A Multi-variate Discrimination Technique Based on Range-Searching

We present a fast and transparent multi-variate event classification technique, called PDE-RS, which is based on sampling the signal and background densities in a multi-dimensional phase space using range-searching. The employed algorithm is presented in detail and its behaviour is studied with simple toy examples representing basic patterns of problems often encountered in High Energy Physics data analyses. In addition an example relevant for the search for instanton-induced processes in deep-inelastic scattering at HERA is discussed. For all studied examples, the new presented method performs as good as artificial Neural Networks and has furthermore the advantage to need less computation time. This allows to carefully select the best combination of observables which optimally separate the signal and background and for which the simulations describe the data best. Moreover, the systematic and statistical uncertainties can be easily evaluated. The method is therefore a powerful tool to find a small number of signal events in the large data samples expected at future particle colliders.Comment: Submitted to NIM, 18 pages, 8 figure

Overview of T and D-T results in JET with ITER-like wall

In 2021 JET exploited its unique capabilities to operate with T and D–T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D–T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements—new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14 MeV neutron yield monitors—as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D–T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D–T plasmas to date and expanding our understanding of isotopes and D–T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D–T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D–T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in (Litaudon et al Nucl. Fusion accepted), while JET experience on T and D–T operations is presented in (King et al Nucl. Fusion submitted)

The ultrasonographic appearance of renal medullary striations and their association with renal disease and renal histopathology in domestic cats.

Medullary striations (MS) have been anecdotally observed on ultrasound of feline kidneys; however, their significance is unknown. Aims of this retrospective, case control, pilot study were to describe the appearance, prevalence, and clinicopathological correlates of MS in a referral feline population. Still images from 1247 feline abdominal ultrasound studies performed between 2011 and 2021 were reviewed. Cats with MS were identified and compared with age-matched controls. Serum urea, creatinine, calcium, phosphate, and calcium-phosphate-product, plus urine specific gravity, urine protein: creatinine ratio (UPC), prevalence of active sediment (defined as > 5 red (RBC) or white blood cells (WBC) per high-power field) and prevalence of positive urine culture were compared between MS and control groups using the Mann-Whitney U test or Fisher's Exact test. Data are presented as median [range]. 27 cats were identified as having MS, giving a prevalence of 2.2% with a significantly higher proportion being seen in males (P = 0.018). Medullary striation cats had significantly higher UPC values than controls (0.46 [0.16-7.57] vs. 0.16 [0.07-2.27]; P = 0.006). Cats with MS were more likely to have active urinary sediments (39% vs 8%, P = 0.023), but no difference in prevalence of positive urinary cultures was observed between groups. There was no significant difference in other parameters between MS and control cats. Renal histopathology performed in three MS cats revealed focal regions of linear medullary fibrosis. Medullary striations are associated with proteinuria and urinary tract inflammation in cats, which may reflect renal tubular dysfunction and/or inflammation. Hence identification might allow for earlier detection of renal pathology

The ultrasonographic appearance of renal medullary striations and their association with renal disease and renal histopathology in domestic cats.

Medullary striations (MS) have been anecdotally observed on ultrasound of feline kidneys; however, their significance is unknown. Aims of this retrospective, case control, pilot study were to describe the appearance, prevalence, and clinicopathological correlates of MS in a referral feline population. Still images from 1247 feline abdominal ultrasound studies performed between 2011 and 2021 were reviewed. Cats with MS were identified and compared with age-matched controls. Serum urea, creatinine, calcium, phosphate, and calcium-phosphate-product, plus urine specific gravity, urine protein: creatinine ratio (UPC), prevalence of active sediment (defined as > 5 red (RBC) or white blood cells (WBC) per high-power field) and prevalence of positive urine culture were compared between MS and control groups using the Mann-Whitney U test or Fisher's Exact test. Data are presented as median [range]. 27 cats were identified as having MS, giving a prevalence of 2.2% with a significantly higher proportion being seen in males (P = 0.018). Medullary striation cats had significantly higher UPC values than controls (0.46 [0.16-7.57] vs. 0.16 [0.07-2.27]; P = 0.006). Cats with MS were more likely to have active urinary sediments (39% vs 8%, P = 0.023), but no difference in prevalence of positive urinary cultures was observed between groups. There was no significant difference in other parameters between MS and control cats. Renal histopathology performed in three MS cats revealed focal regions of linear medullary fibrosis. Medullary striations are associated with proteinuria and urinary tract inflammation in cats, which may reflect renal tubular dysfunction and/or inflammation. Hence identification might allow for earlier detection of renal pathology

Facilitation by 8-OH-DPAT of passive avoidance performance in rats after inactivation of 5-HT(1A) receptors

1. Pretraining administration of 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT 0.1 mg kg(−1)), a 5-HT(1A) receptor agonist, or buspirone (1 mg kg(−1)), a 5-HT(1A) receptor partial agonist, markedly impaired passive avoidance retention in rats 24 h later. The effect of 8-OH-DPAT was prevented by the 5-HT(1A) receptor antagonists, NAN-190 and WAY-100635, at doses without any intrinsic effect. 2. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ 10 mg kg(−1)), an alkylating agent that inactivates different G-protein coupled receptors, impaired retention performance when given 48 h pretraining. The disruptive effect of EEDQ was reversed by 8-OH-DPAT or buspirone, given 30 min before training. 3. Non-specific actions did not account for 8-OH-DPAT-induced reversal of the EEDQ effect since no significant difference in locomotor activity or in pain threshold was found between rats receiving EEDQ or EEDQ+8-OH-DPAT. 4. When NAN-190 (1 mg kg(−1)) or WAY-100635 (0.5 mg kg(−1)) were given before 8-OH-DPAT to EEDQ-pretreated animals, the reversal by 8-OH-DPAT of EEDQ-induced retention impairment was still more pronounced. However, no EEDQ reversal by 8-OH-DPAT was found when 5-HT(1A) receptors were protected by WAY-100635 (10 mg kg(−1)) 30 min before EEDQ. 5. In the hippocampus of EEDQ-treated rats, 5-HT(7) receptors were less inactivated than 5-HT(1A) receptors and significant increases were found in 5-HT(1A) but not in 5-HT(7) receptor mRNA levels. Ritanserin and methiothepin (10 mg kg(−1) each), antagonists with higher affinity at 5-HT(7) than at 5-HT(1A) receptors, prevented the retention impairment induced by EEDQ but did not significantly protect against 5-HT(7) receptor inactivation. 6. The results indicate that the facilitatory effect of 8-OH-DPAT is not mediated through 5-HT(1A) receptors and suggest that other 8-OH-DPAT-sensitive receptors could be involved in the dual effect of 8-OH-DPAT on passive avoidance performance in rats

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease