The crucial relationship between vancomycin minimum inhibitory concentration and therapeutic efficacy against methicillin-resistant coagulase-negative staphylococci.

The area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio was used as an indicator of the clinical efficacy of vancomycin. However, the target AUC/MIC has not been set for methicillin-resistant coagulase-negative staphylococci (MR-CNS), and the effectiveness of vancomycin in strains with high MIC is unknown. Therefore, we aimed to investigate the relationship between the vancomycin MIC and therapeutic efficacy in patients with MR-CNS bacteremia. The primary outcome was the difference in treatment failure rate when the MR-CNS vancomycin MIC was 1 or 2 µg/mL. The treatment failure rate did not significantly differ between the two groups (MIC 1 vs. MIC 2: 27.0% vs. 31.0%; p = 0.779). As a result of multivariate analysis, AUC/MIC0-24 h ≤230 was extracted as risk factor for treatment failure, suggesting the importance of a sufficient initial loading dose and early blood concentration monitoring to increase AUC/MIC0-24 h for successful treatment.

Assessing and Evaluating HbS Concentration in Asymptomatic Sickle Cell Patients and Patients With Sickle Cell Crisis Through High-Performance Liquid Chromatography (HPLC) in a Tertiary Hospital in Central India.

Background Sickle cell disease (SCD) is a significant health concern, particularly due to the variability in disease severity and frequency of crisis episodes among patients. Accurate assessment of HbS concentrations is crucial for understanding the disease's progression and severity. This study aimed to assess and evaluate HbS concentrations in sickle cell patients and those experiencing sickle cell crisis using high-performance liquid chromatography (HPLC). The objectives included screening individuals for SCD, diagnosing the disease using Hb electrophoresis, estimating HbS concentration via HPLC, and comparing HbS concentration values between sickle cell patients and those in crisis. Methods An analytical study design was employed at Jawaharlal Nehru Medical College, Sawangi, Wardha, Maharashtra, involving 80 participants diagnosed with SCD. Data collection included clinical assessments, routine sickling tests, Hb electrophoresis, and HPLC for HbS concentration measurement. Descriptive and inferential statistics were utilized for data analysis, including chi-square tests, Mann-Whitney U tests, and regression analyses. Results Significant differences in HbS concentrations were observed between different patient groups. Individuals with the SS pattern exhibited higher HbS levels than those with the AS pattern (p = 0.001). Non-crisis patients had significantly higher mean HbS concentrations than crisis patients (p = 0.001). A moderate positive correlation (0.476, p = 0.001) was found between HbS concentrations and clinical outcomes. No significant differences in HbS concentrations were noted based on sex or age group. Longitudinal analysis revealed a significant increase in HbS levels over time (p = 0.001). Conclusion The study underscores the importance of HbS concentration measurement in understanding the severity and progression of SCD. HPLC proves to be a valuable tool in accurately estimating HbS levels, aiding in better clinical management of the disease.

Production of eicosapentaenoic acid by Vacuoliviride crystalliferum under 20% CO2 conditions.

Utilizing flue gas CO2 to co-produce eicosapentaenoic acid (EPA) with microalgae is considered an ideal approach for combating climate change and reducing cultivation costs. However, microalgal species that can efficiently produce EPA under high-CO2 conditions are scarce. This study identified that the eustigmatophycean strain Vacuoliviride crystalliferum demonstrates rapid growth under 20 % CO2 conditions (0.22 vvm), achieving a biomass concentration and productivity of 3.90 g/L and 229.26 mg/L/d, respectively. The EPA content and EPA productivity were found to be 4.28 % (w/w) and 9.80 mg/L/d, respectively. Additionally, an improved biomass concentration of 3.39 g/L and EPA content and productivity of 4.32 % (w/w) and 11.28 mg/L/d were obtained in a 30 L up-scaled cultivation system. Taken together, these findings suggest that V. crystalliferum is a promising candidate for integrating flue gas sequestration with EPA production.

Effects of Transverse Abdominis Plane (TAP) Block on the MACBAR of Sevoflurane in Gynecologic Patients with Laparoscopic Pneumoperitoneal Stimulation: An Up-Down Sequential Allocation Study.

Purpose: This study aimed to observe the effect of bilateral transverse abdominis plane (TAP) block on the MACBAR of sevoflurane in gynecological patients with laparoscopic pneumoperitoneal stimulation. Patients and Methods: Fifty patients who underwent laparoscopic surgery were randomly assigned to either the control group (n= 25) or the TAP block group (n= 25). Patients in the TAP block group were subjected to a bilateral transversal abdominal muscle plane block with 0.33% ropivacaine (20 mL on each side) guided by ultrasound. The control group received an equal volume of normal saline. The MACBAR of sevoflurane in each group was determined using a sequential allocation technique. Results: The MACBAR of sevoflurane in the TAP block group was significantly lower than that in the control group (4.20% [95% confidence interval {CI}, 4.02%-4.38%] vs 5.03% [95% CI, 4.89%-5.18%]). Conclusion: Bilateral TAP block can reduce the MACBAR of sevoflurane in gynecological patients with pneumoperitoneum stimulation. Trial Registration Number: ChiCTR2100046517. The trial is publicly available and registered at www.chictr.org.cn on May 18, 2021.

Low-cost, immediate, general-purpose, and high-throughput (LIGHt) smartphone colorimetric screening assay for water-soluble protein.

An efficient and rapid method for the detection of total soluble protein in tobacco leaves, utilizing a smartphone-based colorimetric approach has been developed. The proposed low-cost, immediate, general-purpose, and high-throughput (LIGHt) smartphone colorimetric screening assay integrates commercially available microplates, enabling on-site, high-throughput screening of tobacco leaf quality. The study involves preparing protein standard solutions and constructing standard curves using both spectrophotometric and smartphone-based methods. The LIGHt smartphone colorimetry yielded an average relative standard deviation of 10.6 %, a limit of detection of 2 µg/mL, and an average recovery of 93 %. The results demonstrated a comparable performance between intensities from the blue channel and the absorbance values in reflecting protein concentrations, validating the feasibility of utilizing smartphone colorimetry for protein concentration determination. Our approach demonstrates the potential for practical implementation in the field, providing a cost-effective and user-friendly solution for rapid quality assessment in the tobacco industry. The LIGHt smartphone colorimetry enhances quality control practices in the tobacco sector and offers a promising tool for on-site production quality testing in various industries, such as fruits and vegetables.

Customized Li+ Solvation Sheath at the Poly(ethylene oxide)-Based Electrolyte/Ultrahigh-Nickel Cathode Interface toward Room-Temperature Solid-State Lithium Batteries.

The matching of poly(ethylene oxide) (PEO)-based electrolytes with ultrahigh-nickel cathode materials is crucial for designing new-generation high-energy-density solid-state lithium metal batteries (SLMBs), but it is limited by serious interfacial side reactions between PEO and ultrahigh-nickel materials. Here, a high-concentration electrolyte (HCE) interface with a customized Li+ solvation sheath is constructed between the cathode and the electrolyte. It induces the formation of an anion-regulated robust cathode/electrolyte interface (CEI), reduces the unstable free-state solvent, and finally achieves the compatibility of PEO-based electrolytes with ultrahigh-nickel cathode materials. Meanwhile, the corrosion of the Al current collector caused by lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) ions is prevented by lithium difluoro(oxalato)borate (LiDFOB) ions. The synergistic effect of the double lithium salt is achieved by a well-tailored ratio of TFSI- and DFOB- in the first solvation sheath of Li+. Compared with reported PEO-based SLMBs matched with ultrahigh-nickel (Ni ≥ 90%) cathodes, the SLMB in this work delivers a high discharge specific capacity of 216.4 mAh g-1 (0.1C) even at room temperature. This work points out a direction to optimize the cathode/electrolyte interface.

Identification of Key Toxic Substances Considering Metabolic Activation: A Combination of Transcriptome and Nontarget Analysis.

There have been numerous studies using effect-directed analysis (EDA) to identify key toxic substances present in source and drinking water, but none of these studies have considered the effects of metabolic activation. This study developed a comprehensive method including a pretreatment process based on an in vitro metabolic activation system, a comprehensive biological effect evaluation based on concentration-dependent transcriptome (CDT), and a chemical feature identification based on nontarget chemical analysis (NTA), to evaluate the changes in the toxic effects and differences in the chemical composition after metabolism. Models for matching metabolites and precursors as well as data-driven identification methods were further constructed to identify toxic metabolites and key toxic precursor substances in drinking water samples from the Yangtze River. After metabolism, the metabolic samples showed a general trend of reduced toxicity in terms of overall biological potency (mean: 3.2-fold). However, metabolic activation led to an increase in some types of toxic effects, including pathways such as excision repair, mismatch repair, protein processing in endoplasmic reticulum, nucleotide excision repair, and DNA replication. Meanwhile, metabolic samples showed a decrease (17.8%) in the number of peaks and average peak area after metabolism, while overall polarity, hydrophilicity, and average molecular weight increased slightly (10.3%). Based on the models for matching of metabolites and precursors and the data-driven identification methods, 32 chemicals were efficiently identified as key toxic substances as main contributors to explain the different transcriptome biological effects such as cellular component, development, and DNA damage related, including 15 industrial compounds, 7 PPCPs, 6 pesticides, and 4 natural products. This study avoids the process of structure elucidation of toxic metabolites and can trace them directly to the precursors based on MS spectra, providing a new idea for the identification of key toxic pollutants of metabolites.

A higher area under the concentration-time curve/minimum inhibitory concentration target as a potential prognostic factor for vancomycin treatment of methicillin-resistant Staphylococcus aureus meningitis: A case report.

The area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) - guided approach is recommended for vancomycin therapeutic drug monitoring in severe methicillin-resistant Staphylococcus aureus (MRSA) infection. However, evidence regarding the efficacy of vancomycin AUC-guided strategies for the treatment of systemic infections is limited. This case report describes the successful treatment of MRSA meningitis, with vancomycin using a higher AUC/MIC target. A 61-year-old woman who underwent ventriculoperitoneal (VP) shunt placement for subarachnoid hemorrhage, developed MRSA meningitis due to shunt infection. Vancomycin was administered intravenously, with concurrent monitoring of serum and cerebrospinal fluid (CSF) vancomycin concentrations and AUC/MIC. On post-operative day (POD) 24 of VP shunt placement, the vancomycin trough concentration and AUC/MIC were 12.0 µg/mL and 515, respectively, with persistently positive CSF culture. On POD 28, the trough concentration and AUC/MIC were 18.6 µg/mL and 610, respectively. There were no major adverse events, and CSF culture turned negative on POD 30. The vancomycin CSF-to-serum ratio was approximately 41 %. For patients with MRSA meningitis, we suggest an optimal therapeutic range with a vancomycin AUC/MIC target near the upper limit of the therapeutic window.

Effect of Common Cold on Serum Clozapine Concentrations in Hospitalized Patients with Schizophrenia.

Objective: The present study aims to investigate the effect of common cold on the serum clozapine concentrations in hospitalized patients with schizophrenia. Methods: A total of 65 schizophrenic patients with common cold receiving clozapine treatment were retrospectively enrolled. The demographic data, medication situation, clozapine concentration, and parameters of routine haematological and biochemical laboratory tests were obtained from the medical record system. The serum clozapine concentration and clozapine concentration/dose (C/D) ratios between the baseline period and cold period were compared by paired-sample t tests. Association between the changes in serum concentration and C/D ratios of clozapine and changes in white blood cell (WBC) and neutrophil (NE) counts was evaluated using Pearson correlation analysis. Results: The serum clozapine concentration (t = -9.856, P < 0.001) and clozapine C/D ratios (t = -10.071, P < 0.001) were found to be significantly elevated in the cold period compared to the baseline period. Moreover, the changes in the serum clozapine concentration were found to be significantly elevated in female patients compared to male patients (t = -2.483, P = 0.017). Furthermore, changes in the serum clozapine concentration were positively correlated to the changes in WBC (r = 0.303, P = 0.014) and NE (r = 0.315, P = 0.011) counts. Similarly, changes in clozapine C/D ratios were positively correlated to the changes in WBC (r = 0.275, P = 0.027) and NE (r = 0.328, P = 0.008) counts. Conclusion: The serum clozapine concentrations in patients with schizophrenia during the common cold period were increased, which might by related to the elevated WBC and NE counts.

Risk factors associated with blood transfusion in liver transplantation.

To explore preoperative and operative risk factors for red blood cell (RBC) transfusion requirements during liver transplantation (LT) and up to 24 h afterwards. We evaluated the associations between risk factors and units of RBC transfused in 176 LT patients using a log-binomial regression model. Relative risk was adjusted for age, sex, and the model for end-stage liver disease score (MELD) (adjustment 1) and baseline hemoglobin concentration (adjustment 2). Forty-six patients (26.14%) did not receive transfusion. Grafts from cardiac-death donors were used in 32.61% and 31.54% of non-transfused and transfused patients, respectively. The transfused group required more reoperation for bleeding (P = 0.035), longer mechanical ventilation after LT (P < 0.001), and longer ICU length of stay (P < 0.001). MELD and hemoglobin concentrations determined RBC requirements. For each unit of increase in the MELD score, 2% more RBC units were transfused, and non-transfusion was 0.83-fold less likely. For each 10-g/L higher hemoglobin concentration at baseline, 16% less RBC transfused, and non-transfusion was 1.95-fold more likely. Ascites was associated with 26% more RBC transfusions. With an increase of 2 mm from the baseline in the A10FIBTEM measurement of maximum clot firmness, non-transfusion was 1.14-fold more likely. A 10-min longer cold ischemia time was associated with 1% more RBC units transfused, and the presence of post-reperfusion syndrome with 45% more RBC units. We conclude that preoperative correction of anemia should be included in LT. An intervention to prevent severe hypotension and fibrinolysis during graft reperfusion should be explored.Trial register: European Clinical Trials Database (EudraCT 2018-002,510-13) and ClinicalTrials.gov (NCT01539057).

Effect of close-up metabolizable protein supply on colostrum yield, composition, and immunoglobulin G concentration and associations with prepartum metabolic indicators of Holstein cows.

The prepartum diet as well as individual metabolic status of the cow influences colostrum parameters. The objectives of this study were to 1) investigate the effect of increasing prepartum dietary MP supply on colostrum yield, composition, and immunoglobulin G (IgG) concentration, and 2) identify prepartum metabolic indicators associated with these outcomes. Multiparous Holstein cows (n = 96) were blocked by expected calving date and randomly assigned to 1 of 2 prepartum diets formulated to contain a control (CON; 85 g of MP/kg DM; 1,175 g of MP/d) or high (HI; 113 g of MP/kg DM; 1,603 g of MP/d) level of MP starting at 28 d before expected calving. Both prepartum diets were formulated to supply Met and Lys at an equal amount of 1.24 and 3.84 g/Mcal of metabolizable energy (ME), respectively. Metabolic indicators were determined in serum (albumin, glutamate dehydrogenase, cholesterol, aspartate transaminase, total protein, total bilirubin, and IgG) or plasma (Ca, glucose, fatty acids, BHB, and urea nitrogen) twice weekly in a subset of cows (n = 60). Colostrum was harvested at 3.6 ± 2.4 h from calving and yield as well as concentrations of IgG, fat, protein, and Ca were determined. Cows were retrospectively grouped based on the typical volume of colostrum needed for 2 colostrum meals (<6 or ≥ 6 kg), IgG concentration (<100 or ≥ 100 g/L), as well as the median concentrations of fat (<4.4 or ≥ 4.4%), protein (<16.5 or ≥ 16.5%), Ca (<0.21 or ≥ 0.21%), and total colostrum ME (<8.65 or ≥ 8.65 Mcal). Data were analyzed using mixed effects ANOVA, with repeated measures where applicable. Feeding HI tended to increase colostrum yield in cows entering parity 2 (9.4 vs. 7.2 ± 0.9 kg), but treatment did not affect yield from cows entering parity ≥3 (5.1 vs. 6.4 ± 1.0 kg). Supply of MP did not affect concentrations of IgG, fat, protein, or Ca. Cows that produced ≥ 6 kg vs. those producing <6 kg of colostrum had lower plasma concentrations of glucose. Metabolic indicators were not associated with IgG group. Colostrum fat ≥4.4% was associated with cows having lower prepartum concentrations of glucose, total protein, albumin, and aspartate transaminase activity. Colostrum protein ≥ 16.5% was associated with lower circulating serum IgG and elevated cholesterol. Elevated glucose as well as lower cholesterol and BHB concentrations were associated with colostrum Ca ≥ 0.21%. Further, higher albumin and fatty acids as well as lower glucose concentrations were associated with a greater colostrum energy output. In conclusion, increasing prepartum MP supply tended to increase colostrum yield in cows entering parity 2, but did not affect the composition or IgG concentration. The observed associations between metabolic indicators and colostrum parameters suggest that slight adjustment in metabolism during late gestation might be necessary to support colostrogenesis, but the causality of these relationships should be considered.

Steering the Selectivity of CORR from Acetate to Ethanol via Tailoring the Thermodynamic Activity of Water.

The electrochemical conversion of carbon monoxide (CO) into oxygenated C2+ products at high rates and selectivity offers a promising approach for the two-step conversion of carbon dioxide (CO2). However, a major drawback of the CO electrochemical reduction in alkaline electrolyte is the preference for the acetate pathway over the more valuable ethanol pathway. Recent research has shed light on the significant impact of thermodynamic water activity on the electrochemical CO2 reduction reaction pathways, but less is understood for the electrochemical reduction of CO. In this study, we investigated how the water activity at the electrified interface can be enhanced to adjust the selectivity between acetate and ethanol. We employed an ionomer modifier to lower the local concentration of alkali ions (via Donnan exclusion), successfully enhancing ethanol production while suppressing acetate formation. We observed a remarkable improvement in the Faradaic efficiency of ethanol and alcohol (i.e. ethanol, propanol etc), which reached 42.5% and 55.1%, respectively, at a current density of 700 mA cm-2. The partial current densities of ethanol and alcohol reached 698 and 942 mA cm-2 at 2000 mA cm-2. Furthermore, we achieved a 3.7-fold increase in the ethanol/acetate ratio, providing clear evidence of our successful modulation of product selectivity.

Research progress on high-concentration oxygen therapy after cerebral hemorrhage.

Recently, the role of high-concentration oxygen therapy in cerebral hemorrhage has been extensively discussed. This review describes the research progress in high-concentration oxygen therapy after cerebral hemorrhage. High-concentration oxygen therapy can be classified into two treatment methods: hyperbaric and normobaric high-concentration oxygen therapy. Several studies have reported that high-concentration oxygen therapy uses the pathological mechanisms of secondary ischemia and hypoxia after cerebral hemorrhage as an entry point to improve cerebral oxygenation, metabolic rate, cerebral edema, intracranial pressure, and oxidative stress. We also elucidate the mechanisms by which molecules such as Hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor, and erythropoietin (EPO) may play a role in oxygen therapy. Although people are concerned about the toxicity of hyperoxia, combined with relevant literature, the evidence discussed in this article suggests that as long as the duration, concentration, pressure, and treatment interval of patients with cerebral hemorrhage are properly understood and oxygen is administered within the treatment window, it can be effective to avoid hyperoxic oxygen toxicity. Combined with the latest research, we believe that high-concentration oxygen therapy plays an important positive role in injuries and outcomes after cerebral hemorrhage, and we recommend expanding the use of normal-pressure high-concentration oxygen therapy for cerebral hemorrhage.

Plasma aldosterone concentrations elevation in hypertensive patients: the dual impact on hyperuricemia and gout.

Background: Prior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS's end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients. Methods: Our study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)'s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC's effects across diverse conditions and among different subgroups. Results: Multivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings. Conclusion: This study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship.

The relationship between clinical impairment and blood drug concentration: Comparison between the most prevalent traffic relevant drug groups.

AIM: The aim of the present study was to investigate the relationship between blood concentrations of four different drug classes; ethanol, benzodiazepines, amphetamines and tetrahydrocannabinol (THC) and driver impairment as assessed by a clinical test of impairment (CTI). METHODS: Data was retrieved from a national database on CTI assessments and accompanying blood drug concentrations from apprehended drivers. All drug concentrations in blood were quantified using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS), and compared to the results of the CTI which were categorized as either "not impaired", "mildly impaired", "moderately impaired", or "considerably impaired". RESULTS: A total number of 15 514 individual mono drug-cases collected over 9 years was included. 89 % were men and the median age was 34 years. In addition, 3 684 individual cases with similar age and gender distribution where no drugs were detected, were included as a reference group. For ethanol and benzodiazepines the percentage of clinically impaired cases increased markedly from lower to higher concentration windows, from 60 % to 97 % for ethanol and from 38 % to 76 % for benzodiazepines. The corresponding increase for amphetamines and THC was modest, from 43 % to 58 % for amphetamines and from 41 % to 55 % for THC. The correlation between drug concentration and degree of impairment was high for ethanol (Spearman´s rho=0.548, p<0.001) and relatively high for benzodiazepines (Spearman´s rho=0.377, p<0.001), but low for amphetamines (Spearman´s rho=0.078, p<0.001) and THC (Spearman´s rho=0.100, p<0.001). CONCLUSION: The percentage of impaired drivers increased with increasing blood drug concentration for all four drug classes, most pronounced for ethanol and benzodiazepines and much less for amphetamines and THC. The median blood drug concentration increased with increasing magnitude of impairment for ethanol and benzodiazepines, while this was much less pronounced for amphetamines and THC. The ranges of drug concentrations, however, were wide for all four drug classes in all impairment categories as assessed by individual clinical examination.

Tungsten-needle intensifies microwave-sustained plasma accelerating direct H2S conversion to H2.

Direct sustainable conversion of hydrogen sulfide (H2S) enables collaborative recovery of H and S resources via a metal-enhanced microwave plasma strategy, avoiding the hydrogen waste in the traditional Claus process. However, the metal size effect on microwave plasma property, the optimal process parameters, and the enhancement mechanism remain unclear in H2S conversion. Herein, the optimal tungsten needle (diameter: 1 mm, length: 60 mm, and tip angle: 10°) is experimentally proven for intensifying microwave discharge in multi-mode cavities. Theoretical calculations and plasma distribution reveal that the optimized tungsten needle achieves the ideal coupling with the microwave field, exhibiting extreme electric field augmentation around the needle tip. Tungsten-needle intensifies microwave-sustained plasma, realizing 40.2 % (90.1 %) conversion of 100 % (10 %) concentration H2S to H2 at a low microwave power of 300 W with a good stability of 30 hrs. Low power, large flow rate, and high H2S concentration are beneficial for improving energy efficiency. The excitation of microwave plasma is accompanied by a massive generation of highly energetic electrons. The direct high-energy electron-H2S collision contributes a lot to H2S splitting, especially for high-concentration H2S. In-situ optical emission spectroscopy confirms the vital S and H radicals in the plasma. The free radical reactions triggered by electron collisions are responsible for the production of H2 and S. This work opens an avenue to sustainable and low-carbon hydrogen production from the direct conversion and utilization of H2S.

Finnish Pediatric Surgery Hub - From Centralization to Collective Learning and Sharing of Expertise.

AIM OF THE STUDY: Continuous surgical developments, growing awareness of patient representatives and limited health-care resources are pushing for innovative approaches to ensure equal high-quality pediatric surgical care. We aimed to describe early experiences and assess surgical safety of a novel nationwide pediatric surgery collaborative initiative. METHODS: In 2021, general pediatric surgeons representing all five independent university hospitals performing neonatal surgery in Finland initiated national collaboration, the Finnish pediatric surgery hub (FPSH), for sharing of surgical expertise and collective learning. For each case addressed by FPSH, place of care and surgical team were decided individually, and when deemed necessary, operations were performed in cooperation. Operations performed during 2021-2023 and associated early (<30 days) postoperative complications were analyzed according to Clavien-Madadi classification. RESULTS: Of the total 40 surgeries managed co-operatively by FPSH, 30 (75%) took place in local university hospitals and 10 in Helsinki University Hospital. There were 34 (85%) elective and 6 urgent cases, which were operated within median 1 (range, 1-3) days. Most frequent underlying diagnoses included anorectal malformations, esophageal atresia and Hirschsprung disease. Overall, 12 (30%) had any early postoperative complications, all Clavien-Madadi grade IIIB or lower, and five patients (13%) were reoperated. Rate or grade of complications was not associated with place of care. In addition to regular virtual case meetings, national care protocols and research projects were introduced. CONCLUSION: These preliminary findings suggest that our national collaborative initiative, FPSH, not only provided practical and safe framework for sharing of surgical expertise but also for collective learning. LEVEL OF EVIDENCE: III.

[Reform proposal "Occasional surgical oncology" : Medical strategic analysis and ramifications of the draft bill within the framework of the Hospital Treatment Improvement Act (KHVVG) from the perspective of a university hospital]. / Reformvorhaben "Gelegenheits-Onkochirurgie" : Medizinstrategische Analyse und Auswirkungen der Gesetzesinitiative im Rahmen des Krankenhausversorgungsverbesserungsgesetzes (KHVVG) aus der Perspektive eines Universitätsklinikums.

BACKGROUND: Cancer remains the second most common cause of death in Germany. Performance management and specialization concepts in medicine have the potential to positively influence the care and chances of survival of patients. OBJECTIVE: From the perspective of the University Hospital Freiburg (UKF), the legislative initiative within the framework of the Hospital Treatment Improvement Act (KHVVG) results in a number of medical strategic implications. This article explains and discusses the background, objectives and contents of the reform project "Occasional surgical oncology" and provides perspectives on strategic fields of action. MATERIAL AND METHODS: Analysis and interpretation of the draft of the Act for improvement of the treatment quality in hospitals and on the reform of the remuneration structures (Federal Government draft act). RESULTS: From the point of view of the UKF hospitals should engage in cooperative discussions with neighboring hospitals at the earliest opportunity to shape regional healthcare with the goals of mapping the local allocation of oncology patients for optimal treatment, mitigating the loss of patients at affected locations and preparing for patient growth at facilities that will continue to provide treatment in surgical oncology. DISCUSSION: The ongoing legislative process and the fact that a reliable analysis of relevant treatment areas will be possible for hospitals in the first half of 2025, presents particular challenges for hospitals and the strategic planning of activities. The gaps in the bill presented in this article should be urgently addressed to avoid undermining the project's goals and to support the hospitals remaining in the healthcare system in their preparations.

Formulation and Validation of an Extended Sigmoid Emax Model in Pharmacodynamics.

PURPOSE OR OBJECTIVE: Drug concentration-response curves (DRCs) are crucial in pharmacology for assessing the drug effects on biological systems. The widely used sigmoid Emax model, which accounts for response saturation, relies heavily on the effective drug concentration ( E D 50 ). This reliance can lead to validation errors and inaccuracies in model fitting. The Emax model cannot generate multiple DRCs, raising concerns about whether the dataset is fully utilized. METHODS: This study formulates an extended Emax (eEmax) model designed to overcome these limitations. The eEmax model generates multiple DRCs from a single dataset by using various estimated α ' s ∈ 0,100 , while keeping E D α fixed, rather than estimating an E D 50 value as in the Emax model. RESULTS: This model effectively captures a broader range of concentration-response behavior, including non-sigmoidal patterns, thus providing greater flexibility and accuracy compared to the Emax model. Validation using various drug-response data and PKPD frameworks demonstrates the eEmax model's improved accuracy and versatility in handling concentration-response data. CONCLUSIONS: The eEmax model provides a robust and flexible method for drug concentration-response analysis, facilitating the generation of multiple DRCs from a single dataset and reducing the possibility of validation errors. This model is particularly valuable for its ease of use and its capability to fully utilize datasets, providing its potential in PKPD modeling and drug discovery.

Data-Driven Insights into the Contamination of Polycyclic Aromatic Hydrocarbons in Marine Bays.

The synthesis of polycyclic aromatic hydrocarbon (PAH) data allows us to quantify and gain insights into the spatiotemporal dynamics of PAH contamination in marine bays. Here, a data synthesis framework was developed to understand data-driven insights into the spatiotemporal levels, compositional profiles, and potential sources of PAHs in water and sediment of marine bays. PAHs were detected in 69 bays worldwide, with contamination hotspots located in Asian bays. PAH concentrations in pre-2000 were significantly lower than those in the 2000s and post-2010, while the dominant species in water and sediment were 2-3 ring and 4-6 ring PAHs, respectively. The composition patterns of PAHs included 2-3 ring, 3-5 ring, and 4-5 ring dominant categories, but no significant distance decay relationship was found in the composition similarity due to international energy trade. Temporal dynamic patterns of concentrations included Descending-, Ascending-, and Inverted V-type, whereas over longer time spans, the pattern is more similar to the Inverted V-type owing to the reductions in emission intensity. PAHs were derived from both petrogenic and pyrolytic sources, with combustion from both coal and petroleum being the dominant source. These data-driven discoveries provide quantitative insights into the spatiotemporal patterns in the concentration and composition of PAHs, contributing to the mitigation of PAH contamination.