The Italian clinical experience with adalimumab in Crohn's disease: Eleven clinical cases

This supplement contains 11 clinical cases from 11 Italian inflammatory bowel disease (IBD) specialists, giving an overview of clinical practice with regard to the use of adalimumab in the management of Crohn’s disease (CD)

Mathematical model for preoperative identification of obstructed nasal subsites

The planning of experimental studies for evaluation of nasal airflow is particularly challenging given the difficulty in obtaining objective measurements in vivo. Although standard rhinomanometry and acoustic rhinometry are the most widely used diagnostic tools for evaluation of nasal airflow, they provide only a global measurement of nasal dynamics, without temporal or spatial details. Furthermore, the numerical simulation of nasal airflow as computational fluid dynamics technology is not validated. Unfortunately, to date, there are no available diagnostic tools to objectively evaluate the geometry of the nasal cavities and to measure nasal resistance and the degree of nasal obstruction, which is of utmost importance for surgical planning. To overcame these limitations, we developed a mathematical model based on Bernoulli's equation, which allows clinicians to obtain, with the use of a particular direct digital manometry, pressure measurements over time to identify which nasal subsite is obstructed. To the best of our knowledge, this is the first study to identify two limiting curves, one below and one above an average representative curve, describing the time dependence of the gauge pressure inside a single nostril. These upper and lower curves enclosed an area into which the airflow pattern of healthy individuals falls. In our opinion, this model may be useful to study each nasal subsite and to objectively evaluate the geometry and resistances of the nasal cavities, particularly in preoperative planning and follow-up

Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29)

Spectrally-resolved UV photodesorption of CH4 in pure and layered ices

Context. Methane is among the main components of the ice mantles of insterstellar dust grains, where it is at the start of a rich solid-phase chemical network. Quantification of the photon-induced desorption yield of these frozen molecules and understanding of the underlying processes is necessary to accurately model the observations and the chemical evolution of various regions of the interstellar medium. Aims. This study aims at experimentally determining absolute photodesorption yields for the CH4 molecule as a function of photon energy. The influence of the ice composition is also investigated. By studying the methane desorption from layered CH4:CO ice, indirect desorption processes triggered by the excitation of the CO molecules is monitored and quantified. Methods. Tunable monochromatic VUV light from the DESIRS beamline of the SOLEIL synchrotron is used in the 7 - 13.6 eV (177 - 91 nm) range to irradiate pure CH4 or layers of CH4 deposited on top of CO ice samples. The release of species in the gas phase is monitored by quadrupole mass spectrometry and absolute photodesorption yields of intact CH4 are deduced. Results. CH4 photodesorbs for photon energies higher than ~9.1 eV (~136 nm). The photodesorption spectrum follows the absorption spectrum of CH4, which confirms a desorption mechanism mediated by electronic transitions in the ice. When it is deposited on top of CO, CH4 desorbs between 8 and 9 eV with a pattern characteristic of CO absorption, indicating desorption induced by energy transfer from CO molecules. Conclusions. The photodesorption of CH4 from the pure ice in various interstellar environments is around 2.0 x 10^-3 molecules per incident photon. Results on CO-induced indirect desorption of CH4 provide useful insights for the generalization of this process to other molecules co-existing with CO in ice mantles

Cosmic Rays: The Second Knee and Beyond

We conduct a review of experimental results on Ultra-High Energy Cosmic Rays (UHECR's) including measurements of the features of the spectrum, the composition of the primary particle flux and the search for anisotropy in event arrival direction. We find that while there is a general consensus on the features in the spectrum -- the Second Knee, the Ankle, and (to a lesser extent) the GZK Cutoff -- there is little consensus on the composition of the primaries that accompany these features. This lack of consensus on the composition makes interpretation of the agreed upon features problematic. There is also little direct evidence about potential sources of UHECRs, as early reports of arrival direction anisotropies have not been confirmed in independent measurements.Comment: 46 pages, 30 figures. Topical Review to appear in J. Physics

Mongersen, an oral SMAD7 antisense oligonucleotide, and crohn's disease

Background Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. Methods In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. Results The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P = 0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease. Conclusions We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo

Mathematical model for preoperative identification of obstructed nasal subsites

La realizzazione di studi sperimentali per la valutazione dei flussi aerei nasali è particolarmente indaginosa, data la difficoltà di ottenere in vivo unaccurata misurazione degli stessi. Inoltre, sebbene la rinomanometria standard e la rinometria acustica rappresentino i metodi più utilizzati nella pratica clinica, esse forniscono solo una misura globale ed approssimativa dei flussi aerei nasali, senza definirne i particolari temporali o spaziali. Allo stesso modo gli studi sulla fluidodinamica computazionale rappresentano solo una simulazione numerica, ben lontana da quelle che sono le variabili anatomiche e fisiologiche delle cavità nasali. Pertanto, ad oggi, non esistono ancora strumenti diagnostici in grado di misurare oggettivamente la geometria delle cavità nasali, le resistenze ed il grado di ostruzione nei diversi sotto-siti nasali, elemento questultimo fondamentale per una corretta programmazione chirurgica. Allo scopo di superare i limiti della diagnostica standard abbiamo elaborato un modello matematico basato sullequazione di Bernoulli applicata alle cavità nasali di soggetti sani per lo studio dei gradienti pressori di vari sotto-siti nasali, che sono stati misurati grazie ad un particolare manometro digitale. Il nostro studio, unico in letteratura, ha identificato due curve limite che racchiudono unarea rappresentativa entro cui cadono i livelli normali di flusso in corrispondenza del vestibolo nasale. Il modello descritto potrebbe essere utile per studiare tutti i sotto-siti nasali sede di ostruzione ai fini di una corretta programmazione chirurgica e di un valido follow-up postoperatorio

Azathioprine for prevention of clinical recurrence in Crohn's disease patients with severe endoscopic recurrence: an IG-IBD randomized double-blind trial

The recurrence of Crohn's Disease after ileo-colonic resection is a crucial issue. Severe endoscopic lesions increase the risk of developing early symptoms. Prevention and treatment of post-operative Endoscopic Recurrence (ER) have been studied with conflicting results. We compare effi cacy of azathioprine (AZA) vs. high-dose 5-aminosalicylic acid (5-ASA) in preventing clinical recurrence and treating severe post-operative ER

Results from the first use of low radioactivity argon in a dark matter search

Liquid argon is a bright scintillator with potent particle identification properties, making it an attractive target for direct-detection dark matter searches. The DarkSide-50 dark matter search here reports the first WIMP search results obtained using a target of low-radioactivity argon. DarkSide-50 is a dark matter detector, using two-phase liquid argon time projection chamber, located at the Laboratori Nazionali del Gran Sasso. The underground argon is shown to contain Ar-39 at a level reduced by a factor (1.4 +- 0.2) x 10^3 relative to atmospheric argon. We report a background-free null result from (2616 +- 43) kg d of data, accumulated over 70.9 live-days. When combined with our previous search using an atmospheric argon, the 90 % C.L. upper limit on the WIMP-nucleon spin-independent cross section based on zero events found in the WIMP search regions, is 2.0 x 10^-44 cm^2 (8.6 x 10^-44 cm^2, 8.0 x 10^-43 cm^2) for a WIMP mass of 100 GeV/c^2 (1 TeV/c^2 , 10 TeV/c^2).Comment: Accepted by Phys. Rev.

Metadata stewardship in nanosafety research: learning from the past, preparing for an "on-the-fly" FAIR future

Introduction: Significant progress has been made in terms of best practice in research data management for nanosafety. Some of the underlying approaches to date are, however, overly focussed on the needs of specific research projects or aligned to a single data repository, and this “silo” approach is hampering their general adoption by the broader research community and individual labs. Methods: State-of-the-art data/knowledge collection, curation management FAIRification, and sharing solutions applied in the nanosafety field are reviewed focusing on unique features, which should be generalised and integrated into a functional FAIRification ecosystem that addresses the needs of both data generators and data (re)users. Results: The development of data capture templates has focussed on standardised single-endpoint Test Guidelines, which does not reflect the complexity of real laboratory processes, where multiple assays are interlinked into an overall study, and where non-standardised assays are developed to address novel research questions and probe mechanistic processes to generate the basis for read-across from one nanomaterial to another. By focussing on the needs of data providers and data users, we identify how existing tools and approaches can be re-framed to enable “on-the-fly” (meta) data definition, data capture, curation and FAIRification, that are sufficiently flexible to address the complexity in nanosafety research, yet harmonised enough to facilitate integration of datasets from different sources generated for different research purposes. By mapping the available tools for nanomaterials safety research (including nanomaterials characterisation, non-standard (mechanistic-focussed) methods, measurement principles and experimental setup, environmental fate and requirements from new research foci such as safe and sustainable by design), a strategy for integration and bridging between silos is presented. The NanoCommons KnowledgeBase has shown how data from different sources can be integrated into a one-stop shop for searching, browsing and accessing data (without copying), and thus how to break the boundaries between data silos. Discussion: The next steps are to generalise the approach by defining a process to build consensus (meta)data standards, develop solutions to make (meta)data more machine actionable (on the fly ontology development) and establish a distributed FAIR data ecosystem maintained by the community beyond specific projects. Since other multidisciplinary domains might also struggle with data silofication, the learnings presented here may be transferable to facilitate data sharing within other communities and support harmonization of approaches across disciplines to prepare the ground for cross-domain interoperability. Visit WorldFAIR online at http://worldfair-project.eu. WorldFAIR is funded by the EC HORIZON-WIDERA-2021-ERA-01-41 Coordination and Support Action under Grant Agreement No. 101058393