Hydrologic models are conventionally constrained and evaluated using point measurements of streamflow, which represents an aggregated catchment measure. As a consequence of this single objective focus, model parametrization and model parameter sensitivity are typically not reflecting other aspects of catchment behavior. Specifically for distributed models, the spatial pattern aspect is often overlooked. Our paper examines the utility of multiple performance measures in a spatial sensitivity analysis framework to determine the key parameters governing the spatial variability of predicted actual evapotranspiration (AET). Latin hypercube one-at-a-time (LHS-OAT) sampling strategy with multiple initial parameter sets was applied using the mesoscale hydrologic model (mHM) and a total of 17 model parameters were identified as sensitive. The results indicate different parameter sensitivities for different performance measures focusing on temporal hydrograph dynamics and spatial variability of actual evapotranspiration. While spatial patterns were found to be sensitive to vegetation parameters, streamflow dynamics were sensitive to pedo-transfer function (PTF) parameters. Above all, our results show that behavioral model definition based only on streamflow metrics in the generalized likelihood uncertainty estimation (GLUE) type methods require reformulation by incorporating spatial patterns into the definition of threshold values to reveal robust hydrologic behavior in the analysis.

Background. This is a retrospective analysis of the results of treatment for varicose veins using the sandwich technique with cyanoacrylate glue and foam sclerotherapy. This novel method al-lows for substantial reduction of amount of glue needed for the vein closure, and minimizes the risk of granuloma formation and allergic reaction related to the epifascial administration of cy-anoacrylate. Methods: This technique was used in 60 patients, 77 intrafascial veins were managed. Vein closures were performed with Venex cyanoacrylate glue and 1-3% polidocanol foam. All proce-dures were done under ultrasonographic control, though direct percutaneous punctures of target veins. Follow-up were scheduled 1-3 week after the procedure. If revealed, unclosed segments of the target veins were obliterated at these follow-up visits, with glue and/or sclerotherapy. Results. There were no serious adverse events intra- or postprocedurally. The technical success rate was 100%. The primary success rate at 1-3 week follow-up was 84.4%. The primary assisted success rate, after additional closures, was 100%. Conclusions. We demonstrated that the treatment for varicose veins, using sandwich tech-nique, which combines cyanoacrylate glue and foam sclerotherapy, can be safe and efficient.

Rainfall runoff modeling has been a subject of interest for decades due to a need to understand a catchment system for management, for example regarding extreme event occurrences such as flooding. Tropical catchments are particularly prone to the hazards of extreme precipitation and the internal drivers of change in the system, such as deforestation and land use change. A model framework of dynamic TOPMODEL, DECIPHeR v1 - considering the flexibility, modularity and portability - and Generalized Likelihood Uncertainty Estimation (GLUE) method are both used in this study. They reveal model performance for the streamflow simulation in a tropical catchment, i.e. the Kelantan River in Malaysia, that is prone to flooding and experiences high rates of land use change. 32 years' continuous simulation at a daily time scale simulation along with uncertainty analysis resulted in a Nash Sutcliffe Efficiency (NSE) score of 0.42 from the highest ranked parameter set, while 25.35% of the measurement falls within the uncertainty boundary based on a behavioral threshold NSE 0.3. The performance and behavior of the model in the continuous simulation suggests a limited ability of the model to represent the system, particularly along the low flow regime. In contrast, the simulation of eight peak flow events achieves moderate to good fit, with the four peak flow events simulation returning an NSE > 0.5. Nonetheless, the parameter scatterplot from both the continuous simulation and analyses of peak flow events indicate unidentifiability of all model parameters. This may be attributable to the catchment modelling scale. The results demand further investigation regarding the heterogeneity of parameters and calibration at multiple scales.

Purpose: Glue inhalation is a common unconventional substance of abuse and it contains neurotoxic and volatile solvents. We examined the toxicity profile and CNS activities of glue inhalation in Wistar rats.Methods: Acute toxicity was investigated using graded concentrations of 0.5, 1, and 2 mL of glue inhalation (n=3/group) for 4 hours in phase one followed by concentrations of 5, 10, and 20 mL of glue (n=1/group) for 4 hours in phase two. These animals were then observed for signs of toxicity and/or mortality for 24hours. The sub-acute toxicity was studied using 24 male Wistar rats at graded concentrations of Air, 2, 4 and 8mL glue (n=6/group) for 28 days. Blood samples were collected for biochemical and haematological evaluations, and vital organs (lung, liver, kidney, heart, brain, and eye) were used for histological analysis. Behavioural studies were carried out using Elevated Plus Maze, Hole Board Test, Open Field Test, Tail Suspension Test and Forced Swim Test. Dependence and abstinence effect were also evaluated. Results: The Lethal Dose (LD₅₀) of the inhalational glue was 14.14 ml. Glue significantly increased liver function parameters like TB, DB, ALP, ALT, TP, electrolyte levels (K⁺ and HCO₃) but reduced cholesterol level in exposed rats. Glue inhalation had significant anxiolytic and depressant effects on the rats at concentrations of 4mL and 8mL. Histological analysis revealed liver and lung tissue abnormalities and subconjunctival inflammation in eye tissue at 8mL. Conclusion: The study therefore suggests that glue inhalation has anxiolytic and depressant effects in Wistar rats.

Proteolysis Targeting Chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD) with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focusses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.

Background: A new access technique was developed to reduce postoperative adverse events after the extraction of impacted maxillary wisdom teeth. Hence, this study aimed to assess the occurrence of adverse events after extraction of maxillary impacted wisdom teeth using traditional or modified access. Methods: Two different surgical incision designs were used for bilateral wisdom tooth extractions in 30 patients. The traditional incision was performed distal to the second molar in the center of the tuberosity, followed by a buccal releasing incision. After tooth extraction the wound was secured by sutures. The new technique consists of an oblique incision from the distal palatal aspect of the tuberosity towards the buccal aspect of the second molar. After tooth extraction, cyanoacrylate glue was used on the wound. Results: Lower pain was reported by patients at the site treated with the new technique (p<0.01). Edema, postsurgical bleeding, and hematoma were similar in both groups. The surgical time was shorter for the new technique (p<0.01). Conclusions: The new technique applied for the extraction of impacted maxillary wisdom teeth reduced postsurgical pain and the duration of surgery.

Background: To date, FM using middle ear packing has rarely reported. In this study, we hypothesized that middle ear packing with dexamethasone soaked gelfoam and fibrin glue over the fat graft could promote the success rate of TMP closure regardless of perforation size. Methods: Between January 2005 and July 2020, a total of 209 patients who underwent fat myringoplasty due to chronic TMP at tertiary referral center were encountered and analyzed. The success rate and audiologic outcome was analyzed. Results: The mean successful TM closure rate was 88.0 %. The success rate by different age generation was not significant difference. The size of the perforation grade showed no significant difference. The perforation site by anterior or posterior was not significant. The preoperative mean threshold of AC, BC and ABG were 55.71, 12.98 and 42.73 dB respectively. The postoperative mean threshold of AC, BC and ABG were 23.67, 12.98 and 10.69 dB. The change of preoperative and postoperative hearing showed statistically significant. Conclusion: From our results, the simple trimming of the perforation edge and middle ear packing with external ear canal packing using fibrin glue induced the stable adhesion between the remnant TM and the fat graft.