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BackgroundTechnological progress in artificial intelligence has led to the increasing popularity of virtual assistants, i.e., embodied or disembodied conversational agents that allow chatting with a technical system in a natural language. However, only little comprehensive research is conducted about patients' perceptions and possible applications of virtual assistant in healthcare with cancer patients. This research aims to investigate the key acceptance factors and value-adding use cases of a virtual assistant for patients diagnosed with cancer.MethodsQualitative interviews with eight former patients and four doctors of a Dutch radiotherapy institute were conducted to determine what acceptance factors they find most important for a virtual assistant and gain insights into value-adding applications. The unified theory of acceptance and use of technology (UTAUT) was used to structure perceptions and was inductively modified as a result of the interviews. The subsequent research model was triangulated via an online survey with 127 respondents diagnosed with cancer. A structural equation model was used to determine the relevance of acceptance factors. Through a multigroup analysis, differences between sample subgroups were compared.ResultsThe interviews found support for all factors of the UTAUT: performance expectancy, effort expectancy, social influence and facilitating conditions. Additionally, self-efficacy, trust, and resistance to change, were added as an extension of the UTAUT. Former patients found a virtual assistant helpful in receiving information about logistic questions, treatment procedures, side effects, or scheduling appointments. The quantitative study found that the constructs performance expectancy (ß = 0.399), effort expectancy (ß = 0.258), social influence (ß = 0.114), and trust (ß = 0.210) significantly influenced behavioral intention to use a virtual assistant, explaining 80% of its variance. Self-efficacy (ß = 0.792) acts as antecedent of effort expectancy. Facilitating conditions and resistance to change were not found to have a significant relationship with user intention.ConclusionsPerformance and effort expectancy are the leading determinants of virtual assistant acceptance. The latter is dependent on a patient’s self-efficacy. Therefore, including patients during the development and introduction of a VA in cancer treatment is important. The high relevance of trust indicates the need for a reliable, secure service that should be promoted as such. Social influence suggests using doctors in endorsing the VA.

Purpose This study aimed to establish the functional impact of displacement of urogenital organs after abdominoperineal resection (APR) using validated questionnaires. Methods Patients who underwent APR for primary or recurrent rectal cancer (2001–2018) with evaluable pre- and postoperative radiological imaging and completed urinary (UDI-6, IIQ-7) and sexual questionnaires (male, IIEF; female, FSFI, FSDS-R) were included from 16 centers. Absolute displacement of the internal urethral orifice, posterior bladder wall, distal end of the prostatic urethra, and cervix were correlated to urogenital function by calculating Spearman’s Rho (ρ). Median function scores were compared between minimal or substantial displacement using median split. Results There were 89 male and 36 female patients included, of whom 45 and 19 were sexually active after surgery. Absolute displacement of the internal urethral orifice and posterior bladder wall was not correlated with UDI-6 in men (ρ = 0.119 and ρ = 0.022) nor in women (ρ = − 0.098 and ρ = − 0.154). In men with minimal and substantial displacement of the internal urethral orifice, median UDI-6 scores were 10 (IQR 0–22) and 17 (IQR 5–21), respectively, with corresponding scores of 25 (IQR 10–46) and 21 (IQR 16–36) in women. Displacement of the cervix and FSDS-R were correlated (ρ = 0.433) in sexually active patients. Conclusion This first analysis on functional impact of urogenital organ displacement after APR suggests that more displacement of the cervix might be associated with worse sexual function, while the data does not indicate any potential functional impact of bladder displacement. Studies are needed to further explore this underexposed topic.

Fetal Alcohol Spectrum Disorders affect up to 5% of the population, with additional children affected by prenatal drug exposures. The majority of these children display symptoms of ADHD and poor emotional dysregulation, a common reason for seeking psychiatric care. However, high prevalence of comorbid look-alike symptoms and limited availability of evidence-based treatments complicates psychiatric decision making in this population. The goal of the current study is to report on the effectiveness of psychotropic medications in a case series of 16 individuals with prenatal alcohol/drug exposure and propose a model for psychiatric care for this population. In addition to traditional subjective reports, an objective continuous performance test (T.O.V.A.®) was used to aid with guiding treatment. We found that T.O.V.A.®-scores improved on average from - 6.5 to - 2.9 with our psychiatric approach (p = 0.03). T.O.V.A.®-measurements were helpful in differentiating ADHD symptoms from comorbid symptoms and to guide decision-making on starting and changing medications.

This study aimed to establish the functional impact of displacement of urogenital organs after abdominoperineal resection (APR) using validated questionnaires.Patients who underwent APR for primary or recurrent rectal cancer (2001-2018) with evaluable pre- and postoperative radiological imaging and completed urinary (UDI-6, IIQ-7) and sexual questionnaires (male, IIEF; female, FSFI, FSDS-R) were included from 16 centers. Absolute displacement of the internal urethral orifice, posterior bladder wall, distal end of the prostatic urethra, and cervix were correlated to urogenital function by calculating Spearman's Rho (ρ). Median function scores were compared between minimal or substantial displacement using median split.There were 89 male and 36 female patients included, of whom 45 and 19 were sexually active after surgery. Absolute displacement of the internal urethral orifice and posterior bladder wall was not correlated with UDI-6 in men (ρ = 0.119 and ρ = 0.022) nor in women (ρ = - 0.098 and ρ = - 0.154). In men with minimal and substantial displacement of the internal urethral orifice, median UDI-6 scores were 10 (IQR 0-22) and 17 (IQR 5-21), respectively, with corresponding scores of 25 (IQR 10-46) and 21 (IQR 16-36) in women. Displacement of the cervix and FSDS-R were correlated (ρ = 0.433) in sexually active patients.This first analysis on functional impact of urogenital organ displacement after APR suggests that more displacement of the cervix might be associated with worse sexual function, while the data does not indicate any potential functional impact of bladder displacement. Studies are needed to further explore this underexposed topic.

Objectives: To determine and compare the diagnostic accuracy of assessing injuries on cervical spine computed tomography (CT) scans by trained emergency physicians and radiologists, both in a non-clinical setting. Methods: In this comparative diagnostic accuracy study, 411 cervical spine CT scans, of which 120 contained injuries (fractures and/or dislocations), were divided into 8 subsets. Eight emergency physicians received focused training and assessed 1 subset each before and after training. Four radiologists assessed 2 subsets each. Diagnostic accuracy between both groups was compared. The reference standard used was a multiverified data set, assessed by radiologists, neurosurgeons, and emergency physicians. The neurosurgeons also classified whether an "injury in need of stabilizing therapy" (IST) was present. Results: Posttraining, the emergency physicians demonstrated increased sensitivity and specificity for identifying cervical spine injuries compared to pretraining: sensitivity 88% (95% confidence interval [CI] 80% to 93%) versus 80% (95% CI 72% to 87%) and specificity 89% (95% CI 85% to 93%) versus 86% (95% CI 81% to 89%). When comparing the trained emergency physicians to the group of radiologists, no difference in sensitivity was found, 88% (95% CI 80% to 83%); however, the radiologists showed a significantly higher specificity (P

Additional file 2. An exemplary mockup of conversations with the Exemplary Virtual assistant.

Additional file 1. Interview Guideline.

Aim: This study aimed to quantify displacement of urogenital organs after abdominoperineal resection (APR), and to explore patient and treatment characteristics associated with displacement. Method: Patients from 16 centres who underwent APR for primary or recurrent rectal cancer (2001–2018) with evaluable preoperative and 6–18 months postoperative radiological imaging were included in the study. Anatomical landmarks on sagittal images were related to a coordinate system based on reference lines between fixed bony structures and absolute displacements were calculated using the Pythagorean theorem. Rotation of landmarks was measured relative to a pubic-S5 reference line. Results: There were 248 patients included of which 171 were men and 77 women. The median displacement of the internal urethral orifice was 25 mm in men (maximum 65), and 17 mm in women (maximum 50). Rotation of the internal urethral orifice was in a caudal direction in 160/170 (94%) of men and 65/73 (89%) of women, with a median of 32 degrees (maximum 85) and 33 degrees (maximum 83), respectively. Displacements of the posterior bladder wall, distal end of prostatic urethra and cervix were significantly correlated with the internal urethral orifice. In linear regression analysis, biological mesh reconstruction of the pelvic floor and visceral interposition were significantly associated with increased displacement of the internal urethral orifice, and female gender and any filling of the presacral space with decreased displacement. Conclusions: Substantial absolute displacement and rotation of urogenital organs after APR for rectal cancer were observed, but with high variability among both men and women, and being significantly associated with reconstructive interventions.

Africa is severely affected by floods, with an increasing vulnerability to these events in the most recent decades. Our improved preparation against and response to this hazard would benefit from an enhanced understanding of the physical processes at play. Here, a database of 399 African stream gauges is used to analyze the seasonality of observed annual maximum flood, precipitation and soil moisture between 1981 and 2018. The database includes a total of 11,302 flood events, covering most African regions. The analysis is based on directional statistics to compare the annual maximum river flood with annual maximum rainfall and soil moisture. The results show that the annual maximum flood in most areas is more strongly linked to the annual peak of soil moisture than of annual maximum precipitation. In addition, the interannual variability of flood magnitudes is better explained by the variability of annual maximum soil moisture than by the variability in the annual maximum precipitation. These results have important implications for flood forecasting and the analysis of the long-term evolution of these hydrological hazards in relation with their drivers.

Psychiatric symptoms in children with Fetal Alcohol Spectrum Disorders (FASD) present with high prevalence and morbidity, often across symptom domains, e.g. ADHD-like symptoms, emotional dysregulation and sleep problems. Polypharmacy is often used, but no empirically-based guidelines exist regarding optimal treatment for these children. Moreover, stimulant use in these children is controversial as their responsiveness may be different due to altered neural circuitry associated with prenatal alcohol exposure. The objective of this review is to give an overview of existing data on pharmacological treatments of neurobehavioral symptoms in FASD. Our literature review yielded limited and conflicting clinical data on the effectiveness of pharmacological treatments for psychiatric symptoms in children with FASD, with some symptom domains lacking data altogether. We emphasize the need for clinical trials to guide pharmacological treatments in this complex population.

Quantifying the magnitude and frequency of extreme precipitation events is key in translating climate observations to planning and engineering design. Past efforts have mostly focused on the estimation of daily extremes using gauge observations. Recent development of high-resolution global precipitation products, now allow estimation of global extremes. This research aims to quantitatively characterize the spatiotemporal behavior of precipitation extremes, by calculating extreme precipitation return levels for multiple durations on the global domain using the Multi-Source Weighted-Ensemble Precipitation (MSWEP) dataset. Both classical and novel extreme value distributions are used to provide insight into the spatial patterns of precipitation extremes. Our results show that the traditional Generalized Extreme Value (GEV) distribution and Peak-Over-Threshold (POT) methods, which only use the largest events to estimate precipitation extremes, are not spatially coherent. The recently developed Metastatistical Extreme Value (MEV) distribution, that includes all precipitation events, leads to smoother spatial patterns of local extremes. For durations of 5 and 10 days, however, there are less events per year to fit the distribution (37 and 22 on average, respectively), leading to larger inter-annual variability and possible overestimation of the extremes. While the GEV and POT methods predict a consistent shift from heavy to thin tails with increasing duration, the MEV method predicts a relatively constant heaviness of the tail for any precipitation duration, opening up an important research question on what is the ‘correct’ tail behavior of extreme precipitation for different durations. The generated extreme precipitation return levels and corresponding parameters are provided as the Global Precipitation EXtremes (GPEX) dataset. These data can be useful for studying the underlying physical processes causing the spatiotemporal variations of the heaviness of extreme precipitation distributions.

Understanding the magnitude and frequency of extreme precipitation events is a core component of translating climate observations to planning and engineering design. This research aims to capture extreme precipitation return levels at the global scale. A benchmark of the current climate is created using the global Multi-Source Weighted-Ensemble Precipitation (MSWEP-V2, coverage 1979-2017 at 0.1 arc degree resolution) data, by using both classical and novel extreme value distributions. Traditional extreme value distributions, such as the Generalized Extreme Value (GEV) distribution use annual maxima to estimate precipitation extremes, whereas the novel Metastatistical Extreme Value (MEV) distribution also includes the ordinary precipitation events. Due to this inclusion the MEV is less sensitive to local extremes and thus provides a more reliable and smoothened spatial pattern. The global scale application of methods allows analysis of the complete spatial patterns of the extremes. The generated database of precipitation extremes for high return periods is particularly relevant in otherwise data-sparse regions to provide a benchmark for local engineers and planners.

We introduce the Precipitation Probability DISTribution (PPDIST) dataset, a collection of global high-resolution (0.1°) observation-based climatologies (1979–2018) of the occurrence and peak intensity of precipitation (P) at daily and 3-hourly time-scales. The climatologies were produced using neural networks trained with daily P observations from 93,138 gauges and hourly P observations (resampled to 3-hourly) from 11,881 gauges worldwide. Mean validation coefficient of determination (R2) values ranged from 0.76 to 0.80 for the daily P occurrence indices, and from 0.44 to 0.84 for the daily peak P intensity indices. The neural networks performed significantly better than current state-of-the-art reanalysis (ERA5) and satellite (IMERG) products for all P indices. Using a 0.1 mm 3 h−1 threshold, P was estimated to occur 12.2%, 7.4%, and 14.3% of the time, on average, over the global, land, and ocean domains, respectively. The highest P intensities were found over parts of Central America, India, and Southeast Asia, along the western equatorial coast of Africa, and in the intertropical convergence zone. The PPDIST dataset is available via www.gloh2o.org/ppdist., Measurement(s) hydrological precipitation process • precipitation occurrence • precipitation intensity Technology Type(s) Neural networks models • Gauge or Meter Device • satellite imaging of a planet • reanalyses Factor Type(s) daily and 3-hourly time-scales • year of data collection Sample Characteristic - Environment climate system Sample Characteristic - Location Earth (planet) Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12815585

The Department of Higher Education and Training Teaching Grant for Scholarship of Teaching and Learning.

Sufficient and accurate hydro-meteorological data are essential to manage water resources. Recently developed global re-analysis datasets have significant potential in providing these data, especially in regions such as Southern Africa that are both vulnerable and data poor. These global re-analysis datasets have, however, not yet been exhaustively validated and it is thus unclear to what extent these are able to adequately capture the climatic variability of water resources, in particular for extreme events such as floods. This article critically assesses the potential of a recently developed global Water Resource Re-analysis (WRR) dataset developed in the EU FP7 eartH2Observe project for identifying floods, focussing on the occurrence of floods in the Limpopo River basin in Southern Africa. The discharge outputs of seven global models and ensemble mean of those models as available in the WRR dataset are analysed and compared against two benchmarks of flood events in the Limpopo River basin. The first benchmark is based on observations from the available stations, while the second is developed based on flood events that have led to damages as reported in global databases of damaging flood events. Results show that while the WRR dataset provides useful data for detecting the occurrence of flood events in the Limpopo River basin, variation exists amongst the global models regarding their capability to identify the magnitude of those events. The study also reveals that the models are better able to capture flood events at stations with a large upstream catchment area. Improved performance for most models is found for the 0.25 degrees resolution global model, when compared to the lower resolution 0.5 degrees models, thus underlining the added value of increased resolution global models. The skill of the global hydrological models in identifying the severity of flood events in poorly gauged basins such as the Limpopo can be used to estimate the impacts of those events using the benchmark of reported damaging flood events developed at the basin level, though could be improved if further detail on location and impacts are included in disaster databases. Large-scale models such as those included in the WRR dataset are used by both global and continental forecasting systems, and this study sheds light on the potential these have in providing information useful for local scale flood risk management. In conclusion, this study offers valuable insights in the applicability of global re-analysis data for identifying impacting flood events in data sparse regions.

Contains fulltext : 167519.pdf (Publisher’s version ) (Open Access) Irregular 24 h light/dark cycles with night-time light exposure and a low amplitude are disruptive for sleep, mood and circadian rhythms. Nevertheless such lighting conditions are quite common in medical care facilities. A controlled clinical trial among 196 cardiology ward patients (mean age 66.5 ± 13.1 years SD) investigated how a patient room lighting intervention affects sleep, appraisal and mood across hospitalization. Patients were either assigned to a standardly-lit room or to a room with an interventional lighting system offering a dynamic 24 h light/dark cycle with low nocturnal light exposure and 2 h of bright light (1750 lux) during daytime. Measures included wrist actigraphy and questionnaires assessing alertness, sleep quality, anxiety, depression and lighting appraisal. The median length of hospitalization was 5 days in both study arms. Subjective scores on sleep, alertness, anxiety and depression did not differ between arms. Lighting appraisal in intervention rooms was better as compared to standardly-lit rooms, both in patients (P < 0.001) and staff (P < 0.005). Actigraphic sleep duration of patients improved by 5.9 min (95% CI: 0.6-11.2; P = 0.03 intervention x time effect) per hospitalization day with interventional lighting instead of standard lighting. After 5 days of hospitalization, sleep duration in the lighting intervention rooms increased by 29 min, or a relative 7.3%, as compared to standardly-lit rooms. A 24 h lighting system with enhanced daytime brightness and restricted nocturnal light exposure can improve some aspects of appraisal and objective sleep in hospital patients. More clinical research is needed to establish the best lighting strategy to promote healing and wellbeing within healthcare settings. 11 p.

The ability of intraspinal bone marrow stromal cell (BMSC) transplants to elicit repair is thought to result from paracrine effects by secreted trophic factors including brain-derived neurotrophic factor (BDNF). Here we used gene therapy to increase or silence BDNF production in BMSCs to investigate the role of BDNF in BMSC-mediated neuroprotection. In a spinal cord organotypic culture, BMSC-conditioned medium significantly enhanced spinal motoneuron survival by 64% compared with culture medium only. Only conditioned medium of BDNF-hypersecreting BMSCs sustained this neuroprotective effect. In a rat model of spinal cord contusion, a BDNF-dependent neuroprotective effect was confirmed; only with a subacute transplant of BDNF-hypersecreting BMSCs were significantly more spared motoneurons found at 4 weeks postinjury compared with vehicle controls. Spared nervous tissue volume was improved by 68% with both control BMSCs and BDNF-hypersecreting BMSCs. In addition, blood vessel density in the contusion with BDNF-hypersecreting BMSCs was 35% higher compared with BMSC controls and sixfold higher compared with vehicle controls. BDNF-silenced BMSCs did not survive the first week of transplantation, and no neuroprotective effect was found at 4 weeks after transplantation. Together, our data broaden our understanding of the role of BDNF in BMSC-mediated neuroprotection and successfully exploit BDNF dependency to enhance anatomical spinal cord repair.

Cell therapy for nervous tissue repair is limited by low transplant survival. We investigated the effects of a polyurethane-based reverse thermal gel, poly(ethylene glycol)–poly(serinol hexamethylene urethane) (ESHU) on bone marrow stromal cell (BMSC) transplant survival and repair using a rat model of spinal cord contusion. Transplantation of BMSCs in ESHU at three days post-contusion resulted in a 3.5-fold increase in BMSC survival at one week post-injury and a 66% increase in spared nervous tissue volume at four weeks post-injury. These improvements were accompanied by enhanced hindlimb motor and sensorimotor recovery. In vitro, we found that ESHU protected BMSCs from hydrogen peroxide-mediated death, resulting in a four-fold increase in BMSC survival with two-fold fewer BMSCs expressing the apoptosis marker, caspase 3 and the DNA oxidation marker, 8-oxo-deoxyguanosine. We argue that ESHU protected BMSCs transplanted is a spinal cord contusion from death thereby augmenting their effects on neuroprotection leading to improved behavioral restoration. The data show that the repair effects of intraneural BMSC transplants depend on the degree of their survival and may have a widespread impact on cell-based regenerative medicine.

Transplantation of bone marrow-derived mesenchymal stem cells (MSCs) is a promising therapy for spinal cord repair. Its potential, however, is limited by poor survival of the cells in the damaged nervous tissue. A number of studies have tried to improve MSC transplant survival, yet often with limited or short-term effects. Survival enhancing strategies include optimizing timing of transplantation, suppressing the immune response, transplantation within a scaffold to limit anoikis, reducing reactive oxygen species and/or macrophages, genetically modifying MSCs, and electrical stimulation of the spinal cord. This review provides an overview of studies that have investigated MSC survival after transplantation into animal models of spinal cord injury.

Several recent reports have suggested that peroxisome proliferator-activated receptors (PPARs) may be involved in the development of neoplasias in different tissue types. The present study was undertaken to determine whether PPARs play a role in skin physiology and tumorigenesis. In an initiation-promotion study, SENCAR mice treated topically with the PPARalpha ligands conjugated linoleic acid and 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy-14643) exhibited an approximately 30% lower skin tumor yield compared with mice treated with vehicle. The PPARgamma and PPARdelta activators troglitazone and bezafibrate, respectively, exerted little, if any, inhibitory activity. PPARalpha was detected in normal and hyperplastic skin and in papillomas and carcinomas by immunohistochemistry. In addition, PPARalpha, PPARdelta/PPARbeta, and PPARgamma protein levels were analyzed by immunoblotting in normal epidermis and papillomas. Surprisingly, the levels of all three isoforms were increased significantly in tumors as opposed to normal epidermis. In primary keratinocyte cultures, protein levels of PPARalpha and, to a lesser extent, PPARgamma were markedly increased when the cells were induced to differentiate with high-calcium (0.12 mM) conditions. In addition, we observed that Wy-14643 enhanced transcriptional activity of a peroxisome proliferator-response element-driven promoter in a mouse keratinocyte cell line. These results demonstrate that keratinocytes express functional PPARalpha, that PPARalpha may play a role in differentiation, and that ligands for PPARalpha are moderately protective against skin tumor promotion. We conclude that selective PPARalpha ligands may exert their protective role against skin tumor promotion by ligand activation of PPARalpha.

Department of Pulmonology, University of Limburg, Maastricht, Netherlands.In this study, the release of bactericidal/permeability-increasing protein (BPI), which is stored in polymorphonuclear leukocytes (PMNL), was analyzed in a whole blood ex vivo system. Of the microbial products tested, lipopolysaccharide (LPS) most potently induced BPI release; FMLP, serum-treated zymosan (STZ), and lipoteichoic acid (LTA) also induced BPI release. In addition, the inflammatory mediator tumor necrosis factor (TNF)-alpha potently activated PMNL in whole blood, via TNF receptor p55, to release BPI, whereas interleukin (IL)-1, IL-8, platelet activating factor, and C5a were poor inducers of BPI release. STZ and phorbol myristate acetate, but not LPS, FMLP, or LTA, stimulated isolated PMNL to release BPI. BPI was released in comparable magnitude with the azurophilic granule protein elastase. Furthermore, both proteins were released with similar kinetics, which started within 30 min after onset of stimulation and lasted 1-4 h.

Relationship management is becoming more important in direct marketing. Measuring the strength of relationships is important, since relationship strength can be used as a segmentation variable. However, in measuring relationship strength, usually one or more behavioral indicators are used (e.g., the R/F/M formula), so that these indicators measure customer quality instead of relationship quality, which is mainly determined by customer perceptions. This paper shows some preliminary results of a relationship audit, which is dependent on customer attitudes towards the relationship.

Bone marrow stromal cell (BMSC) transplantation has shown promise for repair of the spinal cord. We showed earlier that a BMSC transplant limits the loss of spinal nervous tissue after a contusive injury. Here, we addressed the premise that BMSC-mediated tissue sparing underlies functional recovery in adult rats after a contusion of the thoracic spinal cord. Our results reveal that after 2 months BMSCs had elicited a significant increase in spared tissue volumes and in blood vessel density in the contusion epicenter. A strong functional relationship existed between spared tissue volumes and blood vessel density. BMSC-transplanted rats exhibited significant improvements in motor, sensorimotor, and sensory functions, which were strongly correlated with spared tissue volumes. Retrograde tracing revealed that rats with BMSCs had twice as many descending brainstem neurons with an axon projecting beyond the contused spinal cord segment and these correlated strongly with the improved motor/sensorimotor functions but not sensory functions. Together, our data indicate that tissue sparing greatly contributes to BMSC-mediated functional repair after spinal cord contusion. The preservation/formation of blood vessels and sparing/regeneration of descending brainstem axons may be important mediators of the BMSC-mediated anatomical and functional improvements.

Characterization of two monoclonal antibodies directed against bactericidal/permeability-increasing protein.Dentener MA, Smit FT, Francot GJ, Buurman WA.Department of Surgery, University of Limburg, Maastricht, Netherlands.In this study the production and characterization of two monoclonal antibodies (MAbs), 4E3 and 5D7, against the bactericidal/permeability-increasing protein (BPI) were described. Using ELISAs, both 4E3 and 5D7 were shown to detect recombinant (r) BPI. Furthermore, natural BPI present in polymorphonuclear leukocytes (PMNL) was detected by both 4E3 and 5D7. The use of both MAbs in flow cytometry revealed that PMNL expressed low levels of cell-surface BPI. Lipopolysaccharide (LPS) was shown to block the interaction between anti-BPI MAb and rBPI. In addition, the MAbs blocked biologic activity of rBPI. The inhibition by BPI of LPS activation of the limulus amebocyte lysate assay and of LPS-induced tumor necrosis factor-alpha release by monocytes was prevented by 4E3 and 5D7. Both MAbs are specifically directed against BPI and can inhibit BPI bioactivity

Contains fulltext : 96846.pdf (Publisher’s version ) (Closed access) PURPOSE: The assessment of the capacity of bone marrow stromal cells (BMSC) to repair the nervous system using gene expression profiling. The evaluation of effects of long-term culturing on the gene expression profile of BMSC. METHODS: Fourty four k whole genome rat microarrays were used to study gene expression of cultured BMSC at passage (P)3 and to compare expression profiles between P3 and P14 BMSC. Quantitative PCR was employed to validate the microarray results. RESULTS: P3 BMSC expressed genes involved in neural developmental events such as glial differentiation, neuron proliferation, and neurite formation. They also express genes encoding for growth factors and for proteins involved in growth factor signaling. A total of 6687 genes were co-expressed in P3 and P14 BMSC. Of these co-expressed genes, 3% (202 genes) was differentially expressed with 159 genes higher in P3 BMSC and 43 genes higher in P14 BMSC. The gene expression patterns were independently validated using quantitative PCR. Functional data mining by Gene Ontology (GO)-analysis revealed that 85/159 and 22/43 genes were annotated in the GO database. In P3 BMSC, 53 GO-classes were overrepresented with several involved in organ development, cell proliferation, and neural repair. In P14 BMSC, three GO-classes were overrepresented with one involved in organ development. CONCLUSIONS: Our gene profiling results suggested a decreased plasticity and repair aptitude of long-term cultured BMSC. Our data indicated the use of early passage BMSC for neural repair approaches.

The central nervous system (CNS) has limited capacity for self-repair. Current treatments are often incapable of reversing the debilitating effects of CNS diseases that result in permanent and/or progressive physical and cognitive impairments. One promising repair strategy is transplantation of stem cells, which can potentially replace lost neurons and/or glia or promote repair through secretion of trophic factors. Various types of stem cells exist, each with their own advantages and disadvantages. Although no consensus exists regarding the optimal cell type to use, moderate functional improvements have been shown in animal models of CNS diseases using different types of stem cells. However, the precise mechanism of action behind their beneficial effects remains unknown. In addition, many barriers to clinical use still need to be resolved before transplantation of stem cells can be used as effective biologics. These barriers include--depending on the stem cell type--possible tumor formation, difficulty with harvest, limited in vivo differentiation and integration, and ethical issues regarding use.

Contains fulltext : 80699.pdf (Publisher’s version ) (Open Access) Bone marrow stromal cells (BMSC) transplanted into the contused spinal cord may support repair by improving tissue sparing. We injected allogeneic BMSC into the moderately contused adult rat thoracic spinal cord at 15 min (acute) and at 3, 7, and 21 days (delayed) post-injury and quantified tissue sparing and BMSC survival up to 4 weeks post-transplantation. BMSC survival within the contusion at 7 days post-transplantation was significantly higher with an acute injection (32%) and 3-day delayed injection (52%) than with a 7- or 21-day delayed injection (9% both; p < 0.01). BMSC survival at 28 days post-transplantation was close to 0 in all paradigms, indicating rejection. In contused rats without a BMSC transplant (controls), the volume of spared tissue gradually decreased until 46% (p < 0.001) of the volume of a comparable uninjured spinal cord segment at 49 days post-injury. In rats with BMSC, injected at 15 min, 3, or 7 days post-injury, spared tissue volume was significantly higher in grafted rats than in control rats at the respective endpoints (i.e., 28, 31, and 35 days post-injury). Acute and 3-day delayed but not 7- and 21-day delayed injection of BMSC significantly improved tissue sparing, which was strongly correlated (r = 0.79-1.0) to BMSC survival in the first week after injection into the contusion. Our data showed that neuroprotective effects of BMSC transplanted into a moderate rat spinal cord contusion depend strongly on their survival during the first week post-injection. Acutely injected BMSC elicit more tissue sparing than delayed injected BMSC.

At the Maastricht Faculty of Economics and Business Administration, the educational approach is based on problem-based learning (PBL). Ten to twelve students in a group, guided by a tutor, discuss problems developed by the staff. This academic year, about 28 groups are formed of all the first year’s economics students. The tutorial group meets twice a week during two-hour sessions. During the first hour students report on previously discussed problems and during the second hour they discuss new problems and generate new learning objectives.

Relationship management is becoming more important, also in direct marketing. Measuring the strength of relationships is relevant, since relationship strength can be used as a segmentation variable. However, in measuring relationship strength, mostly one or more behavioral indicators are used (e.g. the R/F/M-formula). So, these indicators measure customer quality instead of relationship quality, which is mainly determined by customer perceptions. This paper shows some preliminary results of a relationship audit, which depends on customer attitudes towards the relationship.

In order to meet the durability criteria for PEM Fuel Cells, needed for their successful application in transport, more insight is needed into which conditions have a detrimental effect on the long term performance, and which materials improvements are needed to make PEMFC better suited to withstand some of these conditions that are unavoidable in practice. To obtain such insights ex situ model studies under well-defined conditions as well as in situ accelerated stress tests under more realistic conditions have been combined. MEAs using state of the art materials have been subjected to 57 freeze/thaw cycles or 30,000 voltage cycles. Both conditions lead to a decrease in electrochemical surface area; in addition, voltage cycling leads to significant oxygen transport losses. Model studies in perchloric acid revealed that both platinum and carbon corrode when exposed to high potentials at high temperatures. Decreasing temperature leads to a significant decrease in the corrosion rates.

Editor—Inequality of provision of health care because of postcode prescribing is more complex than suggested by Ashcroft.1 Some differences may indeed result from differences in priorities and values between purchasers, but whether a service is funded depends on rates of ill health and funding locally.