•We directly compared LSM in brain tumors and ischemic stroke patients.•Known neuro-anatomical correlates were found, but differed between etiologies.•Differences in lesion topography and volume only ...partly drive divergent findings.•Lesion-behavior associations are influenced by the etiology causing the lesion.•Similarities across etiologies were mostly found in white matter tracts.
Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary because of how they affect brain tissue and how they are distributed. The inclusion of different etiologies would increase the statistical power but has been critically debated. Meanwhile, findings from lesion studies are a valuable resource for clinicians and used across different etiologies. Therefore, the main objective of the present study was to directly compare lesion-symptom maps for memory and language functions from two populations, a tumor versus a stroke population.
Data from two different studies were combined. Both the brain tumor (N = 196) and stroke (N = 147) patient populations underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For this study, we selected two internationally widely used standardized cognitive tasks, the Rey Auditory Verbal Learning Test and the Verbal Fluency Test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce lesion-symptom maps for these cognitive tasks for both populations separately and combined.
Our lesion-symptom mapping results for the separate patient populations largely followed the expected neuroanatomical pattern based on previous literature. Substantial differences in lesion distribution hindered direct comparison. Still, in brain areas with adequate coverage in both groups, considerable LSM differences between the two populations were present for both memory and fluency tasks. Post-hoc analyses of these locations confirmed that the cognitive consequences of focal brain damage varied between etiologies.
The differences in the lesion-symptom maps between the stroke and tumor population could partly be explained by differences in lesion volume and topography. Despite these methodological limitations, both the lesion-symptom mapping results and the post-hoc analyses confirmed that etiology matters when investigating the cognitive consequences of lesions with lesion-symptom mapping. Therefore, caution is advised with generalizing lesion-symptom results across etiologies.
Preconception care has been acknowledged as an intervention to reduce perinatal mortality and morbidity. However, utilization of preconception care is low because of low awareness of availability and ...benefits of the service. An outreach strategy was employed to promote uptake of preconception care consultations. Its effect on the uptake of preconception care consultations was evaluated within the Healthy Pregnancy 4 All study.
We conducted a community-based intervention study. The outreach strategy for preconception care consultations included four approaches: (1) letters from municipal health services; (2) letters from general practitioners; (3) information leaflets by preventive child healthcare services and (4) encouragement by peer health educators. The target population was set as women aged 18 to 41 years in 14 Dutch municipalities with relatively high perinatal morbidity and mortality rates. We evaluated the effect of the outreach strategy by analyzing uptake of preconception care consultations between February 2013 and December 2014. Registration data of applications for preconception care as well as participant questionnaires were obtained for analysis.
The outreach strategy led to 587 applications for preconception care consultations. The majority of applications (n = 424; 72%) were prompted by the invitation letters (132,129) from the municipalities and general practitioners. The effect of the municipal letter seemed to fade out after 3 months.
Outreach strategies amongst the general population promote uptake of preconception care consultations, although on a small scale and with a temporary effect.
Deep learning has shown remarkable results for image analysis and is expected to aid individual treatment decisions in health care. Treatment recommendations are predictions with an inherently causal ...interpretation. To use deep learning for these applications in the setting of observational data, deep learning methods must be made compatible with the required causal assumptions. We present a scenario with real-world medical images (CT-scans of lung cancer) and simulated outcome data. Through the data simulation scheme, the images contain two distinct factors of variation that are associated with survival, but represent a collider (tumor size) and a prognostic factor (tumor heterogeneity), respectively. When a deep network would use all the information available in the image to predict survival, it would condition on the collider and thereby introduce bias in the estimation of the treatment effect. We show that when this collider can be quantified, unbiased individual prognosis predictions are attainable with deep learning. This is achieved by (1) setting a dual task for the network to predict both the outcome and the collider and (2) enforcing a form of linear independence of the activation distributions of the last layer. Our method provides an example of combining deep learning and structural causal models to achieve unbiased individual prognosis predictions. Extensions of machine learning methods for applications to causal questions are required to attain the long-standing goal of personalized medicine supported by artificial intelligence.
Child sexual abuse (CSA) is a worldwide problem with serious consequences. No recognizable symptom pattern for suspected CSA has yet been identified in very young children. We aim to investigate ...psychosocial symptoms in a sample of children with confirmed or strongly suspected CSA and the interpretations given to such symptoms by independent clinical experts. Secondly we examined whether experts were able to identify confirmed victims of severe CSA. A qualitative study including inductive content analysis of medical files and focus group discussions with independent experts on the interpretation of psychosocial symptoms was conducted. We included 125 children (76 boys, 60.8%, and 49 girls, 39.2%; median age 3.3 years; age range 0–11) who were involved in the Amsterdam sexual abuse case (ASAC) and had been examined for strongly suspected CSA. We identified four themes among the psychosocial symptoms: problems concerning emotions, behavior, toilet training, and development, whether or not associated with the daycare center or the perpetrator. Clinical experts identified signs of posttraumatic stress disorder (PTSD), regression in continence skills (not otherwise explained), and problems triggered by exposure to the perpetrator or the abuse location as concerning symptoms for CSA. Less concerning symptoms were designated as worrisome if they were numerous and there was no clear explanation for these symptoms. A clear symptom pattern was lacking and about half of the confirmed severe victims of CSA did not display any psychosocial problems. Therefore, it is difficult for experts to identify confirmed CSA victims. Thus, the assessment of suspected CSA should be over time and multidisciplinary.
Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment with curative intent for peritoneal metastasis of colorectal cancer (CRC). Currently, there is ...no standardized HIPEC protocol: choice of drug, perfusate temperature, and duration of treatment vary per institute. We investigated the temperature-dependent effectiveness of drugs often used in HIPEC.
The effect of temperature on drug uptake, DNA damage, apoptosis, cell cycle distribution, and cell growth were assessed using the temperature-dependent IC50 and Thermal Enhancement Ratio (TER) values of the chemotherapeutic drugs cisplatin, oxaliplatin, carboplatin, mitomycin-C (MMC), and 5-fluorouracil (5-FU) on 2D and 3D CRC cell cultures at clinically relevant hyperthermic conditions (38-43 °C/60 min).
Hyperthermia alone decreased cell viability and clonogenicity of all cell lines. Treatment with platinum-based drugs and MMC resulted in G2-arrest. Platinum-based drugs display a temperature-dependent synergy with heat, with increased drug uptake, DNA damage, and apoptosis at elevated temperatures. Apoptotic levels increased after treatment with MMC or 5-FU, without a synergy with heat.
Our in vitro results demonstrate that a 60-min exposure of platinum-based drugs and MMC are effective in treating 2D and 3D CRC cell cultures, where platinum-based drugs require hyperthermia (>41 °C) to augment effectivity, suggesting that they are, in principle, suitable for HIPEC.
Migrants from Turkey and Morocco are among the largest ethnic minority groups in several European countries. In this review, we aimed to systematically search, assess and describe the available ...literature on cardiovascular disease (CVD), obesity and other endogenous cardiovascular risk factors among these groups. Although the number of publications covering this topic among Turkish and Moroccan migrants has increased in the past decades, studies among these groups, especially the Moroccan, are still limited. There is a particular lack of information on CVD mortality and morbidity rates. Furthermore, studies are often hampered by low participation rates, small sample sizes and self‐reported data. This further complicates drawing sound conclusions on CVD and risk factors among these migrant groups. The results with regard to CVD morbidity and mortality rates are inconclusive. With regard to CVD risk factors, we tentatively conclude that obesity and diabetes are more common among Turkish and Moroccan migrant groups in Europe than the western European population. In the Turkish population there is also a fair amount of evidence for unfavourable high‐density lipoprotein cholesterol levels. However, more research on this topic among these major ethnic minorities is of high importance.
Context. Forsterite is one of the crystalline dust species that is often observed in protoplanetary disks and solar system comets. Being absent in the interstellar medium, it must be produced during ...the disk lifetime. It can therefore serve as a tracer of dust processing and disk evolution, which can lead to a better understanding of the physical processes occurring in the disk, and possibly planet formation. However, the connection of these processes with the overall disk crystallinity remains unclear. Aims. We aim to characterize the forsterite abundance and spatial distribution in the disk of the Herbig Be star HD 100546, to investigate if a connection exists with the large disk gap. Methods. We use a 2D radiative transfer code, MCMax, to model the circumstellar dust around HD 100546. We use VISIR Q-band imaging to probe the outer disk geometry and mid-infrared features to model the spatial distribution of forsterite. The temperature-dependent shape of the 69 μm feature observed with Herschel⋆⋆⋆/PACS is used as a critical tool to constrain this distribution. Results. We find a crystalline mass fraction of 40–60%, located close to the disk wall between 13 and 20 AU, and possibly farther out at the disk surface. The forsterite is in thermal contact with the other dust species. We put an upper limit on the iron content of forsterite of 0.3%. Conclusions. Optical depth effects play a key role in explaining the observed forsterite features, hiding warm forsterite from view at short wavelengths. The disk wall acts as a showcase: it displays a localized high abundance of forsterite, which gives rise to a high observed crystallinity, while the overall mass fraction of forsterite is a factor of ten lower.
Child sexual abuse (CSA) is a worldwide problem with serious consequences. We hypothesized that worrisome sexual behavior and knowledge would frequently be reported in children assessed after CSA. We ...therefore investigated (A) what types of sexual behaviors and knowledge were reported by parents of young children assessed for CSA; (B) in what cases such behaviors and knowledge were worrisome; and (C) how such children responded verbally and non-verbally during child interviews. We conducted a mixed-methods study, including qualitative inductive content analysis and quantitative analysis. It included 125 children (76 boys, 60.8%; median age 3.3 years, age range 0-11), all involved in the Amsterdam sexual abuse case (ASAC) and examined for highly suspected (
= 71) or confirmed CSA (
= 54). We identified themes from (1) the parent reports: sexual behavior (e.g., self-stimulation, touching others, imitation of sexual acts), fears and anxiety with regard to sexuality, and sexual utterances (sexual slang, references to sexual acts); and (2) the child interviews: behavioral reactions (avoidance, distractive behaviors), emotional reactions (anger, aggression), and verbal reactions (conspicuous utterances, refusal to talk about specific subjects). In 37% of the children the sexual behavior was deemed worrisome or very worrisome. Clinicians who assess children for CSA are advised to focus in particular on sexual behavior problems and inappropriate sexual knowledge.
The purpose of this study was to determine the prevalence of Campylobacter in fresh vegetables and fruits at retail level in the Netherlands, and to estimate its implications on the importance of ...vegetables and fruits as risk factor for campylobacteriosis.
Thirteen of the 5640 vegetable and fruit samples were Campylobacter positive, resulting in a prevalence of 0.23% (95% confidence interval (Cl): 0.12–0.39%). The prevalence of packaged products (0.36%, 95% Cl: 0.17–0.66) was significantly higher than of unpackaged products (0.07; 95% Cl: 0.01–0.27). No statistical differences were found between seasons.
Combining the mean prevalence found in this study with data on the consumption of vegetables and fruits, an exposure of 0.0048 campylobacters ingested per person per day in the Netherlands by transmission via vegetables and fruits, was calculated. This exposure, as input in a Beta-Poisson dose–response model, resulted in an estimated number of 5.3×105 cases of infection with Campylobacter per year for the whole Dutch population. This constitutes the consumption of raw vegetables and fruits, especially when packaged, to be a risk factor for Campylobacter infections.
► The prevalence of Campylobacter in vegetables/fruits in the Netherlands was 0.23%. ► The prevalence was significantly higher for packaged than for unpackaged products. ► This study indicates raw vegetables/fruits as a risk factor for campylobacteriosis.
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