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Yvan Vandenplas,1 Helen A Brough,2– 4 Alessandro Fiocchi,5 Mohamad Miqdady,6 Zakiudin Munasir,7 Silvia Salvatore,8 Nikhil Thapar,9 Carina Venter,10 Mario C Vieira,11 Rosan Meier12,13 1Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium; 2Department Women and Children’s Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 3Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London, UK; 4Children’s Allergy Service, Evelina Children’s Hospital, Guy’s and St. Thomas’s NHS Foundation Trust, London, UK; 5Translational Research in Pediatric Specialities Area, Division of Allergy, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio, Rome, Italy; 6Department of Pediatrics, Sheikh Khalifa Medical City, College of Medicine & Health Sciences, Khalifa University, Khalifa, United Arab Emirates; 7Department of Child Health, Ciptomangunkusumo Hospital-Medical Faculty Universitas Indonesia, Jakarta, Indonesia; 8Pediatric Department, Hospital “F. Del Ponte”, University of Insubria, Varese, Italy; 9Gastroenterology, Hepatology and Liver Transplant, Queensland Children’s Hospital, Brisbane, Queensland, Australia; 10University of Colorado, Children’s Hospital Colorado, Denver, CO, USA; 11Center for Pediatric Gastroenterology -Hospital Pequeno Príncipe, Curitiba, Brazil; 12Department of Paediatrics, Imperial College, London, UK; 13Department Nutrition and Dietetics, University of Winchester, Winchester, UKCorrespondence: Yvan VandenplasVrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, BelgiumEmail Yvan.vandenplas@uzbrussel.beAbstract: Exclusive breast feeding is recommended in all guidelines as the first choice feeding. Cow milk allergy (CMA) can be diagnosed by a diagnostic elimination diet for 2 to 4 weeks with a hypo-allergenic formula, followed by a challenge test with intact cow milk protein. The most often used hypo-allergenic formula for the diagnostic elimination diet and the therapeutic diet is a CM based extensive hydrolysate. CM-based partial hydrolysates cannot be recommended in the management of CMA because of insufficient efficacy and possible reactions, but about half of the infants with CMA may tolerate a partial hydrolysate. The pros and cons of other dietary options are discussed in this paper. The use of an amino acid-based formula and/or rice based hydrolysate formula during the diagnostic elimination and therapeutic diet is debated. When available, there is sufficient evidence to consider rice hydrolysates as an adequate alternative to CM-based hydrolysates, since some infants will still react to the CM hydrolysate. The pros and cons of dietary options such as soy formula, buckwheat, almond, pea or other plant based dietary products are discussed. Although the majority of the plant-based beverages are nutritionally inadequate, some are nutritionally adapted for toddlers. However, accessibility and content vary by country and, thus far there is insufficient evidence on the efficacy and tolerance of these plant-based drinks (except for soy formula and rice hydrolysates) to provide an opinion on them.Conclusion: A diagnostic elimination diet, followed by a challenge remains the diagnostic standard. The use of an awareness tool may result in a decrease of delayed diagnosis. Breastmilk remains the ideal source of nutrition and when not available a CM extensively hydrolyzed formula, rice hydrolysate or amino acid formula should be recommended. More evidence is needed regarding plant-based drinks.Keywords: amino acid formula, challenge test, cow milk allergy, hydrolysate, plant-based drink, rice hydrolysate, soy formula

Carlotta Franchi,1 Giulia Lancellotti,2 Marco Bertolotti,2 Simona Di Salvatore,2 Alessandro Nobili,1 Pier Mannuccio Mannucci,3 Chiara Mussi,2,* Ilaria Ardoino1,* On Behalf of the REPOSI (REgistro POliterapie SIMI and Società Italiana di Medicina Interna) Study Group1Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy; 2Division of Geriatrics, Department of Biomedical, metabolic and Neural Sciences and Center for Gerontological Evaluation and Research, Università di Modena e Reggio Emilia, Modena, Italy; 3Scientific Direction, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy*These authors contributed equally to this workCorrespondence: Carlotta FranchiUnit of Pharmacoepidemiological Research in Older People, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, Milano, 20156, ItalyTel +39 02 39014580Fax +39 02 39001916Email carlotta.franchi@marionegri.itObjective: To assess how lipid-lowering drugs (LLDs) are administered in the hospitalized patients aged 65 and older and their association with clinical outcomes according to their health-related profiles.Design: This is a retrospective study based on data from REPOSI (REgistro POliterapie SIMI – Italian Society of Internal Medicine) register, an Italian network of internal medicine hospital wards.Setting and Participants: A total of 4642 patients with a mean age of 79 years enrolled between 2010 and 2018.Methods: Socio-demographic characteristics, functional abilities, cognitive skills, laboratory parameters and comorbidities were used to investigate the health state profiles by using multiple correspondence analysis and clustering. Logistic regression was used to assess whether LLD prescription was associated with patients’ health state profiles and with short-term mortality.Results: Four clusters of patients were identified according to their health state: two of them (Cluster III and IV) were the epitome of frailty conditions with poor short-term outcomes, whereas the others included healthier patients. The average prevalence of LLD use was 27.6%. The lowest prevalence was found among the healthier patients in Cluster I and among the oldest frail patients with severe functional and cognitive impairment in Cluster IV. The highest prevalence was among multimorbid patients in Cluster III (OR=4.50, 95% CI=3.76– 5.38) characterized by a high cardiovascular risk. Being prescribed with LLDs was associated with a lower 3-month mortality, even after adjusting for cluster assignment (OR=0.59; 95% CI = 0.44– 0.80).Conclusion: The prevalence of LLD prescription was low and in overall agreement with guideline recommendations and with respect to patients’ health state profiles.Keywords: statins, health state profile, multimorbidity, polypharmacy

NGC 1068 is a nearby, widely studied Seyfert II galaxy presenting radio, infrared, X-ray, and γ-ray emission, along with strong evidence for high-energy neutrino emission. Recently, the evidence for neutrino emission was explained in a multimessenger model, whereby the neutrinos originate from the corona of the active galactic nucleus. In this environment, γ-rays are strongly absorbed, so that an additional contribution is necessary, for instance, from the circumnuclear starburst ring. In this work, we discuss whether the radio jet can be an alternative source of the γ-rays between about 0.1 and 100 GeV, as observed by Fermi-LAT. In particular, we include both leptonic and hadronic processes, namely, accounting for inverse Compton emission and signatures from pp as well as pγ interactions. In order to constrain our calculations, we used VLBA and ALMA observations of the radio knot structures, which are spatially resolved at different distances from the supermassive black hole. Our results show that the best leptonic scenario for the prediction of the Fermi-LAT data is provided by the radio knot closest to the central engine. For that to be the case, a magnetic field strength of ∼1 mG is needed as well as a strong spectral softening of the relativistic electron distribution at (1 − 10) GeV. However, we show that neither such a weak magnetic field strength, nor such a strong softening is expected for that knot. A possible explanation for the ∼10 GeV γ-rays could potentially be provided by hadronic pion production in case of a gas density ≳104 cm−3. Nonetheless, this process is not found to contribute significantly to the low-energy end of the Fermi-LAT range. We conclude that the emission sites in the jet are not sufficient to explain the γ-rays across the whole Fermi-LAT energy band. [ABSTRACT FROM AUTHOR]

Stefano Salvatore,1 Montserrat Espuña-Pons,2 Andrea Tubaro3 1Urogynecology Unit, Obstetrics and Gynecology Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy; 2Urogynecology Unit, ICGON, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain; 3Department of Urology, Sant’Andrea Hospital, Sapienza University, Rome, ItalyCorrespondence: Stefano SalvatoreUrogynecology Unit, Obstetrics and Gynecology Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, ItalyTel +39 02 26432579Email stefanosalvatore@hotmail.comAbstract: Urgency, defined as “a sudden, compelling desire to pass urine which is difficult to defer”, is not always reported by patients with overactive bladder, and is not usually described in these words. Urgency is known to have a strong negative impact on patients’ quality of life and requires attention from healthcare professionals, as they play a key role in establishing the diagnosis and in deciding, together with the patient, the most appropriate treatment. This topic was debated during the symposium “Urinary Urgency: A Symptom in Need of a Cure?”, held at the 11th Annual Meeting of the European Urogynaecology Association (EUGA) in October 2018 in Milan, Italy. The presentation of two clinical cases, those of a young, active woman and a retired teacher, illustrated the importance of this cornerstone symptom and demonstrated how fesoterodine may represent an important option in the management of this condition. The experts concluded that the physician should not leave urgency undeclared or untreated; that the patient should be involved in the choice of treatment; and that fesoterodine, which offers flexible dosing and has proven, consistent positive results on urgency episodes and urgency urinary incontinence, with very low/no risk of impairment of cognitive function, appears to be one of the good choices in the treatment of this symptom.Keywords: antimuscarinic agents, cognitive function, fesoterodine, incontinence, overactive bladder

A variety of good management practices have been recommended to minimize the impact of water runoff from production nurseries. However, studies have not been conducted to gauge which management practices nursery producers are most likely to adopt in response to education and increased government oversight. We surveyed 85 production nurseries in Southern California about their existing practices to limit the impacts of runoff from their facilities. Of these, 65 in Ventura County were resurveyed with the same questionnaire within 2 years. The positive response rate for following good management practices was 65%, compared to 57% in the initial survey. There were significant increases in every category of practices surveyed, and significant changes in the adoption of 38 specific practices. This suggests that nurseries are amenable to adopting management practices within a short time span in areas where there is increased governmental oversight and educational opportunities for growers.

Objective: This study aimed to evaluate histological modifications of the vaginal mucosa after repeated microablative fractional CO2 laser treatments. As secondary objectives we evaluated the clinical effects associated with repeated microablative fractional CO2 laser treatments using validated questionnaires. Methods: A prospective intervention study was performed in the Division of Gynecology and Obstetrics, Urogynecology Unit, IRCCS San Raffaele Scientific Institute with 15 postmenopausal women complaining of genitourinary syndrome of menopause symptoms. The cohort of patients was submitted to at least two previous laser treatment cycles in the past years. The Vaginal Health Index (VHI), visual analog scale (VAS), Female Sexual Function Index (FSFI), Urinary Distress Inventory-6 (UDI-6), International Consultation on Incontinence Questionnaire – Urinary Incontinence (ICIQ-UI) and 5-point Likert scale were used. Moreover, histological examinations were carried out on all samples. Results: At 4weeks after the last treatment, the VHI score and all FSFI items were significantly increased compared with baseline. We observed a statistically significant decrease in both frequency and severity for all urinary symptoms after the follow-up. We observed a statistically significant increase in the number of epithelial cell layers with a consequent increase in epithelial thickness, in the number of glycogen-filled cells and in the number of papillae after the laser treatment. No signs of fibrosis were observed as neovascularization was observed in each woman. Conclusions: This is the first study demonstrating the histological persistency of efficacy in repeated annually laser treatment cycles, with tissue changes always leading to regenerative results without any sign of fibrosis. [ABSTRACT FROM AUTHOR]

The paper tests longitudinally the hypothesis that educational subcultures in terms of which students interpret their role and their educational setting affect the probability of dropping out of higher education. A logistic regression model was performed to predict drop out at the beginning of the second academic year for the 823 freshmen of a three-year bachelor degree in psychology at an Italian university. The model uses both measures of students' educational subculture and incoming levels of knowledge and skills. The probability of dropping out was used as dependent variable. Results show that the probability of dropping out is significantly associated with students' educational subculture--but not with their incoming level of knowledge and skills. Our results suggest the need to recognize the meaning as a legitimate variable of research and of intervention in the field of educational success.

The thirty-nine extant genera of Conoderinae known to occur in North America, Central America, and the Caribbean are reviewed based on external morphology. An identification key is provided along with diagnoses, distributions, species counts, and natural history information, when known, for each genus. Morphological character systems of importance for weevil classification are surveyed, potential relationships among the tribes and genera are discussed, and groups most in need of taxonomic and phylogenetic attention are identified. The following genera are transferred to new tribes: Acoptus LeConte, 1876 from the Lechriopini to the Othippiini (new placement) and the South American genus Hedycera Pascoe, 1870 from the Lechriopini to the Piazurini (new placement). Philides Champion, 1906 and Philinna Champion, 1906 are transferred from the Lechriopini to Conoderinae incertae sedis (new placement) although their placement as conoderines is uncertain. The species Copturomimus cinereus Heller, 1895 is designated as the type species of the genus Copturomimus Heller, 1895.

Qubit measurements are central to quantum information processing. In the field of superconducting qubits, standard readout techniques are limited not only by the signal-to-noise ratio, but also by state relaxation during the measurement. In this work, we demonstrate that the limitation due to relaxation can be suppressed by using the many-level Hilbert space of superconducting circuits: In a multilevel encoding, the measurement is corrupted only when multiple errors occur. Employing this technique, we show that we can directly resolve transmon gate errors at the level of one part in 10^{3}. Extending this idea, we apply the same principles to the measurement of a logical qubit encoded in a bosonic mode and detected with a transmon ancilla, implementing a proposal by Hann et al. [Phys. Rev. A 98, 022305 (2018)PLRAAN2469-992610.1103/PhysRevA.98.022305]. Qubit state assignments are made based on a sequence of repeated readouts, further reducing the overall infidelity. This approach is quite general, and several encodings are studied; the codewords are more distinguishable when the distance between them is increased with respect to photon loss. The trade-off between multiple readouts and state relaxation is explored and shown to be consistent with the photon-loss model. We report a logical assignment infidelity of 5.8×10^{-5} for a Fock-based encoding and 4.2×10^{-3} for a quantum error correction code (the S=2, N=1 binomial code). Our results not only improve the fidelity of quantum information applications, but also enable more precise characterization of process or gate errors.

One option for Extension professionals wishing to use free statistical software is to use online calculators, which are useful for common, simple analyses. A second option is to use a free computing environment capable of performing statistical analyses, like R-project. R-project is free, cross-platform, powerful, and respected, but may be difficult for beginners to learn. Using a graphical user interface allows new users to perform common analyses using pull-down menus and dialog boxes without programming knowledge. An example of an R-project program, performing a linear regression and producing relevant plots and statistics, is included.

Over the past 4 years, rain barrel programming for residents has been implemented in both Northern Virginia and New Jersey as a method for educating the public about stormwater management and water conservation. Program participants demonstrated a significant increase in knowledge of water resource issues. Follow-up surveys showed 58% of New Jersey respondents and 48% of Virginia respondents adopted at least one additional best management practice at home. Results show that the enthusiasm for rain barrels can be used as an opportunity to educate and enable residents to be water resource managers on their own properties.

Vulvovaginal atrophy (VVA) is a chronic progressive condition that involves the genital and lower urinary tracts, related to the decrease of serum estrogenic levels when menopause occurs. The definition of genitourinary syndrome of menopause (GSM) is a medically more accurate, all-encompassing and publicly acceptable term than VVA. Due to the chronic progressive trend of GSM, symptoms tend to reappear after the cessation of therapy, and frequently long-term treatment is required. First-line therapies include vulvar and vaginal lubricant or moisturizers, and, in the case of failure, low-dose vaginal estrogens are the preferred pharmacological therapy. Populations of patients, such as breast cancer (BC) survivors, are affected by iatrogenic GSM symptoms with concerns about the use of hormonal therapies. The non-ablative erbium:YAG laser and the fractional microablative CO2 vaginal laser are the two main lasers evaluated for GSM treatment. The aim of this comprehensive review is to report the efficacy and safety of Er:YAG and CO2 vaginal lasers for GSM treatment. Vaginal laser therapy has been demonstrated to be effective in restoring vaginal health, improving VVA symptoms and sexual function. The data suggest that both Er:YAG and CO2 vaginal lasers are safe energy-based therapeutic options for management of VVA and/or GSM symptoms in postmenopausal women and BC survivors. [ABSTRACT FROM AUTHOR]

The progression of non-alcoholic fatty liver disease (NAFLD) and the development of hepatic fibrosis is caused by changes in redox balance, leading to an increase of reactive oxygen species (ROS) levels. NAFLD patients are at risk of progressing to non-alcoholic steatohepatitis (NASH), associated to cardiovascular diseases (CVD), coronary heart disease and stroke. Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. The present work was directed to determine whether use of an inhibitor of HO-1 activity affects lipid metabolism and fibrosis process in hepatic cells. Oil Red assay and mRNA analysis were used to evaluate the triglycerides content and the lipid metabolism pathway in HepG2 cells. ROS measurement, RT-PCR and Soluble collagen assay were used to assess the intracellular oxidant, the fibrosis pathway and the soluble collagen in LX2 cells. The activity of HO-1 was inhibited using Tin Mesoporphyrin IX (SnMP). Our study demonstrates that a non-functional HO system results in an increased lipid storage and collagen release in hepatocytes. Consequently, an increase of HO-1 levels may provide a therapeutic approach to address the metabolic alterations associated with NAFLD and its progression to NASH.