Self-Supervised Versus Supervised Training for Segmentation of Organoid Images

The process of annotating relevant data in the field of digital microscopy can be both time-consuming and especially expensive due to the required technical skills and human-expert knowledge. Consequently, large amounts of microscopic image data sets remain unlabeled, preventing their effective exploitation using deep-learning algorithms. In recent years it has been shown that a lot of relevant information can be drawn from unlabeled data. Self-supervised learning (SSL) is a promising solution based on learning intrinsic features under a pretext task that is similar to the main task without requiring labels. The trained result is transferred to the main task - image segmentation in our case. A ResNet50 U-Net was first trained to restore images of liver progenitor organoids from augmented images using the Structural Similarity Index Metric (SSIM), alone, and using SSIM combined with L1 loss. Both the encoder and decoder were trained in tandem. The weights were transferred to another U-Net model designed for segmentation with frozen encoder weights, using Binary Cross Entropy, Dice, and Intersection over Union (IoU) losses. For comparison, we used the same U-Net architecture to train two supervised models, one utilizing the ResNet50 encoder as well as a simple CNN. Results showed that self-supervised learning models using a 25\% pixel drop or image blurring augmentation performed better than the other augmentation techniques using the IoU loss. When trained on only 114 images for the main task, the self-supervised learning approach outperforms the supervised method achieving an F1-score of 0.85, with higher stability, in contrast to an F1=0.78 scored by the supervised method. Furthermore, when trained with larger data sets (1,000 images), self-supervised learning is still able to perform better, achieving an F1-score of 0.92, contrasting to a score of 0.85 for the supervised method

Pumping in quantum dots and non-Abelian matrix Berry phases

We have investigated pumping in quantum dots from the perspective of non-Abelian (matrix) Berry phases by solving the time dependent Schr{\"o}dinger equation exactly for adiabatic changes. Our results demonstrate that a pumped charge is related to the presence of a finite matrix Berry phase. When consecutive adiabatic cycles are performed the pumped charge of each cycle is different from the previous ones

LEO and the Big Blue Marble, a Bad Combination for Albedo Errors

Almost all satellites fly Sunsensors for launch and early orbit (LEOP) and safe mode operations. More than 90% of these are analogue Sunsensors with either an analogue or digital interface. The later are quite often referred to as digital Sunsensors but contrary to a true digital Sunsensor, analogue Sunsensors with a digital interface are still largely affected by albedo generated error signals. Depending on the positioning of the sensor on the satellite, the satellites altitude, and the local node time, albedo errors can lead to significant measurement inaccuracies. This paper describes some research into albedo induced errors in analogue fine Sunsensors as performed while using the data generated by the NAPA-2 satellite. This Satellite was built and is operated by ISISpace. This 6 unit Cubesat has one Auriga startracker and three MAUS Sunsensors on board allowing to compare the startracker determined attitude with the Sunsensor determined attitude. Although the study results are far from complete, preliminary results shown a strong influence of the Earth’s albedo on the measurement accuracy of the Sunsensor

Scope effects of respondent uncertainty in contingent valuation : evidence from motorized emission reductions in the city of Nairobi, Kenya

This study analyzed the scope effects of respondent uncertainty in contingent valuation (CV) by evaluating whether willingness to pay (WTP) estimates were sensitive to changes in the magnitudes of motorized emission reductions in the city of Nairobi, Kenya. The WTP estimates were elicited through the conventional payment card (PC), stochastic payment card (SPC) and the polychotomous payment card (PPC) formats. While SPC and PPC formats were used to capture respondent uncertainty, the PC format captured respondent certainty regarding the amounts individuals were WTP for emission reductions. Based on parametric and nonparametric analysis, the results show that certain (PC) respondents stated significantly larger WTP amounts for larger emission reductions than for smaller reductions. Conversely, uncertain (SPC and PPC) respondents stated smaller amounts for larger emission reductions than certain (PC) respondents. The implication is that though respondents were sensitive to the scope of motorized emission reductions, respondent uncertainty lowered their sensitivity to scope.CEEPA, University of Pretoria, Republic of South Africa and CIC, Vrije University Amsterdam, The Netherlands.http://journals.cambridge.org/action/displayJournal?jid=EDE2017-05-06hb2016Agricultural Economics, Extension and Rural Developmen

Applicability of somatic monitoring instructions in clinical practice guidelines on antipsychotic drug use

BACKGROUND: Clinical practice guidelines (CPGs) recommend the monitoring of somatic parameters in patients treated with antipsychotic drugs in order to detect adverse effects. The objective of this study was to assess, in adult and (frail) elderly populations, the consistency and applicability of the somatic monitoring instructions recommended by established CPGs prior to and during antipsychotic drug use. METHODS: A search for national and international CPGs was performed by querying the electronic database PubMed and Google. Somatic monitoring instructions were assessed for adult and (frail) elderly populations separately. The applicability of somatic monitoring instructions was assessed using the Systematic Information for Monitoring (SIM) score. Somatic monitoring instructions were considered applicable when a minimum SIM score of 3 was reached. RESULTS: In total, 16 CPGs were included, with a total of 231 somatic monitoring instructions (mean: 14; range: 0-47). Of the somatic monitoring instructions, 87% were considered applicable, although critical values and how to respond to aberrant values were only present in 28 and 52% of the available instructions respectively. Only 1 CPG presented an instruction specifically for (frail) elderly populations. CONCLUSIONS: We emphasize the need for a guideline with somatic monitoring instructions based on the SIM definition for both adult and (frail) elderly populations using antipsychotic drugs. In addition, CPGs should state that clear agreements should be made regarding who is responsible for interventions and somatic monitoring prior to and during antipsychotic drug use

Understanding the effects of sleep deprivation and acute social stress on cognitive performance using a comprehensive approach

Different professionals (e.g. in the military) have to perform cognitive challenging tasks in multi-stressor environments. However, our understanding how combined stressors interact and affect cognitive performance is limited (Van Dongen & Belenky, 2009). This study examined how sleep deprivation (SD) and acute social stress affect cognitive performance in isolation and in combination, and used a comprehensive approach to find evidence for a (shared) mechanism. Recent research suggests that SD leads to higher amounts of proinflammatory markers (i.e. cytokines) in the blood, which assumedly contribute to a decline in cognitive performance (Irwin, 2019; Shields et al., 2017). In addition, acute social stressors have also been shown to elicit an immune response, as reflected by circulating cytokines in blood (Marsland et al., 2017; Prather et al., 2014). These findings suggest that different stressors may affect cognitive performance through an effect on the immune system. We therefore hypothesize that individuals showing a high proinflammatory response to a combination of two stressors (SD and acute social stress) are more vulnerable to cognitive decline compared to individuals showing a lower proinflammatory response. To test this hypothesis, we measured not only cognitive performance, but also the physiological response and biochemical determinants of metabolism and inflammation at baseline and after SD, but also in response to an acute social stressor (Tkacheenko & Dinges, 2018)

Role of intestinal P-glycoprotein in the plasma and fecal disposition of docetaxel in humans

Multidrug resistance (MDR)-1-P-glycoprotein (P-gp) is a drug-transporting protein that is abundantly present in biliary ductal cells and epithelial cells lining the gastrointestinal tract. Here, we have determined the role of P-gp in the metabolic disposition of the antineoplastic agent docetaxel (Taxotere) in humans. Pharmacokinetic profiles were evaluated in five cancer patients receiving treatment cycles with docetaxel alone (100 mg/m2 i.v. over a 1-h period) and in combination with a new potent inhibitor of P-gp activity, R101933 (200-300 mg b.i.d.). The terminal disposition half-life and total plasma clearance of docetaxel were not altered by treatment with oral R101933 (P > or = 0.27). The cumulative fecal excretion of docetaxel, however, was markedly reduced from 8.47 +/- 2.14% (mean +/- SD) of the dose with the single agent to less than 0.5% in the presence of R101933 (P = 0.0016). Levels of the major cytochrome P450 3A4-mediated metabolites of docetaxel in feces were significantly increased after combination treatment with R101933 (P = 0.010), indicating very prominent and efficient detoxification of reabsorbed docetaxel into hydroxylated compounds before reaching the systemic circulation. It is concluded that intestinal P-gp plays a principal role in the fecal elimination of docetaxel by modulating reabsorption of the drug after hepatobiliary secretion. In addition, the results indicate that inhibition of P-gp activity in normal tissues by effective modulators, and the physiological and pharmacological consequences of this treatment, cannot be predicted based on plasma drug monitoring alone

High-Sugar, High-Saturated-Fat Dietary Patterns Are Not Associated with Depressive Symptoms in Middle-Aged Adults in a Prospective Study

Background: The consumption of unhealthy "Western" dietary patterns has been previously associated with depressive symptoms in different populations. Objective: We examined whether high-sugar and high-saturated-fat dietary patterns are associated with depressive symptoms over 5 y in a British cohort of men and women. Methods: We used data from the Whitehall II study in 5044 individuals (aged 35-55 y). Diet was assessed at phase 7 (2003-2004) using a validated food-frequency questionnaire. Dietary patterns were derived by using reduced rank regression with sugar, saturated fat, and total fat as response variables. The Center for Epidemiological Studies-Depression (CES-D) scale was used to assess depressive symptoms (CES-D sum score ≥16 and/or use of antidepressant medication) at phase 7 and at phase 9 (2008-2009). We applied logistic regression analyses to test the association between dietary patterns and depressive symptoms. All analyses were stratified by sex. Results: In total, 398 cases of recurrent and 295 cases of incident depressive symptoms were observed. We identified 2 dietary patterns: a combined high-sugar and high-saturated-fat (HSHF) and a high-sugar dietary pattern. No association was observed between the dietary patterns and either incidence of or recurrent depressive symptoms in men or women. For example, higher consumption of the HSHF dietary pattern was not associated with recurrent depressive symptoms in men (model 3, quartile 4: OR: 0.67; 95% CI: 0.36, 1.23; P-trend = 0.13) or in women (model 3, quartile 4: OR: 1.26; 95% CI: 0.58, 2.77; P-trend = 0.97). Conclusion: Among middle-aged men and women living in the United Kingdom, dietary patterns containing high amounts of sugar and saturated fat are not associated with new onset or recurrence of depressive symptoms

Measurement of fraction unbound paclitaxel in human plasma

The clinical pharmacokinetic behavior of paclitaxel (Taxol) is distinctly nonlinear, with disproportional increases in systemic exposure with an increase in dose. We have recently shown that Cremophor EL, the formulation vehicle used for i.v. administration of paclitaxel, alters drug distribution as a result of micellar entrapment of paclitaxel, and we speculated that the free drug fraction (fu) is dependent on dose and time-varying concentrations of Cremophor EL in the central plasma compartment. To test this hypothesis, a reproducible equilibrium dialysis method has been developed for the measurement of paclitaxel fu in plasma. Equilibrium dialysis was performed at 37 degrees C in a humidified atmosphere of 5% CO(2) using 2.0-ml polypropylene test tubes. Experiments were carried out with 260-microliter aliquots of plasma containing a tracer amount of [G-(3)H]paclitaxel with high-specific activity against an equal volume of 0.01 M phosphate buffer (pH 7.4). Drug concentrations were measured by both reversed-phase HPLC and liquid scintillation counting. Using this method, fu has been measured in three patients receiving three consecutive 3-weekly courses of paclitaxel at dose levels of 135, 175, and 225 mg/m(2) and found to range between 0.036 and 0.079. The method was also used to define concentration-time profiles of unbound drug, estimated from the product of the total plasma concentration and fu