THE CONFLUENCE RATIO OF THE TRANSYLVANIAN BASIN RIVERS

There are many possibilities to assess the hydrological and geomorphological evolution of a territory. Among them, one remarks the confluence ratio of the rivers belonging to different catchment areas. The values of this indicator may provide information regarding the stage of evolution of the fluvial landforms in the Transylvanian Basin. Also, the values may serve for the calculation of other parameters of catchment areas like: the degree of finishing of the drainage basin for its corresponding order, the density of river segments within a catchment area etc. To calculate the confluence ratio, 35 catchment areas of different orders have been selected. The confluence ratio varies between 3.04 and 6.07. The large range of values demonstrates the existence of a heterogeneous lithology and of morphological and hydrographical contrasts from one catchment area to the other. The existence of values above 5, correlated also with observations in the field, reveals an accelerated dynamics of the geomorphological processes in those catchment areas. This dynamic is mainly supported by the high landform fragmentation due to the first order rivers. In contrast, the catchment areas that have a confluence ratio below 5 are in a more advanced stage of evolution with stable slopes, unable to initiate new first order river segments

Applying System Engineering to Pharmaceutical Safety

While engineering techniques are used in the development of medical devices and have been applied to individual healthcare processes, such as the use of checklists in surgery and ICUs, the application of system engineering techniques to larger healthcare systems is less common. System safety is the part of system engineering that uses modeling and analysis to identify hazards and to design the system to eliminate or control them. In this paper, we demonstrate how to apply a new, safety engineering static and dynamic modeling and analysis approach to healthcare systems. Pharmaceutical safety is used as the example in the paper, but the same approach is potentially applicable to other complex healthcare systems. System engineering techniques can be used in re-engineering the system as a whole to achieve the system goals, including both enhancing the safety of current drugs while, at the same time, encouraging the development of new drugs

Alzheimer’s disease marker phospho-tau181 is not elevated in the first year after moderate-severe TBI

Background: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer’s disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer’s disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. Methods: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer’s disease, with healthy controls. Results: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer’s disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. Conclusions: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration

Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury

Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication

Noble gas and carbon isotope systematics at the seemingly inactive Ciomadul volcano (Eastern‐Central Europe, Romania): evidence for volcanic degassing

Ciomadul is the youngest volcano in the Carpathian-Pannonian Region, Eastern-Central Europe, which last erupted 30 ka. This volcano is considered to be inactive, however, combined evidence from petrologic and magnetotelluric data, as well as seismic tomography studies suggest the existence of a subvolcanic crystal mush with variable melt content. The volcanic area is characterized by high CO2 gas output rate, with a minimum of 8.7 × 103 t yr-1. We investigated 31 gas emissions at Ciomadul to constrain the origin of the volatiles. The δ13C-CO2 and 3He/4He compositions suggest the outgassing of a significant component of mantle-derived fluids. The He isotope signature in the outgassing fluids (up to 3.10 Ra) is lower than the values in the peridotite xenoliths of the nearby alkaline basalt volcanic field (R/Ra 5.95Ra±0.01) which are representative of a continental lithospheric mantle and significantly lower than MORB values. Considering the chemical characteristics of the Ciomadul dacite, including trace element and Sr- Nd and O isotope compositions, an upper crustal contamination is less probable, whereas the primary magmas could have been derived from an enriched mantle source. The low He isotopic ratios could indicate a strongly metasomatized mantle lithosphere. This could be due to infiltration of subduction-related fluids and postmetasomatic ingrowth of radiogenic He. The metasomatic fluids are inferred to have contained subducted carbonate material resulting in a heavier carbon isotope composition (13C is in the range of -1.4 to -4.6 ‰) and an increase of CO2/3He ratio. Our study shows the magmatic contribution to the emitted gases