Dutch Corporate Finance, 1602-1850

Early Modern Dutch corporate finance had two notable features, a remarkable ease of raising large amounts of capital and a flexible legal framework. Having pioneered new corporate forms with two intercontinental tradi

An Admiralty for Asia: Isaac le Maire and conflicting conceptions about the corporate governance of the VOC

The Dutch East India Company or VOC in 1602 showed many characteristics of modern corporations, including limited liability, freely transferable shares, and well-defined managerial functions. However, we challenge the notion of the VOC as the precursor of modern corporations to argue that the company was a hybrid, combining elements from traditional partnerships with a governance structure modeled on existing public-private partnerships. The company’s charter r

The Formative Years of the Modern Corporation: The Dutch East India Company VOC, 1602-1623

With their legal personhood, permanent capital with transferable shares, separation of ownership and management, and limited liability for both shareholders and managers, the Dutch East India Company (VOC) and subsequently the English East India Company (EIC) are generally considered a major institutional breakthrough. Our analysis of the business operations and notably the financial policy of the VOC during the company’s first two decades in existence shows that its c

Modelo de degeneración del disco intervertebral por punción de la cola de ratas Wistar: evaluación histológica y radiográfica

OBJETIVO: descrever a caracterização histológica e radiográfica do método de indução da degeneração do disco intervertebral da cauda de ratos Wistar induzida por meio de punção. MÉTODOS: ratos Wistar machos adultos foram anestesiados, radiografados e submetidos à punção dos discos intervertebrais localizados entre a sexta e a sétima e a oitava e nona vértebras coccígeas. Para a punção foi utilizada agulha de 20G, que foi introduzida até o ânulo fibroso, e foi realizada dupla rotação de 360º, mantendo-se a mesma posição durante 30 segundos antes da retirada. O disco intermediário aos segmentos lesados (7-8) não foi puncionado e foi utilizado como controle. Foi selecionado o período pós-lesão de 30 dias (n=9) para sacrifício e análise dos discos intervertebrais. Os animais foram radiografados 30 dias após a lesão para análise da altura do disco intervertebral. Os segmentos da cauda foram removidos, fixados e desmineralizados, processados e corados com Hematoxilina-Eosina para avaliação histológica. RESULTADOS: a análise radiográfica revelou a redução significativa da altura dos discos lesados em relação ao controle. A avaliação histológica revelou alterações no núcleo pulposo e ânulo fibroso dos discos lesados em relação ao controle. Não foram observadas diferenças na intensidade de lesão entre os discos proximal e distal. CONCLUSÃO: a degeneração do disco intervertebral da cauda de ratos Wistar induzida por meio de punção mostrou ser método reprodutível para estudo da degeneração do disco intervertebral. Esse modelo mostrou validade para avaliação experimental de novas intervenções terapêuticas nos processos de degeneração do disco intervertebral.OBJECTIVE: to report the induction of intervertebral disc degeneration of the rat caudal spine by needle puncture and its radiographic and histologic characterization. METHODS: adult male Wistar rats were anesthetized, submitted to the X-Ray and then to the needle puncture (20G) of intervertebral disc between the sixth and seventh (proximal segment) and the eighth and ninth (distal segment) coccygeal vertebrae. Radiographies were taken 30 days after lesion for analysis of intervertebral disc height. The intermediate disc (7-8) to injured segments was not punctured and was considered as control. All segments were removed, fixed and demineralized, processed and stained with Hematoxylin-Eosin for histological evaluation. RESULTS: radiographic analysis revealed significant reduction in disc height of lesioned discs compared to control. Similarly, histological analysis revealed significant changes in the nucleus pulposus and annulus fibrosus of the lesioned discs (proximal and distal) relative to the control. There was no difference in the intensity of injury between the proximal and distal discs. CONCLUSION: the experimental model of tail intervertebral disc degeneration by needle puncture reproduced the steps of the intervertebral disc degeneration, assessed by different instruments, and it can be used for experimental evaluation of new therapeutic interventions for intervertebral disc degeneration process.OBJETIVO: describir la caracterización histológica y radiográfica del método de inducción de la degeneración del disco intervertebral de la cola de ratas Wistar, inducida por medio de la punción. MÉTODOS: ratas Wistar machos adultos fueron anestesiados, radiografiados y sometidos a la punción de los discos intervertebrales localizados, entre la sexta y la séptima; y la octava y novena vértebras coccígeas. Para la punción, fue utilizada una aguja de 20G, que fue introducida hasta el ánulo fibroso, y fue realizada una dupla rotación de 360º, manteniendo esta posición durante 30 segundos, previamente a la retirada. El disco intermediario a los segmentos lesionados (7-8) no fue puncionado y fue considerado como control. Fue seleccionado el periodo post-lesión de 30 días (n=9) para sacrificio y análisis de los discos intervertebrales. Los animales fueron radiografiados 30 días después de la lesión para análisis de la altura del disco intervertebral. Los segmentos de la cola fueron removidos, fijados y desmineralizados, procesados y coloreados con hematoxilina-eosina para evaluación histológica. RESULTADOS: el análisis radiográfico mostró una reducción significativa de la altura de los discos lesionados en relación al control. La evaluación histológica mostró alteraciones en el núcleo pulposo y el ánulo fibroso de los discos lesionados en relación al control. No fueron observadas diferencias en la intensidad de la lesión entre los discos proximal y distal. CONCLUSIÓNES: la degeneración del disco intervertebral de la cola de ratas Wistar inducida por medio de punción mostró ser un método reproducible para el estudio de la degeneración del disco intervertebral. Ese modelo mostró validez para la evaluación experimental de nuevas intervenciones terapéuticas en los procesos de la degeneración del disco intervertebral.Capes - PNPDFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Triggering receptor expressed on myeloid cells (TREM)-2 Impairs host defense in experimental melioidosis

Triggering receptor expressed on myeloid cells (TREM) -1 and TREM-2 are key regulators of the inflammatory response that are involved in the clearance of invading pathogens. Melioidosis, caused by the "Tier 1" biothreat agent Burkholderia pseudomallei, is a common form of community-acquired sepsis in Southeast-Asia. TREM-1 has been suggested as a biomarker for sepsis and melioidosis. We aimed to characterize the expression and function of TREM-1 and TREM-2 in melioidosis.Wild-type, TREM-1/3 (Trem-1/3-/-) and TREM-2 (Trem-2-/-) deficient mice were intranasally infected with live B. pseudomallei and killed after 24, and/or 72 h for the harvesting of lungs, liver, spleen, and blood. Additionally, survival studies were performed. Cellular functions were further analyzed by stimulation and/or infection of isolated cells. TREM-1 and TREM-2 expression was increased both in the lung and liver of B. pseudomallei-infected mice. Strikingly, Trem-2-/-, but not Trem-1/3-/-, mice displayed a markedly improved host defense as reflected by a strong survival advantage together with decreased bacterial loads, less inflammation and reduced organ injury. Cellular responsiveness of TREM-2, but not TREM-1, deficient blood and bone-marrow derived macrophages (BMDM) was diminished upon exposure to B. pseudomallei. Phagocytosis and intracellular killing of B. pseudomallei by BMDM and alveolar macrophages were TREM-1 and TREM-2-independent.We found that TREM-2, and to a lesser extent TREM-1, plays a remarkable detrimental role in the host defense against a clinically relevant Gram-negative pathogen in mice: TREM-2 deficiency restricts the inflammatory response, thereby decreasing organ damage and mortality

The Association between Muscle Quantity and Overall Survival Depends on Muscle Radiodensity: A Cohort Study in Non-Small-Cell Lung Cancer Patients

The prognostic value of CT-derived muscle quantity for overall survival (OS) in patients with non-small-cell lung cancer (NSCLC) is uncertain due to conflicting evidence. We hypothesize that increased muscle quantity is associated with better OS in patients with normal muscle radiodensity but not in patients with fatty degeneration of muscle tissue and low muscle radiodensity. We performed an observational cohort study in NSCLC patients treated with radiotherapy. A deep learning algorithm was used to measure muscle quantity as psoas muscle index (PMI) and psoas muscle radiodensity (PMD) on computed tomography. The potential interaction between PMI and PMD for OS was investigated using Cox proportional-hazards regression. Baseline adjustment variables were age, sex, histology, performance score and body mass index. We investigated non-linear effects of continuous variables and imputed missing values using multiple imputation. We included 2840 patients and observed 1975 deaths in 5903 patient years. The average age was 68.9 years (standard deviation 10.4, range 32 to 96) and 1692 patients (59.6%) were male. PMI was more positively associated with OS for higher values of PMD (hazard ratio for interaction 0.915; 95% confidence interval 0.861-0.972; p-value 0.004). We found evidence that high muscle quantity is associated with better OS when muscle radiodensity is higher, in a large cohort of NSCLC patients treated with radiotherapy. Future studies on the association between muscle status and OS should accommodate this interaction in their analysis for more accurate and more generalizable results

Imaging heterogeneity of peptide delivery and binding in solid tumors using SPECT imaging and MRI

Background: As model system, a solid-tumor patient-derived xenograft (PDX) model characterized by high peptide receptor expression and histological tissue homogeneity was used to study radiopeptide targeting. In this solid-tumor model, high tumor uptake of targeting peptides was expected. However, in vivo SPECT images showed substantial heterogeneous radioactivity accumulation despite homogenous receptor distribution in the tumor xenografts as assessed by in vitro autoradiography. We hypothesized that delivery of peptide to the tumor cells is dictated by adequate local tumor perfusion. To study this relationship, sequential SPECT/CT and MRI were performed to assess the role of vascular functionality in radiopeptide accumulation. Methods: High-resolution SPECT and dynamic contrast-enhanced (DCE)-MRI were acquired in six mice bearing PC295 PDX tumors expressing the gastrin-releasing peptide (GRP) receptor. Two hours prior to SPECT imaging, animals received 25 MBq 111In(DOTA-(βAla)2-JMV594) (25 pmol). Images were acquired using multipinhole SPECT/CT. Directly after SPECT imaging, MR images were acquired on a 7.0-T dedicated animal scanner. DCE-MR images were quantified using semi-quantitative and quantitative models. The DCE-MR and SPECT images were spatially aligned to compute the correlations between radioactivity and DCE-MRI-derived parameters over the tumor. Results: Whereas histology, in vitro autoradiography, and multiple-weighted MRI scans all showed homogenous tissue characteristics, both SPECT and DCE-MRI showed heterogeneous distribution patterns throughout the tumor. The average Spearman’s correlation coefficient between SPECT and DCE-MRI ranged from 0.57 to 0.63 for the “exchange-related” DCE-MRI perfusion parameters. Conclusions: A positive correlation was shown between exchange-related DCE-MRI perfusion parameters and the amount of radioactivity accumulated as measured by SPECT, demonstrating that vascular function was an important aspect of radiopeptide distribution in solid tumors. The combined use of SPECT and MRI added crucial information on the perfusion efficiency versus radiopeptide upt

Prognostic factors for overall survival of stage III non-small cell lung cancer patients on computed tomography: a systematic review and meta-analysis

INTRODUCTION: Prognosis prediction is central in treatment decision making and quality of life for non-small cell lung cancer (NSCLC) patients. However, conventional computed tomography (CT) related prognostic factors may not apply to the challenging stage III NSCLC group. The aim of this systematic review was therefore to identify and evaluate CT-related prognostic factors for overall survival (OS) of stage III NSCLC. METHODS: The Medline, Embase, and Cochrane electronic databases were searched.After study selection, risk of bias was estimated for the included studies. Meta-analysis of univariate results was performed when sufficient data were available. RESULTS: 1,595 of the 11,996 retrieved records were selected for full text review, leading to inclusion of 65 studies that reported data of 144,513 stage III NSCLC patients andcompromising 26 unique CT-related prognostic factors. Relevance and validity varied substantially, few studies had low relevance and validity. Only four studies evaluated the added value of new prognostic factors compared with recognized clinical factors. Included studies suggested gross tumor volume (meta-analysis: HR=1.22, 95%CI: 1.05-1.42), tumor diameter, nodal volume, and pleural effusion, are prognostic in patients treated with chemoradiation. Clinical T-stage and location (right/left) were likely not prognostic within stage III NSCLC. Inconclusive are several radiomic features, tumor volume, atelectasis, location (pulmonary lobes, central/peripheral), interstitial lung abnormalities, great vessel invasion, pit-fall sign, and cavitation. CONCLUSIONS: Tumor-size and nodal size-related factors are prognostic for OS in stage III NSCLC. Future studies should carefully report study characteristics and contrast factors with guideline recognized factors to improve evidence evaluation and validation

Cognitive Impairment in Long-Term Survivors of Testicular Cancer More Than 20 Years after Treatment

SIMPLE SUMMARY: Impaired cognition can be a late effect after treatment in long-term testicular cancer survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very-long-term survivors after treatment. In this study, we enrolled testicular cancer survivors with a follow-up duration ≥ 20 years—and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular damage and aging parameters. We included 184 testicular cancer survivors (66 chemotherapy patients, 53 radiotherapy patients, and 65 orchiectomy only patients) and 70 healthy controls. The median follow-up was 26 years. Testicular cancer survivors performed worse on cognitive tests compared to controls. In univariate analysis, the presence of hypogonadism was associated with lower cognitive scores. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. ABSTRACT: Background: Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls. Methods: In this cross-sectional multicenter cohort study, we enrolled TC survivors (treated with orchiectomy followed by CT or RT or orchiectomy only)—with a follow-up duration ≥ 20 years—and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, Category Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular aging parameters, including carotid pulse wave velocity (c-PWV) and advanced glycation end products (AGEs). Results: We included 184 TC survivors (66 CT patients, 53 RT patients, and 65 orchiectomy-only patients) and 70 healthy controls. The median follow-up was 26 years (range: 20–42). TC survivors had a lower combined score of the cognitive tests (mean cumulative Z-score −0.85; 95% CI −1.39 to −0.33) compared to controls (mean 0.67; 95% CI −0.21 to 1.57, p < 0.01). In univariate analysis, the presence of hypogonadism (β −1.50, p < 0.01), high c-PWV (β −0.35, p = 0.09), and high AGEs (β −1.27, p = 0.02) were associated with lower cognitive scores, while only AGEs (β −1.17, p = 0.03) remained a significant predictor in multivariate analysis (Model R2 0.31, p < 0.01). Conclusions: Long-term TC survivors performed worse on cognitive tests compared to controls. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. Trial Registration: NCT02572934