A hydrogen beam to characterize the ASACUSA antihydrogen hyperfine spectrometer

The antihydrogen programme of the ASACUSA collaboration at the antiproton decelerator of CERN focuses on Rabi-type measurements of the ground-state hyperfine splitting of antihydrogen for a test of the combined Charge-Parity-Time symmetry. The spectroscopy apparatus consists of a microwave cavity to drive hyperfine transitions and a superconducting sextupole magnet for quantum state analysis via Stern-Gerlach separation. However, the small production rates of antihydrogen forestall comprehensive performance studies on the spectroscopy apparatus. For this purpose a hydrogen source and detector have been developed which in conjunction with ASACUSA's hyperfine spectroscopy equipment form a complete Rabi experiment. We report on the formation of a cooled, polarized, and time modulated beam of atomic hydrogen and its detection using a quadrupole mass spectrometer and a lock-in amplification scheme. In addition key features of ASACUSA's hyperfine spectroscopy apparatus are discussed.

Personalized Systemic Therapies in Hereditary Cancer Syndromes

Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth and survival, and may represent an ideal target for the personalized treatment of hereditary tumors. PARP inhibitors for the treatment of BRCA and PALB2-associated tumors, immune checkpoint inhibitors for tumors associated with the Lynch Syndrome, HIF-2α inhibitor in the VHL-related cancers and, finally, selective RET inhibitors for the treatment of MEN2-associated medullary thyroid cancer are the most successful examples of how a germline PVs can be exploited to develop effective personalized therapies and improve the outcome of these patients. The present review aims to describe and discuss the personalized systemic therapies for inherited cancer syndromes that have been developed and investigated in clinical trials in recent decades

A retrospective whole-genome sequencing analysis of carbapenem and colistin-resistant klebsiella pneumoniae nosocomial strains isolated during an MDR surveillance program

Multidrug-resistant Klebsiella pneumoniae (MDR Kp), in particular carbapenem-resistant Kp (CR-Kp), has become endemic in Italy, where alarming data have been reported on the spread of colistin-resistant CR-Kp (CRCR-Kp). During the period 2013–2014, 27 CRCR-Kp nosocomial strains were isolated within the Modena University Hospital Policlinico (MUHP) multidrug resistance surveillance program. We retrospectively investigated these isolates by whole-genome sequencing (WGS) analysis of the resistome, virulome, plasmid content, and core single nucleotide polymorphisms (cSNPs) in order to gain insights into their molecular epidemiology. The in silico WGS analysis of the resistome revealed the presence of genes, such as blaKPC, related to the phenotypically detected resistances to carbapenems. Concerning colistin resistance, the plasmidic genes mcr 1–9 were not detected, while known and new genetic variations in mgrB, phoQ, and pmrB were found. The virulome profile revealed the presence of type-3 fimbriae, capsular polysaccharide, and iron acquisition system genes. The detected plasmid replicons were classified as IncFIB(pQil), IncFIB(K), ColRNAI, IncX3, and IncFII(K) types. The cSNPs genotyping was consistent with the multi locus sequence typing (MLST) and with the distribution of mutations related to colistin resistance genes. In a nosocomial drug resistance surveillance program, WGS proved to be a useful tool for elucidating the spread dynamics of CRCR-Kp nosocomial strains and could help to limit their diffusion

New plasmid calibrators for geminivirus-resistant (EMB-PV051-1 event) common bean (Phaseolus vulgaris L.) quantitation using simplex and duplex qPCR.

The geminivirus-resistant common bean, Embrapa 5.1, was the first commercial genetically modified (GM) event developed in Latin America by the Brazilian Agricultural Research Corp.. Therein novel standard reference plasmids were constructed for species-specific (pLEC) and event-specific (pFGM) qualitative and quantitative detection of Embrapa 5.1 GM common bean. To establish these plasmids as certified reference materials (CRM) for Embrapa 5.1 GM common bean, two DNA extraction protocols, simplex and duplex qPCR using two different operators (experimenters) were tested. The efficiency values ranged from 92% to 110% for the simplex and duplex reactions considering both operators. The limit of detection was enough to detect at least 0.1% GM content. These plasmids are suitable to be used as CRM for Embrapa 5.1 GM common bean. They will be useful for survey of food labels for compliance with legislation about GMO content in Brazil and in other countries where GM common bean is not yet approved for commercialization

Exercise training improves vascular function in patients with Alzheimer’s disease

Purpose: Vascular dysfunction has been demonstrated in patients with Alzheimer’s disease (AD). Exercise is known to positively affect vascular function. Thus, the aim of our study was to investigate exercise-induced effects on vascular function in AD. Methods: Thirty-nine patients with AD (79 ± 8 years) were recruited and randomly assigned to exercise training (EX, n = 20) or control group (CTRL, n = 19). All subjects performed 72 treatment sessions (90 min, 3 t/w). EX included moderate–high-intensity aerobic and strength training. CTRL included cognitive stimuli (visual, verbal, auditive). Before and after the 6-month treatment, the vascular function was measured by passive-leg movement test (PLM, calculating the variation in blood flow: ∆peak; and area under the curve: AUC) tests, and flow-mediated dilation (FMD, %). A blood sample was analyzed for vascular endothelial growth factor (VEGF). Arterial blood flow (BF) and shear rate (SR) were measured during EX and CTRL during a typical treatment session. Results: EX group has increased FMD% (+ 3.725%, p ' 0.001), PLM ∆peak (+ 99.056 ml/min, p = 0.004), AUC (+ 37.359AU, p = 0.037) and VEGF (+ 8.825 pg/ml, p = 0.004). In the CTRL group, no difference between pre- and post-treatment was found for any variable. Increase in BF and SR was demonstrated during EX (BF + 123%, p ' 0.05; SR + 134%, p ' 0.05), but not during CTRL treatment. Conclusion: Exercise training improves peripheral vascular function in AD. These ameliorations may be due to the repetitive increase in SR during exercise which triggers NO and VEGF upregulation. This approach might be included in standard AD clinical practice as an effective strategy to treat vascular dysfunction in this population

Epidemiology and complications of late-onset sepsis: An Italian area-based study

Background Most studies regarding late-onset sepsis (LOS) address selected populations (i.e., neonates with low birth weight or extremely preterm neonates). Studying all age groups is more suitable to assess the burden of single pathogens and their clinical relevance. Methods This is a retrospective regional study involving paediatric departments and NICUs in Emilia-Romagna (Italy). Regional laboratory databases were searched from 2009 to 2012. Records of infants (aged 4 to 90 days) with a positive blood or cerebrospinal fluid (CSF) culture were retrospectively reviewed and analysed according to acquisition mode (whether hospital- or community-acquired). Results During the study period, there were 146,682 live births (LBs), with 296 patients experiencing 331 episodes of LOS (incidence rate: 2.3/1000 LBs). Brain lesions upon discharge from the hospital were found in 12.3% (40/296) of cases, with death occurring in 7.1% (23/296; 0.14/ 1000 LBs). With respect to full-term neonates, extremely preterm or extremely low birth weight neonates had very high risk of LOS and related mortality (> 100- and > 800-fold higher respectively). Hospital-acquired LOS (n = 209) was significantly associated with very low birth weight, extremely preterm birth, pneumonia, mechanical ventilation, and death (p< 0.01). At multivariate logistic regression analysis, catecholamine support (OR = 3.2), central venous line before LOS (OR = 14.9), and meningitis (OR = 44.7) were associated with brain lesions or death in hospital-acquired LOS (area under the ROC curve 0.81, H-L p = 0.41). Commonly identified pathogens included coagulase-negative staphylococci (CoNS n = 71, 21.4%), Escherichia coli (n = 50, 15.1%), Staphylococcus aureus (n = 41, 12.4%) and Enterobacteriaceae (n = 41, 12.4%). Group B streptococcus was the predominant cause of meningitis (16 of 38 cases, 42%). Most pathogens were sensitive to first line antibiotics. Conclusions This study provides the first Italian data regarding late-onset sepsis (LOS) in all gestational age groups. Compared to full-term neonates, very high rates of LOS and mortality occurred in neonates with a lower birth weight and gestational age. Group B streptococcus was the leading cause of meningitis. Excluding CoNS, the predominant pathogens were Escherichia coli and Staphylococcus aureus. Neonates with hospital-acquired LOS had a worse outcome. Antibiotic associations, recommended for empirical treatment of hospital- or community-acquired LOS, were adequate

Monte-Carlo based performance assessment of ASACUSA's antihydrogen detector

An antihydrogen detector consisting of a thin BGO disk and a surrounding plastic scintillator hodoscope has been developed. We have characterized the two-dimensional positions sensitivity of the thin BGO disk and energy deposition into the BGO was calibrated using cosmic rays by comparing experimental data with Monte-Carlo simulations. The particle tracks were defined by connecting BGO hit positions and hits on the surrounding hodoscope scintillator bars. The event rate was investigated as a function of the angles between the tracks and the energy deposition in the BGO for simulated antiproton events, and for measured and simulated cosmic ray events. Identification of the antihydrogen Monte Carlo events was performed using the energy deposited in the BGO and the particle tracks. The cosmic ray background was limited to 12 mHz with a detection efficiency of 81 %. The signal-to-noise ratio was improved from 0.22 s^{-1/2} obtained with the detector in 2012 to 0.26 s^{-1/2} in this work

Electromechanical delay components during skeletal muscle contraction and relaxation in patients with myotonic dystrophy type 1

The electromechanical delay during muscle contraction and relaxation can be partitioned into mainly electrochemical and mainly mechanical components by an EMG, mechanomyographic, and force combined approach. Components duration and measurements reliability were investigated during contraction and relaxation in a group of patients with myotonic dystrophy type 1 (DM1, n=13) and in healthy controls (n=13). EMG, mechanomyogram, and force were recorded in DM1 and in age- and body-matched controls from tibialis anterior (distal muscle) and vastus lateralis (proximal muscle) muscles during maximum voluntary and electrically-evoked isometric contractions. The electrochemical and mechanical components of the electromechanical delay during muscle contraction and relaxation were calculated off-line. Maximum strength was significantly lower in DM1 than in controls under both experimental conditions. All electrochemical and mechanical components were significantly longer in DM1 in both muscles. Measurements reliability was very high in both DM1 and controls. The high reliability of the measurements and the differences between DM1 patients and controls suggest that the EMG, mechanomyographic, and force combined approach could be utilized as a valid tool to assess the level of neuromuscular dysfunction in this pathology, and to follow the efficacy of pharmacological or non-pharmacological interventions

A method for successful collection of multicores and gravity cores from Antarctic subglacial lakes

During the 2018–2019 Antarctic field season, the Subglacial Antarctic Lakes Scientific Access project team cleanly accessed Mercer Subglacial Lake, West Antarctica, to sample water and sediments beneath 1087 m of overlying ice. A multicorer was successful in sampling the sediment–water interface, with 4 deployments retrieving 10 cores between 0.3 and 0.4 m in length. Gravity coring was also successful, retrieving cores of 0.97 and 1.78 m in glacial diamict. However, sediment cores retrieved by the gravity cores were shorter than the core barrel penetration (as measured by mud streaks on the outside of the coring system), indicating that the system can likely be improved. This manuscript describes the design, implementation, successes, and lessons learned while coring sediments in a subglacial lake

Measurements of the reaction pˉp→ϕη\bar{p}p \to \phi \eta of antiproton annihilation at rest at three hydrogen target densities

The proton-antiproton annihilation at rest into the $\phi\eta$ final state was measured for three different target densities: liquid hydrogen, gaseous hydrogen at NTP and at a low pressure of 5 mbar. The yield of this reaction in the liquid hydrogen target is smaller than in the low-pressure gas target. The branching ratios of the $\phi\eta$ channel were calculated on the basis of simultaneous analysis of the three data samples. The branching ratio for annihilation into $\phi\eta$ from the $^3S_1$ protonium state turns out to be about ten times smaller as compared to the one from the $^1P_1$ state.Comment: 10 pages, 3 Postscript figures. Accepted by Physics Letters