Design, Fabrication, and Testing of a Capsule With Hybrid Locomotion for Gastrointestinal Tract Exploration

Abstract—This paper describes a novel solution for the active lo-comotion of a miniaturized endoscopic capsule in the gastrointesti-nal (GI) tract. The authors present the design, development, and testing of a wireless endocapsule with hybrid locomotion, where hybrid locomotion is defined as the combination between internal actuation mechanisms and external magnetic dragging. The cap-sule incorporates an internal actuating legged mechanism, which modifies the capsule profile, and small permanent magnets, which interact with an external magnetic field, thus imparting a dragging motion to the device. The legged mechanism is actuated whenever the capsule gets lodged in collapsed areas of the GI tract. This allows modification of the capsule profile and enables magnetic dragging to become feasible and effective once again. A key com-ponent of the endoscopic pill is the internal mechanism, endowed with a miniaturized brushless motor and featuring compact design, and adequate mechanical performance. The internal mechanism is able to generate a substantial force, which allows the legs to open against the intestinal tissue that has collapsed around the capsule body. An accurate simulation of the performance of the minia-turized motor under magnetic fields was carried out in order to define the best configuration of the internal permanent magnets (which are located very close to the motor) and the best tradeoff operating distance for the external magnet, which is responsible for magnetically dragging the capsule. Finally, a hybrid capsule was developed generating 3.8 N at the tip of the legged mechanism and a magnetic link force up to 135 mN. The hybrid capsule and its wireless control were extensively tested in vitro, ex vivo, and in vivo, thus confirming fulfilment of the design specifications and demon-strating a good ability to manage collapsed areas of the intestinal tract. Index Terms—Capsule endoscopy, endoscopic capsule, magnetic locomotion, robotic surgery. I

Delayed priming promotes CNS regeneration post-rhizotomy in Neurocan and Brevican-deficient mice

A wealth of literature has provided evidence that reactive tissue at the site of CNS injury is rich in chondroitin sulfate proteoglycans which may contribute to the non-permissive nature of the CNS. We have recently demonstrated using a murine model of human brachial plexus injury that the chondroitin sulfate proteoglycans Neurocan and Brevican are differentially expressed by two subsets of astrocytes in the spinal cord dorsal root entry zone (DREZ) following dorsal root lesion (Beggah et al., Neuroscience 133: 749-762, 2005). However, direct evidence for a growth-inhibitory role of these proteoglycans in vivo is still lacking. We therefore performed dorsal root lesion (rhizotomy) in mice deficient in both Neurocan and Brevican. Rhizotomy in these animals resulted in no significant increase in the number of sensory fibres regenerating through the DREZ compared to genetically matched controls. Likewise, a conditioning peripheral nerve lesion prior to rhizotomy, which increases the intrinsic growth capacity of sensory neurons, enhanced growth to the same extent in transgenic and control mice, indicating that absence of these proteoglycans alone is not sufficient to further promote entry into the spinal cord. In contrast, when priming of the median nerve was performed at a clinically relevant time, i.e. 7 weeks post-rhizotomy, the growth of a subpopulation of sensory axons across the DREZ was facilitated in Neurocan/Brevican-deficient, but not in control animals. This demonstrates for the first time that (i) Neurocan and/or Brevican contribute to the non-permissive environment of the DREZ several weeks after lesion and that (ii) delayed stimulation of the growth program of sensory neurons can facilitate regeneration across the DREZ provided its growth-inhibitory properties are attenuated. Post-injury enhancement of the intrinsic growth capacity of sensory neurons combined with removal of inhibitory chondroitin sulfate proteoglycans may therefore help to restore sensory function and thus attenuate the chronic pain resulting from human brachial plexus injur

Design of a novel bimanual robotic system for single-port laparoscopy

Abstract—This paper presents the design and fabrication of Single-Port lapaRoscopy bImaNual roboT (SPRINT), a novel tele-operated robotic system for minimally invasive surgery. SPRINT, specifically designed for single-port laparoscopy, is a high-dexterity miniature robot, able to reproduce the movement of the hands of the surgeon, who controls the system through a master interface. It comprises two arms with six degrees of freedom (DOFs) that can be individually inserted and removed in a 30-mm-diameter umbilical access port. The system is designed to leave a central lumen free during operations, thus allowing the insertion of other laparoscopic tools. The four distal DOFs of each arm are actuated by on-board brushless dc motors, while the two proximal DOFs of the shoulder are actuated by external motors. The constraints gen-erated by maximum size and power requirements led to the design of compact mechanisms for the actuation of the joints. The wrist is actuated by three motors hosted in the forearm, with a peculiar differential mechanism that allows us to have intersecting roll– pitch–roll axes. Preliminary tests and validations were performed ex vivo by surgeons on a first prototype of the system. Index Terms—Bimanual robot, miniature robotic arm, mini-mally invasive surgery, robotic surgery, single-port laparoscopy (SPL). I

Unprecedented studies of the low-energy negatively charged kaons interactions in nuclear matter by AMADEUS

The AMADEUS experiment aims to provide unique quality data of $K^-$ hadronic interactions in light nuclear targets, in order to solve fundamental open questions in the non-perturbative strangeness QCD sector, like the controversial nature of the $\Lambda(1405)$ state, the yield of hyperon formation below threshold, the yield and shape of multi-nucleon $K^-$ absorption, processes which are intimately connected to the possible existence of exotic antikaon multi-nucleon clusters. AMADEUS takes advantage of the DA$\Phi$NE collider, which provides a unique source of monochromatic low-momentum kaons and exploits the KLOE detector as an active target, in order to obtain excellent acceptance and resolution data for $K^-$ nuclear capture on H, ${}^4$He, ${}^{9}$Be and ${}^{12}$C, both at-rest and in-flight. During the second half of 2012 a successful data taking was performed with a dedicated pure carbon target implemented in the central region of KLOE, providing a high statistic sample of pure at-rest $K^-$ nuclear interactions. For the future dedicated setups involving cryogenic gaseous targets are under preparation.Comment: 14 pages, 6 figure

On the analytic solution of the pairing problem: one pair in many levels

We search for approximate, but analytic solutions of the pairing problem for one pair of nucleons in many levels of a potential well. For the collective energy a general formula, independent of the details of the single particle spectrum, is given in both the strong and weak coupling regimes. Next the displacements of the solutions trapped in between the single particle levels with respect to the unperturbed energies are explored: their dependence upon a suitably defined quantum number is found to undergo a transition between two different regimes.Comment: 30 pages, AMS Latex, 8 figures. Submitted to Phys. Rev.

Beta-delayed gamma decay of 26P: Possible evidence of a proton halo

Background: Measurements of $\beta$ decay provide important nuclear structure information that can be used to probe isospin asymmetries and inform nuclear astrophysics studies. Purpose: To measure the $\beta$-delayed $\gamma$ decay of $^{26}$P and compare the results with previous experimental results and shell-model calculations. Method: A $^{26}$P fast beam produced using nuclear fragmentation was implanted into a planar germanium detector. Its $\beta$-delayed $\gamma$-ray emission was measured with an array of 16 high-purity germanium detectors. Positrons emitted in the decay were detected in coincidence to reduce the background. Results: The absolute intensities of $^{26}$P $\beta$-delayed $\gamma$-rays were determined. A total of six new $\beta$-decay branches and 15 new $\gamma$-ray lines have been observed for the first time in $^{26}$P $\beta$-decay. A complete $\beta$-decay scheme was built for the allowed transitions to bound excited states of $^{26}$Si. $ft$ values and Gamow-Teller strengths were also determined for these transitions and compared with shell model calculations and the mirror $\beta$-decay of $^{26}$Na, revealing significant mirror asymmetries. Conclusions: A very good agreement with theoretical predictions based on the USDB shell model is observed. The significant mirror asymmetry observed for the transition to the first excited state ($\delta=51(10)\%$) may be evidence for a proton halo in $^{26}$P.Comment: 15 pages, 10 figures, 7 table

Inhibition of mapk signalling promotes cell cycle arrest and sensitises intrahepatic cholangiocarcinoma cells to chemotherapy

Introduction: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, accounting for approximately 15% of cases of primary liver cancer. Although new treatments have increased survival for many other cancers, including the more common primary hepatocellular carcinoma, treatment strategies and survival for patients with ICC have seen little improvement. Our previous studies suggest that the mitogen-activated protein kinase (MAPK) signalling plays a central role in the regulation of cell proliferation in human ICC. However the molecular mechanisms are poorly understood. In this study, we aim to explore whether inhibition of the MAPK pathway and its downstream effectors enhances the sensitisation of ICC cells to the chemotherapeutic agent cisplatinum. Method: We used a combinatorial approach of immunohistochemical and gene expression analyses to investigate the expression of MAPK-related genes in ICC tumours. Furthermore, by using in-vitroand in-vivoanalyses we have characterised the function of a novel MAPK downstream effector in ICC cells. Results: The expression of MAPK signalling was determined by immunohistochemical staining in tumour samples from a cohort of 14 ICC patients. High expression of phospho-activated MAPK was observed in 71.4% (10/14) of ICC cases as compared with surrounding nontumour tissue. Likewise, expression of JDP, a downstream effector of the MAPK signalling, was scored as high intensity in 64.3% (9/14). Strikingly, elevated expression of JDP transcripts was also observed in two independent cohorts of human ICC (n = 149 and n = 109 per group, respectively) compared to surrounding normal liver tissue. Consistent with the in-vivo analyses of human samples, immunoblotting analyses showed constitutive activation of MAPK and expression of JDP in ICC-derived cells (i.e. SG231, CCLP-1 and HuCCT1). Using loss-of-function analyses, we demonstrates that knockdown of JDP in ICC-derived cells resulted in cell cycle arrest and reduced expression of cell cycle regulators (i.e. cyclins), and had minimal effect on apoptosis. Chemical inhibition of JDP significantly sensitises ICC-derived cells to cisplatinum (P < 0.001). Conclusion: These results demonstrate that enhanced activation of MAPK signalling is important for ICC cell proliferation and suggest that targeting its downstream effectors is a potential therapeutic strategy for ICC

Are GPs under-investigating older patients presenting with symptoms of ovarian cancer? Observational study using General Practice Research Database

Background: Recent studies suggest that older patients in the United Kingdom are not benefiting as much from improvements in cancer treatments as their younger counterparts. We investigate whether this might be partly due to differential referral rates using ovarian cancer as an example. Methods: From the General Practice Research Database (GPRD), we identified all women aged 40–80 years on 1 June 2002 with a Read code for ovarian cancer between 1 June 2002 and 31 May 2007. Using these records, we compared the GPRD incidence of ovarian cancer with rates compiled from the UK cancer registries and investigated the relationship between age and coded investigations for suspected ovarian cancer. Results: The GPRD rates peaked earlier, at 70–74, and were lower than registry rates for nearly all ages particularly for patients over 59. The proportion investigated or referred by the GP decreased significantly with age and delays between first coded symptom and investigation showed a U-shaped distribution by age. Conclusions: GPs appear to be less likely to recognise and to refer patients presenting with ovarian cancer as they get older. If our findings extend to other cancers, lack of or delays in referral to secondary care may partly explain poor UK cancer mortality rates of older people

A Taxonomy of Causality-Based Biological Properties

We formally characterize a set of causality-based properties of metabolic networks. This set of properties aims at making precise several notions on the production of metabolites, which are familiar in the biologists' terminology. From a theoretical point of view, biochemical reactions are abstractly represented as causal implications and the produced metabolites as causal consequences of the implication representing the corresponding reaction. The fact that a reactant is produced is represented by means of the chain of reactions that have made it exist. Such representation abstracts away from quantities, stoichiometric and thermodynamic parameters and constitutes the basis for the characterization of our properties. Moreover, we propose an effective method for verifying our properties based on an abstract model of system dynamics. This consists of a new abstract semantics for the system seen as a concurrent network and expressed using the Chemical Ground Form calculus. We illustrate an application of this framework to a portion of a real metabolic pathway