Working alone together Bruns, Hille C
Academy of Management journal,
02/2013, Letnik:
56, Številka:
1
Journal Article
Recenzirano
This study develops theory on how coordination occurs in collaboration across multiple expert domains. Ethnographic fieldwork at two top U.S. universities explored the emerging field of systems ...biology cancer research, an extreme case of cross-functional work. Scientists make diverse contributions compatible by engaging in the coordination practices of joint assessment and consultation and in the collaborative practices of counterprojection and alignment. The study advances a process model of coordination as an ensemble of different types of practices that drive collaboration across domains. Insights into how experts coordinate work within domains and how this affects temporal dynamics of collective work have implications for the literature on cross-functional coordination, innovation, and practice.
Radical environmental change that provokes population decline can impose constraints on the sources of genetic variation that may enable evolutionary rescue. Adaptive toxicant resistance has rapidly ...evolved in Gulf killifish (
) that occupy polluted habitats. We show that resistance scales with pollution level and negatively correlates with inducibility of aryl hydrocarbon receptor (AHR) signaling. Loci with the strongest signatures of recent selection harbor genes regulating AHR signaling. Two of these loci introgressed recently (18 to 34 generations ago) from Atlantic killifish (
). One introgressed locus contains a deletion in
that confers a large adaptive advantage selection coefficient (
) = 0.8. Given the limited migration of killifish, recent adaptive introgression was likely mediated by human-assisted transport. We suggest that interspecies connectivity may be an important source of adaptive variation during extreme environmental change.
Mortality after liver surgery in Germany Filmann, N.; Walter, D.; Schadde, E. ...
British journal of surgery,
October 2019, Letnik:
106, Številka:
11
Journal Article
Recenzirano
Background
Mortality rates after liver surgery are not well documented in Germany. More than 1000 hospitals offer liver resection, but there is no central regulation of infrastructure requirements or ...outcome quality.
Methods
Hospital mortality rates after liver resection were analysed using the standardized hospital discharge data (Diagnosis‐Related Groups, ICD‐10 and German operations and procedure key codes) provided by the Research Data Centre of the Federal Statistical Office and Statistical Offices of the Länder in Wiesbaden, Germany.
Results
A total of 110 332 liver procedures carried out between 2010 and 2015 were identified. The overall hospital mortality rate for all resections was 5·8 per cent. The mortality rate among 17 574 major hepatic procedures was 10·4 per cent. Patients who had surgery for colorectal liver metastases (CRLMs) had the lowest mortality rate among those with malignancy (5·5 per cent), followed by patients with gallbladder cancer (7·1 per cent), hepatocellular carcinoma (9·3 per cent) and intrahepatic cholangiocarcinoma (11·0 per cent). Patients with extrahepatic cholangiocarcinoma had the highest mortality rate (14·6 per cent). The mortality rate for extended hepatectomy was 16·2 per cent and the need for a biliodigestive anastomosis increased this to 25·5 per cent. Failure to rescue after complications led to mortality rates of more than 30 per cent in some subgroups. There was a significant volume–outcome relationship for CRLM surgery in very high‐volume centres (mean 26–60 major resections for CRLMs per year). The mortality rate was 4·6 per cent in very high‐volume centres compared with 7·5 per cent in very low‐volume hospitals (odds ratio 0·60, 95 per cent c.i. 0·42 to 0·77; P < 0·001).
Conclusion
This analysis of outcome data after liver resection in Germany suggests that hospital mortality remains high. There should be more focused research to understand, improve or justify factors leading to this result, and consideration of centralization of liver surgery.
Antecedentes
En Alemania, los datos de mortalidad después de la cirugía no están bien documentados. En más de 1.000 hospitales se realizan resecciones hepáticas, pero no existe una regulación central de los prerrequisitos estructurales necesarios y de la calidad de los resultados.
Métodos
Las tasas de mortalidad hospitalaria relacionadas con las resecciones hepáticas se analizaron utilizando los datos estandarizados del alta hospitalaria (Diagnóstico de grupos relacionados, DRG), la clasificación internacional de enfermedades 10 (ICD10) y la clave de procedimientos y operaciones (códigos OPS) proporcionados por el RDC de la Oficina Federal de Estadística y Oficinas de Estadística de Länder en Wiesbaden, Alemania.
Resultados
Se identificaron un total de 110.332 procedimientos hepáticos (de 2010 a 2015). La tasa global de mortalidad hospitalaria para todas las resecciones fue del 5,8%. Las resecciones hepáticas mayores (n = 15.333) presentaron una mortalidad del 10,4%. Los pacientes con metástasis hepáticas colorrectales (colorectal liver metastases, CRLM) tuvieron la mortalidad más baja de entre los pacientes con neoplasias malignas (5,5%), seguidos de los pacientes con cáncer de vesícula biliar (7,1%), colangiocarcinoma intrahepático (intrahepatic colangiocarcinoma, iCC) (11,0%) y carcinoma hepatocelular (hepatocellular carcinoma, HCC) (9,3%). Los pacientes con colangiocarcinoma extrahepático (extrahepatic cholangiocarcinoma, eCC) presentaron la mortalidad más alta (14,6%). Las hepatectomías extendidas (16,2%) y la necesidad de una anastomosis biliodigestiva (biliodigestive anastomosis, BDA) aumentaron la mortalidad a un 25,5%. La falta de solución de algunas complicaciones llevó a tasas de mortalidad de más del 30% en algunos subgrupos. Hubo una relación significativa volumen‐resultado para las CRLM en centros de alto volumen (25,3 a 59,7 resecciones mayores/año; razón de oportunidades, odds ratio, OR
0,60, i.c. del 95%: 0,42‐0,77; P < 0,001), lo que resultó en una disminución en las tasas de mortalidad de 7,5/6,4/7,5/6,5% a 4,6%.
Conclusión
El análisis de los resultados después de la resección hepática en Alemania muestra una alta mortalidad hospitalaria inesperada. Este análisis indica la necesidad de efectuar una investigación más específica para comprender, mejorar o justificar los factores que determinan estos hallazgos.
Mortality following liver surgery has been analysed using data from the Federal Statistical Office from 2010 to 2015. Overall mortality in more than 100 000 resections was 5·8 per cent, and that after major resections was 10·4 per cent. A volume–outcome relationship was evident after major resections for colorectal liver metastases (CRLMs) in centres performing more than 25 major resections per year, with the mortality rate decreasing from more than 6·5 per cent to 4·6 per cent. DRG, Diagnosis‐Related Groups; ECC, extrahepatic cholangiocarcinoma; BDA, biliodigestive anastomosis.
Case for centralilzation of liver surgery
The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed ...to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome.
This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan–Meier method.
Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval CI 35.9–66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6–34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8–21.3) in patients with unresectable disease (P < 0.001).
Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for pre-planned and continuous evaluation for metastatic resection in high-volume centres.
NCT00433927.
•We report a central review for resectability of 448 patients with metastatic colorectal cancer receiving first-line therapy (FIRE-3 trial).•Twenty-two percent of the patients before systemic therapy and 53% of the patients at best response were considered candidates for resection.•Actual reported resectability was 16% in the evaluated cohort.•Actual resection rates were significantly associated with treatment context (university hospital versus other hospitals/practices).
In biological tissues, 19F magnetic resonance (MR) enables the non-invasive, background-free detection of 19F-containing biomarkers. However, the signal-to-noise ratio (SNR) is usually low because ...biomarkers are typically present at low concentrations. Measurements at low magnetic fields further reduce the SNR. In a proof-of-principal study we applied LED-based photo-chemically induced dynamic nuclear polarization (photo-CIDNP) to amplify the 19F signal at 0.6 T. For the first time, 19F MR imaging (MRI) and spectroscopy (MRS) of a fully biocompatible model system containing the antiviral drug favipiravir has been successfully performed. This fluorinated drug has been used to treat Ebola and COVID-19. Since the partially cyclic reaction scheme for photo-CIDNP allows for multiple data acquisitions, averaging further improved the SNR. The mean signal gain factor for 19F has been estimated to be in the order of 103. An in-plane resolution of 0.39 × 0.39 mm2 enabled the analysis of spatially varying degrees of hyperpolarization. The minimal detectable amount of favipiravir per voxel was estimated to about 500 pmol. The results show that 19F photo-CIDNP is a promising method for the non-invasive detection of suitable 19F-containing drugs and other compounds with very low levels of the substance.
The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) ...thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer.
Histopathologic regression following neoadjuvant treatment (NT) of oesophageal cancer is a prognostic factor of survival, but the nodal status is not considered. Here, a score combining both to ...improve prediction of survival after neoadjuvant therapy is developed.
Seven hundred and fifteen patients with oesophageal squamous cell (SCC) or adenocarcinoma (AC) undergoing NT and esophagectomy were analysed. Histopathologic response was classified according to percentage of vital residual tumour cells (VRTC): complete response (CR) without VRTC, major response with <10% VRTC, minor response with >10% VRTC. Nodal stage was classified as ypN0 and ypN+. Kaplan-Meier and Cox regression were used for survival analysis.
Survival analysis identified three groups with significantly different mortality risks: (1) low-risk group for CR (ypT0N0) with 72% 5-year overall survival (5y-OS), (2) intermediate-risk group for minor/major responders and ypN0 with 59% 5y-OS, and (3) high-risk group for minor/major responders and ypN+ with 20% 5y-OS (p < 0.001). Median survival in AC and SCC cohorts were comparable (3.8 (CI 95%: 3.1, 5.3) vs. 4.6 years (CI 95%: 3.3, not reached), p = 0.3).
Histopathologic regression and nodal status should be combined for estimating AC and SCC prognosis. Poor survival in the high-risk group highlights need for adjuvant therapy.
BACKGROUND AND PURPOSE
BAF312 is a next‐generation sphingosine 1‐phosphate (S1P) receptor modulator, selective for S1P1 and S1P5 receptors. S1P1 receptors are essential for lymphocyte egress from ...lymph nodes and a drug target in immune‐mediated diseases. Here, we have characterized the immunomodulatory potential of BAF312 and the S1P receptor‐mediated effects on heart rate using preclinical and human data.
EXPERIMENTAL APPROACH
BAF312 was tested in a rat experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological recordings of G‐protein‐coupled inwardly rectifying potassium (GIRK) channels were carried out in human atrial myocytes. A Phase I multiple‐dose trial studied the pharmacokinetics, pharmacodynamics and safety of BAF312 in 48 healthy subjects.
KEY RESULTS
BAF312 effectively suppressed EAE in rats by internalizing S1P1 receptors, rendering them insensitive to the egress signal from lymph nodes. In healthy volunteers, BAF312 caused preferential decreases in CD4+ T cells, Tnaïve, Tcentral memory and B cells within 4–6 h. Cell counts returned to normal ranges within a week after stopping treatment, in line with the elimination half‐life of BAF312. Despite sparing S1P3 receptors (associated with bradycardia in mice), BAF312 induced rapid, transient (day 1 only) bradycardia in humans. BAF312‐mediated activation of GIRK channels in human atrial myocytes can fully explain the bradycardia.
CONCLUSION AND IMPLICATIONS
This study illustrates species‐specific differences in S1P receptor specificity for first‐dose cardiac effects. Based on its profound but rapidly reversible inhibition of lymphocyte trafficking, BAF312 may have potential as a treatment for immune‐mediated diseases.
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