Community policing in the Netherlands: A continuously changing constant

__Abstract__ 1977 was an important year for the Dutch police as it was then that a seminal strategy document called ‘A Changing Police was published that would set the course for the next three decades. The writers of the report felt that for the police to bridge the growing gap between them and the society they serve, they would have to be innovative, and think outside of their usual security paradigms. They found their solution in community policing and the strategy document laid out the framework for Community Policing (COP) in the Netherlands. This document was widely considered a milestone in the development of Dutch policing (see Cachet et al. 1998). However, by 2005, the Dutch Board of Chief Commissioners felt it necessary to publish a new strategy document to once again map out the future of Dutch Policing. After nearly three decades, the Dutch police was again in need of a shared philosophy that would serve as a foundation for their mandate. This new document was titled ‘The Police in Evolution’ (PIE) but it stayed true to the values of COP by once again focusing on the local community and stressing community policing. In this paper we explore the establishment and development of Dutch COP. We look at several distinct phases in the long term development of Dutch COP, and examine the factors that explain the shifts that have taken place in the way Dutch COP is carried out. We ask also about the prospects of Dutch COP in the future. The paper will consist of four sections. In the first Section, we examine the historical roots and the development of Dutch COP since its inception in 1977. In Section 2, we look at the current state of affairs for COP in the Netherlands. In the third section, we put forward several explanations for the significant shifts that have taken place over the course of the COP’s 30-year history. In the fourth section, we discuss the prospects for Dutch COP in the coming years. Section 5 presents our conclusions

An isogeometric analysis framework for ventricular cardiac mechanics

The finite element method (FEM) is commonly used in computational cardiac simulations. For this method, a mesh is constructed to represent the geometry and, subsequently, to approximate the solution. To accurately capture curved geometrical features many elements may be required, possibly leading to unnecessarily large computation costs. Without loss of accuracy, a reduction in computation cost can be achieved by integrating geometry representation and solution approximation into a single framework using the Isogeometric Analysis (IGA) paradigm. In this study, we propose an IGA framework suitable for echocardiogram data of cardiac mechanics, where we show the advantageous properties of smooth splines through the development of a multi-patch anatomical model. A nonlinear cardiac model is discretized following the IGA paradigm, meaning that the spline geometry parametrization is directly used for the discretization of the physical fields. The IGA model is benchmarked with a state-of-the-art biomechanics model based on traditional FEM. For this benchmark, the hemodynamic response predicted by the high-fidelity FEM model is accurately captured by an IGA model with only 320 elements and 4,700 degrees of freedom. The study is concluded by a brief anatomy-variation analysis, which illustrates the geometric flexibility of the framework. The IGA framework can be used as a first step toward an efficient workflow for an improved understanding of, and clinical decision support for, the treatment of cardiac diseases like heart rhythm disorders

Cost analysis of robot-assisted versus open transthoracic esophagectomy for resectable esophageal cancer. Results of the ROBOT randomized clinical trial

Background: The previously published ROBOT trial demonstrated that robot assisted minimally invasive esophagectomy (RAMIE) is associated with a lower percentage of postoperative complications compared to open esophagectomy (OTE) for patients with esophageal cancer. The implications of these results on healthcare costs are important given the increased attention for cost-reduction in healthcare. Therefore the aim of this study was to report the hospital costs of RAMIE compared to OTE as treatment for esophageal cancer. Methods: The ROBOT trial randomized 112 patients with esophageal cancer between RAMIE and OTE through January 2012 and August 2016 in a single tertiary care academic centre in the Netherlands. The primary outcome of the current study was hospital costs from the day of esophagectomy until 90 days after discharge based on Time-Driven Activity-Based Costing methodology. Secondary outcomes included the incremental cost-effectiveness ratio per complication prevented and risk factors for increased hospital costs. Results: Of the 112 included patients, 109 patients underwent an esophagectomy, of whom 54 RAMIE and 55 OTE. The mean total hospital costs were comparable between RAMIE €40211 and OTE €39495 (mean difference €-715; bias-corrected and accelerated confidence interval € −14831 to 14783, p = 0.932). At a willingness-to-pay threshold of €20.000 to €25.000 (i.e. estimated additional costs to the hospital to treat patients with a complication) RAMIE had a probability 62%–70% of being cost effective to prevent postoperative complications. In multivariable regression analysis, major postoperative complications were the main driver of hospital costs after esophagectomy (€31839, p = 0.009). Conclusion: In this randomized trial RAMIE resulted in fewer postoperative complications compared to OTE without increasing total hospital costs

The Circular Stapled Esophagogastric Anastomosis in Esophagectomy: No Differences in Anastomotic Insufficiency and Stricture Rates Between the 25 mm and 28 mm Circular Stapler

Background: For patients undergoing an Ivor Lewis esophagectomy with a circular stapled anastomosis, the optimal diameter of the used circular stapler to restore continuity is unknown. The aim of this study was to compare the 25 mm stapled versus the 28 mm stapled esophagogastric anastomosis after Ivor Lewis esophagectomy, focusing on anastomotic insufficiency and postoperative anastomotic strictures. Methods: Between February 2008 and June 2019, 349 consecutive patients underwent Ivor Lewis esophagectomy with gastric conduit reconstruction and circular stapled anastomosis. Patient characteristics and postoperative results, such as anastomotic insufficiency rates, postoperative anastomotic stricture rates, time to anastomotic stricture rate, and the number of dilatations, were recorded in a prospective database and analyzed. Results: In 222 patients (64%), the 25 mm circular stapler was used and in 127 patients (36%) the 28 mm circular stapler was used. There were no differences in baseline characteristics. Anastomotic insufficiency rates were comparable between the 25 mm (12%) and the 28 mm groups (11%) (p = 0.751). There were no differences between postoperative anastomotic strictures in the 25 mm (14%) and the 28 mm groups (14%) (p = 0.863). Within patients with postoperative anastomotic strictures, a median number of 2 dilatations were observed in each group (p = 0.573) without differences in the time to first diagnosis (p = 0.412). Conclusion: There were no differences in anastomotic insufficiency and postoperative anastomotic stricture rates between the 25 mm and the 28 mm circular stapled esophagogastric anastomosis after Ivor Lewis esophagectomy. Both the 25 mm and 28 mm stapler can be safely used to create a circular stapled esophagogastric anastomosis to restore continuity after esophagectomy

The copper-transporting capacity of ATP7A mutants associated with Menkes disease is ameliorated by COMMD1 as a result of improved protein expression

Menkes disease (MD) is an X-linked recessive disorder characterized by copper deficiency resulting in a diminished function of copper-dependent enzymes. Most MD patients die in early childhood, although mild forms of MD have also been described. A diversity of mutations in the gene encoding of the Golgi-resident copper-transporting P1B-type ATPase ATP7A underlies MD. To elucidate the molecular consequences of the ATP7A mutations, various mutations in ATP7A associated with distinct phenotypes of MD (L873R, C1000R, N1304S, and A1362D) were analyzed in detail. All mutants studied displayed changes in protein expression and intracellular localization parallel to a dramatic decline in their copper-transporting capacity compared to ATP7A the wild-type. We restored these observed defects in ATP7A mutant proteins by culturing the cells at 30°C, which improves the quality of protein folding, similar to that which as has recently has been demonstrated for misfolded ATP7B, a copper transporter homologous to ATP7A. Further, the effect of the canine copper toxicosis protein COMMD1 on ATP7A function was examined as COMMD1 has been shown to regulate the proteolysis of ATP7B proteins. Interestingly, in addition to adjusted growth temperature, binding of COMMD1 partially restored the expression, subcellular localization, and copper-exporting activities of the ATP7A mutants. However, no effect of pharmacological chaperones was observed. Together, the presented data might provide a new direction for developing therapies to improve the residual exporting activity of unstable ATP7A mutant proteins, and suggests a potential role for COMMD1 in this process

Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma

Background. Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in neuroblastoma to determine their prognostic value. Methods. We used Southern blot analysis to study the allelic loss of chromosomes 1p, 4p, 11q, and 14q, the duplication of chromosome 17q, and the amplification of the N-myc oncogene in 89 neuroblastomas. We also determined the nuclear DNA content of the tumor cells. Results. Allelic loss of chromosome 1p, N-myc amplification, and extra copies of chromosome 17q were significantly associated with unfavorable outcomes. In a multivariate analysis, loss of chromosome 1p was the most powerful prognostic factor. It provided strong prognostic information when it was included in multivariate models containing the prognostic factors of age and stage or serum ferritin level and stage. Among the patients with stage I, II, or IVS disease, the mean (±SD) three-year event-free survival was 100 percent in those without allelic loss of chromosome 1p and 34±15 percent in those with such loss; the rates of three- year event-free survival among the patients with stage III and stage IV disease were 53±10 percent and 0 percent, respectively. Conclusions. The loss of chromosome 1p is a strong prognostic factor in patients with neuroblastoma, independently of age and stage. It reliably identifies patients at high risk in stages I, II, and IVS, which are otherwise clinically favorable. More intensive therapy may be considered in these patients. Patients in stages III and IV with allelic loss of chromosome 1p have a very poor outlook, whereas those without such loss are at moderate risk

Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes

Neuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma. These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization. In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours

Nationwide Association of Surgical Performance of Minimally Invasive Esophagectomy With Patient Outcomes

IMPORTANCE: Suboptimal surgical performance is hypothesized to be associated with less favorable patient outcomes in minimally invasive esophagectomy (MIE). Establishing this association may lead to programs that promote better surgical performance of MIE and improve patient outcomes.OBJECTIVE: To investigate associations between surgical performance and postoperative outcomes after MIE.DESIGN, SETTING, AND PARTICIPANTS: In this nationwide cohort study of 15 Dutch hospitals that perform more than 20 MIEs per year, 7 masked expert MIE surgeons assessed surgical performance using videos and a previously developed and validated competency assessment tool (CAT). Each hospital submitted 2 representative videos of MIEs performed between November 4, 2021, and September 13, 2022. Patients registered in the Dutch Upper Gastrointestinal Cancer Audit between January 1, 2020, and December 31, 2021, were included to examine patient outcomes.EXPOSURE: Hospitals were divided into quartiles based on their MIE-CAT performance score. Outcomes were compared between highest (top 25%) and lowest (bottom 25%) performing quartiles. Transthoracic MIE with gastric tube reconstruction.MAIN OUTCOME AND MEASURE: The primary outcome was severe postoperative complications (Clavien-Dindo ≥3) within 30 days after surgery. Multilevel logistic regression, with clustering of patients within hospitals, was used to analyze associations between performance and outcomes.RESULTS:In total, 30 videos and 970 patients (mean [SD] age, 66.6 [9.1] years; 719 men [74.1%]) were included. The mean (SD) MIE-CAT score was 113.6 (5.5) in the highest performance quartile vs 94.1 (5.9) in the lowest. Severe postoperative complications occurred in 18.7% (41 of 219) of patients in the highest performance quartile vs 39.2% (40 of 102) in the lowest (risk ratio [RR], 0.50; 95% CI, 0.24-0.99). The highest vs the lowest performance quartile showed lower rates of conversions (1.8% vs 8.9%; RR, 0.21; 95% CI, 0.21-0.21), intraoperative complications (2.7% vs 7.8%; RR, 0.21; 95% CI, 0.04-0.94), and overall postoperative complications (46.1% vs 65.7%; RR, 0.54; 95% CI, 0.24-0.96). The R0 resection rate (96.8% vs 94.2%; RR, 1.03; 95% CI, 0.97-1.05) and lymph node yield (mean [SD], 38.9 [14.7] vs 26.2 [9.0]; RR, 3.20; 95% CI, 0.27-3.21) increased with oncologic-specific performance (eg, hiatus dissection, lymph node dissection). In addition, a high anastomotic phase score was associated with a lower anastomotic leakage rate (4.6% vs 17.7%; RR, 0.14; 95% CI, 0.06-0.31).CONCLUSIONS AND RELEVANCE: These findings suggest that better surgical performance is associated with fewer perioperative complications for patients with esophageal cancer on a national level. If surgical performance of MIE can be improved with MIE-CAT implementation, substantially better patient outcomes may be achievable.</p

Nationwide Association of Surgical Performance of Minimally Invasive Esophagectomy With Patient Outcomes

IMPORTANCE: Suboptimal surgical performance is hypothesized to be associated with less favorable patient outcomes in minimally invasive esophagectomy (MIE). Establishing this association may lead to programs that promote better surgical performance of MIE and improve patient outcomes.OBJECTIVE: To investigate associations between surgical performance and postoperative outcomes after MIE.DESIGN, SETTING, AND PARTICIPANTS: In this nationwide cohort study of 15 Dutch hospitals that perform more than 20 MIEs per year, 7 masked expert MIE surgeons assessed surgical performance using videos and a previously developed and validated competency assessment tool (CAT). Each hospital submitted 2 representative videos of MIEs performed between November 4, 2021, and September 13, 2022. Patients registered in the Dutch Upper Gastrointestinal Cancer Audit between January 1, 2020, and December 31, 2021, were included to examine patient outcomes.EXPOSURE: Hospitals were divided into quartiles based on their MIE-CAT performance score. Outcomes were compared between highest (top 25%) and lowest (bottom 25%) performing quartiles. Transthoracic MIE with gastric tube reconstruction.MAIN OUTCOME AND MEASURE: The primary outcome was severe postoperative complications (Clavien-Dindo ≥3) within 30 days after surgery. Multilevel logistic regression, with clustering of patients within hospitals, was used to analyze associations between performance and outcomes.RESULTS:In total, 30 videos and 970 patients (mean [SD] age, 66.6 [9.1] years; 719 men [74.1%]) were included. The mean (SD) MIE-CAT score was 113.6 (5.5) in the highest performance quartile vs 94.1 (5.9) in the lowest. Severe postoperative complications occurred in 18.7% (41 of 219) of patients in the highest performance quartile vs 39.2% (40 of 102) in the lowest (risk ratio [RR], 0.50; 95% CI, 0.24-0.99). The highest vs the lowest performance quartile showed lower rates of conversions (1.8% vs 8.9%; RR, 0.21; 95% CI, 0.21-0.21), intraoperative complications (2.7% vs 7.8%; RR, 0.21; 95% CI, 0.04-0.94), and overall postoperative complications (46.1% vs 65.7%; RR, 0.54; 95% CI, 0.24-0.96). The R0 resection rate (96.8% vs 94.2%; RR, 1.03; 95% CI, 0.97-1.05) and lymph node yield (mean [SD], 38.9 [14.7] vs 26.2 [9.0]; RR, 3.20; 95% CI, 0.27-3.21) increased with oncologic-specific performance (eg, hiatus dissection, lymph node dissection). In addition, a high anastomotic phase score was associated with a lower anastomotic leakage rate (4.6% vs 17.7%; RR, 0.14; 95% CI, 0.06-0.31).CONCLUSIONS AND RELEVANCE: These findings suggest that better surgical performance is associated with fewer perioperative complications for patients with esophageal cancer on a national level. If surgical performance of MIE can be improved with MIE-CAT implementation, substantially better patient outcomes may be achievable.</p

Mitochondrial DNA methylation in metabolic associated fatty liver disease

INTRODUCTION: Hepatic lipid accumulation and mitochondrial dysfunction are hallmarks of metabolic associated fatty liver disease (MAFLD), yet molecular parameters underlying MAFLD progression are not well understood. Differential methylation within the mitochondrial DNA (mtDNA) has been suggested to be associated with dysfunctional mitochondria, also during progression to Metabolic Steatohepatitis (MeSH). This study further investigates whether mtDNA methylation is associated with hepatic lipid accumulation and MAFLD.METHODS: HepG2 cells were constructed to stably express mitochondria-targeted viral and prokaryotic cytosine DNA methyltransferases (mtM.CviPI or mtM.SssI for GpC or CpG methylation, respectively). A catalytically inactive variant (mtM.CviPI-Mut) was constructed as a control. Mouse and human patients' samples were also investigated. mtDNA methylation was assessed by pyro- or nanopore sequencing.RESULTS AND DISCUSSION: Differentially induced mtDNA hypermethylation impaired mitochondrial gene expression and metabolic activity in HepG2-mtM.CviPI and HepG2-mtM.SssI cells and was associated with increased lipid accumulation, when compared to the controls. To test whether lipid accumulation causes mtDNA methylation, HepG2 cells were subjected to 1 or 2 weeks of fatty acid treatment, but no clear differences in mtDNA methylation were detected. In contrast, hepatic Nd6 mitochondrial gene body cytosine methylation and Nd6 gene expression were increased in mice fed a high-fat high cholesterol diet (HFC for 6 or 20 weeks), when compared to controls, while mtDNA content was unchanged. For patients with simple steatosis, a higher ND6 methylation was confirmed using Methylation Specific PCR, but no additional distinctive cytosines could be identified using pyrosequencing. This study warrants further investigation into a role for mtDNA methylation in promoting mitochondrial dysfunction and impaired lipid metabolism in MAFLD.</p