Endoscopic Tactile Capsule for Non-Polypoid Colorectal Tumour Detection

An endoscopic tactile robotic capsule, embedding miniaturized MEMS force sensors, is presented. The capsule is conceived to provide automatic palpation of non-polypoid colorectal tumours during colonoscopy, since it is characterized by high degree of dysplasia, higher invasiveness and lower detection rates with respect to polyps. A first test was performed employing a silicone phantom that embedded inclusions with variable hardness and curvature. A hardness-based classification was implemented, demonstrating detection robustness to curvature variation. By comparing a set of supervised classification algorithms, a weighted 3-nearest neighbor classifier was selected. A bias force normalization model was introduced in order to make different acquisition sets consistent. Parameters of this model were chosen through a particle swarm optimization method. Additionally, an ex-vivo test was performed to assess the capsule detection performance when magnetically-driven along a colonic tissue. Lumps were identified as voltage peaks with a prominence depending on the total magnetic force applied to the capsule. Accuracy of 94 % in hardness classification was achieved, while a 100 % accuracy is obtained for the lump detection within a tolerance of 5 mm from the central path described by the capsule. In real application scenario, we foresee our device aiding physicians to detect tumorous tissues

Fluidic haptic interface for mechano-tactile feedback

Notable advancements have been achieved in providing amputees with sensation through invasive and non-invasive haptic feedback systems such as mechano-, vibro-, electrotactile and hybrid systems. Purely mechanical-driven feedback approaches, however, have been little explored. In this paper, we now created a haptic feedback system that does not require any external power source (such as batteries) or other electronic components. The system is low-cost, lightweight, adaptable and robust against external impact (such as water). Hence, it will be sustainable in many aspects. We have made use of latest multimaterial 3D printing technology (Stratasys Objet500 Connex3) being able to fabricate a soft sensor and a mechano-tactile feedback actuator made of a rubber (TangoBlack Plus) and plastic (VeroClear) material. When forces are applied to the fingertip sensor, fluidic pressure inside the system acts on the membrane of the feedback actuator resulting in mechano-tactile sensation. We present the design, fabrication and validation of the proposed haptic feedback system. Our ∅7 mm feedback actuator is able to transmit a force range between 0.2 N (the median touch threshold) and 2.1 N (the maximum force transmitted by the feedback actuator at a 3 mm indentation) corresponding to force range exerted to the fingertip sensor of 1.2 − 18.49 N

Separability of neural responses to standardised mechanical stimulation of limbs

Abstract Considerable scientific and technological efforts are currently being made towards the development of neural prostheses. Understanding how the peripheral nervous system responds to electro-mechanical stimulation of the limb, will help to inform the design of prostheses that can restore function or accelerate recovery from injury to the sensory motor system. However, due to differences in experimental protocols, it is difficult, if not impossible, to make meaningful comparisons between different peripheral nerve interfaces. Therefore, we developed a low-cost electronic system to standardise the mechanical stimulation of a rat’s hindpaw. Three types of mechanical stimulations, namely, proprioception, touch and nociception were delivered to the limb and the electroneurogram signals were recorded simultaneously from the sciatic nerve with a 16-contact cuff electrode. For the first time, results indicate separability of neural responses according to stimulus type as well as intensity. Statistical analysis reveal that cuff contacts placed circumferentially, rather than longitudinally, are more likely to lead to higher classification rates. This flexible setup may be readily adapted for systematic comparison of various electrodes and mechanical stimuli in rodents. Hence, we have made its electro-mechanical design and computer programme available onlin

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Impaired Adult Neurogenesis in the Dentate Gyrus of a Triple Transgenic Mouse Model of Alzheimer's Disease

It has become generally accepted that new neurones are added and integrated mainly in two areas of the mammalian CNS, the subventricular zone and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus, which is of central importance in learning and memory. The newly generated cells display neuronal morphology, are able to generate action potentials and receive functional synaptic inputs, i.e. their properties are similar to those found in mature neurones. Alzheimer's disease (AD) is the primary and widespread cause of dementia and is an age-related, progressive and irreversible neurodegenerative disease that deteriorates cognitive functions. Here, we have used male and female triple transgenic mice (3xTg-AD) harbouring three mutant genes (β-amyloid precursor protein, presenilin-1 and tau) and their respective non-transgenic (non-Tg) controls at 2, 3, 4, 6, 9 and 12 months of age to establish the link between AD and neurogenesis. Using immunohistochemistry we determined the area density of proliferating cells within the SGZ of the DG, measured by the presence of phosphorylated Histone H3 (HH3), and their possible co-localisation with GFAP to exclude a glial phenotype. Less than 1% of the HH3 labeled cells co-localised with GFAP. Both non-Tg and 3xTg-AD showed an age-dependent decrease in neurogenesis. However, male 3xTg-AD mice demonstrated a further reduction in the production of new neurones from 9 months of age (73% decrease) and a complete depletion at 12 months, when compared to controls. In addition, female 3xTg-AD mice showed an earlier but equivalent decrease in neurogenesis at 4 months (reduction of 63%) with an almost inexistent rate at 12 months (88% decrease) compared to controls. This reduction in neurogenesis was directly associated with the presence of β-amyloid plaques and an increase in the number of β-amyloid containing neurones in the hippocampus; which in the case of 3xgTg females was directly correlated. These results suggest that 3xTg-AD mice have an impaired ability to generate new neurones in the DG of the hippocampus, the severity of which increases with age and might be directly associated with the known cognitive impairment observed from 6 months of age onwards . The earlier reduction of neurogenesis in females, from 4 months, is in agreement with the higher prevalence of AD in women than in men. Thus it is conceivable to speculate that a recovery in neurogenesis rates in AD could help to rescue cognitive impairment

Digital transformation, for better or worse: a critical multi-level research agenda

For better or worse, digital technologies are reshaping everything, from customer behaviors and expectations to organizational and manufacturing systems, business models, markets, and ultimately society. To understand this overarching transformation, this paper extends the previous literature which has focused mostly on the organizational level by developing a multi‐level research agenda for digital transformation (DT). In this regard, we propose an extended definition of DT as “a socioeconomic change across individuals, organizations, ecosystems, and societies that are shaped by the adoption and utilization of digital technologies.” We suggest four lenses to interpret the DT phenomenon: individuals (utilizing and adopting digital technologies), organizations (strategizing and coordinating both internal and external transformation), ecosystems (harnessing digital technologies in governance and co‐producing value propositions), and geopolitical frameworks (regulating the environments in which individuals and organizations are embedded). Based on these lenses, we build a multi‐level research agenda at the intersection between the bright and dark sides of DT and introduce the PIAI framework, which captures a process of perception, interpretation, and action that ultimately leads to possible impact. The PIAI framework identifies a critical research agenda consisting of a non‐exhaustive list of topics that can assist researchers to deepen their understanding of the DT phenomenon and provide guidance to managers and policymakers when making strategic decisions that seek to shape and guide the DT

Digital transformation, for better or worse: a critical multi-level research agenda

For better or worse, digital technologies are reshaping everything, from customer behaviors and expectations to organizational and manufacturing systems, business models, markets, and ultimately society. To understand this overarching transformation, this paper extends the previous literature which has focused mostly on the organizational level by developing a multi‐level research agenda for digital transformation (DT). In this regard, we propose an extended definition of DT as “a socioeconomic change across individuals, organizations, ecosystems, and societies that are shaped by the adoption and utilization of digital technologies.” We suggest four lenses to interpret the DT phenomenon: individuals (utilizing and adopting digital technologies), organizations (strategizing and coordinating both internal and external transformation), ecosystems (harnessing digital technologies in governance and co‐producing value propositions), and geopolitical frameworks (regulating the environments in which individuals and organizations are embedded). Based on these lenses, we build a multi‐level research agenda at the intersection between the bright and dark sides of DT and introduce the PIAI framework, which captures a process of perception, interpretation, and action that ultimately leads to possible impact. The PIAI framework identifies a critical research agenda consisting of a non‐exhaustive list of topics that can assist researchers to deepen their understanding of the DT phenomenon and provide guidance to managers and policymakers when making strategic decisions that seek to shape and guide the DT.</jats:p

Reducing AD-Like Pathology in 3xTg-AD Mouse Model by DNA Epitope Vaccine — A Novel Immunotherapeutic Strategy

BACKGROUND: The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Abeta(42) (Abeta(1-11)) , a non-self T helper cell epitope (PADRE), and macrophage-derived chemokine (MDC/CCL22) as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype. METHODS AND FINDINGS: We generated pMDC-3Abeta(1-11)-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Abeta antibody, which in turn inhibited accumulation of Abeta pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages. CONCLUSIONS: Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials

Ubiquitin Carboxyl-Terminal Esterase LI (UCHLI) SI8Y Polymorphism in Patients with Cataracts

Background: Cataract is characterized by light-scattering protein aggregates. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a de-ubiquitinating enzyme wit

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012