What One Can Learn From the Cloud Condensation Nuclei (CCN) Size Distributions as Monitored by the BEO Moussala?

In this proceeding we report initial studies into the big data set acquired by the Cloud Condensation Nuclei (CCN) counter of the Basic Environmental Observatory (BEO) Moussala over the whole 2016 year at a frequency of 1 Hz. First, we attempt to reveal correlations between the results for CCN number concentrations on the timescale of a whole year (2016) as averaged over 12 month periods with the meteorological parameters for the same period and with the same time step. Then, we zoom into these data and repeat the study on the timescale of a month for two months from 2016, January and July, with a day time step. For the same two months we show the CCN size distributions averaged over day periods. Finally, we arrive at our main result: typical, in terms of maximal and minimal number concentrations, CCN size distributions for chosen hours, one hour for each month of the year, hence 24 distributions in total. These data show a steady pattern of peaks and valleys independent of the concrete number concentration which moves up and down the number concentrations (y-axis) without significant shifts along the sizes (x-axis).Comment: 6 pages, 4 figure, The 10th Jubilee Conference of the Balkan Physical Union (BPU10), 26-30 August, Sofia, Bulgari

ROOTING OF HAZELNUT (CORYLUS AVELLANA L.) VARIETIES HARDWOOD CUTTINGS

Intensity of rooting on hardwood hazelnut cuttings is evaluated during two consecutive years. The evaluation is conducted on 6 hazelnut varieties (Istarski, Tonda Romana, Extra Yagli, Ludolf, Hall’s Giant, Devianna) in greenhouse conditions at experimental greenhouse of Institute of Agriculture, Skopje. The cuttings are collected during dormancy of the plants, before start of vegetation. Two types of auxins IBA (indole-3-butyric acid) 2%, and NAA (α-naphthalene acetic acid) 0.2% are used. From evaluated varieties, Tonda Romana has the highest percentage of rooting (85.5%) and it is characterized with the highest value of rooted cuttings of first class. At all evaluated varieties, treatment with higher concentration of IBA gives higher percentage of rooted cuttings and higher value of rooted cuttings of first class

First results from the CERN Axion Solar Telescope (CAST)

Hypothetical axion-like particles with a two-photon interaction would be produced in the Sun by the Primakoff process. In a laboratory magnetic field (``axion helioscope'') they would be transformed into X-rays with energies of a few keV. Using a decommissioned LHC test magnet, CAST has been running for about 6 months during 2003. The first results from the analysis of these data are presented here. No signal above background was observed, implying an upper limit to the axion-photon coupling < 1.16 10^{-10} GeV^-1 at 95% CL for m_a <~0.02 eV. This limit is comparable to the limit from stellar energy-loss arguments and considerably more restrictive than any previous experiment in this axion mass range.Comment: 4 pages, accepted by PRL. Final version after the referees comment

The search for solar axions in the CAST experiment

The CAST (CERN Axion Solar Telescope) experiment at CERN searches for solar axions with energies in the keV range. It is possible that axions are produced in the core of the sun by the interaction of thermal photons with virtual photons of strong electromagnetic fields. In this experiment, the solar axions can be reconverted to photons in the transversal field of a 9 Tesla superconducting magnet. At both ends of the 10m-long dipole magnet three different X-ray detectors were installed, which are sensitive in the interesting photon energy range. Preliminary results from the analysis of the 2004 data are presented: g$_{a\gamma}<0.9\times10^{-10}$ GeV$^{-1}$ at 95% C.L. for axion masses m$_{a} <$ 0.02 eV. At the end of 2005, data started to be taken with a buffer gas in the magnet pipes in order to extend the sensitivity to axion masses up to 0.8 eV.The CAST (CERN Axion Solar Telescope) experiment at CERN searches for solar axions with energies in the keV range. It is possible that axions are produced in the core of the sun by the interaction of thermal photons with virtual photons of strong electromagnetic fields. In this experiment, the solar axions can be reconverted to photons in the transversal field of a 9 Tesla superconducting magnet. At both ends of the 10m-long dipole magnet three different X-ray detectors were installed, which are sensitive in the interesting photon energy range. Preliminary results from the analysis of the 2004 data are presented: g$_{a\gamma}<0.9\times10^{-10}$ GeV$^{-1}$ at 95% C.L. for axion masses m$_{a} <$ 0.02 eV. At the end of 2005, data started to be taken with a buffer gas in the magnet pipes in order to extend the sensitivity to axion masses up to 0.8 eV

Incidence and phenotypes of childhood-onset genetic epilepsies:a prospective population-based national cohort

Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (&gt;10 min) febrile seizures; febrile or afebrile status epilepticus (&gt;30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children’s hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9–57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26–14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93–12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24–9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07–7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy

Value of T2 Mapping MRI for Prostate Cancer Detection and Classification.

Currently, multi-parametric prostate MRI (mpMRI) consists of a qualitative T &lt;sub&gt;2&lt;/sub&gt; , diffusion weighted, and dynamic contrast enhanced imaging. Quantification of T &lt;sub&gt;2&lt;/sub&gt; imaging might further standardize PCa detection and support artificial intelligence solutions. To evaluate the value of T &lt;sub&gt;2&lt;/sub&gt; mapping to detect prostate cancer (PCa) and to differentiate PCa aggressiveness. Retrospective single center cohort study. Forty-four consecutive patients (mean age 67 years; median PSA 7.9 ng/mL) with mpMRI and verified PCa by subsequent targeted plus systematic MR/ultrasound (US)-fusion biopsy from February 2019 to December 2019. Standardized mpMRI at 3 T with an additionally acquired T &lt;sub&gt;2&lt;/sub&gt; mapping sequence. Primary endpoint was the analysis of quantitative T &lt;sub&gt;2&lt;/sub&gt; values and contrast differences/ratios (CD/CR) between PCa and benign tissue. Secondary objectives were the correlation between T &lt;sub&gt;2&lt;/sub&gt; values, ISUP grade, apparent diffusion coefficient (ADC) value, and PI-RADS, and the evaluation of thresholds for differentiating PCa and clinically significant PCa (csPCa). Mann-Whitney test, Spearman's rank (r &lt;sub&gt;s&lt;/sub&gt; ) correlation, receiver operating curves, Youden's index (J), and AUC were performed. Statistical significance was defined as P &lt; 0.05. Median quantitative T &lt;sub&gt;2&lt;/sub&gt; values were significantly lower for PCa in PZ (85 msec) and PCa in TZ (75 msec) compared to benign PZ (141 msec) or TZ (97 msec) (P &lt; 0.001). CD/CR between PCa and benign PZ (51.2/1.77), respectively TZ (19.8/1.29), differed significantly (P &lt; 0.001). The best T &lt;sub&gt;2&lt;/sub&gt; -mapping threshold for PCa/csPCa detection was for TZ 81/86 msec (J = 0.929/1.0), and for PZ 110 msec (J = 0.834/0.905). Quantitative T &lt;sub&gt;2&lt;/sub&gt; values of PCa did not correlate significantly with the ISUP grade (r &lt;sub&gt;s&lt;/sub&gt; = 0.186; P = 0.226), ADC value (r &lt;sub&gt;s&lt;/sub&gt; = 0.138; P = 0.372), or PI-RADS (r &lt;sub&gt;s&lt;/sub&gt; = 0.132; P = 0.392). Quantitative T &lt;sub&gt;2&lt;/sub&gt; values could differentiate PCa in TZ and PZ and might support standardization of mpMRI of the prostate. Different thresholds seem to apply for PZ and TZ lesions. However, in the present study quantitative T &lt;sub&gt;2&lt;/sub&gt; values were not able to indicate PCa aggressiveness. 2 TECHNICAL EFFICACY: Stage 2

Magnetic Resonance Imaging-guided Active Surveillance Without Annual Rebiopsy in Patients with Grade Group 1 or 2 Prostate Cancer: The Prospective PROMM-AS Study

Background: Multiparametric magnetic resonance imaging (mpMRI) may allow patients with prostate cancer (PC) on active surveillance (AS) to avoid repeat prostate biopsies during monitoring. Objective: To assess the ability of mpMRI to reduce guideline-mandated biopsy and to predict grade group upgrading in patients with International Society of Urological Pathology grade group (GG) 1 or GG 2 PC using Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scores. The hypothesis was that the AS disqualification rate (ASDQ) rate could be reduced to 15%. Design, setting and participants: PROMM-AS was a prospective study assessing 2-yr outcomes for an mpMRI-guided AS protocol. A 12 mo after AS inclusion on the basis of MRI/transrectal ultrasound fusion-guided biopsy (FBx), all patients underwent mpMRI. For patients with stable mpMRI (PRECISE 1–3), repeat biopsy was deferred and follow-up mpMRI was scheduled for 12 mo later. Patients with mpMRI progression (PRECISE 4–5) underwent FBx. At the end of the study, follow-up FBx was indicated for all patients. Outcome measurements and statistical analysis: We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for upgrading to GG 2 in the GG 1 group, and to GG 3 in the GG 2 group on MRI. We performed regression analyses that included clinical variables. Results and limitations: The study included 101 patients with PC (60 GG 1 and 41 GG 2). Histopathological progression occurred in 31 patients, 18 in the GG 1 group and 13 in the GG 2 group. Thus, the aim of reducing the ASDQ rate to 15% was not achieved. The sensitivity, specificity, PPV, and NPV for PRECISE scoring of MRI were 94%, 64%, 81%, and 88% in the GG 1 group, and 92%, 50%, 92%, and 50%, respectively, in the GG 2 group. On regression analysis, initial prostate-specific antigen (p < 0.001) and higher PRECISE score (4–5; p = 0.005) were significant predictors of histological progression of GG 1 PC. Higher PRECISE score (p = 0.009), initial Prostate Imaging-Reporting and Data System score (p = 0.009), previous negative biopsy (p = 0.02), and percentage Gleason pattern 4 (p = 0.04) were significant predictors of histological progression of GG 2 PC. Limitations include extensive MRI reading experience, the small sample size, and limited follow-up. Conclusions: MRI-guided monitoring of patients on AS using PRECISE scores avoided unnecessary follow-up biopsies in 88% of patients with GG 1 PC and predicted upgrading during 2-yr follow-up in both GG 1 and GG 2 PC. Patient summary: We investigated whether MRI (magnetic resonance imaging) scores can be used to guide whether patients with lower-risk prostate cancer who are on active surveillance (AS) need to undergo repeat biopsies. Follow-up biopsy was deferred for 1 year for patients with a stable score and performed for patients whose score progressed. After 24 months on AS, all men underwent MRI and biopsy. Among patients with grade group 1 cancer and a stable MRI score, 88% avoided biopsy. For patients with MRI score progression, AS termination was correctly recommended in 81% of grade group 1 and 92% of grade group 2 cases

Nanoparticles can wrap epithelial cell membranes and relocate them across the epithelial cell layer

Although the link between the inhalation of nanoparticles and cardiovascular disease is well established, the causal pathway between nanoparticle exposure and increased activity of blood coagulation factors remains unexplained. To initiate coagulation tissue factor bearing epithelial cell membranes should be exposed to blood, on the other side of the less than a micrometre thin air-blood barrier. For the inhaled nanoparticles to promote coagulation, they need to bind lung epithelial-cell membrane parts and relocate them into the blood. To assess this hypothesis, we use advanced microscopy and spectroscopy techniques to show that the nanoparticles wrap themselves with epithelial-cell membranes, leading to the membrane's disruption. The membrane-wrapped nanoparticles are then observed to freely diffuse across the damaged epithelial cell layer relocating epithelial cell membrane parts over the epithelial layer. Proteomic analysis of the protein content in the nanoparticles wraps/corona finally reveals the presence of the coagulation-initiating factors, supporting the proposed causal link between the inhalation of nanoparticles and cardiovascular disease

Mutations in the Gene DNAJC5 Cause Autosomal Dominant Kufs Disease in a Proportion of Cases: Study of the Parry Family and 8 Other Families

Background: The Neuronal Ceroid Lipofuscinoses (NCL) comprise at least nine progressive neurodegenerative genetic disorders. Kufs disease, an adult-onset form of NCL may be recessively or dominantly inherited. Our study aimed to identify genetic mutations associated with autosomal dominant Kufs disease (ADKD). Methodology and Principal Findings We have studied the family first reported with this phenotype in the 1970s, the Parry family. The proband had progressive psychiatric manifestations, seizures and cognitive decline starting in her mid 20s. Similarly affected relatives were observed in seven generations. Several of the affected individuals had post-mortem neuropathological brain study confirmatory for NCL disease. We conducted whole exome sequencing of three affected family members and identified a pLeu116del mutation in the gene DNAJC5, which segregated with the disease phenotype. An additional eight unrelated affected individuals with documented autosomal dominant or sporadic inheritance were studied. All had diagnostic confirmation with neuropathological studies of brain tissue. Among them we identified an additional individual with a p.Leu115Arg mutation in DNAJC5. In addition, a pAsn477Ser change in the neighboring gene PRPF6, a gene previously found to be associated with retinitis pigmentosa, segregated with the ADKD phenotype. Interestingly, two individuals of the Parry family did report visual impairment. Conclusions: Our study confirmed the recently reported association of DNAJC5 mutations with ADKD in two out of nine well-defined families. Sequence changes in PRPF6 have not been identified in other unrelated cases. The association of vision impairment with the expected PRPF6 dysfunction remains possible but would need further clinical studies in order to confirm the co-segregation of the visual impairment with this sequence change