„Disparater Tausch“: Diamanten, Öl und Bürgerkrieg in Afrika

Financing civil wars in Africa depends of the export of raw materials like diamonds or oil as well on the side of government as on the side of rebels. Transnational corporation get big profits by these exports, especially in the monopolised sector of diamond industries. In result, there exists not only an “unequal exchange” because of bad terms of trade, but a “disparate exchange”: natural wealth is exchanged against waste products like weapons and the use of these weapons leads to further destruction and misery

Predicting trajectories of behavioral adjustment in children diagnosed with acute lymphoblastic leukemia

Purpose Previous research showed that children with cancer are at risk for developing behavioral adjustment problems after successful treatment; however, the course of adjustment remains unclear. This study focuses on adjustment trajectories of children during treatment for acute lymphoblastic leukemia (ALL) and aims to distinguish subgroups of patients showing different trajectories during active treatment, and to identify sociodemographic, medical, and psychosocial predictors of the distinct adjustment trajectories. Methods In a multicenter longitudinal study, 108 parents of a child (response rate 80 %) diagnosed with ALL were assessed during induction treatment (T0), after induction/consolidation treatment (T1), and after end of treatment (T2). Trajectories of child behavioral adjustment (Child Behavior Checklist; CBCL) were tested with latent class growth modeling (LCGM) analyses. Results For internalizing behavior, a three-trajectory model was found: a group that experienced no problems (60 %), a group that experienced only initial problems (30 %), and a group that experienced chronic problems (10 %). For externalizing behavior, a three-trajectory model was also found: a group that experienced no problems (83 %), a group that experienced chronic problems (12 %), and a group that experienced increasing problems (5 %). Only parenting stress and baseline QoL (cancer related) were found to contribute uniquely to adjustment trajectories. Conclusions The majority of the children (77 %) showed no or transient behavioral problems during the entire treatment as reported by parents. A substantial group (23 %) shows maladaptive trajectories of internalizing behavioral problems and/or externalizing behavioral problems. Screening for risk factors for developing problems might be helpful in early identification of these children

Stable sulforaphane protects against gait anomalies and modifies bone microarchitecture in the spontaneous STR/Ort model of osteoarthritis

Osteoarthritis (OA), affecting joints and bone, causes physical gait disability with huge socio-economic burden; treatment remains palliative. Roles for antioxidants in protecting against such chronic disorders have been examined previously. Sulforaphane is a naturally occurring antioxidant. Herein, we explore whether SFX-01®, a stable synthetic form of sulforaphane, modifies gait, bone architecture and slows/reverses articular cartilage destruction in a spontaneous OA model in STR/Ort mice. Sixteen mice (n = 8/group) were orally treated for 3 months with either 100 mg/kg SFX-01® or vehicle. Gait was recorded, tibiae were microCT scanned and analysed. OA lesion severity was graded histologically. The effect of SFX-01® on bone turnover markers in vivo was complemented by in vitro bone formation and resorption assays. Analysis revealed development of OA-related gait asymmetry in vehicle-treated STR/Ort mice, which did not emerge in SFX-01®-treated mice. We found significant improvements in trabecular and cortical bone. Despite these marked improvements, we found that histologically-graded OA severity in articular cartilage was unmodified in treated mice. These changes are also reflected in anabolic and anti-catabolic actions of SFX-01® treatment as reflected by alteration in serum markers as well as changes in primary osteoblast and osteoclast-like cells in vitro. We report that SFX-01® improves bone microarchitecture in vivo, produces corresponding changes in bone cell behaviour in vitro and leads to greater symmetry in gait, without marked effects on cartilage lesion severity in STR/Ort osteoarthritic mice. Our findings support both osteotrophic roles and novel beneficial gait effects for SFX-01® in this model of spontaneous OA

The Dutch Consumer Quality Index: an example of stakeholder involvement in indicator development

Background: Like in several other Western countries, in the Dutch health care system regulated competition has been introduced. In order to make this work, comparable information is required about the performance of health care providers in terms of effectiveness, safety and patient experiences. Without further coordination, external actors will all try to force health care providers to be transparent. For health care providers this might result in a situation in which they have to deliver data for several sets of indicators, defined by different actors. Therefore, in the Netherlands an effort is made to define national sets of performance indicators and related measuring instruments. In this article, the following questions are addressed, using patient experiences as an example: - When and how are stakeholders involved in the development of indicators and instruments that measure the patients' experiences with health care providers? - Does this involvement lead to indicators and instruments that match stakeholders' information needs? Discussion: The Dutch experiences show that it is possible to implement national indicator sets and to reach consensus about what needs to be measured. Preliminary evaluations show that for health care providers and health insurers the benefits of standardization outweigh the possible loss of tailor-made information. However, it has also become clear that particular attention should be given to the participation of patient/consumer organisations. Summary: Stakeholder involvement is complex and time-consuming. However, it is the only way to balance the information needs of all the parties that ask for and benefit from transparency, without frustrating the health care system.

Magnetic resonance imaging-based bone imaging of the lower limb: Strategies for generating high-resolution synthetic computed tomography

This study aims at assessing approaches for generating high-resolution magnetic resonance imaging- (MRI-) based synthetic computed tomography (sCT) images suitable for orthopedic care using a deep learning model trained on low-resolution computed tomography (CT) data. To that end, paired MRI and CT data of three anatomical regions were used: high-resolution knee and ankle data, and low-resolution hip data. Four experiments were conducted to investigate the impact of low-resolution training CT data on sCT generation and to find ways to train models on low-resolution data while providing high-resolution sCT images. Experiments included resampling of the training data or augmentation of the low-resolution data with high-resolution data. Training sCT generation models using low-resolution CT data resulted in blurry sCT images. By resampling the MRI/CT pairs before the training, models generated sharper images, presumably through an increase in the MRI/CT mutual information. Alternatively, augmenting the low-resolution with high-resolution data improved sCT in terms of mean absolute error proportionally to the amount of high-resolution data. Overall, the morphological accuracy was satisfactory as assessed by an average intermodal distance between joint centers ranging from 0.7 to 1.2 mm and by an average intermodal root-mean-squared distances between bone surfaces under 0.7 mm. Average dice scores ranged from 79.8% to 87.3% for bony structures. To conclude, this paper proposed approaches to generate high-resolution sCT suitable for orthopedic care using low-resolution data. This can generalize the use of sCT for imaging the musculoskeletal system, paving the way for an MR-only imaging with simplified logistics and no ionizing radiation

Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs

BACKGROUND: Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. METHODS AND FINDINGS: To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 10(10) particles, two logs lower than that used previously. CONCLUSIONS: Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 10(10) rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate

Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours.

Malignant rhabdoid tumour (MRT) is an often lethal childhood cancer that, like many paediatric tumours, is thought to arise from aberrant fetal development. The embryonic root and differentiation pathways underpinning MRT are not firmly established. Here, we study the origin of MRT by combining phylogenetic analyses and single-cell mRNA studies in patient-derived organoids. Comparison of somatic mutations shared between cancer and surrounding normal tissues places MRT in a lineage with neural crest-derived Schwann cells. Single-cell mRNA readouts of MRT differentiation, which we examine by reverting the genetic driver mutation underpinning MRT, SMARCB1 loss, suggest that cells are blocked en route to differentiating into mesenchyme. Quantitative transcriptional predictions indicate that combined HDAC and mTOR inhibition mimic MRT differentiation, which we confirm experimentally. Our study defines the developmental block of MRT and reveals potential differentiation therapies

SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors

Malignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human cancer, yet their contribution to tumorigenesis remains in many cases poorly understood. Here, we study derailed regulatory landscapes as a consequence of SMARCB1 loss in the context of MRT. Our multi-omics approach on patient-derived MRT organoids reveals a dramatic reshaping of the regulatory landscape upon SMARCB1 reconstitution. Chromosome conformation capture experiments subsequently reveal patient-specific looping of distal enhancer regions with the promoter of the MYC oncogene. This intertumoral heterogeneity in MYC enhancer utilization is also present in patient MRT tissues as shown by combined single-cell RNA-seq and ATAC-seq. We show that loss of SMARCB1 activates patient-specific epigenetic reprogramming underlying MRT tumorigenesis

What is the prevalence of fear of cancer recurrence in cancer survivors and patients? A systematic review and individual participant data meta-analysis

This study was supported by the Dutch Cancer Society (KWF) grant number 10936.Objective Care for fear of cancer recurrence (FCR) is considered the most common unmet need among cancer survivors. Yet the prevalence of FCR and predisposing factors remain inconclusive. To support targeted care, we provide a comprehensive overview of the prevalence and severity of FCR among cancer survivors and patients, as measured using the short form of the validated Fear of Cancer Recurrence Inventory (FCRI-SF). We also report on associations between FCR and clinical and demographic characteristics. Methods This is a systematic review and individual participant data (IPD) meta-analysis on the prevalence of FCR. In the review, we included all studies that used the FCRI-SF with adult (≥18 years) cancer survivors and patients. Date of search: 7 February 2020. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. Results IPD were requested from 87 unique studies and provided for 46 studies comprising 11,226 participants from 13 countries. 9311 respondents were included for the main analyses. On the FCRI-SF (range 0–36), 58.8% of respondents scored ≥13, 45.1% scored ≥16 and 19.2% scored ≥22. FCR decreased with age and women reported more FCR than men. FCR was found across cancer types and continents and for all time periods since cancer diagnosis. Conclusions FCR affects a considerable number of cancer survivors and patients. It is therefore important that healthcare providers discuss this issue with their patients and provide treatment when needed. Further research is needed to investigate how best to prevent and treat FCR and to identify other factors associated with FCR. The protocol was prospectively registered (PROSPERO CRD42020142185).Publisher PDFPeer reviewe

Towards patient-led follow-up after curative surgical resection of stage I, II and III colorectal cancer (DISTANCE-trial): a study protocol for a stepped-wedge cluster-randomised trial

Background: Colorectal cancer (CRC) is among the most frequently diagnosed cancers. Approximately 20–30% of stage I-III CRC patients develop a recurrent tumour or metastases after curative surgical resection. Post-operative follow-up is indicated for the first five years after curative surgical resection. As intensified follow-up after curative surgical resection has shown no effect on survival, patient organisations and policy makers have advocated for a more patient-centred approach to follow-up. The objective of this study is to successfully implement patient-led, home-based follow-up (PHFU) in six hospitals in The Netherlands, with as ultimate aim to come to a recommendation for a patient-centred follow-up schedule for stage I-III CRC patients treated with surgical resection with curative intent. Methods: This study is designed as a stepped-wedge cluster-randomised trial (SW-CRT) in six participating centres. During the trial, three centres will implement PHFU after six months; the other three centres will implement PHFU after 12 months of inclusion in the control group. Eligible patients are those with pT2-4N0M0 or pT1-4N1-2M0 CRC, who are 18 years or older and have been free of disease for 12 months after curative surgical resection. The studied intervention is PHFU, starting 12 months after curative resection. The in-hospital, standard-of-care follow-up currently implemented in the participating centres functions as the comparator. The proportion of patients who had contact with the hospital regarding CRC follow-up between 12–24 months after curative surgical resection is the primary endpoint of this study. Quality of life, fear of cancer recurrence, patient satisfaction, cost-effectiveness and survival are the secondary endpoints. Discussion: The results of this study will provide evidence on whether nationwide implementation of PHFU for CRC in The Netherlands will be successful in reducing contact between patient and health care provider. Comparison of PROMs between in-hospital follow-up and PHFU will be provided. Moreover, the cost-effectiveness of PHFU will be assessed. Trial registration: Dutch Trail Register (NTR): NL9266 (Registered on January 1st, 2021)