The COSINUS (Cryogenic Observatory for SIgnatures seen in Next-generation Underground Searches) experiment aims at the detection of dark matter-induced recoils in sodium iodide (NaI) crystals ...operated as scintillating cryogenic calorimeters. The detection of both scintillation light and phonons allows performing an event-by-event signal to background discrimination, thus enhancing the sensitivity of the experiment. The choice of using NaI crystals is motivated by the goal of probing the long-standing DAMA/LIBRA results using the same target material. The construction of the experimental facility is foreseen to start by 2021 at the INFN Gran Sasso National Laboratory (LNGS) in Italy. It consists of a cryostat housing the target crystals shielded from the external radioactivity by a water tank acting, at the same time, as an active veto against cosmic ray-induced events. Taking into account both environmental radioactivity and intrinsic contamination of materials used for cryostat, shielding and infrastructure, we performed a careful background budget estimation. The goal is to evaluate the number of events that could mimic or interfere with signal detection while optimising the geometry of the experimental setup. In this paper we present the results of the detailed Monte Carlo simulations we performed, together with the final design of the setup that minimises the residual amount of background particles reaching the detector volume.
Background
Two main minimal access adrenalectomy techniques are available: laparoscopic transperitoneal (LTA) and posterior retroperitoneoscopic adrenalectomy (PRA). This study aims to compare these ...approaches in an updated meta-analysis of randomised controlled (RCT) and non-randomised comparative (NRT) trials.
Methods
A systematic search of comparative LTA and PRA studies was performed. Standard demographic and surgical data were recorded. Outcome measures compared included: operative time, estimated blood loss (EBL), conversion to open, post-operative pain, time to oral intake and ambulation, early morbidity, hospital length of stay (HLOS) and mortality. Quality of RCTs and NRTs was assessed using Cochrane and ROBINS-I, respectively, and heterogeneity using the
I
2
test. Dichotomous and continuous variables were compared using odds ratios and mean/standard difference. Studies were then combined using the Mantel–Haenszel method. Meta-analysis was performed by fixed- and random-effect models.
Results
Following exclusions, 12 studies were included in the analysis: 3 RCTs and 9 NRTs. These reported a total of 775 patients: 341 (44%) PRA and 434 (56%) LTA. Demographics were similar except for tumour size which was smaller (by 0.78 cm) in PRA (
p
= 0.003). Significant differences in outcome were seen in EBL (18 mls less in PRA,
p
= 0.006), time to oral intake (3.4 h sooner in PRA
p
= 0.009) and HLOS (shorter in PRA by 0.84 day,
p
= 0.001).
Conclusions
This analysis demonstrates that while PRA tends to be performed for smaller tumours it allows for less EBL, earlier post-operative oral intake and shorter hospital stays. In appropriately selected patients, it represents an invaluable tool in the endocrine surgeon’s armamentarium.
Aims of the study
The ability of Yersinia enterocolitica strains to form biofilms and the capacity of different alkaloids to inhibit biofilm formation were investigated.
Methods and Results
The ...capacity to form biofilm on polystyrene of 31 Y. enterocolitica strains was evaluated. Biofilm and quorum sensing (QS) inhibition of 17 alkaloids were assayed; furthermore, minimum biofilm inhibitory concentration (MBIC) was determined. The capacity to form biofilms among the examined strains seemed to be a strain‐related feature. The best biofilm inhibitors at 100 µmol l−1 were oliverine (1), guatterine (3), liriodenine (4), oliveridine (5) and pachypodanthine (6), which showed biofilm inhibition higher than 87%. Pachypodanthine (6) was the most effective compound with MBIC value of 12·5 µmol l−1 at subinhibitory concentration and also was able to inhibit QS system and reduce yenR expression at this concentration.
Conclusion
This is the first study to demonstrate that oliverine, liriodenine, and pachypodanthine are able to inhibit biofilm formation of Y. enterocolitica without critically disturbing its growing capacity. At MBIC, pachypodanthine inhibited biofilm formation and QS.
Significance and Impact of the Study
The use of aporphinoid alkaloids as biofilms inhibitory agents might potentially be useful to treat biofilm‐associated infections in the future.
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The c-MYC oncogene transcription factor has been implicated in cell cycle regulation controlling cell growth and proliferation. It is tightly regulated in normal cells, but has been ...shown to be deregulated in cancer cells, and is thus an attractive target for oncogenic therapies. Building upon previous SAR, a series of analogues containing benzimidazole core replacements were prepared and evaluated, leading to the identification of imidazopyridazine compounds that were shown to possess equivalent or improved c-MYC HTRF pEC50 values, lipophilicity, solubility, and rat pharmacokinetics. The imidazopyridazine core was therefore determined to be superior to the original benzimidazole core and a viable alternate for continued lead optimization and medicinal chemistry campaigns.
Contrast-free autofluorescence (AF) of the parathyroid glands (PTGs) and thyroid tissue occurs in the near-infrared (NIR) spectrum on excitation by light in the upper range of the visible spectrum or ...lower NIR spectrum.
, PTGs autofluoresce more brightly than thyroid (by a factor of 2-20 times) and appear as a bright spot against surrounding thyroid, muscle or fat on a processed image which is generated in real-time. NIR-AF of PTGs was first described in 2009 although NIR-AF had previously been used in several other clinical applications. Since then there has been a great amount of interest in the use of NIR-AF in thyroid and parathyroid surgery with over 25 published reports of the utilisation of both self-built and proprietary NIR-AF devices in neck endocrine surgery. All of these reports have confirmed the feasibility of NIR-AF intraoperatively and its ability to detect PTGs, although the reported accuracy varies from 90-100%. Reports of the effect of NIR-AF on relevant clinical endpoints i.e., post-operative hypoparathyroidism in thyroidectomy and persistent disease in parathyroidectomy are however scant. There has been one multicentre clinical trial of NIR-AF in thyroidectomy but this did not report clinical outcomes and two single-centre, non-randomised studies which did report post-operative hypoparathyroidism but with differing results: one showing no benefit in 106 NIR-AF
. 163 controls and one, a reduction of early hypocalcaemia from 20% to 5% in 93 NIR-AF patients
. 420 controls. There were only 2 cases of permanent hypoparathyroidism across both studies and therefore no significant observable difference in this key outcome variable. In parathyroidectomy, possible variability of the AF signal due to composition of a PTG adenoma, secondary/tertiary disease and MEN1 as well as depth-penetration preventing detection of sub-surface PTGs would imply that NIR-AF in its current form is not well-placed to improve cure-rates in hyperparathyroidism, which may already be as high as 98%. Thus far, no study has addressed this. Despite the promising results of NIR-AF, the absence of data demonstrating an improvement in outcomes and the cost of its use currently limit its use in routine clinical practice, especially in a publicly funded healthcare system with budgetary constraints. However, it can be utilised in research settings and this should be undertaken within the context of well-designed and conducted randomised, multi-centre, appropriately powered studies, which will assist in establishing its role in neck endocrine surgery.
In the quest for direct dark matter detection, innovative approaches to lower the detection threshold and explore the sub-GeV mass range, have gained high relevance in the last decade. This study ...presents the pioneering use of Gallium Arsenide (GaAs) as a low-temperature calorimeter for probing dark matter-electron interactions within the DAREDEVIL (DARk-mattEr DEVIces for Low energy detection) project. Our experimental setup features a GaAs crystal at an ultralow temperature of 15 mK, coupled with a Neutron Transmutation Doped Germanium (NTD-Ge) thermal sensor for precise energy estimation. This configuration is the first step towards detecting single electrons scattered by dark matter particles within the GaAs crystal, to improve the sensitivity to low-mass dark matter candidates significantly. Taking advantage of the production of optical phonons in polar materials such as GaAs gives the possibility to study the scattering of sub-MeV dark matter. This paper presents a detailed analysis of the detector’s response, using a calibration spectrum using
α
particles and X-ray events. While the results do not meet the ambitious eV scale threshold yet, they establish a solid benchmark for assessing the detector’s current performance and sensitivity. This work not only highlights the detector’s potential but also sets the stage for future enhancements aimed at achieving the eV threshold, underscoring the promising direction of this detector technology. These findings demonstrate the feasibility of using GaAs as a cryogenic calorimeter and hence open new avenues for investigating the elusive nature of dark matter through innovative direct detection techniques.
Recent developments of the nuclear emulsion technology led to the production of films with nanometric silver halide grains suitable to track low energy nuclear recoils with submicrometric length. ...This improvement opens the way to a directional Dark Matter detection, thus providing an innovative and complementary approach to the on-going WIMP searches. An important background source for these searches is represented by neutron-induced nuclear recoils that can mimic the WIMP signal. In this paper we provide an estimation of the contribution to this background from the intrinsic radioactive contamination of nuclear emulsions. We also report the neutron-induced background as a function of the read-out threshold, by using a GEANT4 simulation of the nuclear emulsion, showing that it amounts to about 0.06 per year per kilogram, fully compatible with the design of a 10 kg × year exposure.
Foodborne diseases have become a health issue worldwide, mainly due to the consumption of contaminated foods that are either raw, improperly heat treated or cross‐contaminated after adequate heat ...treatment foods. A group of alkaloids extracted from plants were tested to evaluate their antimicrobial effect against different strains of Yersinia enterocolitica and other foodborne bacteria. The results obtained reveal that oliveridine and pachypodanthine inhibited Y. enterocolitica growth, with MIC values of 25 μmol l−1 and 100 μmol l−1 respectively. The results indicated that both alkaloids are good growth inhibitors, but oliveridine showed greater inhibitory effect with lower MIC values. Inhibitory alkaloids can be developed as potential antimicrobials in food system to prevent or treat foodborne diseases, thus contributing to solve the global issue of contaminated food consumption.
Significance and Impact of the Study
Alkaloids are abundant secondary metabolites in plants and represent one of the most widespread class of compounds endowed with multiple and varied pharmacological properties. In this work, we propose two aporphinoid alkaloids extracted from plants as new antimicrobial agents. Oliveridine and pachypodanthine inhibited Yersinia enterocolitica growth for up to 96 h of culture. This is the first reported study of the activity of these alkaloids as antimicrobial compounds.
Significance and Impact of the Study: Alkaloids are abundant secondary metabolites in plants and represent one of the most widespread class of compounds endowed with multiple and varied pharmacological properties. In this work, we propose two aporphinoid alkaloids extracted from plants as new antimicrobial agents. Oliveridine and pachypodanthine inhibited Yersinia enterocolitica growth for up to 96 h of culture. This is the first reported study of the activity of these alkaloids as antimicrobial compounds.
The OPERA experiment at the Gran Sasso underground laboratory was designed to study νμ → ντ oscillations in appearance mode in the CNGS neutrino beam. In this paper we report the detection of the 5th ...ντ candidate event found in the analysis of an enlarged data sample. Given the number of analysed events and the low background, νμ → ντ oscillations have been established with a significance of 5.1σ. The analysis of the present electron neutrino sample in the framework of the 3 + 1 sterile model is also presented. Finally the analysis of the muon charge ratio in the cosmic ray sample is discussed.
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