Towards a procedure-optimised steerable catheter for deep-seated neurosurgery

In recent years, steerable needles have attracted significant interest in relation to minimally invasive surgery (MIS). Specifically, the flexible, programmable bevel-tip needle (PBN) concept was successfully demonstrated in vivo in an evaluation of the feasibility of convection-enhanced delivery (CED) for chemotherapeutics within the ovine model with a 2.5 mm PBN prototype. However, further size reductions are necessary for other diagnostic and therapeutic procedures and drug delivery operations involving deep-seated tissue structures. Since PBNs have a complex cross-section geometry, standard production methods, such as extrusion, fail, as the outer diameter is reduced further. This paper presents our first attempt to demonstrate a new manufacturing method for PBNs that employs thermal drawing technology. Experimental characterisation tests were performed for the 2.5 mm PBN and the new 1.3 mm thermally drawn (TD) PBN prototype described here. The results show that thermal drawing presents a significant advantage in miniaturising complex needle structures. However, the steering behaviour was affected due to the choice of material in this first attempt, a limitation which will be addressed in future work

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to Saccharomyces cerevisiae var. boulardii CNCM I-3799 and reducing gastrointestinal discomfort pursuant to Article 13(5) of Regulation (EC) No 1924/2006

<p>Following an application from Lesaffre International/Lesaffre Human Care, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of France, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to <em>Saccharomyces cerevisiae</em> var. <em>boulardii</em> CNCM I-3799 and reducing gastro-intestinal discomfort. The food constituent that is the subject of the health claim, <em>S. cerevisiae</em> var. <em>boulardii</em> CNCM I-3799, is sufficiently characterised. The claimed effect, reduction of gastro-intestinal discomfort, is a beneficial physiological effect. The target population proposed by the applicant is subjects from 18 to 74 years old with bowel discomfort. The Panel notes that none of the studies provided for the substantiation of the claim was conducted with the strain which is the subject of the claim (<em>S. cerevisiae </em>var<em>. boulardii </em>CNCM I-3799), except for two animal studies and one <em>in vitro</em> study. Upon an EFSA request, the applicant indicated that the rest of the studies provided were conducted with the strain produced by Biocodex Laboratories (<em>S. cerevisiae </em>var. <em>boulardii </em>HANSEN CBS 5926). The applicant also stated that the strain, which is the subject of the claim, <em>S. cerevisiae </em>var<em>. boulardii </em>CNCM I-3799, is equivalent to <em>S. cerevisiae </em>var<em>. boulardii </em>HANSEN CBS 5926, based on a comparative PCR inter-delta element analysis of both strains provided in the application. The Panel considered that the evidence provided was insufficient to establish that the strains <em>S. cerevisiae</em> var. <em>boulardii</em> CNCM I-3799 and HANSEN CBS 5926 are identical and, upon EFSA request for further information, additional evidence was not provided by the applicant. A cause and effect relationship cannot be established between the consumption of <em>S. cerevisiae</em> var. <em>boulardii</em> CNCM I-3799 and reducing gastro-intestinal discomfort.</p&gt

Phenotypes and Clinical Genotypes of Bruxism Patients: A Systematic Review

Background. Bruxism is a phenomenon where psychological and exogenous biological factors act in greater percentage. Several genetic polymorphisms have been described in GABAA receptors, and some have been associated with motor limitations, such as the rs1805057 polymorphism of the GABRB1 gene (GABAA), which found a haplotype associated with a lower limitation in movement in acute pain processes. The aim to identify the clinical phenotypes in bruxism patients. Eligibility criteria were as follows: observational studies, case control studies, odds ratios, bruxism, patients, and a keyword search that included [[bruxism]], OR [[temporomandibular joint disorders]] OR [[sleep bruxism]], OR [[awake bruxism]], OR [[polymorphism]] or [[GABAA]], or [[serotonin]] , using the Boolean operators AND, OR and NOT. Were included 210 identified records in databases; 50 records from other sources; 117 records were deleted after determining they were duplicates; 42 studies were included in qualitative synthesis ; finally, who met inclusion requirements 5 studies were included in synthesis. The comparison of global DNA methylation profiles in patients with bruxism shows a possible genetic influence on their etiology, indicating that patients with HTR2A rs2770304 alleles are at increased risk. the HTR2A rs2770304 allele leads to an increased risk of bruxism

F2move: fMRI-compatible haptic object manipulation system for closed-loop motor control studies

Functional neuroimaging plays a key role in addressing open questions in systems and motor neuroscience directly applicable to brain machine interfaces. Building on our low-cost motion capture technology (fMOVE), we developed f2MOVE, an fMRI-compatible system for 6DOF goal-directed hand and wrist movements of human subjects enabling closed-loop sensorimotor haptic experiments with simultaneous neuroimaging. f2MOVE uses a high-zoom lens high frame rate camera and a motion tracking algorithm that tracks in real-time the position of special markers attached to a hand-held object in a novel customized haptic interface. The system operates with high update rate (120 Hz) and sufficiently low time delays (<; 20 ms) to enable visual feedback while complex, goal-oriented movements are recorded. We present here both the accuracy of our motion tracking against a reference signal and the efficacy of the system to evoke motor control specific brain activations in healthy subjects. Our technology and approach thus support the real-time, closed-loop study of the neural foundations of complex haptic motor tasks using neuroimaging

Diffusion-weighted imaging for evaluating inflammatory activity in Crohn's disease: comparison with histopathology, conventional MRI activity scores, and faecal calprotectin

PURPOSE: To evaluate whether the extent of enteric diffusion-weighted imaging (DWI) signal abnormality reflects inflammatory burden in Crohn's disease (CD), and to compare qualitative and quantitative grading. METHODS: 69 CD patients (35 male, age 16-78) undergoing MR enterography with DWI (MRE-D) and the same-day faecal calprotectin (cohort 1) were supplemented by 29 patients (19 male, age 16-70) undergoing MRE-D and terminal ileal biopsy (cohort 2). Global (cohort 1) and terminal ileal (cohort 2) DWI signal was graded (0 to 3) by 2 radiologists and segmental apparent diffusion coefficient (ADC) calculated. Data were compared to calprotectin and a validated MRI activity score [MEGS] (cohort 1), and a histopathological activity score (eAIS) (cohort 2) using nonparametric testing and rank correlation. RESULTS: Patients with normal (grades 0 and 1) DWI signal had lower calprotectin and MEGS than those with abnormal signal (grades 2 and 3) (160 vs. 492 μg/l, p = 0.0004, and 3.3 vs. 21, p  120 μg/l) were 83% and 52%, respectively. There was a negative correlation between ileal MEGS and ADC (r = -0.41, p = 0.017). There was no significant difference in eAIS between qualitative DWI scores (p = 0.42). Mean ADC was not different in those with and without histological inflammation (2077 vs. 1622 × 10(-6)mm(2)/s, p = 0.10) CONCLUSIONS: Qualitative grading of DWI signal has utility in defining the burden of CD activity. Quantitative ADC measurements have poor discriminatory ability for segmental disease activity

Herpesvirus skin disease in free-living common frogs Rana temporaria in Great Britain

Infectious disease is a significant driver of global amphibian declines, yet despite this, relatively little is known about the range of pathogens that affect free-living amphibians. Recent detection of the tentatively named Ranid herpesvirus 3 (RHV3), associated with skin disease in free-living common frogs Rana temporaria in Switzerland, helps to address this paucity in knowledge, but the geographic distribution and epidemiology of the pathogen remains unclear. Syndromic surveillance for ranid herpesvirus skin disease was undertaken throughout Great Britain (GB), January 2014 to December 2016. Reports of common frogs with macroscopic skin lesions with a characteristic grey appearance were solicited from members of the public. Post-mortem examination was conducted on one affected frog found dead in 2015 at a site in England. In addition, archived samples from an incident involving common frogs in England in 1997 with similar macroscopic lesions were further investigated. Transmission electron microscopy identified herpes-like virions in skin lesions from both the 1997 and 2015 incidents. RHV3, or RHV3-like virus, was detected in skin lesions from the 2015 case by PCR and sequencing. Our findings indicate that herpesvirus skin disease is endemic in common frogs in GB, with widespread distribution at apparently low prevalence. Further research into the role of host immunity, virus latency and the significance of infection to host survival is required to better understand the epidemiology and impact of cutaneous herpesvirus infections in amphibian populations

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson &amp; Johnson and Bayer

AI-KG: an Automatically Generated Knowledge Graph of Artificial Intelligence

Scientific knowledge has been traditionally disseminated and preserved through research articles published in journals, conference proceedings, and online archives. However, this article-centric paradigm has been often criticized for not allowing to automatically process, categorize, and reason on this knowledge. An alternative vision is to generate a semantically rich and interlinked description of the content of research publications. In this paper, we present the Artificial Intelligence Knowledge Graph (AI-KG), a large-scale automatically generated knowledge graph that describes 820K research entities. AI-KG includes about 14M RDF triples and 1.2M reified statements extracted from 333K research publications in the field of AI, and describes 5 types of entities (tasks, methods, metrics, materials, others) linked by 27 relations. AI-KG has been designed to support a variety of intelligent services for analyzing and making sense of research dynamics, supporting researchers in their daily job, and helping to inform decision-making in funding bodies and research policymakers. AI-KG has been generated by applying an automatic pipeline that extracts entities and relationships using three tools:DyGIE++, Stanford CoreNLP, and the CSO Classifier. It then integrates and filters the resulting triples using a combination of deep learning and semantic technologies in order to produce a high-quality knowledge graph. This pipeline was evaluated on a manually crafted gold standard, yielding competitive results. AI-KG is available under CC BY 4.0 and can be downloaded as a dump or queried via a SPARQL endpoint

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction