Monitoring of microdisplacements in Golyamata Tsepnatina cave, Madara plateau, NE Bulgaria

The only early medieval rock bas-relief in Europe Madara Horseman is included in UNESCO World Heritage List. This article presents the results from an in situ monitoring of microdisplacements across fissure forming the Golyamata Tsepnatina Cave located at the edge of Madara Plateau above the Horseman, NE Bulgaria. Additionally, we studied movements along cracks behind the plateau edge, which are related to the dynamics of peripheral plateau parts and shaped the rock slices. Monitoring involves the use of a 3D extensometer model TM-71 installed in the cave as well as five sets of pin marks installed across the cracks behind the plateau edge. The results obtained since 1990 indicate formation of a new rock slice from the cliff due to the gravitational extension of rock massif. The established horizontal microdisplacements of the rock slice to SSE imply the existence of a possible active fault with left-lateral component of movements at the base of the plateau. We established influences from near and distant earthquakes with epicenters in NE Bulgaria (Provadia), Romania (Vrancea), and Turkey (Izmit). The graphs of established movements mark continuously ongoing process of shear processes along the slice forming cracks.Key words: rock deformations, seismic effects, monitoring, microdisplacements, Madara Plateau, Bulgaria.Spremljanje mikropremikov v jami Goljamata Cepnatina, Visoka planota Madara, SV BolgarijaEdini zgodnjesrednjeveški skalni relief v Evropi, Madarski konjenik, je vključen v Unescovo svetovno dediščino. Ta prispevek obravnava rezultate in situ meritev mikropremikov v razpoki, v kateri je oblikovana jama Goljamata cepnatina, ki se nahaja na robu visoke planote Madara nad Madarskim konjenikom v SV Bolgariji. Dodatno smo proučevali tudi premike razpok za robom visoke planote, ki so odvisni od dinamike robnih delov visoke planote in oblikujejo kamninske bloke. Monitoring vključuje uporabo 3D-ekstenzometra model TM-71, ki je nameščen v jami. Dodatno vključuje tudi pet merilnikov premikov, ki so nameščeni v razpokah za robom visoke planote. Rezultati, ki smo jih pridobili od leta 1990, kažejo nastajanje novih kamninskih blokov iz klifa zaradi gravitacijskega razpiranja kamninske mase. Ugotovljeni vodoravni mikropremiki kamninskih blokov v smeri proti JJV, kažejo, da je možen aktiven prelom z levo-zmično komponento v podlagi visoke planote. Ugotovili smo vplive bližnjih in oddaljenih potresov z epicentri v SV Bolgariji (Provadija), Romuniji (Vrancea) in Turčiji (Izmit). Grafi ugotovljenih premikov kažejo dolgotrajne strižne procese vzdolž kamninskih blokov, ki oblikujejo razpoke.Ključne besede: deformacije kamnin, seizmični učinki, monitoring, mikropremiki, Madara visoka planota, Bolgarija.

Serological and Molecular Detection of Coxiella Burnetii in Clinical Samples from Veterinarians and Cattle Farm Workers from Gabrovo Region, Bulgaria

Coxiella burnetii, which causes Q fever, is a highly infectious agent that is widespread around the world.  During the last decades, the number of cases reported in Bulgaria varied from year to year. The present study aimed to determine the frequency of C. burnetii infection using ELISA and conventional PCR among freelance veterinarians and cattle farm workers in Gabrovo province, Bulgaria. In the period April 2020 to June, 2021 a total of 154 blood samples of target group was tested in the National Reference Laboratory of Cell cultures, rickettsia and oncogenic viruses (NRL CCROV) at NCIPD - Sofia. Diagnosis of C. burnetii was performed by indirect enzyme-linked immunosorbent assay ELISA (anti-Coxiella burnetii ph. II IgG/IgM) and by end-point PCR technique (to detect the sodB gene region of C. burnetii). By indirect ELISA assay of the tested 154 clinical samples, anti-C. burnetii positive ph. II IgM antibodies were registered in 37% of samples. A relatively high percentage are affected in the active age between 50-60 years old. Anti-C. burnetii positive ph. II IgG antibodies were proven at 50% of tested samples. A positive PCR signal for C. burnetii DNA was obtained at 37/154 (20% of samples) and follows the above reported trend of acute infection of active age patients. Around 10% of tested samples were positive for three C. burnetii laboratory markers. We conclude that Q fever is endemic in Bulgaria. More research is necessary in different Bulgarian regions to set the human risk groups, to diagnose acute and chronic Q fever and to determine the economic impact of Q fever in the cattle industry. In the NRL CCROV was developed diagnostic scheme including complex methods to improve early laboratory diagnosis of C. burnetii, allowing taking proper treatment of suspected with Q fever patients

Mini Review: Q Fever (Coxiellosis): Epidemiology, Pathogenesis and Current Laboratory Diagnosis

Q fever is zooantroponozis with global distribution caused by the strictly intracellular bacterium Coxiella burnetii. Causative agent of Q fever is an obligate intracellular parasite, classified in the genus Coxiella, family Coxiellaceae, class Gammaproteobacteria. The importance of the disease was assessed both in terms of human health and the serious economic damage they cause on livestock. Clinical manifestation of Q fever in humans is characterized by a wide variety - from asymptomatic infection to a chronic disease that can be fatal. Several basic methods have been developed to detection of C. burnetii. PCR and C. burnetii genomic sequences in whole blood are a sensitive and safe method of detection, with >90% sensitivity. A four-fold or greater rise of (CF) antibody (phase 2) between the paired sera is also diagnostic approach. Sensitivity of a four-fold rise in titre has been estimated as 73% ÷78% and specificity has been estimated as 90%, respectively. EIA is method with highly sensitive and specific. EIA detect IgM and then IgG antibodies which develop to phase II antigens in 10 to 14 days from symptom onset. IFA tests are of particular value for confirmation of acute infection and for diagnosis of chronic infection with high sensitivity. The technique detected IgG, IgM and IgA immunoglobulin classes. Suitable specimens for C. burnetii detection are blood samples. Although scientific interest in Q fever has always existed, a number of facts concerning the unforeseen nature of the epidemic, various clinical manifestations both in humans and in animals, the opportunities for chronic and other features of infection remain unclear. For this reason, timely and highly sensitive laboratory diagnosis is crucial for the outcome of the disease and subsequent treatment and monitoring

Pojavnost bakterije Coxiella burnetii u mliječnim stadima u pokrajini Gabrovo, Bugarska, ustanovljena serološkim i molekularnim analizama uzoraka mlijeka iz cisterni

This study investigated the occurrence of Coxiella burnetii in dairy cattle, goat herds and sheep flocks in the Gabrovo Region, central Bulgaria, to identify the potential sources of Coxiella burnetii infection diagnosed in veterinarians and farm workers in this region. To detect infection on livestock farms, we tested bulk-tank milk (BTM) for the presence of antibodies and/or the Coxiella burnetiid genome using ELISA and PCR, respectively. A total of 81 herds were tested, including 23 dairy cattle herds, 43 sheep herds, 9 goat flocks, and 6 mixed flocks (sheep and goats). By ELISA, antibodies against Coxiella burnetii were detected in 30.4% of the BTM tested samples from cattle farms, 60.4% of the sheep farms, and 11.1% of the goat BTM samples. The results were inconclusive in 6.98% of the tested sheep milk samples and 11.1% of the goat milk samples. There was a statistically significant correlation between the herd size and the ELISA S/P % values on the dairy cattle farms. Excretion of the pathogen in milk was detected by PCR in 9 out of 67 BTM samples, including 5 out of 19 cattle BTM samples, 3 out of 39 sheep BTM samples and 1 out of 5 goat BTM ones. The results indicate that C. burnetii infection is widely prevalent in the region, which calls for adequate control and prophylactic measures to reduce the health risks from the transmission of this zoonosis to humans.U ovom je radu istraživana pojavnost bakterije Coxiella burnetii u stadima mliječnih krava, koza i ovaca u pokrajini Gabrovo, središnja Bugarska. Rezultati bi trebali pomoći pri otkrivanju potencijalnih izvora zaraze navedenom bakterijom u veterinara i poljoprivrednih radnika u tom području. Kako bi se otkrila infekcija na stočnim farmama, mlijeko iz velikih spremnika (BTM) testirano je na prisutnost protutijela i/ili genoma bakterije Coxiella burnetii primjenom testa ELISA i PCR-om. Testirano je ukupno 81 stado, uključujući 23 stada mliječnih krava, 43 stada ovaca, 9 stada koza i 6 mješovitih stada (ovce i koze). Testom ELISA otkrivena su protutijela na bakteriju Coxiella burnetii u 30,4% uzoraka iz BTM-a s farmi krava, 60,4% s farmi ovaca i 11,1% uzoraka BTM-a s farmi koza. Pouzdani zaključci nisu mogli biti doneseni u slučaju 6,98% uzoraka mlijeka ovaca i 11,1% uzoraka mlijeka koza. Uočena je statistički znakovita korelacija između veličine stada i postotne vrijednosti ELISA S/P u mliječnih krava. Izlučivanje patogena u mlijeko otkriveno je PCR-om u 9 od 67 uzoraka BTM-a, uključujući 5 od 19 uzoraka mlijeka krava, 3 od 39 uzoraka mlijeka ovaca i 1 od 5 uzoraka mlijeka koza. Rezultati su pokazali da je infekcija bakterijom C. burnetii široko rasprostranjena u pokrajini Gabrovo, što zahtijeva odgovarajuće mjere kontrole i profilakse kako bi se smanjili zdravstveni rizici od prijenosa ovog zoonotskog uzročnika na ljude

Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy The SCARLET Randomized Clinical Trial

Importance: Previous research suggested that soluble human recombinant thrombomodulin may reduce mortality among patients with sepsis-associated coagulopathy. Objective: To determine the effect of human recombinant thrombomodulin vs placebo on 28-day all-cause mortality among patients with sepsis-associated coagulopathy. Design, Setting, and Participants: The SCARLET trial was a randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 study conducted in intensive care units at 159 sites in 26 countries. All adult patients admitted to one of the participating intensive care units between October 2012 and March 2018 with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure, defined as an international normalized ratio greater than 1.40 without other known etiology and a platelet count in the range of 30 to 150 × 10 9/L or a greater than 30% decrease in platelet count within 24 hours, were considered for inclusion. The final date of follow-up was February 28, 2019. Interventions: Patients with sepsis-associated coagulopathy were randomized and treated with an intravenous bolus or a 15-minute infusion of thrombomodulin (0.06 mg/kg/d [maximum, 6 mg/d]; n = 395) or matching placebo (n = 405) once daily for 6 days. Main Outcome and Measures: The primary end point was 28-day all-cause mortality. Results: Among 816 randomized patients, 800 (mean age, 60.7 years; 437 [54.6%] men) completed the study and were included in the full analysis set. In these patients, the 28-day all-cause mortality rate was not statistically significantly different between the thrombomodulin group and the placebo group (106 of 395 patients [26.8%] vs 119 of 405 patients [29.4%], respectively; P =.32). The absolute risk difference was 2.55% (95% CI, -3.68% to 8.77%). The incidence of serious major bleeding adverse events (defined as any intracranial hemorrhage; life-threatening bleeding; or bleeding event classified as serious by the investigator, with administration of at least 1440 mL [typically 6 units] of packed red blood cells over 2 consecutive days) was 23 of 396 patients (5.8%) in the thrombomodulin group and 16 of 404 (4.0%) in the placebo group. Conclusions and Relevance: Among patients with sepsis-associated coagulopathy, administration of a human recombinant thrombomodulin, compared with placebo, did not significantly reduce 28-day all-cause mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT01598831

Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy The SCARLET Randomized Clinical Trial

Importance: Previous research suggested that soluble human recombinant thrombomodulin may reduce mortality among patients with sepsis-associated coagulopathy. Objective: To determine the effect of human recombinant thrombomodulin vs placebo on 28-day all-cause mortality among patients with sepsis-associated coagulopathy. Design, Setting, and Participants: The SCARLET trial was a randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 study conducted in intensive care units at 159 sites in 26 countries. All adult patients admitted to one of the participating intensive care units between October 2012 and March 2018 with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure, defined as an international normalized ratio greater than 1.40 without other known etiology and a platelet count in the range of 30 to 150 × 10 9/L or a greater than 30% decrease in platelet count within 24 hours, were considered for inclusion. The final date of follow-up was February 28, 2019. Interventions: Patients with sepsis-associated coagulopathy were randomized and treated with an intravenous bolus or a 15-minute infusion of thrombomodulin (0.06 mg/kg/d [maximum, 6 mg/d]; n = 395) or matching placebo (n = 405) once daily for 6 days. Main Outcome and Measures: The primary end point was 28-day all-cause mortality. Results: Among 816 randomized patients, 800 (mean age, 60.7 years; 437 [54.6%] men) completed the study and were included in the full analysis set. In these patients, the 28-day all-cause mortality rate was not statistically significantly different between the thrombomodulin group and the placebo group (106 of 395 patients [26.8%] vs 119 of 405 patients [29.4%], respectively; P =.32). The absolute risk difference was 2.55% (95% CI, -3.68% to 8.77%). The incidence of serious major bleeding adverse events (defined as any intracranial hemorrhage; life-threatening bleeding; or bleeding event classified as serious by the investigator, with administration of at least 1440 mL [typically 6 units] of packed red blood cells over 2 consecutive days) was 23 of 396 patients (5.8%) in the thrombomodulin group and 16 of 404 (4.0%) in the placebo group. Conclusions and Relevance: Among patients with sepsis-associated coagulopathy, administration of a human recombinant thrombomodulin, compared with placebo, did not significantly reduce 28-day all-cause mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT01598831

Pseudorapidity densities of charged particles with transverse momentum thresholds in pp collisions at √ s = 5.02 and 13 TeV

The pseudorapidity density of charged particles with minimum transverse momentum (pT) thresholds of 0.15, 0.5, 1, and 2 GeV/c is measured in pp collisions at the center of mass energies of √s=5.02 and 13 TeV with the ALICE detector. The study is carried out for inelastic collisions with at least one primary charged particle having a pseudorapidity (η) within 0.8pT larger than the corresponding threshold. In addition, measurements without pT-thresholds are performed for inelastic and nonsingle-diffractive events as well as for inelastic events with at least one charged particle having |η|2GeV/c), highlighting the importance of such measurements for tuning event generators. The new measurements agree within uncertainties with results from the ATLAS and CMS experiments obtained at √s=13TeV.