Inscriptions of some historically known persons in Postojnska jama

Imenski rov (Rov starih podpisov), the Old Cave (Stara jama), was the only part of Postojnska jama known for several centuries until 1818 when Luka Čeč discovered the access to the inner parts of the cave. Here we documented ca. 400 inscriptions. About 100 more were also recorded in the historic part of Predjama Cave. From these signatures we correlated 19 with independently historically known persons, less than 5% of the total. The correlation is firm for 15 names, but only tentative for Bellegarde, Kotze, Mihanović and Karl von Zur. The oldest one is that of Johann Melchior Ott(o) of 1642, a painter in the service of Johann Anton zu Eggenberg (1610–1649) the owner of the Castle of Adelsberg at the time, whose coat of arms Ott drew as well. The next oldest is the name Josef Anton Nagel 1748 who also left Latin inscriptions in Predjama cave and in Sloup Cavern, Moravia. All other inscriptions of historic persons are younger than 1800 including those of Franz Graf von Hohenwart, Joseph Petsch Ritter von Löwengreif and Alois Schaffenrath (each with several inscriptions). Noteworthy are also the signatures of Josef Franz Eggenhöfner (1801 or 1809, and 1820; developer of Grotta di Padriciano), Johann Natterer (biologist, 1815, who stayed 19 years in Brazil and laid the basis of the zoological department of the Natural History Museum in Vienna), Karl Beyrich (1819, botanist who died during an expedition in Arkansas, 1834), Giuseppe de Volpi (1820, from Trieste who published first evidence of the cave bear presence in Postojnska jama), Johann Fercher, mine supervisor, and his team of miners from Idrija who signed during their survey of the cave in 1833, Johann Ritter von Hauer (1836 in Pisani rov, Vienna, Imperial Councelor of War and Palaeontologist), Ivan Andrej Perko (the later director of the cave) and several cave guides. Members of the nobility or state employees include Bellegard, Adrienne Brandis Desenffans and her brother Karl Graf Desenffans, Carl von Kotze, and Mihanović

Permski kras v sadri ob južnem robu gorovja Harz (Nemčija), vpliv tektonike na regionalno geologijo in kraško hidrogeologijo

The Harz Mountains in Germany are a south-tilting block of variscan-folded Devonian and Carboniferous rocks thrust over Mesozoic sediment along its northern border. Along the South Harz the overlying, unfolded upper-most Carboniferous, Permian and Buntsandstein (lower Triassic) series are exposed in a wide belt. They include a thick series of Upper Permian (“Zechstein”) evaporitic rocks, dipping with about 10° S to SW, representing a nearly continuous sulfate and carbonate karst area about 90 km long, covering 338 km². In his dissertation, the first author compiled a new geological map for the Zechstein at a scale of 1:10,000 and deduced a tectonic model to advance our understanding of the karstic features. Karstification determines the morphology of the South Harz including over 180 registered caves, thousands of sinkholes, uvalas, sinking creeks and large karstic springs. Specifically, lines of sinkholes appear to follow faults. By detailed mapping of the three lowermost Zechstein cycles, a dense matrix of faults is revealed. 85° to 125° striking faults reoccur every few 500 m, formed during the Harz-lifting compressional phase during the Upper Cretaceous. Many of these faults are reverse with a Nward thrust. This leads to repetitive exposure of the strata, causing the broadening of the Zechstein outcrop beyond what would be caused by the dip of the series alone. In other areas, horstand graben-structures are present, resulting in kilometer-long Lower Buntsandstein ridges. Below ground, the groundwater flowing southward along the dip is diverted into the direction of diachronicalthe strike, thus causing strike-parallel depressions, valleys and sinkhole rows. In the final extension phase, faults striking 150° to 180° have caused graben-structures, allowing groundwater and surface rivers to flow southward, breaking through the escarpment of the overlying Lower Buntsandstein. Therefore, the tectonic structure of the South Harz determines its hydrology and the karst features apparent at the surface. The tectonic situation of the three largest karstic springs, the Salza Spring at Förste, the Rhume Spring, and the Salza Spring at Nordhausen is discussed along with more shallow karstic settings of the Hainholz/Beierstein, the Trogstein and the area of Hainrode.Gorovje Harz v Nemčiji zajema proti jugu nagnjene in v varistični orogenezi nagubane devonijske in karbonske kamnine, ki so na svoji južni meji narinjene na mezozojske sedimente. Ob južnem delu tega gorovja v širokem pasu izdanjajo navzgor ležeče nenagubane zgornjekarbonske, permske in spodnjetriasne (Buntsandstein) serije. Te vključujejo debelo zaporedje zgornjepermskih (Zechstein) evaporitnih kamnin, ki vpadajo za približno 10° proti J do JZ. To je skoraj kontinuiran sulfatni in karbonatni kraški teren, ki je dolg približno 90 km in se razteza na površini 338 km². V disertaciji je prvi avtor naredil novo geološko karto Zechsteina v merilu 1 : 10.000 in prikazal tektonski model, s čimer je nadgradil razumevanje kraških pojavov. Zakrasevanje je značilno za morfologijo južnega Harza in vključuje več kot 180 registriranih jam, tisoč in več vrtač ter uvale, ponore in velike kraške izvire. Kaže se, da nizi vrtač sledijo prelomom. S podrobnim kartiranjem treh najnižjih zechsteinskih ciklov se je razkrila gosta mreža prelomov. Prelomi smeri 85° do 125°, ki so nastali v zgornji kredi med kompresijsko fazo dviganja Harza, se pojavljajo vsakih nekaj 500 m. Veliko teh prelomov je reverznih prelomov z narivi proti severu. To povzroča, da se vidne plasti ponavljajo in se tako izdanek Zechsteina razširi mnogo bolj, kot le zaradi samega vpada plasti. V drugih delih terena najdemo strukture, kot sta horst in udorina, v kilometer dolgih spodnjetriasnih Buntsandsteinskih hrbtih. Pod površjem teče podtalnica proti jugu, skladno z vpadom in v smeri slemenitve, kar povzroča slemenitvi vzporedne nize depresij, dolin in vrtač. V zadnji fazi ekstenzije so prelomi smeri 150° do 180° povzročili strukturne udorine, zaradi česar podtalnica in površinske reke tečejo proti jugu in sekajo strmo pobočje spodnjega Buntsandsteina. Tektonska struktura južnega Harza določa hidrologijo in površinske kraške pojave. Tektonske razmere treh največjih kraških izvirov Salza v Försteju, Rhume in Salza v Nordhausenu so predstavljene skupaj s plitvimi kraškimi pogoji območij Hainholz/Beierstein, Trogstein in Hainrode

The Story of the 1833 Fercher Survey, Postojnska Jama, Continues: An Additional Document and Newly Discovered Inscriptions

Publications, archived documents and inscriptions help with the reconstruction of the history of Postojnska jama. Until recently, the circumstances of the first mayor cave survey ever undertaken were not well known. It is the so called Fercher Survey conducted in winter 1833; a cooperation between the Mine Office in Idrija and the Cave Administration that surveyed the entire cave known at the time. Documents from the Archive of the Karst Research Institute and an inscription in the Tartarus of Postojnska jama gave a first insight into this story (Kempe, 2005). The survey suggested that (in what is now Male jama) a connection could be blasted to shorten the visitor route. Now a further letter dated 5th September, was found shedding light on this mining attempt begun in summer 1833. In the letter the Cave Administration massively attacks the Mine Office. They claim that either the survey was not accurate or that the breakthrough was attempted at a wrong site. In consequence they demanded their expenses back, threatening with an investigation by the precinct administration. We also found three more inscriptions of the Fercher Party, in Pisani rov and in the Old Cave, one by Fercher and two by the miner Tracha

The History of Postojnska Jama: The 1748 Joseph Anton Nagel Inscriptions in Jama near Predjama and Postojnska Jama

Jama near Predjama and Postojnska Jama, Slovenia, are known for their rich body of historic inscriptions spanning over several centuries. Early explorers and visitors left names, dates and symbols. Here we present the inscriptions by the mathematician Josef Anton Nagel (1717-1794). Nagel and the painter and engineer Alois Schaffenrath (1794-1836) are the only ones that we can trace in both of the caves. Nagel visited the caves in July 1748 on order of Emperor Franz I. The inscription in Jama near Predjama is (for cave inscriptions) rather long and written in Latin, giving name, profession, cause and date of the visit, while the inscription in Postojnska Jama is rather short, giving only name and date of visit. Unfortunately the inscription in Jama near Predjama is already partly obliterated by an incautious visitor

A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5).

AIM: To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) vs insulin aspart (IAsp) used in continuous subcutaneous insulin infusion (CSII) in participants with type 1 diabetes (T1D). MATERIALS AND METHODS: This was a double-blind, treat-to-target, randomized, 16-week trial investigating CSII treatment with faster aspart (n = 236) or IAsp (n = 236). All available information, regardless of treatment discontinuation, was used for the evaluation of effect. RESULTS: Faster aspart was non-inferior to IAsp regarding the change from baseline in glycated haemoglobin (HbA1c; primary endpoint). The mean HbA1c changed from 58.4 mmol/mol (7.5%) at baseline to 57.8 mmol/mol (7.4%) with faster aspart and to 56.8 mmol/mol (7.4%) with IAsp after 16 weeks' treatment, with an estimated treatment difference (ETD) of 1.0 mmol/mol (95% confidence interval [CI] 0.14; 1.87) or 0.09% (95% CI 0.01; 0.17; P < 0.001) for non-inferiority (0.4% margin; P < 0.02 for statistical significance in favour of IAsp). Faster aspart was superior to IAsp in change from baseline in 1-hour postprandial glucose (PPG) increment after a meal test (ETD -0.91 mmol/L [95% CI -1.43; -0.39] or -16.4 mg/dL [95% CI -25.7; -7.0]; P = 0.001), with statistically significant reductions also at 30 minutes and 2 hours. The improvement in PPG was reflected in the change from baseline in 1-hour interstitial glucose increment after all meals (ETD -0.21 mmol/L [95% CI -0.31; -0.11] or -3.77 mg/dL [95% CI -5.53; -2.01]). There was no statistically significant difference in the overall rate of severe or blood glucose-confirmed hypoglycaemia (estimated rate ratio 1.00 [95% CI 0.85; 1.16]). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and 4-week run-in periods (4 vs 0). CONCLUSIONS: Faster aspart provides an effective and safe option for CSII treatment in T1D.NovoNordis

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study

Aims: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). Methods: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. Results: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c 40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. Conclusions: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy

A trial to evaluate the effect of the sodium–glucose co‐transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA‐HF)

Background: Sodium–glucose co‐transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown. Design and methods: The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF) is an international, multicentre, parallel group, randomized, double‐blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N‐terminal pro B‐type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2. The trial is event‐driven, with a target of 844 primary outcomes. Secondary outcomes include the composite of total heart failure hospitalizations (including repeat episodes), and cardiovascular death and patient‐reported outcomes. A total of 4744 patients have been randomized. Conclusions: DAPA‐HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

The History of Postojnska Jama: The 1748 Joseph Anton Nagel Inscriptions in Jama near Predjama and Postojnska Jama

Jama near Predjama and Postojnska Jama, Slovenia, are known for their rich body of historic inscriptions spanning over several centuries. Early explorers and visitors left names, dates and symbols. Here we present the inscriptions by the mathematician Josef Anton Nagel (1717-1794). Nagel and the painter and engineer Alois Schaffenrath (1794-1836) are the only ones that we can trace in both of the caves. Nagel visited the caves in July 1748 on order of Emperor Franz I. The inscription in Jama near Predjama is (for cave inscriptions) rather long and written in Latin, giving name, profession, cause and date of the visit, while the inscription in Postojnska Jama is rather short, giving only name and date of visit. Unfortunately the inscription in Jama near Predjama is already partly obliterated by an incautious visitor