Ultra-pure NaI(Tl) crystals are the key element for a model-independent verification of the long standing DAMA result and a powerful means to search for the annual modulation signature of dark matter ...interactions. The SABRE collaboration has been developing cutting-edge techniques for the reduction of intrinsic backgrounds over several years. In this paper we report the first characterization of a 3.4 kg crystal, named NaI-33, performed in an underground passive shielding setup at LNGS. NaI-33 has a record low
39
K contamination of 4.3 ± 0.2 ppb as determined by mass spectrometry. We measured a light yield of 11.1 ± 0.2 photoelectrons/keV and an energy resolution of 13.2% (FWHM/E) at 59.5 keV. We evaluated the activities of
226
Ra and
228
Th inside the crystal to be
5.9
±
0.6
μ
Bq/kg and
1.6
±
0.3
μ
Bq/kg, respectively, which would indicate a contamination from
238
U and
232
Th at part-per-trillion level. We measured an activity of 0.51 ± 0.02 mBq/kg due to
210
Pb out of equilibrium and a
α
quenching factor of 0.63 ± 0.01 at 5304 keV. We illustrate the analyses techniques developed to reject electronic noise in the lower part of the energy spectrum. A cut-based strategy and a multivariate approach indicated a rate, attributed to the intrinsic radioactivity of the crystal, of
∼
1 count/day/kg/keV in the 5–20 keV region.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Treatment of moderate‐to‐severe atopic dermatitis (AD) in the elderly may be challenging, due to side‐effects of traditional anti‐inflammatory drugs and to comorbidities often found in ...this age group. Furthermore, efficacy and safety of innovative drugs such as dupilumab are not yet well known.
Objectives
A multicentre retrospective, observational, real‐life study on the efficacy and safety of dupilumab was conducted in a group of patients aged ≥65 years and affected by severe AD. Their main clinical features were also examined.
Methods
Data of elderly patients with severe (EASI ≥24) AD treated with dupilumab at label dosage for 16 weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P‐NRS, S‐NRS and DLQI) scores at baseline and after 16 weeks of treatment.
Results
Two hundred and seventy‐six patients were enrolled in the study. They represented 11.37% of all patients with severe AD. Flexural eczema was the most frequent clinical phenotype, followed by prurigo nodularis. The coexistence of more than one phenotype was found in 63/276 (22.82%) subjects. Data on the 16‐week treatment with dupilumab were available for 253 (91.67%) patients. Efficacy of dupilumab was demonstrated by a significant reduction of all the scores. No statistically significant difference regarding efficacy was found in elderly patients when compared to the group of our AD patients aged 18–64 years, treated with dupilumab over the same period. Furthermore, only 18 (6.52%) patients discontinued the drug due to inefficacy. Sixty‐one (22.51%) patients reported adverse events, conjunctivitis and flushing being the most frequent. One (0.36%) patient only discontinued dupilumab due to an adverse event.
Conclusions
Therapy with dupilumab led to a significant improvement of AD over a 16‐week treatment period, with a good safety profile. Therefore, dupilumab could be considered as an efficacious and safe treatment for AD also in the elderly.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Cadmium, polyamines and SNP elevated endogenous NO contents and reduced root growth rates. The NO-trapping agent cPTIO considerably reverted root growth inhibition confirming that NO was, at least in ...part, responsible for this inhibition. However, other ROS might also be involved in Cd and Spm phytotoxicity.
To further explore the biochemical basis of Cd toxicity in developing wheat seedlings, we studied the possible role of nitric oxide (NO) and polyamines as signaling molecules involved in metal-induced root growth inhibition. When used at 0.1
mM, sodium nitroprusside, a NO-releasing compound, inhibited root growth to a similar extent as Cd and enhanced the polyamine contents as Cd also did. Putrescine and spermidine treatments caused significant decreases in root growth with spermine giving the greatest level of inhibition (77% reduction). The simultaneous addition of Cd and inhibitors of putrescine biosynthesis (DFMA and DFMO) prevented increases in putrescine levels but did not restore normal root growth. NO content, as evidenced by the fluorescent probe DAF-FM diacetate, was found to be significantly increased in the roots of both Cd and polyamine treated plants, especially in those exposed to spermine. The effect was specific for NO since the NO scavenger cPTIO almost suppressed the fluorescent signal. Concerning the oxidative status of the root system, only Cd and spermine enhanced lipid peroxidation in roots. At the same time, all treatments led to a significant increase in levels of the non-enzymatic antioxidant defense glutathione. Our results strongly suggest that Cd and spermine treatments induce NO formation in wheat roots which, in turn, is involved in root growth inhibition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We present new results on the radiopurity of a 3.4-kg NaI(Tl) crystal scintillator operated in the SABRE proof-of-principle detector setup. The amount of potassium contamination, determined by the ...direct counting of radioactive 40K, is found to be 2.2 ± 1.5 ppb , lowest ever achieved for NaI(Tl) crystals. With the active veto, the average background rate in the crystal in the 1–6 keV energy region of interest (ROI) is 1.20 ± 0.05 counts / day / kg / keV , which is a breakthrough since the DAMA/LIBRA experiment. Our background model indicates that the rate is dominated by 210Pb and that about half of this contamination is located in the polytetrafluoroethylene reflector. We discuss ongoing developments of the crystal manufacture aimed at the further reduction of the background, including data from purification by zone refining. A projected background rate lower than ∼ 0.2 counts / day / kg / keV in the ROI is within reach. These results represent a benchmark for the development of next-generation NaI(Tl) detector arrays for the direct detection of dark matter particles.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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To find and to test the therapeutic effectiveness (and the limited adverse effects) of a new drug is a long and expensive process. It has been estimated a period of ten years and an ...expense of the order of one billion USD are required. Meanwhile, even if a promising molecule has been identified, there is the need for operative methods for its delivery. The extreme case is given by gene therapy, in which molecules with tremendous in-vitro efficacy cannot be used in practice because of the lack in useful vector systems to deliver them. Most of the recent efforts in pharmaceutical sciences are focused on the development of novel drug delivery systems (DDSs).
In this review, the work done recently on the development and testing of novel DDSs, with particular emphasis on the results obtained by European research, is summarized. In the first section of the review the DDSs are analyzed accordingly with their scale-size: starting from nano-scale (liposomes, nanoparticles), up to the micro-scale (microparticles), until the macroscopic world is reached (granules, matrix systems). In the following two sections, non-conventional testing methods (mechanical methods and bio-relevant dissolution methods) are presented; at last, the importance of mathematical modeling to describe drug release and related phenomena is reported.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Marianecci C, Rinaldi F, Di Marzio L, et al. Int J Nanomedicine. 2014;9(1):635–651. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns ...were raised regarding the alleged duplication of TEM images in Figure 1. Specifically, * Figure 1A, F1, appears to have been duplicated with the same image for Figure 1C, F3 and Figure 1D, F3AG. The authors did respond to our queries but were unable to explain how the duplication of images occurred, nor were they able to provide the original TEM images from the reported study. The decision was made to retract the article and the authors were notified of this. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper
Summary
Background
Hidradenitis suppurativa (HS), also referred to as acne inversa, is a debilitating skin disease characterized by inflammatory nodules, chronic abscesses and tunnels (fistulae and ...sinuses). The association with pilonidal sinus disease (PSD) is frequently reported but not well documented.
Objectives
To determine the prevalence and characteristics of inflammatory skin lesions located in the intergluteal fold (IGF) of patients with HS.
Methods
This was an international multicentre retrospective cross‐sectional study based on data collection from a large cohort of patients with HS with and without histopathology.
Results From a total of 2465 patients with HS included in the study, 661 (27%) reported lesions in the IGF. These patients were significantly more often smokers and had more severe HS. Of the 238 patients with an available clinical diagnosis, intergluteal‐HS (IG‐HS) was diagnosed in 52 patients (22%) and PSD was diagnosed in 186 patients (78%). IG‐HS was associated with the localization of HS in the proximity of the IGF, including the buttocks, genitals and the anus. There was a possibility of misclassification bias in this study as a clinical/image‐based diagnosis or histopathology of the IGF lesions was not always available.
Conclusions
The high prevalence of PSD suggests a strong link between both entities. Therefore, it may be useful to identify common pathophysiological mechanisms and develop common therapeutic strategies.
What's already known about this topic?
The occurrence of pilonidal sinus disease has not been clearly reported among patients with hidradenitis suppurativa/acne inversa.
What does this study add?
This is the first study that investigated the prevalence of pilonidal sinus disease among a large cohort of patients and identified the patient characteristics.
Risk factors that might help to improve the management of patients were identified.
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Linked Comment: Frew and Navrazhina. Br J Dermatol 2019; 181:1121.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Primary cutaneous follicle center lymphoma (PCFCL) is a rare low-grade cutaneous B-cell lymphoma. Clinically, PCFCL is usually an erythematous subcutaneous nodule or an infiltrated plaque. The ...dermoscopy is non-specific and it is characterized by polymorphous vascular pattern, arborizing vessels over a salmon-colored background and white areas. We reported a case of a 36-year-old woman presented with a rapidly growing, flashed-color, exophytic, soft consistency nodule on her scalp. Dermoscopy showed a diffuse structureless, skin-color area associated with a rare arborizing vascular pattern and brown circles. We reported a peculiar clinical and dermoscopic variant. This clinical presentation of PCFCL is unusual and represents a pitfall in the early clinical diagnosis. Histopathology is mandatory for a correct diagnosis.
Parkinson’s Disease is a neurological condition distinguished by characteristic motor symptoms including tremor and slowness of movement. To enable the frequent assessment of PD patients, this paper ...introduces the cloudUPDRS app, a Class I medical device that is an active transient non-invasive instrument, certified by the Medicines and Healthcare products Regulatory Agency in the UK. The app follows closely Part III of the Unified Parkinson’s Disease Rating Scale which is the most commonly used protocol in the clinical study of PD; can be used by patients and their carers at home or in the community unsupervised; and, requires the user to perform a sequence of iterated movements which are recorded by the phone sensors. The cloudUPDRS system addresses two key challenges towards meeting essential consistency and efficiency requirements, namely: (i) How to ensure high-quality data collection especially considering the unsupervised nature of the test, in particular, how to achieve firm user adherence to the prescribed movements; and (ii) How to reduce test duration from approximately 25 min typically required by an experienced patient, to below 4 min, a threshold identified as critical to obtain significant improvements in clinical compliance. To address the former, we combine a bespoke design of the user experience tailored so as to constrain context, with a deep learning approach based on Recurrent Convolutional Neural Networks, to identify failures to follow the movement protocol. We address the latter by developing a machine learning approach to personalize assessments by selecting those elements of the test that most closely match individual symptom profiles and thus offer the highest inferential power, hence closely estimating the patent’s overall score.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We report on the characterization of the response of windowless silicon avalanche photo-diodes to electrons in the 90-900 eV energy range. The electrons were provided by a monoenergetic electron gun ...present in the LASEC laboratories of University of Roma Tre. We find that the avalanche photo-diode generates a current proportional to the current of electrons hitting its active surface. The gain is found to depend on the electron energy Ee, and varies from 2.147±0.027 (for Ee=90 eV) to 385.8±3.3 (for Ee=900 eV), when operating the diode at a bias of Vapd=350 V. This is the first time silicon avalanche photo-diodes are employed to measure electrons with Ee<1 keV.
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