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The $$^{27}\hbox {Al}(\hbox {p},\alpha )^{24}\hbox {Mg}$$ 27 Al ( p , α ) 24 Mg reaction, which drives the destruction of $$^{27}$$ 27 Al and the production of $$^{24}\hbox {Mg}$$ 24 Mg in stellar hydrogen burning, has been investigated via the Trojan Horse Method (THM), by measuring the $$^2\hbox {H}(^{27}\hbox {Al},\alpha ^{24}\hbox {Mg})\hbox {n}$$ 2 H ( 27 Al , α 24 Mg ) n three-body reaction. The experiment covered a broad energy range ($$E_\mathrm{c.m.}\le \,1.5\,\hbox {MeV}$$ E c . m . ≤ 1.5 MeV ), aiming to investigate those of interest for astrophysics. The results confirm the THM as a valuable technique for the experimental study of fusion reactions at very low energies and suggest the presence of a rich pattern of resonances in the energy region close to the Gamow window of stellar hydrogen burning (70–120 keV), with potential impact on astrophysics. To estimate such an impact a second run of the experiment is needed, since the background due the three-body reaction hampered to collect enough data to resolve the resonant structures and extract the reaction rate.

Peripheral artery disease (PAD) is a leading cause of cardiovascular morbidity and mortality; however, the extent to which genetic factors increase risk for PAD is largely unknown. Using electronic health record data, we performed a genome-wide association study in the Million Veteran Program testing ~32 million DNA sequence variants with PAD (31,307 cases and 211,753 controls) across veterans of European, African and Hispanic ancestry. The results were replicated in an independent sample of 5,117 PAD cases and 389,291 controls from the UK Biobank. We identified 19 PAD loci, 18 of which have not been previously reported. Eleven of the 19 loci were associated with disease in three vascular beds (coronary, cerebral, peripheral), including LDLR, LPL and LPA, suggesting that therapeutic modulation of low-density lipoprotein cholesterol, the lipoprotein lipase pathway or circulating lipoprotein(a) may be efficacious for multiple atherosclerotic disease phenotypes. Conversely, four of the variants appeared to be specific for PAD, including F5 p.R506Q, highlighting the pathogenic role of thrombosis in the peripheral vascular bed and providing genetic support for Factor Xa inhibition as a therapeutic strategy for PAD. Our results highlight mechanistic similarities and differences among coronary, cerebral and peripheral atherosclerosis and provide therapeutic insights.

Introduction Janssen received reports of needle detachments for Risperdal® CONSTA® and, in response, redesigned the kit. Objective The study objective was to estimate the rate of Risperdal® CONSTA® needle detachments prior to and after the introduction of a redesigned kit. Methods This retrospective study used record abstraction in the US Department of Veterans Affairs (VA). The 3 phases included: (1) a pilot study for methods evaluation in a sample of 6 hospitals with previously reported detachments; (2) a baseline study to ascertain the baseline detachment rate; and (3) a follow-up study to ascertain the rate for the redesigned kit. Administrative codes and natural language processing with clinical review were used to identify detachments. Results Pilot: we identified a subset of spontaneously reported detachments and several previously unreported events. In the baseline study (original device), from January through December 2013, 22 needle detachments were identified among 47,934 administrations of the drug in a census of administrations in the VA; an incidence of 0.0459%. In the follow-up study (redesigned device), from December 2015 through December 2016, there were 14 reported detachments in 41,819 injections, 0.0335%. This represents a reduction of 27% from the baseline. Conclusion This approach enabled us to identify needle detachments we would not have otherwise found (“solicited”). However, it likely resulted in incomplete outcome ascertainment. While this may have resulted in lower overall rates, it did not bias the comparison of the baseline and follow-up studies. The results showed that the redesigned Risperdal® CONSTA® kit reduced the incidence of needle detachment events in the VA. Funding Janssen Pharmaceuticals, Inc.

Identifying occurrences of medication side effects and adverse drug events (ADEs) is an important and challenging task because they are frequently only mentioned in clinical narrative and are not formally reported. We developed a natural language processing (NLP) system that aims to identify mentions of symptoms and drugs in clinical notes and label the relationship between the mentions as indications or ADEs. The system leverages an existing word embeddings model with induced word clusters for dimensionality reduction. It employs a conditional random field (CRF) model for named entity recognition (NER) and a random forest model for relation extraction (RE). Final performance of each model was evaluated separately and then combined on a manually annotated evaluation set. The micro-averaged F1 score was 80.9% for NER, 88.1% for RE, and 61.2% for the integrated systems. Outputs from our systems were submitted to the NLP Challenges for Detecting Medication and Adverse Drug Events from Electronic Health Records (MADE 1.0) competition (Yu et al. in http://bio-nlp.org/index.php/projects/39-nlp-challenges , 2018). System performance was evaluated in three tasks (NER, RE, and complete system) with multiple teams submitting output from their systems for each task. Our RE system placed first in Task 2 of the challenge and our integrated system achieved third place in Task 3. Adding to the growing number of publications that utilize NLP to detect occurrences of ADEs, our study illustrates the benefits of employing innovative feature engineering.

Endovenously administered oncolytic viruses extravasate and penetrate poorly into tumors. iRGD is a cyclic peptide that enhances tumor penetration when conjugated or coadministered with different types of molecules such as drugs, nanoparticles or phages. iRGD-mediated tumor penetration occurs in three steps: binding to αv-integrins on tumor vasculature or tumor cells, exposure by proteolysis of a C-terminal motif that binds to neuropilin-1 (NRP-1) and cell internalization. We have genetically inserted the iRGD peptide in the fiber C terminus of ICOVIR15K, an oncolytic tumor-retargeted adenovirus to increase its tumor penetration. In vitro, NRP-1 interaction improved binding and internalization of the virus in different cancer cells overexpressing integrins and NRP-1. However, such NRP-1-mediated internalization did not affect transduction or cytotoxicity. In vivo, iRGD did not change the normal organ transduction pattern, with liver and spleen as main targeted organs. In tumors, however, iRGD enhanced transduction and early adenovirus dissemination through the tumor mass leading to an improved antitumor efficacy.

Chikungunya infection is a febrile illness, which currently is afflicting the Caribbean islands including the Dominican Republic. We would like to report our experience with Chikungunya-related musculoskeletal manifestations in our arthritis clinics in the Dominican Republic. A total of 514 patients presented for the first time to our arthritis clinic exhibiting musculoskeletal manifestations, 473/514 (92 %) exhibiting symmetric polyarthralgias, 344/514 (67 %) arthritis, and 385 (75 %) skin rash. The great majority 457.46 (89 %) exhibited very good clinical response to nonsteroidal anti-inflammatory drugs (NSAIDs), 370 (72 %) require low-dose steroids, and only 5 patients (0.97 %) required methotrexate therapy. In addition, of a total of 328 patients with rheumatoid arthritis on biological treatment, 53 exhibited Chikungunya-related musculoskeletal manifestations; 51/53 (96.2 %) exhibited symmetric polyarthralgias, 25/53 (47.1 %) arthritis, and 13/53 (24.5 %) tendinopathy. Of most patients, 51/53 responded to NSAIDs, of which, 23 patients only responded partially, and in total 25 (47.1 %) required low-dose steroids. Disease-modifying antirheumatic drug (DMARD) therapy including biologics remained unchanged in this population.

An excitation function of the ground-state gamma (0)-ray capture transition in C-12(alpha, gamma)O-16 at theta (gamma) = 90 degrees was obtained in far geometry using six Ge detectors, where the study of the reaction was initiated in inverse kinematics involving a windowless gas target. The detectors observed predominantly the El capture amplitude. The data at E = 1.32 to 2.99 MeV lead to an extrapolated astrophysical S factor S-E1(E-0) = 90 +/- 15 keV b at E-0 = 0.3 MeV (for the case of constructive interference between the two lowest E1 sources), in good agreement with previous works. However, a novel Monte Carlo approach in the data extrapolation reveals systematic differences between the various data sets such that a combined analysis of all available data sets could produce a biased estimate of the S-E1(E-0) value. As a consequence, the case of destructive interference between the two lowest E1 sources with S-E1(E-0) = 8 +/- 3 keV b cannot be ruled out rigorously.

The cross-section of 8 Li( $\alpha $ ,n)11 B has been measured at $E_{\rm cm}$ = 1.25 MeV to be $\sigma (E) = 500$ mb using novel techniques, i.e. a 8 Li radioactive ion beam produced at the tandem in Catania in combination with a 4 He gas cell and a $4\pi $ neutron detector. The value is in fair agreement with previous work strengthening the model of inhomogeneous Big Bang nucleosynthesis.

We describe a dedicated experiment to measure the neutron yield produced by a 62MeV proton beam impinging on a beryllium thick target. The energy was chosen as close as possible to the 70MeV considered for the ADS layout described in this Focus Point. The neutron yield and energy spectra were measured at several angles with respect to the beam direction. The experiment was performed at the INFN Laboratori Nazionali del Sud in Catania, Italy, using the proton beam delivered by the Superconducting Cyclotron (CS).

The event-by-event determination of the impact parameter from particle multiplicity emitted in heavy-ion collisions is considered. The associate problem of the determination of the particle multiplicity on both multi-event and event-by-event basis is formulated and discussed. It is shown that a multi-event data analysis procedure allows an accurate determination of the multipolicity distribution of the emitted particles even with not necessarily large total efficiency and granularity detection systems. In the event-by-event data analysis procedure a fold-to-multiplicity conversion based on the Bayes strategy is adopted. It is shown that a reliable event-by-event multiplicity determination and multiplicity resolution definition cannot prescind from a multi-event analysis of the full data set. It is found that the resolution of the event-by-event fold-to-multiplicity conversion procedure depends on the characteristics of the detection system, but not exclusively. The dependence on the particular multiplicity distribution investigated is discussed. It is concluded that event-by-event high-resolution impact parameter measurements can only be performed with very efficient and granular detection systems, but a gross event classification into central and peripheral collisions can be performed even with detection efficiency as low asΩ=0.3.

We studied endocrine functions at baseline and after TRH and LHRH stimulation in a group of 7 young male patients with genetic hemochromatosis (HE) without liver damage (i.e. fibrosis and cirrhosis). In five patients endocrine re-evaluations after complete iron depletion was also performed. Mean basal testosterone (T), FSH, LH and PRL were significantly lower than in controls. Serum T increased normally after HCG stimulation. The normal or high increments of LH after LHRH stimulation suggest that secretion capacity of LH was intact and that hypothalamic dysfunction could be responsible for the preclinical gonadal deficiency found in our patients. The response of PRL to TRH indicates that secretion capacity of lactotrophs although present, was decreased and did not improve after phlebotomy therapy. After iron depletion the two patients with the lowest basal T levels showed the highest increments indicating that in the early stages of hypothalamic-pituitary damage gonadal dysfunction is still reversible in HE patients.

Photons emitted in the28Si+64Ni and32S+64Ni reactions at 143 MeV and 156 MeV incident energy respectively, have been detected in coincidence with the ejected charged fragments. An array of 48 BaF2γ-rays detector and 6 solid state silicon detector telescopes have been used. Photon energy spectra measured in the energy range from 2 to 20 MeV in coincidence with ejectiles coming from deep inelastic reactions, are consistent with statistical emission from the reaction products.

Measurements of photofission fragment angular distributions of238U between 5.1 and 6.0 MeV are presented. As γ-source the intense bremsstrahlung beam from the Catania University Microtron is used. The results are analysed within the framework of the double-humped barrier model with a potential constructed with three smoothly joined parabolae and a damping term in the second well. The values of the fission barrier parameters for the involved 2+0, 1−0 and 1−11 channels are extracted and a comparison with the theoretical predictions and experimental results in the literature is made. Delayed-fission contributions for the involved channels are taken into account in the 1−1 channel parameter determination.