenerative medicine products in the UK

Aims Regenerative medicine is an emerging field with the potential to provide widespread improvement in healthcare and patient well-being via the delivery of therapies which can restore, regenerate or repair damaged tissue. As an industry, it could significantly contribute to economic growth if products are successfully commercialized. However, to date, relatively few products have reached the market due to a variety of barriers, including a lack of funding and regulatory hurdles. The present study analyzes industry perceptions of the barriers to commercialization which currently impede the success of the regenerative medicine industry in the UK. Materials & Methods The analysis is based on twenty interviews with leading industrialists in the field. Results The study revealed that scientific research on regenerative medicine is thriving in the UK. Unfortunately, lack of access to capital, regulatory hurdles, lack of clinical evidence leading to problems with reimbursement, as well as the culture of the NHS do not provide a good environment for the commercialization of RM products. Conclusions Policy interventions, including increased translational government funding, a change in NHS and NICE organisation and policies as well regulatory clarity would likely improve the general outcomes for the regenerative medicine industry in the UK

Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney

Over 100,000 individuals in the United States currently await kidney transplantation, while 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney’s architecture and function, and permit perfusion, filtration, secretion, absorption, and drainage of urine. We decellularized rat, porcine, and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells, then perfused these cell-seeded constructs in a whole organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused via their intrinsic vascular bed. When transplanted in orthotopic position in rat, the grafts were perfused by the recipient’s circulation, and produced urine via the ureteral conduit in vivo

Selective laser sintering of hydroxyapatite reinforced polyethylene composites for bioactive implants and tissue scaffold development

Selective laser sintering (SLS) has been investigated for the production of bioactive implants and tissue scaffolds using composites of high-density polyethylene (HDPE) reinforced with hydroxyapatite (HA) with the aim of achieving the rapid manufacturing of customized implants. Single-layer and multilayer block specimens made of HA-HDPE composites with 30 and 40 vol % HA were sintered successfully using a CO2 laser sintering system. Laser power and scanning speed had a significant effect on the sintering behaviour. The degree of particle fusion and porosity were influenced by the laser processing parameters, hence control can be attained by varying these parameters. Moreover, the SLS processing allowed exposure of HA particles on the surface of the composites and thereby should provide bioactive products. Pores existed in the SLS-fabricated composite parts and at certain processing parameters a significant fraction of the pores were within the optimal sizes for tissue regeneration. The results indicate that the SLS technique has the potential not only to fabricate HA-HDPE composite products but also to produce appropriate features for their application as bioactive implants and tissue scaffolds

Gamma rays and neutrinos from the Crab Nebula produced by pulsar accelerated nuclei

We investigate the consequences of the acceleration of heavy nuclei (e.g. iron nuclei) by the Crab pulsar. Accelerated nuclei can photodisintegrate in collisions with soft photons produced in the pulsar's outer gap, injecting energetic neutrons which decay either inside or outside the Crab Nebula. The protons from neutron decay inside the nebula are trapped by the Crab Nebula magnetic field, and accumulate inside the nebula producing gamma-rays and neutrinos in collisions with the matter in the nebula. Neutrons decaying outside the Crab Nebula contribute to the Galactic cosmic rays. We compute the expected fluxes of gamma-rays and neutrinos, and find that our model could account for the observed emission at high energies and may be tested by searching for high energy neutrinos with future neutrino telescopes currently in the design stage.Comment: 8 pages, 4 figures, LaTeX uses revtex.sty, submitted to Phys. Rev. Let

On the Absorption of High Energy Gamma-Rays by Intergalactic Infrared Radiation

We present a new calculation of the intergalactic $\gamma$-ray pair-production absorption coefficient as a function of both energy and redshift up to the redshift of 3C279, z = 0.54. In reexamining this problem, we make use of new observational data on the intergalactic infrared radiation field (IIRF), together with recent theoretical models of the galactic spectral energy distributions of the IIRF from stars and dust reradiation and estimates of the IIRF from galaxy counts and {\it COBE} results. We present our results for two fairly well defined IIRF spectral energy distributions, one of which is within $1 \sigma$ of our previous estimate of the IIRF at $\sim 20$ $\mu$m. We then apply our results to the $\gamma$-ray spectrum of Mrk 421, and obtain good agreement with the observational data, including the recent results of the {\it HEGRA} group.Comment: Plain TeX file with text in abs96.tex, 3 postscript figures (Fig. 1 - ircobe.eps, Fig. 2 - taupl.eps, Fig. 3 - mki.eps), stylefile epsf.sty included, accepted for publication in the Astrophysical Journa

The CAT Imaging Telescope for Very-High-Energy Gamma-Ray Astronomy

The CAT (Cherenkov Array at Themis) imaging telescope, equipped with a very-high-definition camera (546 fast phototubes with 0.12 degrees spacing surrounded by 54 larger tubes in two guard rings) started operation in Autumn 1996 on the site of the former solar plant Themis (France). Using the atmospheric Cherenkov technique, it detects and identifies very high energy gamma-rays in the range 250 GeV to a few tens of TeV. The instrument, which has detected three sources (Crab nebula, Mrk 421 and Mrk 501), is described in detail.Comment: 24 pages, 15 figures. submitted to Elsevier Preprin

BaFe12O19 single-particle-chain nanofibers : preparation, characterization, formation principle, and magnetization reversal mechanism

BaFe12O19 single-particle-chain nanofibers have been successfully prepared by an electrospinning method and calcination process, and their morphology, chemistry, and crystal structure have been characterized at the nanoscale. It is found that individual BaFe12O19 nanofibers consist of single nanoparticles which are found to stack along the nanofiber axis. The chemical analysis shows that the atomic ratio of Ba/Fe is 1:12, suggesting a BaFe12O19 composition. The crystal structure of the BaFe12O19 single-particle-chain nanofibers is proved to be M-type hexagonal. The single crystallites on each BaFe12O19 single-particlechain nanofibers have random orientations. A formation mechanism is proposed based on thermogravimetry/differential thermal analysis (TG-DTA), X-ray diffraction (XRD), and transmission electron microscopy (TEM) at six temperatures, 250, 400, 500, 600, 650, and 800 �C. The magnetic measurement of the BaFe12O19 single-particle-chain nanofibers reveals that the coercivity reaches a maximum of 5943 Oe and the saturated magnetization is 71.5 emu/g at room temperature. Theoretical analysis at the micromagnetism level is adapted to describe the magnetic behavior of the BaFe12O19 single-particle-chain nanofibers

Entangled-State Cycles of Atomic Collective-Spin States

We study quantum trajectories of collective atomic spin states of $N$ effective two-level atoms driven with laser and cavity fields. We show that interesting ``entangled-state cycles'' arise probabilistically when the (Raman) transition rates between the two atomic levels are set equal. For odd (even) $N$, there are $(N+1)/2$ ($N/2$) possible cycles. During each cycle the $N$-qubit state switches, with each cavity photon emission, between the states $(|N/2,m>\pm |N/2,-m>)/\sqrt{2}$, where $|N/2,m>$ is a Dicke state in a rotated collective basis. The quantum number $m$ ($>0$), which distinguishes the particular cycle, is determined by the photon counting record and varies randomly from one trajectory to the next. For even $N$ it is also possible, under the same conditions, to prepare probabilistically (but in steady state) the Dicke state $|N/2,0>$, i.e., an $N$-qubit state with $N/2$ excitations, which is of particular interest in the context of multipartite entanglement.Comment: 10 pages, 9 figure

Hybrid machine learning to localize atrial flutter substrates using the surface 12-lead electrocardiogram

Aims Atrial flutter (AFlut) is a common re-entrant atrial tachycardia driven by self-sustainable mechanisms that cause excitations to propagate along pathways different from sinus rhythm. Intra-cardiac electrophysiological mapping and catheter ablation are often performed without detailed prior knowledge of the mechanism perpetuating AFlut, likely prolonging the procedure time of these invasive interventions. We sought to discriminate the AFlut location [cavotricuspid isthmus-dependent (CTI), peri-mitral, and other left atrium (LA) AFlut classes] with a machine learning-based algorithm using only the non-invasive signals from the 12-lead electrocardiogram (ECG). Methods and results Hybrid 12-lead ECG dataset of 1769 signals was used (1424 in silico ECGs, and 345 clinical ECGs from 115 patients—three different ECG segments over time were extracted from each patient corresponding to single AFlut cycles). Seventy-seven features were extracted. A decision tree classifier with a hold-out classification approach was trained, validated, and tested on the dataset randomly split after selecting the most informative features. The clinical test set comprised 38 patients (114 clinical ECGs). The classifier yielded 76.3% accuracy on the clinical test set with a sensitivity of 89.7%, 75.0%, and 64.1% and a positive predictive value of 71.4%, 75.0%, and 86.2% for CTI, peri-mitral, and other LA class, respectively. Considering majority vote of the three segments taken from each patient, the CTI class was correctly classified at 92%. Conclusion Our results show that a machine learning classifier relying only on non-invasive signals can potentially identify the location of AFlut mechanisms. This method could aid in planning and tailoring patient-specific AFlut treatments

Observations of TeV photons at the Whipple Observatory

The Whipple Observatory 10 m gamma‐ray telescope has been used to search for TeV gamma‐ray emission from a number of objects. This paper reports observations of six galactic and three extragalactic objects using the Cherenkov image technique. With the introduction of a high‐resolution camera (1/4° pixel) in 1988, the Crab Nebula was detected at a significance level of 20 σ in 30 hours of on‐source observation. Upper limits at a fraction of the Crab flux are set for most of the other objects, based on the absence of any significant dc excess or periodic effect when an a priori Monte Carlo determined imaging selection criterion (the ‘‘azwidth cut’’) is employed. There are weak indications that one source, Hercules X‐1, may be an episodic emitter. The Whipple detection system will be improved shortly with the addition of a second reflector 11 m in diameter (GRANITE) for stereoscopic viewing of showers. The combination of the two‐reflector system should have a signal‐to‐noise advantage of 103 over a simple nonimaging Cherenkov receiver.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87437/2/47_1.pd