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We report a case of a 73-year-old woman affected by Lemmel's syndrome, a rare type of obstructive jaundice caused by a periampullary duodenal diverticulum. The patient was admitted to the Emergency Department for pneumonia associated with mild epigastric pain and vomiting. While hospitalized for antibiotic treatment, the appearance of jaundice led us to discover a periampullary duodenal diverticulum by endoscopy and CT scan. The jaundice was successfully managed endoscopically with removal of food debris from the diverticulum.

BackgroundSafe and potent antiretroviral medications in child-friendly formulations are needed to treat young children living with HIV-1. We aimed to select dosing for a dispersible tablet formulation of dolutegravir that achieved pharmacokinetic exposures similar to those in adults, and was safe and well tolerated in young children.MethodsInternational Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) P1093 is a phase 1-2 ongoing multicentre, open-label, non-comparative study of dolutegravir. A 5 mg dispersible tablet formulation of dolutegravir was studied in children aged 4 weeks to less than 6 years old, weighing at least 3 kg, with HIV RNA of greater than 1000 copies per mL and no previous treatment with integrase strand transfer inhibitor recruited from IMPAACT clinical research sites in Africa, the Americas, and Asia. Doses were selected on the basis of intensive pharmacokinetic evaluation on days 5-10, with safety and tolerability assessed up to 48 weeks. The primary objectives of this study are to evaluate the pharmacokinetics of dolutegravir in combination with optimised background therapy and to establish the dose of dolutegravir that achieves the targeted 24-h trough concentration and 24-h area under the curve for infants, children, and adolescents with HIV-1, to establish the safety and tolerability of dolutegravir at 24 and 48 weeks, and to select a dose that achieves similar exposure to the dolutegravir 50 mg once daily dose in adults. This analysis included participants treated with the proposed dose of dolutegravir dispersible tablets in two stages for each of three age cohorts. This trial is registered at ClinicalTrials.gov (NCT01302847) and is ongoing.FindingsWe recruited 181 participants from April 20, 2011, to Feb 19, 2020; of these, 96 received dolutegravir dispersible tablets. This analysis included 73 (35, 48% female) participants who received the final proposed dose with median (range) age of 1 year (0·1 to 6·0), weight (minimum-maximum) of 8·5 kg (3·7 to 18·5), plasma HIV-1 RNA concentration of 4·2 log10 copies per mL (2·1 to 7·0), and CD4% of 24·0% (0·3 to 49·0); 64 (87·7%) were treatment-experienced. The selected dose within each age cohort (≥2 years to

Surveys on Serial Transverse Enteroplasty (STEP) published in international literature (1 January 2003- 31 May 2021) were searched. Articles were included from 17 countries: 1/23 comparative and 22/23 cohort studies. STEP was performed on 308 patients: pediatrics, adults, and mixed ages. Pediatric group included 16 studies and the adult 6. Pre-STEP residual small bowell (SB) length for pediatrics and adults ranged from 18 to 26 cm and from 30 to 70 cm, respectively. Post-STEP increased SB length for pediatrics and adults ranged between 42 and 100% and 50% and 176%, respectively. For pediatrics, enteral autonomy was reached in 32.22% of cases, parenteral nutrition (PN) dependence was 36.11%, a repeated STEP procedure (Re-STEP) was needed in 17.22%, and a bowel transplant was performed in 6.11%. In adults, enteral autonomy was achieved in 52.38%, while PN dependence was 37.1%, and no Re-STEP or transplantation were required. For the mixed group, post-STEP bowel length increased from 2 to 50 cm, enteral autonomy was obtained in 43%, PN dependence was 57%, without reported Re-STEP or transplantation. Mortality rates were between 5.55% (pediatric) and 7.14% (adults). Preoperative length with preservation of ileocecal valve represented the main predictive factors to achieve enteral autonomy.

Optimum filters are granted increasing recognition as valuable tools for parametric estimation in many scientific and technical fields. The DPLMS method, introduced some twenty years ago, is effective among the synthesis algorithms since it derives the optimum filters directly from the experimental signal and noise waveforms. Two new extensions of the DPLMS method are here presented. The first one speeds up the synthesis phase and improves the energy estimation by synthesizing optimum filters with automatically designed flat-top length. The second one improves the quality of parameter estimation in multi-channel systems by taking advantage of the inter-channel noise correlation properties. The theoretical and functional aspects behind the DPLMS method for optimum filter synthesis are first recalled and illustrated in more detail. The two new DPLMS extensions are subsequently introduced from the theoretical viewpoint and more thoroughly considered from the applicative perspective. The DPLMS optimum filters have been applied first to simulated signals with various amounts and characteristics of superimposed noise and then to the experimental waveforms acquired from a solid-state Ge detector. The results obtained are considered from both the absolute viewpoint and in comparison with those of more traditional, suboptimal filters. The results demonstrate the effectiveness of the two new DPLMS extensions. For single-channel energy estimations, the optimum filters provide comparatively better results than the other filters. The DPLMS multi-channel optimum filters further enhance the quality of the estimations, compared to single-channel optimum filters, with non-negligible inter-channel noise correlation. The effectiveness and robustness of the DPLMS method in synthesizing high-quality filters for energy estimation will be tested soon within leading-edge multi-channel physics experiments., Comment: 17 pages, 13 figures

Introduction: Condylomas or genital warts (GW) are the most frequently diagnosed sexually transmitted infection (STI) in STI centers in Chile, but there are no population statistics available. Objectives: To describe the prevalence of GW in patients from 18-60 years of age who attend outpatient dermatology, gynecology and urology practice; the demographic characteristics of the patients and the diagnostic and treatment tools. Methods: A sample of Chilean specialists stratified by region, population and gender of patients was provided with a logbook and answered a questionnaire. Results: The GW prevalence was 2.44% for the whole group; 3.76% for the 18-34 age group and 1.29% for the 35-60 years group (p = 0.0000). The average age of patients with GW was 29.4 years in women and 32.7 years in men (p = 0.019). The distribution by age was different according to gender and health system. Visual inspection was the most frequent diagnostic method used and imiquimod cream the most common treatment, however, there were differences in the use of diagnostic and therapeutic tools according to the patient’s gender, specialty of the doctor and health system. Conclusions: The high prevalence of GW confirmed the need and importance of public health interventions to address this problem.

Neutrinoless double-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\beta $$\end{document}β decay of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{76}$$\end{document}76Ge is searched for with germanium detectors where source and detector of the decay are identical. For the success of future experiments it is important to increase the mass of the detectors. We report here on the characterization and testing of five prototype detectors manufactured in inverted coaxial (IC) geometry from material enriched to 88% in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{76}$$\end{document}76Ge. IC detectors combine the large mass of the traditional semi-coaxial Ge detectors with the superior resolution and pulse shape discrimination power of point contact detectors which exhibited so far much lower mass. Their performance has been found to be satisfactory both when operated in vacuum cryostat and bare in liquid argon within the Gerda setup. The measured resolutions at the Q-value for double-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\beta $$\end{document}β decay of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{76}$$\end{document}76Ge (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$Q_{\beta \beta }$$\end{document}Qββ = 2039 keV) are about 2.1 keV full width at half maximum in vacuum cryostat. After 18 months of operation within the ultra-low background environment of the GERmanium Detector Array (Gerda) experiment and an accumulated exposure of 8.5 kg\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\cdot $$\end{document}·year, the background index after analysis cuts is measured to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4.9^{+7.3}_{-3.4}\times 10^{-4} \ \text {counts}/(\text {keV} \cdot \text {kg} \cdot \text {year})$$\end{document}4.9-3.4+7.3×10-4counts/(keV·kg·year) around \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$Q_{\beta \beta }$$\end{document}Qββ. This work confirms the feasibility of IC detectors for the next-generation experiment Legend.

The GERmanium Detector Array (GERDA) experiment searched for the lepton-number-violating neutrinoless double-$\beta$ ($0\nu\beta\beta$) decay of $^{76}$Ge, whose discovery would have far-reaching implications in cosmology and particle physics. By operating bare germanium diodes, enriched in $^{76}$Ge, in an active liquid argon shield, GERDA achieved an unprecedently low background index of $5.2\times10^{-4}$ counts/(keV$\cdot$kg$\cdot$yr) in the signal region and met the design goal to collect an exposure of 100 kg$\cdot$yr in a background-free regime. When combined with the result of Phase I, no signal is observed after 127.2 kg$\cdot$yr of total exposure. A limit on the half-life of $0\nu\beta\beta$ decay in $^{76}$Ge is set at $T_{1/2}>1.8\times10^{26}$ yr at 90% C.L., which coincides with the sensitivity assuming no signal., Comment: 7 pages, 3 figures, submitted to Physical Review Letters

We present the first search for bosonic superweakly interacting massive particles (super-WIMPs) as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-s decay experiment which operates high-purity germanium detectors enriched in ^{76}Ge in an ultralow background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c^{2} to 1 MeV/c^{2}. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c^{2} have been set. As an example, at a mass of 150 keV/c^{2} the most stringent direct limits on the dimensionless couplings of axionlike particles and dark photons to electrons of g_{ae}

Background: On target F-18-Flortaucipir (FTP) binding of Alzheimer's disease tau aggregates and off-target binding of melanocytes have been demonstrated with autoradiography. Objective: We aimed to investigate the hypothesis that if binding in choroid plexus (CP) is due to melanocytes, the signal would be elevated in Black/African American (B/AA) compared to White (W) participants. In addition, we examined whether CP signal affects measurements in adjacent regions, and whether correcting for spill-in effects has an influence on associations between hippocampus (HC) FTP and amyloid or cognition. Methods: FTP race differences in 147 Harvard Aging Brain Study participants (23 B/AA, 124W) were examined in CP, HC, HC covaried for CP, amygdala, inferior temporal gyrus, entorhinal cortex, and fusiform regions. Associations between CP FTP and other regions-of-interest (ROIs) were probed to assess spill-in effects. A statistical regression approach to attenuate CP spill-in was tested by relating adjusted HC SUVR residuals and unadjusted HC SUVR to race, cognition and amyloid. All analyses were covaried for age, sex, education and amyloid deposition, and Bonferroni-corrected for multiple comparisons. Results: B/AA individuals had elevated CP and HC SUVR (p < 0.007), whereas other ROI SUVR and HC SUVR covaried for CP SUVR did not show race differences (p > 0.05). CP SUVR was associated with HC SUVR (p< 10(-14)), but with no other ROI SUVR (p > 0.05). When adjusting HC SUVR for CP SUVR, no race differences in residual HC SUVR were detected, and relationships with amyloid and memory became apparent. Conclusion: Melanocyte FTP binding may account partially for high CP signal. This off-target binding affects mainly HC FTP measurements, which should be interpreted with caution.

In the global landscape of neutrinoless double beta ($0\nu\beta\beta$) decay search, the use of semiconductor germanium detectors provides many advantages. The excellent energy resolution, the negligible intrinsic radioactive contamination, the possibility of enriching the crystals up to 88% in the $^{76}$Ge isotope as well as the high detection efficiency, are all key ingredients for highly sensitive $0\nu\beta\beta$ decay search. The MAJORANA and GERDA experiments successfully implemented the use of germanium (Ge) semiconductor detectors, reaching an energy resolution of $2.53 \pm 0.08$ keV at the Q$_{\beta\beta}$ and an unprecedented low background level of $5.2 \times 10^{-4}$ cts/(keV$\cdot$kg$\cdot$yr), respectively. In this paper, we will review the path of $0\nu\beta\beta$ decay search with Ge detectors from the original idea of E. Fiorini et al. in 1967, to the final recent results of the GERDA experiment setting a limit on the half-life of $^{76}$Ge $0\nu\beta\beta$ decay at $T_{1/2} > 1.8 \times 10^{26}$ yr (90\% C.L.). We will then present the LEGEND project designed to reach a sensitivity to the half-life up to $10^{28}$ yr and beyond, opening the way to the exploration of the normal ordering region., Comment: 28 pages, 15 figures

The GERmanium Detector Array (Gerda) experiment at the Gran Sasso underground laboratory (LNGS) of INFN is searching for neutrinoless double-beta (0νββ) decay of 76Ge. The technological challenge of Gerda is to operate in a “background-free” regime in the region of interest (ROI) after analysis cuts for the full 100 kg·yr target exposure of the experiment. A careful modeling and decomposition of the full-range energy spectrum is essential to predict the shape and composition of events in the ROI around Qββ for the 0νββ search, to extract a precise measurement of the half-life of the double-beta decay mode with neutrinos (2νββ) and in order to identify the location of residual impurities. The latter will permit future experiments to build strategies in order to further lower the background and achieve even better sensitivities. In this article the background decomposition prior to analysis cuts is presented for Gerda Phase II. The background model fit yields a flat spectrum in the ROI with a background index (BI) of $$ {16.04}_{-0.85}^{+0.78}\cdotp {10}^{-3} $$ 16.04 − 0.85 + 0.78 · 10 − 3 cts/(keV·kg·yr) for the enriched BEGe data set and $$ {14.68}_{-0.52}^{+0.47}\cdotp {10}^{-3} $$ 14.68 − 0.52 + 0.47 · 10 − 3 cts/(keV·kg·yr) for the enriched coaxial data set. These values are similar to the one of Phase I despite a much larger number of detectors and hence radioactive hardware components.

Objective Recent studies have shown that positron emission tomography (PET) tracer AV-1451 exhibits high binding affinity for paired helical filament (PHF)-tau pathology in Alzheimer's brains. However, the ability of this ligand to bind to tau lesions in other tauopathies remains controversial. Our goal was to examine the correlation of in vivo and postmortem AV-1451 binding patterns in three autopsy-confirmed non-Alzheimer tauopathy cases. Methods We quantified in vivo retention of [F-18]-AV-1451 and performed autoradiography, [H-3]-AV-1451 binding assays, and quantitative tau measurements in postmortem brain samples from two progressive supranuclear palsy (PSP) cases and a MAPT P301L mutation carrier. They all underwent [F-18]-AV-1451 PET imaging before death. Results The three subjects exhibited [F-18]-AV-1451 in vivo retention predominantly in basal ganglia and midbrain. Neuropathological examination confirmed the PSP diagnosis in the first two subjects; the MAPT P301L mutation carrier had an atypical tauopathy characterized by grain-like tau-containing neurites in gray and white matter with heaviest burden in basal ganglia. In all three cases, autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined, with the exception of entorhinal cortex (reflecting incidental age-related neurofibrillary tangles) and neuromelanin-containing neurons in the substantia nigra (off-target binding). The lack of a consistent significant correlation between in vivo [F-18]-AV-1541 retention and postmortem in vitro binding and tau measures in these cases suggests that this ligand has low affinity for tau lesions primarily made of straight tau filaments. Interpretation AV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in these non-Alzheimer tauopathies. ANN NEUROL 2017;81:117–128

The GERDA experiment searches for the lepton-number-violating neutrinoless double-β decay of ^{76}Ge (^{76}Ge→^{76}Se+2e^{-}) operating bare Ge diodes with an enriched ^{76}Ge fraction in liquid argon. The exposure for broad-energy germanium type (BEGe) detectors is increased threefold with respect to our previous data release. The BEGe detectors feature an excellent background suppression from the analysis of the time profile of the detector signals. In the analysis window a background level of 1.0_{-0.4}^{+0.6}×10^{-3} counts/(keV kg yr) has been achieved; if normalized to the energy resolution this is the lowest ever achieved in any 0νββ experiment. No signal is observed and a new 90% C.L. lower limit for the half-life of 8.0×10^{25} yr is placed when combining with our previous data. The expected median sensitivity assuming no signal is 5.8×10^{25} yr.

Summary Patients with schizophrenia have increased mortality and morbidity compared with the general population. These patients have a 20-year shorter lifespan than peers without schizophrenia, mainly due to premature cardiovascular disease, suicide, and cancer. Patients with severe mental illness are at increased risk for cardiovascular disease related to increased incidence of diabetes, hypertension, smoking, poor diet, obesity, dyslipidaemia, metabolic syndrome, low physical activity, and side-effects of antipsychotic drugs. Some second-generation antipsychotics (eg, clozapine, olanzapine, quetiapine, and risperidone) are associated with an increased risk of weight gain and obesity, impaired glucose tolerance and new-onset diabetes, hyperlipidaemia, and cardiovascular disease. The mechanisms by which schizophrenia and patients with severe mental illness are susceptible to cardiometabolic disorders are complex and include lifestyle risks and direct and indirect effects of antipsychotic drugs. An understanding of these risks might lead to effective interventions for prevention and treatment of cardiometabolic disorders in schizophrenia and severe mental illness.

GERDA is a new generation experiment searching for neutrinoless double beta decay of 76Ge, operating at INFN Gran Sasso Laboratories (LNGS) since 2010. Coaxial and Broad Energy Germanium (BEGe) Detectors have been operated in liquid argon (LAr) in GERDA Phase I. In the framework of the second GERDA experimental phase, both the contacting technique, the connection to and the location of the front end readout devices are novel compared to those previously adopted, and several tests have been performed.In this work, starting from considerations on the energy scale stability of the GERDA Phase I calibrations and physics data sets, an optimized pulse filtering method has been developed and applied to the Phase II pilot tests data sets, and to few GERDA Phase I data sets. In this contribution the detector performances in term of energy resolution and time stability are here presented.The improvement of the energy resolution, compared to standard Gaussian shaping adopted for Phase I data analysis, is discussed and related to the optimized noise filtering capability. The result is an energy resolution better than 0.1% at 2.6 MeV for the BEGe detectors operated in the Phase II pilot tests and an improvement of the energy resolution in LAr of about 8% achieved on the GERDA Phase I calibration runs, compared to previous analysis algorithms.

Background Potential loss of economic resources to recover from public health. Purpose The aim of this work was to present a software project that should support the pharmacist during the control of the correct management of the ‘Agenzia Italiana del Farmaco’ (AIFA) registers. Material and methods Starting from the AIFA platform, we took a census of patients, specialist physicians, drugs with the relevant therapy forms and managed entry agreements (MEAs). All data, reported in the tables, were linked in order that the software would be able to calculate, for each drug, the relevant therapy form and pathology, correct timing between drug request (DR) and drug administration (DA), and the presence of possible ‘suspended’ treatments. Several ALERTS were set up: exceeded the maximum timing for the next administration; administration of the last box, useful for reimbursement, that was automatically cancelled at the next DR; ‘suspended’ treatments. The timing was calculated for relative MEAs. Results Since July 2015, the experimental phase has begun and, at present, data are inputted manually. At present, 837 treatments have been inserted. Thanks to a prototype of the software, we detected 340 suspended treatments in 2015, suspended by physicians following solicitations on the part of the pharmacists. Among them, 82 had the right to reimbursement, but only 54 (66%) have received reimbursement (€200 000). In the first 6 months of 2016, 174 treatments have already been suspended following the intervention of the pharmacist, among them 37 with the right to reimbursement; for all of them, requests have already been forwarded. Conclusion In this initial phase, the software has optimised our work, allowing recovery of financial resources. As the project phase will be ended, we will try to connect our software to the AIFA register, in order to import directly useful data, and we will implement its use in all of our pharmacies. In the third phase of the project, the software will be put at physicians’ disposal to guide them in the correct timings of filling of the forms. References and/or acknowledgements Thanks to all tutors. No conflict of interest

The GERmanium Detector Array (GERDA) experiment, located at the Gran Sasso underground laboratory in Italy, is built for the search of $0\nu\beta\beta$ decay in $^{76}$Ge. GERDA operates bare high purity germanium detectors submersed in liquid Argon (LAr). Phase I of the experiment was completed reaching an exposure of about 21 kg$\cdot$yr with a background level of $10^{-2}$ cts/(ke V $\cdot$ kg $\cdot$ yr). GERDA Phase I set a limit on the $0\nu\beta\beta$ decay of $^{76}$Ge of $T_{1/2}^{0\nu} > 2.1 \cdot 10^{25}$ yr. In Phase II 35 kg of germanium detectors enriched in $^{76}$Ge are operated to reach an exposure of 100 kg$\cdot$yr. The design goal is to reduce the background by one order of magnitude to reach the sensitivity for $T_{1/2}^{0\nu} = \mathcal{O} (10^{26} )$ yr. The Phase II setup comprises thirty newly produced Broad Energy Germanium (BEGe) detectors. They contribute to the background reduction with better energy resolution and enhanced pulse shape discrimination. To achieve the necessary background reduction, the setup was complemented with LAr veto. The hardware upgrade for Phase II was finished and all detectors were deployed in December 2015. We present the first results of Phase II with 10.8 kg$\cdot$yr exposure reached in June 2016.

The GERmanium Detector Array (GERDA) experiment located at the INFN Gran Sasso Laboratory (Italy), is looking for the neutrinoless double beta decay of Ge76, by using high-purity germanium detectors made from isotopically enriched material. The combination of the novel experimental design, the careful material selection for radio-purity and the active/passive shielding techniques result in a very low residual background at the Q-value of the decay, about 1e-3 counts/(keV kg yr). This makes GERDA the first experiment in the field to be background-free for the complete design exposure of 100 kg yr. A search for neutrinoless double beta decay was performed with a total exposure of 47.7 kg yr: 23.2 kg yr come from the second phase (Phase II) of the experiment, in which the background is reduced by about a factor of ten with respect to the previous phase. The analysis presented in this paper includes 12.4 kg yr of new Phase II data. No evidence for a possible signal is found: the lower limit for the half-life of Ge76 is 8.0e25 yr at 90% CL. The experimental median sensitivity is 5.8e25 yr. The experiment is currently taking data. As it is running in a background-free regime, its sensitivity grows linearly with exposure and it is expected to surpass 1e26 yr within 2018., 8 pages, to appear in the proceedings of TAUP2017

Succulence and leaf thickness are important anatomical traits in CAM plants, resulting from the presence of large vacuoles to store organic acids accumulated overnight. A higher degree of succulence can result in a reduction in intercellular air space which constrains internal conductance to CO2. Thus, succulence presents a trade-off between the optimal anatomy for CAM and the internal structure ideal for direct C3 photosynthesis. This study examined how plasticity for the reversible engagement of CAM in the genus Clusia could be accommodated by leaf anatomical traits that could facilitate high nocturnal PEPC activity without compromising the direct day-time uptake of CO2 via Rubisco. Nine species of Clusia ranging from constitutive C3 through C3/CAM intermediates to constitutive CAM were compared in terms of leaf gas exchange, succulence, specific leaf area, and a range of leaf anatomical traits (% intercellular air space (IAS), length of mesophyll surface exposed to IAS per unit area, cell size, stomatal density/size). Relative abundances of PEPC and Rubisco proteins in different leaf tissues of a C3 and a CAM-performing species of Clusia were determined using immunogold labelling. The results indicate that the relatively well-aerated spongy mesophyll of Clusia helps to optimize direct C3-mediated CO2 fixation, whilst enlarged palisade cells accommodate the potential for C4 carboxylation and nocturnal storage of organic acids. The findings provide insight on the optimal leaf anatomy that could accommodate the bioengineering of inducible CAM into C3 crops as a means of improving water use efficiency without incurring detrimental consequences for direct C3-mediated photosynthesis.

Introduction: Quality of life and nutritional status of infants with cow's milk protein allergy (CMA) can be compromised without a proper diagnosis and treatment. Objective: To describe digestive symptoms, family and perinatal history and nutritional status of ≤ 12 month infants with CMA between June 2007 and August 2011. Patients and Method: A retrospective and descriptive study in ≤ 12 month old infants suspecting CMA was performed. Family history, perinatal and clinical characteristics were studied. Cases without food test or open challenge test, or whose reason for consultation corresponded to other pathology were excluded. The program STATA 11.1 was used for statistical analysis and p < 0.05 was considered statistically significant. Results: 40 infants (57.5 % boys), age 3 ± 0.4 months and history of 2 ± 0.3 months presenting the following: 20 of them (50 %), vomiting/regurgitation; 8 (20 %), bloody diarrhea; 4 (10%) failure to thrive; 4 (10%), colic/irritability and bloody normal deposition was present in 3 individuals (7.5 %). Family and perinatal history: 35 (87.5 %) were bottle-fed during the first week of life; 31 (77.5 %) had ≥ 30 year old mothers; 28 (70 %) described 2 family members (parents/siblings) with atopy; 27 (67.5 %) were delivered via cesarean. At the 14 ± 1.4-month follow-up, 19 (47.5 %) responded to extensively hydrolyzed formula ± breastfeeding; 19 to amino acid formula ± breastfeeding and one patient to breastfeeding exclusively. The Z -score for P/E was: -1.05 ± 1.28; T/E: -0.96 ± 1.60; BMI: -0.61 ± 1.03 in the first consultation; after a year, scores improved: P/E: -0.15 ± 1.24; T/E: -0.29 ± 1.14 and BMI: -0.04 ± 1.20 (p < 0.05), independent from formula (p = NS). 23 (74%) tolerated whole milk when reached a year old. Conclusions: In this study, the predominant early symptoms were vomiting, regurgitation and bloody diarrhea. Among the antecedents, early exposure to cow's milk, parental atopy and cesarean delivery were described. With proper treatment, nutritional recovery was observed independent from formula used, and cow's milk tolerance was observed in a high percentage of infants when they reached a year old.

Neutrinoless double electron capture is a process that, if detected, would give evidence of lepton number violation and the Majorana nature of neutrinos. A search for neutrinoless double electron capture of $^{36}$Ar has been performed with germanium detectors installed in liquid argon using data from Phase I of the GERmanium Detector Array (GERDA) experiment at the Gran Sasso Laboratory of INFN, Italy. No signal was observed and an experimental lower limit on the half-life of the radiative neutrinoless double electron capture of $^{36}$Ar was established: $T_{1/2} > $ 3.6 $\times$ 10$^{21}$ yr at 90 % C.I.

Designated a Department of Defense Team Resource Center (TRC) in 2008, Naval Medical Center Portsmouth (NMCP) currently hosts three tri-service health care teams training courses annually. Each consists of didactic learning coupled with simulation-based training exercises to provide an interactive educational experience for health care professionals. Simulated cases are developed to reinforce specific teamwork skills and behaviors, and to incorporate a variety of technologies including standardized patients, manikins, and virtual reality. The course is also the foundation of a research program designed to explore applications of modeling and simulation for enhanced team training in health care. The TRC has adopted two theoretical frameworks for evaluating training efficacy and outcomes, and has used these frameworks to guide a systematic reconfiguration of the infrastructure supporting health care teams training at NMCP.

This study sought to evaluate the diagnostic accuracy of surface-coil 3T magnetic resonance (MR) imaging in the preoperative study of patients with rectal cancer.Thirty patients with histologically proven rectal cancer underwent surface-coil 3T MR imaging with sagittal, paracoronal and para-axial T2-weighted turbo spin echo (TSE) sequences. Slice thickness was 3 mm without gap, field of view 24 cm, matrix 400 × 512. Images were assessed for infiltration of the rectal wall, perirectal fat and pelvic structures. Tumours were staged according to the TNM system, and the MR imaging results were correlated with histopathology.In the patients who underwent MR imaging before and after radiotherapy (group 1), the diagnostic accuracy of 3T MR imaging was 88% for T2, 94% for T3 and 88% for T4 cancers. In those who underwent surgical treatment without preoperative radiotherapy (group 2), the diagnostic accuracy was 90% for T2, 87% for T3 and 87% for T4 cancers.The high signal-to-noise ratio coupled with a large field of view enables surface-coil 3T MR imaging to achieve high levels of diagnostic accuracy in the local staging of rectal cancer, and in particular in assessing infiltration of mesorectum and mesorectal fascia.

Chronic hyperglycemia in diabetes mellitus (DM) increases the risk of cardiovascular complications, including stroke. Blood viscosity is elevated in stroke; therefore, there may also be a relationship between DM and blood viscosity that influences stroke risk. This cross-sectional study compared blood viscosity and non-fasting blood glucose among three groups, diabetes patients and non-DM controls visiting the Integrated Community Health Post (Posbindu) East Pisangan primary healthcare clinic in January and March 2015 (collectively the Posbindu group) and healthy controls from a previous study on blood viscosity in stroke. Blood viscosity was examined by the Digital Microcapillary® system, a recently developed tool allowing for rapid and cost-effective measurement at local clinics. Blood viscosity was significantly higher in diabetes patients compared to the healthy controls (p = 0.000). However, there was no significant correlation between blood glucose and blood viscosity (p = 0.221) or a relationship between DM and blood viscosity among the Posbindu group (p = 0.566). This discrepancy may have been caused by other risk factors influencing blood viscosity in our non-DM controls. Further study is needed to identify these confounding factors. These results suggest that risk factors for high blood viscosity (aside from DM) are common in East Pisangan. In addition, the Digital Microcapillary® system proved effective for blood viscosity screening at a local healthcare clinic.

The GERmanium Detector Array (GERDA) experiment is searching for the neutrinoless double beta decay ( 0νββ ) of the isotope 76 Ge. High-purity germanium crystals enriched in 76 Ge, simultaneously used as source and detector, are directly deployed into ultra-pure, cryogenic liquid argon, which acts both as cooling medium and shield against the external radiation. The second phase of the experiment is taking data since end of 2015 with 20 additional kg of custom-made BEGe-type Germanium detectors and an active LAr veto. In this paper we will summarize the results of the last data release of June 2017. No evidence for a possible signal is found: the lower limit for the half-life of 76 Ge is 8.0·1025 yr at 90% CL. The very low residual background found at the Q -value of the decay, about 10-3 cts/(keV · kg · yr), makes Gerda the first experiment in the field to be background-free for the complete design exposure of 100 kg · yr.

The GERmanium Detector Array (GERDA) is a low background experiment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN designed to search for the rare neutrinoless double beta decay ([Formula: see text]) of [Formula: see text]Ge. In the first phase (Phase I) of the experiment, high purity germanium diodes were operated in a “bare” mode and immersed in liquid argon. The overall background level of [Formula: see text] was a factor of ten better than those of its predecessors. No signal was found and a lower limit was set on the half-life for the [Formula: see text] decay of [Formula: see text]Ge [Formula: see text] yr (90% CL), while the corresponding median sensitivity was [Formula: see text] yr (90% CL). A second phase (Phase II) started at the end of 2015 after a major upgrade. Thanks to the increased detector mass and performance of the enriched germanium diodes and due to the introduction of liquid argon instrumentation techniques, it was possible to reduce the background down to [Formula: see text]. After analyzing 23.2 kg[Formula: see text]⋅[Formula: see text]yr of these new data no signal was seen. Combining these with the data from Phase I a stronger half-life limit of the [Formula: see text]Ge [Formula: see text] decay was obtained: [Formula: see text] yr (90% CL), reaching a sensitivity of [Formula: see text] yr (90% CL). Phase II will continue for the collection of an exposure of 100 kg[Formula: see text]yr. If no signal is found by then the GERDA sensitivity will have reached [Formula: see text] yr for setting a 90% CL. limit. After the end of GERDA Phase II, the flagship experiment for the search of [Formula: see text] decay of [Formula: see text]Ge will be LEGEND. LEGEND experiment is foreseen to deploy up to 1-ton of [Formula: see text]Ge. After ten years of data taking, it will reach a sensitivity beyond 10[Formula: see text] yr, and hence fully cover the inverted hierarchy region.

A search for neutrinoless $\beta\beta$ decay processes accompanied with Majoron emission has been performed using data collected during Phase I of the GERmanium Detector Array (GERDA) experiment at the Laboratori Nazionali del Gran Sasso of INFN (Italy). Processes with spectral indices n = 1, 2, 3, 7 were searched for. No signals were found and lower limits of the order of 10$^{23}$ yr on their half-lives were derived, yielding substantially improved results compared to previous experiments with $^{76}$Ge. A new result for the half-life of the neutrino-accompanied $\beta\beta$ decay of $^{76}$Ge with significantly reduced uncertainties is also given, resulting in $T^{2\nu}_{1/2} = (1.926 \pm 0.095)\cdot10^{21}$ yr.

High Purity Germanium detectors are used in many applications, from nuclear and astro-particle physics, to homeland security or environment protection. Although quite standard configurations are often used, with cryostats, charge sensitive amplifiers and analog or digital acquisition systems all commercially available, it might be the case that a few specific applications, e.g. satellites, portable devices, cryogenic physics experiments, etc. also require the development of a few additional or complementary techniques. An interesting case is for sure GERDA, the Germanium Detector Array experiment, searching for neutrino-less double beta decay of 76Ge at the Gran Sasso National Laboratory of INFN — Italy. In GERDA the entire detector array, composed of semi-coaxial and BEGe naked crystals, is operated suspended inside a cryostat filled with liquid argon, that acts not only as cooling medium and but also as an active shield, thanks to its scintillation properties. These peculiar circumstances, together with the additional requirement of a very low radioactive background from all the materials adjacent to the detectors, clearly introduce significant constraints on the design of the Ge front-end readout electronics. All the Ge readout solutions developed within the framework of the GERDA collaboration, for both Phase I and Phase II, will be briefly reviewed, with their relative strength and weakness compared together and with respect to ideal Ge readout. Finally, the digital processing techniques developed by the GERDA collaboration for energy estimation of Ge detector signals will be recalled.

The GERmanium Detector Array (GERDA) at the Gran Sasso Underground Laboratory (LNGS) searches for the neutrinoless double beta decay (0{\nu}{\beta}{\beta}) of $^{76}$Ge. Germanium detectors made of material with an enriched $^{76}$Ge fraction act simultaneously as sources and detectors for this decay. During Phase I of the experiment mainly refurbished semi-coaxial Ge detectors from former experiments were used. For the upcoming Phase II, 30 new $^{76}$Ge enriched detectors of broad energy germanium (BEGe)-type were produced. A subgroup of these detectors has already been deployed in GERDA during Phase I. The present paper reviews the complete production chain of these BEGe detectors including isotopic enrichment, purification, crystal growth and diode production. The efforts in optimizing the mass yield and in minimizing the exposure of the $^{76}$Ge enriched germanium to cosmic radiation during processing are described. Furthermore, characterization measurements in vacuum cryostats of the first subgroup of seven BEGe detectors and their long-term behavior in liquid argon are discussed. The detector performance fulfills the requirements needed for the physics goals of GERDA Phase~II.

The synthesis and antibacterial activity of oxazolidinones containing dihydro-1,2-oxazine and 2-pyrazoline ring systems are described. Linezolid analogs utilizing dihydro-1,2-oxazines as morpholine mimics were prepared utilizing a nitrosoamine/diene 4+2 cycloaddition strategy. Pyrazolidine, hexahydro-pyridazine, and 2-pyrazoline analogs more closely related to eperezolid were also prepared. The most active of these new oxazolidinones were the dihydro-1,2-oxazine 6 and the 2-pyrazoline 20 both of which had potency similar to linezolid against a panel of Gram-positive bacteria.

Cephalosporin derivatives containing a unique combination of lipophilic C-7 sidechains and polar C-3 thiopyridinium groups were synthesized and found to exhibit potent anti-MRSA activity in vitro and in vivo. The optimum C-7 sidechains utilized were 2,5-dichlorophenylthioacetamido and 2,6-dichloropyrid-4-ylthioacetamido. The C-3 thiopyridinium rings were substituted at nitrogen with amino acid and pyruvic acid groups that were designed to confer aqueous solubility as required for IV formulation. This paper describes the characteristics of these novel cephalosporins and highlights synthetic methods developed to allow their practical, large-scale syntheses.

(1999). 2-(1-AZETIDINYL)- AND 2-(1-PYRROLIDINYL)PYRIDINE via SNAr REACTIONS OF 2-FLUOROPYRIDINE AND 2-PYRIDINYL TRIFLATE. Organic Preparations and Procedures International: Vol. 31, No. 6, pp. 698-701.

A novel protocol which employs commercially available, standard tools and hardware has been developed. This protocol allows for cleavage and collection of IRORI Microkan products in 96 well plate format. Typically, 640 compounds can be cleaved in a 4 hour time period using approximately 3 square feet of space. This protocol has been used successfully for the liberation of thousands of individual compounds, in single compound per well format from the solid phase. Additionally, this protocol is the first example of making IRORI Microkan technology directly compatible with standard 96 position deep well blocks.

The fundamental signal processing techniques for HPGe detector operation, e.g. trapezoidal shaping, zero-area shaping with symmetric baseline subtraction, etc. are briefly reviewed, using both simulated signals and experimental detector waveforms. The relative advantages and disadvantages of the various weighting functions in case of different detector and preamplifier characteristics are derived and the fundamental detector waveform parameters are determined by means of general purpose signal processing techniques (e.g. auto-correlation function, Fourier transform, etc.). The DPLMS algorithm for optimum filter synthesis is finally used to derive appropriate weighting functions for energy estimation.

(1994). A cis-1,2-DIAMINE FROM THE STEREOSELECTIVE REDUCTION OF AN α-AMINO ENAMINE. Organic Preparations and Procedures International: Vol. 26, No. 1, pp. 114-118.

The residential segregation of Penalolen has declined since the early 90's. Currently there are areas of low-income housing areas with building projects of the type condominiums. This geographic closeness between families of different social classes makes this community a special place to observe new types of social relationships. This article provides empirical material about socio-territorial differentiated children and how them represents the phenomenon of urban insecurity and fear, also demonstrates how that feelings configures their urban way of live. Palabras Clave: Inseguridad urbana, representaciones sociales, segregacion residencial, ninos, Penalolen

Obtention efficace et stereoselective de 2,3-diheterotetrahydronaphtalenes par cycloaddition [4+2] d'o-quinodimethane et d'isobenzofurane avec des 1,2-diheteroethylenes en vue de la preparation d'isobenzofuranes differemment substitues et de benzocyclobutanes

A variety of trans-3,4-diaminopiperidines were synthesized regio- and stereoselectively from 1-(carbobenzyloxy)-1,2,3,6-tetrahydropyridine. These compounds are structurally related to the selective κ agonist U-50488. The two key reactions which determine the stereo- and regiochemistry of the final products involve the S N 2 ring opening of an epoxide and an aziridinium species. Reaction of secondary amines with epoxide 3 led to ca. 1.5:1 mixtures of amino alcohols 4 and 5, while S N 2 attack by methylamine on aziridinium intermediate 6 occurs diastereoselectively at C-4 to give diamines 7. Depending upon the isolation procedure, trimethylsilyl iodide cleavage of the carbobenzyloxy group in compounds 8 and 9 provides either N-benzyl compounds 12 and 13 or the unsubstituted piperidines 10 and 11

cis-Diaminotetralins 4 and 10 were converted in 4 steps to benzologs of the novel anticonvulsant U-54494. Attempted alkylation of 4 and 10 with 1,4-dibromobutane provided mixtures of the bis-pyrrolidino compounds and starting free bases together with the desired mono- pyrrolidino compounds 5 and 11. Treatment of these mixtures with ethyl chloroformate followed by Chromatographic separation gave the carbamates 7 and 12. Reduction of these carbamates with LiAlH4 provided the N-methylamino compounds 8 and 14. Finally, benzamide formation gave rise to the analogs of U-54494, compounds 9 and 15.

(1994). A cis-1,2-DIAMINE FROM THE STEREOSELECTIVE REDUCTION OF AN α-AMINO ENAMINE. Organic Preparations and Procedures International: Vol. 26, No. 1, pp. 114-118.

Ten diacids were synthesized via a simple regio- and stereoselective aldol reaction. All of these compounds were good to excellent inhibitors of 14 kDa human platelet PLA2, and many of these derivatives displayed activity in a phorbol-ester induced mouse ear edema assay. One of the new compounds reported here was selected for further development as a potential antipsoriasis agent.