High-grade, Compact spectrometers for Earth observation from smallsats

The market for nano- and microsatellites is developing rapidly. There is a strong focus on 2D imaging of the Earth\u27s surface, with limited possibilities to obtain spectral information. More demanding applications, such as monitoring trace gases and aerosols, or water quality still require advanced spectral imaging instruments, which are large, heavy and expensive. In recent years TNO has investigated and developed different innovative designs to realize advanced spectrometers for space applications in a more compact and cost-effective manner. This offers multiple advantages: A compact instrument can be flown on a much smaller platform (nano- or microsatellite); a low-cost instrument opens up the possibility to fly multiple instruments in a satellite constellation, improving both global coverage and temporal sampling (e.g. multiple overpasses per day to study diurnal processes); in this way a constellation of low-cost instruments may provide added value to the larger scientific and operational satellite missions (e.g. the Copernicus Sentinel missions); and a small, lightweight spectrometer can easily be mounted on a high-altitude UAV (offering high spatial resolution). Moreover, a low-cost instrument may allow us to break through the \u27cost spiral\u27: lower cost will allow us to take more risk and thus progress faster. This may lead to a much faster development cycle than customary for current Earth-observation instruments. Finally, the TNO designs offer flexibility to tune the performance (spectral range, spectral resolution) of the spectrometer to a specific application. Thus, based on the same basic system design, these instruments offer a wide range of applications to a variety of clients, both inside and outside the scientific community using a quasi-recurrent instrument. In this presentation we will illustrate this innovative approach, using the most mature design of a hyperspectral imaging spectrometer (named \u27Tropolite\u27) as an example. Other, less developed, designs will be presented briefly. We will discuss the different design and manufacturing techniques that were used to realize these very compact and low-cost concepts. The first laboratory test results of a Tropolite breadboard will be presented and commented upon. Based on these test results the feasibility to use Tropolite for different applications (e.g. air quality, water quality, …) will be discussed further. Currently, efforts are being made to realize an in-orbit demonstration of Tropolite

PRISMA: A Novel Approach for Deriving Probabilistic Surrogate Safety Measures for Risk Evaluation

Surrogate Safety Measures (SSMs) are used to express road safety in terms of the safety risk in traffic conflicts. Typically, SSMs rely on assumptions regarding the future evolution of traffic participant trajectories to generate a measure of risk. As a result, they are only applicable in scenarios where those assumptions hold. To address this issue, we present a novel data-driven Probabilistic RISk Measure derivAtion (PRISMA) method. The PRISMA method is used to derive SSMs that can be used to calculate in real time the probability of a specific event (e.g., a crash). Because we adopt a data-driven approach to predict the possible future evolutions of traffic participant trajectories, less assumptions on these trajectories are needed. Since the PRISMA is not bound to specific assumptions, multiple SSMs for different types of scenarios can be derived. To calculate the probability of the specific event, the PRISMA method uses Monte Carlo simulations to estimate the occurrence probability of the specified event. We further introduce a statistical method that requires fewer simulations to estimate this probability. Combined with a regression model, this enables our derived SSMs to make real-time risk estimations. To illustrate the PRISMA method, an SSM is derived for risk evaluation during longitudinal traffic interactions. It is very difficult, if not impossible, to objectively compare the relative merits of two SSMs. Instead, we provide a method for benchmarking our derived SSM with respect to expected risk trends. The application of the benchmarking illustrates that the SSM matches the expected risk trends. Whereas the derived SSM shows the potential of the PRISMA method, future work involves applying the approach for other types of traffic conflicts, such as lateral traffic conflicts or interactions with vulnerable road users.Comment: 26 pages, 4 figures, 1 tabl

Family size and intergenerational social mobility during the fertility transition: evidence of resource dilution from the city of Antwerp in nineteenth century Belgium

It has been argued in sociology, economics, and evolutionary anthropology that family size limitation enhances the intergenerational upward mobility chances in modernized societies. If parents have a large flock, family resources get diluted and intergenerational mobility is bound to head downwards. Yet, the empirical record supporting this resource dilution hypothesis is limited. This article investigates the empirical association between family size limitation and intergenerational mobility in an urban, late nineteenth century population in Western Europe. It uses life course data from the Belgian city of Antwerp between 1846 and 1920. Findings are consistent with the resource dilution hypothesis: after controlling for confounding factors, people with many children were more likely to end up in the lower classes. Yet, family size limitation was effective as a defensive rather than an offensive strategy: it prevented the next generation from going down rather than helping them to climb up the social ladder. Also, family size appears to have been particularly relevant for the middle classes. Implications for demographic transition theory are discussed

Prediction of torsional failure in 22 cadaver femora with and without simulated subtrochanteric metastatic defects: a CT scan-based finite element analysis

BACKGROUND: In metastatic bone disease, prophylactic fixation of impending long bone fracture is preferred over surgical treatment of a manifest fracture. There are no reliable guidelines for prediction of pathological fracture risk, however. We aimed to determine whether finite element (FE) models constructed from quantitative CT scans could be used for predicting pathological fracture load and location in a cadaver model of metastatic bone disease. MATERIAL AND METHODS: Subject-specific FE models were constructed from quantitative CT scans of 11 pairs of human femora. To simulate a metastatic defect, a transcortical hole was made in the subtrochanteric region in one femur of each pair. All femora were experimentally loaded in torsion until fracture. FE simulations of the experimental set-up were performed and torsional stiffness and strain energy density (SED) distribution were determined. RESULTS: In 15 of the 22 cases, locations of maximal SED fitted with the actual fracture locations. The calculated torsional stiffness of the entire femur combined with a criterion based on the local SED distribution in the FE model predicted 82% of the variance of the experimental torsional failure load. INTERPRETATION: In the future, CT scan-based FE analysis may provide a useful tool for identification of impending pathological fractures requiring prophylactic stabilization

CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [Ga-68]Ga-Pentixafor/[Lu-177]Lu-Pentixather

PURPOSE: CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [68Ga]Ga-Pentixafor and its therapeutic counterpart [177Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents. METHODS: CXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and MGMT promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [68Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4. RESULTS: Two large mRNA datasets (N = 284; N = 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients-not directly translatable to [68Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or MGMT status or survival. CONCLUSION: Using immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [68Ga]Ga-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with [177Lu]Lu-Pentixather in the future

Resilience Against Traumatic Stress: Current Developments and Future Directions

Given the high prevalence of stress-related mental disorders, their impact on person, family, and society and the paucity of treatment options for most of these disorders, there is currently a pressing need for innovative approaches to deal with these issues and enhance well-being. One approach which has received increasing attention over the last decade is to shift our scientific and clinical focus from risk factors for psychopathology to factors promoting resilience and mental well-being. In order to summarize and evaluate the current state of scientific affairs on the biological basis of resilience, we provide an overview of the literature on animal and human studies of resilience. Because resilience can only truly be operationalized through longitudinal data collection and analyses, we focus primarily on longitudinal studies. This review shows that the concept of resilience is currently being operationalized, measured and even defined in widely variable manners, both within animal and human studies. We further provide an overview of existing and new strategies that could help promote resilience and which are proposed to be implemented more often in clinical situations. Finally, we summarize the challenges the field is facing and provide recommendations for future research

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Background &amp; Aims: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. Methods: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Results: Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018). Conclusions: In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. Impact and implications: This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. Trial registration number: #NCT02900443.</p

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Background &amp; Aims: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. Methods: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Results: Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018). Conclusions: In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. Impact and implications: This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. Trial registration number: #NCT02900443.</p

In vitro modeling of the neurobiological effects of glucocorticoids: A review

Hypothalamic-pituitary adrenal (HPA)axis dysregulation has long been implicated in stress-related disorders such as major depression and post-traumatic stress disorder. Glucocorticoids (GCs) are released from the adrenal glands as a result of HPA-axis activation. The release of GCs is implicated with several neurobiological changes that are associated with negative consequences of chronic stress and the onset and course of psychiatric disorders. Investigating the underlying neurobiological effects of GCs may help to better understand the pathophysiology of stress-related psychiatric disorders. GCs impact a plethora of neuronal processes at the genetic, epigenetic, cellular, and molecular levels. Given the scarcity and difficulty in accessing human brain samples, 2D and 3D in vitro neuronal cultures are becoming increasingly useful in studying GC effects. In this review, we provide an overview of in vitro studies investigating the effects of GCs on key neuronal processes such as proliferation and survival of progenitor cells, neurogenesis, synaptic plasticity, neuronal activity, inflammation, genetic vulnerability, and epigenetic alterations. Finally, we discuss the challenges in the field and offer suggestions for improving the use of in vitro models to investigate GC effects

Effectiveness of behavioural graded activity compared with physiotherapy treatment in chronic neck pain: design of a randomised clinical trial [ISRCTN88733332]

BACKGROUND: Chronic neck pain is a common complaint in the Netherlands with a point prevalence of 14.3%. Patients with chronic neck pain are often referred to a physiotherapist and, although many treatments are available, it remains unclear which type of treatment is to be preferred. The objective of this article is to present the design of a randomised clinical trial, Ephysion, which examines the clinical and cost effectiveness of behavioural graded activity compared with a physiotherapy treatment for patients with chronic non-specific neck pain. METHODS: Eligible patients with non-specific neck pain persisting longer than 3 months will be randomly allocated to either the behavioural graded activity programme or to the physiotherapy treatment. The graded activity programme is based on an operant approach, which uses a time-contingent method to increase the patient's activity level. This treatment is compared with physiotherapy treatment using a pain-contingent method. Primary treatment outcome is the patient's global perceived effect concerning recovery from the complaint. Global perceived effect on daily functioning is also explored as primary outcome to establish the impact of treatment on daily activity. Direct and indirect costs will also be assessed. Secondary outcomes include the patient's main complaints, pain intensity, medical consumption, functional status, quality of life, and psychological variables. Recruitment of patients will take place up to the end of the year 2004 and follow-up measurement will continue until end 2005