Finding the weakest link: mechanical sensitivity in a fish cranial linkage system.

Understanding the physical mechanics behind morphological systems can offer insights into their evolution. Recent work on linkage systems in fish and crustaceans has suggested that the evolution of such systems may depend on mechanical sensitivity, where geometrical changes to different parts of a biomechanical system have variable influence on mechanical outputs. While examined at the evolutionary level, no study has directly explored this idea at the level of the mechanism. We analyse the mechanical sensitivity of a fish cranial linkage to identify the influence of linkage geometry on the kinematic transmission (KT) of the suspensorium, hyoid and lower jaw. Specifically, we answer two questions about the sensitivity of this linkage system: (i) What changes in linkage geometry affect one KT while keeping the other KTs constant? (ii) Which geometry changes result in the largest and smallest changes to KT? Our results show that there are ways to alter the morphology that change each KT individually, and that there are multiple ways to alter a single link that have variable influence on KT. These results provide insight into the morphological evolution of the fish skull and highlight which structural features in the system may have more freedom to evolve than others.

[Prospective DRG coding : Improvement in cost-effectiveness and documentation quality of in-patient hospital care]. / Fallbegleitende DRG-Kodierung : Verbesserung von Wirtschaftlichkeit und Dokumentationsqualität in der stationären Versorgung.

BACKGROUND: In prospective reimbursement schemes a diagnosis-related group (DRG) is assigned to each case according to all coded diagnoses and procedures. This process can be conducted retrospectively after (DC) or prospectively during the hospitalization (PC). The use of PC offers advantages in terms of cost-effectiveness and documentation quality without impairing patient safety. MATERIAL AND METHODS: A retrospective analysis including all DRG records and billing data from 2012 to 2015 of a surgical department was carried out. The use of PC was introduced into the vascular surgery unit (VS) in September 2013, while the remaining surgical units (RS) stayed with DC. Analysis focused on differences between VS and RS before and after introduction of PC. Characteristics of cost-effectiveness were earnings (EBIT-DA), length of stay (LOS), the case mix index (CMI) and the productivity in relation to the DRG benchmark (productivity index, PI). The number of recorded diagnoses/procedures (ND/NP) was an indicator for documentation quality. RESULTS: A total of 1703 cases with VS and 27,679 cases with RS were analyzed. After introduction of PC the EBIT-DA per case increased in VS but not in RS (+3342 Swiss francs vs. +84, respectively, p < 0.001). The CMI increased slightly in both groups (+0.10 VS vs. +0.08 RS, p > 0.05) and the LOS was more reduced in VS than in RS (-0.36 days vs. -0.03 days, p > 0.005). The PI increased in VS but decreased in RS (+0.131 vs. -0.032, p < 0.001), ND increased more in VS (+1.29 VS vs. +0.26 RS, p < 0.001) and NP remained stable in both groups. CONCLUSION: The use of PC helps to significantly improve cost-effectiveness and documentation quality of in-patient hospital care, essentially by optimizing LOS and cost weight in relation to the DRG benchmark, i. e. increasing the PI. The increasing ND indicates an improvement in documentation quality.

Opposing role of Notch1 and Notch2 in a Kras(G12D)-driven murine non-small cell lung cancer model.

Lung cancer is the leading cause of cancer-related deaths worldwide. Recently, we have shown that Notch1 inhibition resulted in substantial cell death of non-small cell lung cancer (NSCLC) cells in vitro. New compounds targeting Notch signal transduction have been developed and are now being tested in clinical trials. However, the tumorigenic role of individual Notch receptors in vivo remains largely unclear. Using a Kras(G12D)-driven endogenous NSCLC mouse model, we analyzed the effect of conditional Notch1 and Notch2 receptor deletion on NSCLC tumorigenesis. Notch1 deficiency led to a reduced early tumor formation and lower activity of MAPK compared with the controls. Unexpectedly, Notch2 deletion resulted in a dramatically increased carcinogenesis and increased MAPK activity. These mice died significantly earlier due to rapidly growing tumor burden. We found that Notch1 regulates Ras/MAPK pathway via HES1-induced repression of the DUSP1 promoter encoding a phosphatase specifically suppressing pERK1/2. Interestingly, Notch1 but not Notch2 ablation leads to decreased HES1 and DUSP1 expression. However, Notch2-depleted tumors showed an appreciable increase in ß-catenin expression, a known activator of HES1 and important lung cancer oncogene. Characteristically for ß-catenin upregulation, we found that the majority of Notch2-deficient tumors revealed an undifferentiated phenotype as determined by their morphology, E-Cadherin and TTF1 expression levels. In addition, these carcinomas showed aggressive growth patterns with bronchus invasion and obstruction. Together, we show that Notch2 mediates differentiation and has tumor suppressor functions during lung carcinogenesis, whereas Notch1 promotes tumor initiation and progression. These data are further supported by immunohistochemical analysis of human NSCLC samples showing loss or downregulation of Notch2 compared with normal lung tissue. In conclusion, this is the first study characterizing the in vivo functions of Notch1 and Notch2 in Kras(G12D)-driven NSCLC tumorigenesis. These data highlight the clinical importance of a thorough understanding of Notch signaling especially with regard to Notch-targeted therapies.

GJB2 mutations and genotype-phenotype correlation in 335 patients from germany with nonsyndromic sensorineural hearing loss: evidence for additional recessive mutations not detected by current methods.

We report on 335 patients (319 families) with mild-to-profound nonsyndromic sensorineural hearing loss. We identified 178 mutated GJB2 alleles representing 29 different sequence changes (including 3 novel mutations: Q7P, N14D, H100Q), and 2 alleles with the deletion del(GJB6-D13S1830) of the GJB6 gene. Eleven GJB2 mutations (119 mutated alleles) were truncating (T), and 18 mutations (59 alleles) were nontruncating (NT). Biallelic GJB2 mutations were found in 71 patients (21.2%; 67 families; 25 different genotypes). Audiograms of 62 patients (56 families) with biallelic GJB2 mutations typically indicated a profound hearing loss with T/T mutations, moderate hearing loss with T/NT mutations, and mild hearing impairment with NT/NT mutations (p < 0.01, Student's t test). From 37 patients (34 families) with biallelic GJB2 mutations, audiograms at different ages were available and indicated progressive hearing loss (>15 dB) in 10 patients (27.0%, 10 families). Interestingly, we identified an unexpectedly large subset of patients (n = 29; 8.7%) presenting with only one GJB2 mutation (n = 14 T/wild-type; n = 15 NT/wild-type). This strongly suggests the presence of additional recessive mutations that are not detected by current GJB2 mutation and GJB6 deletion analyses.

[Economic benefits of overlapping induction: investigation using a computer simulation model]. / Okonomischer Nutzen der überlappenden Einleitung: Untersuchung mithilfe eines Computersimulationsmodells.

The aim of this study was to investigate the potential economic benefit of overlapping anaesthesia induction given that all patient diagnosis-related groups (AP DRG) are used as the model for hospital reimbursement. A computer simulation model was used for this purpose. Due to the resource-intensive production process, the operating room (OR) environment is the most expensive part of the supply chain for surgical disciplines. The economical benefit of a parallel production process (additional personnel, adaptation of the process) as compared to a conventional serial layout was assessed. A computer-based simulation method was used with commercially available simulation software. Assumptions for revenues were made by reimbursement based on AP DRG. Based on a system analysis a model for the computer simulation was designed on a step-by-step abstraction process. In the model two operating rooms were used for parallel processing and two operating rooms for a serial production process. Six different types of surgical procedures based on historical case durations were investigated. The contribution margin was calculated based on the increased revenues minus the cost for the additional anaesthesia personnel. Over a period of 5 weeks 41 additional surgical cases were operated under the assumption of duration of surgery of 89+/-4 min (mean+/-SD). The additional contribution margin was CHF 104,588. In the case of longer surgical procedures with 103+/-25 min duration (mean+/-SD), an increase of 36 cases was possible in the same time period and the contribution margin was increased by CHF 384,836. When surgical cases with a mean procedural time of 243+/-55 min were simulated, 15 additional cases were possible. Therefore, the additional contribution margin was CHF 321,278. Although costs increased in this simulation when a serial production process was changed to a parallel system layout due to more personnel, an increase of the contribution margin was possible, especially with procedures of shorter duration (<120 min). For longer surgical times, the additional costs for the workforce result in a reduced contribution margin depending on the models chosen to handle overtime of the technical OR personnel. Important advantages of this approach for simulation are the use of the historical production data and the reflection of the specificities of the local situation. Computer simulation is an ideal tool to support operation room management, particularly regarding the planning of resource allocation and the coordination of workflow.

[Simulation-based analysis of novel therapy principles. Effects on the efficiency of operating room processes]. / Simulationsbasierte Analyse neuer Therapieprinzipien. Auswirkungen auf die Leistungsfähigkeit der OP-Prozesse.

BACKGROUND: The introduction of innovative drugs in anesthesiological treatment has the potential to improve perioperative efficiency. This article examines the impact of the new muscle relaxant encapsulator Bridion on emergence from anesthesia and on the efficiency of the perioperative organization. METHODS: To analyze the effects of medical innovations, computer simulation was used as an experimental frame. The simulation was based on a realistic model of an operating room setting and used historical data to study the effect of innovation on the operational performance and the economic outcomes. RESULTS: The use of medical innovations in anesthesiological emergence yields new potentials for a hospital under certain conditions. Due to shorter block times and anesthesia-controlled times, additional benefits for the operating room could be realized. This results in an increase of up to 2.4% additional cases during similar working hours and planning periods. CONCLUSION: The introduction of innovative medicines may reveal more efficient and economical conditions in operating rooms. The overall result depends, for example, on the rate of application of the patient's portfolio or the organization and access rules of the surgical suite. Based on the anesthesia-controlled time no general a priori statement about the economic potentials can be confirmed. Future empirical studies should investigate the impact on quality and economic benefits for the entire patient pathway.

Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer.

OBJECTIVE: Docetaxel and carboplatin are active in relapsed ovarian, peritoneal and tubal cancer. Recently, two prospective-randomized trials showed an advantage of carboplatin combination regimen with paclitaxel or gemcitabine over carboplatinum alone in platinum-sensitive cases. The question on the most effective combination with the best tolerable side effects still needs to be answered. METHODS: Eligible patients had recurrent ovarian, peritoneal or tubal cancer (platinum-free interval >6 months), performance status 0-2 and normal bone marrow, renal and hepatic function. 25 patients (age 18-75 years) were enrolled into this phase II trial. Patients with debulking operation of recurrence were excluded from this study. Docetaxel 75 mg/m(2) via 30-min infusion was given on day 1 followed by carboplatin (area under curve [AUC] 5) on day 1. The administration was repeated every 3 weeks over 6 courses. Primary endpoint of this trial was the response rate; secondary endpoints were progression-free survival, overall survival and toxicity. RESULTS: In the intent-to-treat population, there were 16 (64.0%) complete and 2 (8.0%) partial responses resulting in an overall response rate of 72.0%. Three patients (12.0%) showed a stable disease and other 2 patients (8.0%) a progression of cancer. Two patients (8.0%) were not evaluable for response. Neutropenia was the most frequent G3/G4 hematologic toxicity in 15/25 patients (60.0%); but no neutropenic fever occurred in this trial. Diarrhea G3 was the most frequent G3/G4 non-hematologic toxicity in only 3/25 patients (12.0%). Dose-limiting toxicities were hypersensitivity reaction in one and depressive mood alteration requiring therapy in another case. CONCLUSION: Carboplatin in combination with docetaxel is highly active and well tolerated in patients with recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Prospective-randomized trials comparing this with other carboplatin therapeutic doublets in patients with recurrent ovarian cancer are a possible option for the future to answer the question on the best combination regimen.

Toxicity of green tea extracts and their constituents in rat hepatocytes in primary culture.

Recent reports on sporadic cases of liver disorders (acute hepatitis, icterus, hepatocellular necrosis) after ingestion of dietary supplements based on hydro-alcoholic extracts from green tea leaves led to restrictions of the marketing of such products in certain countries of the EU. Since green tea is considered to exert a number of beneficial health effects, and, therefore, green tea products are widely used as dietary supplements, we were interested in the possible mechanism of hepatotoxicity of green tea extracts and in the components involved in such effects. Seven hours after seeding on collagen, rat hepatocytes in primary culture were treated with various hydro-alcoholic green tea extracts (two different native 80% ethanolic dry extracts and an 80% ethanolic dry extract cleared from lipophilic compounds). Cells were washed, and reduction of resazurin, used as a viability parameter monitoring intact mitochondrial function, was determined. It was found that all seven green tea extracts examined enhanced resazurin reduction significantly at a concentration range of 100-500 microg/ml medium, while a significant decrease was observed at 1-3mg/ml medium. Decreased levels were concomitant with abundant necrosis as observed by microscopic inspection of the cultures and with increased leakage of lactate dehydrogenase activity from the cells. In a separate series of experiments, the green tea constituents (-)-epicatechin, (-)-epigallocatechin-3-gallate, caffeine and theanine were tested at concentrations reflecting their levels in a typical green tea extract. Synthetic (+)-epigallocatechin (200 microM) was used for comparison. Cytotoxicity was found with (-)-epigallocatechin-3-gallate only. The concomitant addition of 0.25 mM ascorbate/0.05 mM alpha-tocopherol had no influence on cytotoxicity. In conclusion, our results suggest that high concentrations of green tea extract can exert acute toxicity in rat liver cells. (-)-Epigallocatechin-3-gallate seems to be a key constituent responsible for this effect. The relatively low bioavailability of catechins reported after oral exposure to green tea argues, however, against a causal role of these constituents in the reported liver disorders.

Malassezin--A novel agonist of the arylhydrocarbon receptor from the yeast Malassezia furfur.

The yeast Malassezia furfur converts tryptophan into several indole compounds. One of these, malassezin, was identified as 2-(1H-indol-3-ylmethyl)-1H-indole-3-carbaldehyde (1). It was synthesized from N-Boc-indole-3-carbaldehyde in five steps with 12% overall yield. The compound easily cyclizes to indolo[3,2-b]carbazole (7) which is known to interact with the arylhydrocarbon receptor (AHR). Similarly, malassezin was found to induce cytochrome P450 as an agonist of AHR (EC50 = 1.57 microM) in rat hepatocytes.

Hospital reform and nursing labor market trends in Canada.

OBJECTIVES: Trends in the Canadian registered nurse (RN) workforce during the past 3 decades are examined, and the implications of current hospital sector retrenchment for RN employment are considered. METHODS: A descriptive review using relevant literature and existing databases on the nurse workforce is presented. RESULTS: From the 1960s through the 1980s, the Canadian RN workforce grew exponentially, fueled by expansions in the health-care delivery system under Medicare, rising inpatient acuity and skill-intensive patient care, enhanced access to nursing education, and increases in the numbers of women entering the workforce. Acute care hospitals have and continue to be the predominant employer of RNs. However, the 1990s have witnessed considerable hospital retrenchment, and with that retrenchment the growth of the hospital RN workforce has slowed dramatically. CONCLUSIONS: The ultimate outcomes of hospital retrenchment for the RN workforce remain unclear. Some speculate that the quality of care and working conditions will deteriorate in hospitals, as hospital administrators replace RN staff with lesser trained personnel to reduce costs. Others see change in the hospital sector as an opportunity for RNs to expand their scope of practice and responsibility in outpatient settings. The need for national and international research on the outcomes of hospital restructuring on patient care and the work of RNs is critical to sound policy making.

Promoting nursing practice through nursing research.

ICN is convinced of the importance of nursing research as a means of improving professional education and practice and generating health policies and systems that assure cost-effective use of resources. To this end, ICN is investing heavily in programmes and projects that strengthen the capabilities of ICN and its members to exercise research leadership. Below, three dimensions of research leadership that are important in today's health environment: 1) Fostering research-based practice; 2) Documenting the work and worth of nursing: and 3) Enhancing public understanding of nursing work.

Quality through health policy: the Canadian example.

In Canada, as elsewhere, healthcare policymakers are being asked to make some tough tradeoffs between quality and cost. It is crucial that national nurses' associations take part in these discussions to ensure that nurses' and consumers' interests are well protected. The Canadian Nurses' Association has helped mould national health policy. In the process it has had all the advantages of influence and all the risks of being co-opted by the system itself. Below, an insight into the knowledge gained.

Social reform versus education reform: university nursing education in Canada, 1919-1960.

Nurses' struggle to attain educational parity with other professional groups is closely aligned with the struggle of women for social equality within Canadian institutions. The attempts of nursing educators to shift their perspective from social reform to educational reform and to develop nursing scholarship has been restricted by the cultural views of women. Consequently, nurses' gains in attaining higher education have been realized by reforms in social and health care policies thought suitable for women. With advancement in university nursing education closely tied to social reform, nurses were not expected, nor did they expect, to pursue scholarly enquiry or develop research endeavours. This paper suggests that the feminist movement offers nurses a social and psychological basis from which to complete the educational reform of nursing.