Psychopathologie Grondslagen, determinanten, mechanismen

Deze studie gaat over de zoektocht naar de determinanten, mechanismen en de kenmerken van psychopathologie vanuit wetenschapsfilosofisch perspectief. Zij is ontstaan vanuit de waarneming dat een overvloed aan data gepaard gaat met een armoede aan goed onderbouwde en diepgaande theorieën. In deze studie gaat het om de filosofische grondslagen die voor theorievorming over psychopathologie nodig zijn. Het reflecteren over grondslagen van de psychopathologie krijgt te weinig aandacht. Het gaat daarbij zowel de filosofie van geneeskunde als om de filosofie van de biologie en de psychologie. Het resultaat van deze studie is onder andere dat psychische stoornissen met een chronisch beloop, als ontwikkelingsstoornissen opgevat, onderzocht en gediagnosticeerd moeten worden. Dat heeft ingrijpende consequenties voor het bestaande onderzoek naar kenmerken van patiënten en hun stoornissen. Als de ontwikkelingsdimensie wordt genegeerd, is de waarde van veel gangbaar onderzoek beperkt: het gaat ten koste van het vermogen om inzicht te krijgen in het ontstaan van een psychische stoornis. Verder beperkt het het vermogen om patiënten vroegtijdig en adequaat (preventief) te behandelen. Stoornissen zijn processen waarbij niets geheel en al vaststaat. Er ligt altijd een gunstige verbetering van de toestand van de patiënt binnen het bereik - hoe klein die verandering ook is.LEI Universiteit LeidenPhilosoph

Point Projection Mapping System for Tracking, Registering, Labeling and Validating Optical Tissue Measurements

Validation of newly developed optical tissue sensing techniques for tumor detection during cancer surgery requires an accurate correlation with histological results. Additionally, such accurate correlation facilitates precise data labeling for developing high-performance machine-learning tissue classification models. In this paper, a newly developed Point Projection Mapping system will be introduced, which allows non-destructive tracking of the measurement locations on tissue specimens. Additionally, a framework for accurate registration, validation, and labeling with histopathology results is proposed and validated on a case study. The proposed framework provides a more robust and accurate method for tracking and validation of optical tissue sensing techniques, which saves time and resources compared to conventional techniques available

Pet-related bacterial zoonotic infections:Three cases of severe infections in the immunocompromised host

Pets can have many positive effects on their owners. However, close contact with pets offers optimal conditions for transmission of micro-organisms. Especially immunocompromised patients are at risk for zoonotic infections. Here we describe the diagnosis, microbiology and treatment of three patients with severe zoonotic infections with Helicobacter canis, Pasteurella multocida and Capnocytophaga canimorsus. With this case report we would like to emphasize the importance of awareness for pet-related zoonotic infections in immunocompromised patients

Demographics of paediatric renal replacement therapy in Europe: 2007 annual report of the ESPN/ERA-EDTA registry

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Alternative administration routes and delivery technologies for polio vaccines

Global polio eradication is closer than ever. Replacement of the live attenuated oral poliovirus vaccine (OPV) by inactivated poliovirus vaccine (IPV) is recommended to achieve complete eradication. Limited global production capacity and relatively high IPV costs compared to OPV spur the need for improved polio vaccines. The target product profile of these vaccines includes not only dose sparing but also high stability, which is important for stockpiling, and easy application important for (emergency) vaccination campaigns. In this review, the current status of alternative polio vaccine delivery strategies is given. Furthermore, we discuss the feasibility of these strategies by highlighting challenges, hurdles to overcome, and formulation issues relevant for optimal vaccine delivery

A quantitative AOP of mitochondrial toxicity based on data from three cell lines

Adverse Outcome Pathways (AOPs) are increasingly used to support the integration of in vitro data in hazard assessment for chemicals. Quantitative AOPs (qAOPs) use mathematical models to describe the relationship between key events (KEs). In this paper, data obtained in three cell lines, LHUMES, HepG2 and RPTEC/TERT1, using similar experimental protocols, was used to calibrate a qAOP of mitochondrial toxicity for two chemicals, rotenone and deguelin. The objectives were to determine whether the same qAOP could be used for the three cell types, and to test chemical-independence by cross-validation with a dataset obtained on eight other chemicals in LHUMES cells. Repeating the calibration approach for both chemicals in three cell lines highlighted various practical difficulties. Even when the same readouts of KEs are measured, the mathematical functions used to describe the key event relationships may not be the same. Cross-validation in LHUMES cells was attempted by estimating chemical-specific potency at the molecular initiating events and using the rest of the calibrated qAOP to predict downstream KEs: toxicity of azoxystrobin, carboxine, mepronil and thifluzamide was underestimated. Selection of most relevant readouts and accurate characterization of the molecular initiating event for cross-validation are critical when designing in vitro experiments targeted at calibrating qAOPs.Toxicolog

Histopathology, salivary flow and ultrasonography of the parotid gland:three complementary measurements in primary Sjögren's syndrome

OBJECTIVE: The involvement of salivary glands in primary Sjögren's syndrome (pSS) can be assessed in different ways: histopathology, salivary flow and ultrasonography. To understand the relative value of these different approaches, it is crucial to understand the relationship between them. As we routinely perform these three modalities in the parotid gland for disease evaluation, our aim was to investigate the construct validity between these modalities in one and the same gland. METHODS: Consecutive sicca patients underwent a multidisciplinary diagnostic work-up including parotid gland biopsy, collection of parotid gland-specific saliva and parotid gland ultrasonography. Patients who were classified as pSS according to the ACR-EULAR criteria were included. Construct validity was assessed using Spearman's correlation coefficients. RESULTS: The 41 included pSS patients completed a full work-up within mean time interval of 2.6 months. Correlations between histopathological features and stimulated parotid salivary flow were fair (ρ=-0.123 for focus score, and ρ=-0.259 for percentage of CD45+ infiltrate). Likewise, poor correlations were observed between stimulated parotid salivary flow and parotid ultrasonography (ρ=-0.196). Moderate to good associations were found between the histopathological items focus score and percentage of CD45+ infiltrate, with parotid ultrasound scores (total ultrasound score: ρ = 0.510 and ρ = 0.560; highest for homogeneity: ρ = 0.574 and ρ = 0.633). CONCLUSION: Although pSS associated ultrasonographic findings did correlate with histopathological features, the three modalities that evaluate salivary gland involvement assess different (or at best partly related) constructs. Therefore, histopathology, salivary flow and ultrasonography are complementary measurements and cannot directly replace each other in the work-up of pSS

Size and depth of residual tumor after neoadjuvant chemoradiotherapy in rectal cancer – implications for the development of new imaging modalities for response assessment

With the shift towards organ preserving treatment strategies in rectal cancer it has become increasingly important to accurately discriminate between a complete and good clinical response after neoadjuvant chemoradiotherapy (CRT). Standard of care imaging techniques such as CT and MRI are well equipped for initial staging of rectal tumors, but discrimination between a good clinical and complete response remains difficult due to their limited ability to detect small residual vital tumor fragments. To identify new promising imaging techniques that could fill this gap, it is crucial to know the size and invasion depth of residual vital tumor tissue since this determines the requirements with regard to the resolution and imaging depth of potential new optical imaging techniques. We analyzed 198 pathology slides from 30 rectal cancer patients with a Mandard tumor regression grade 2 or 3 after CRT that underwent surgery. For each patient we determined response pattern, size of the largest vital tumor fragment or bulk and the shortest distance from the vital tumor to the luminal surface. The response pattern was shrinkage in 14 patients and fragmentation in 16 patients. For both groups combined, the largest vital tumor fragment per patient was smaller than 1mm for 38% of patients, below 0.2mm for 12% of patients and for one patient as small as 0.06mm. For 29% of patients the vital tumor remnant was present within the first 0.01mm from the luminal surface and for 87% within 0.5mm. Our results explain why it is difficult to differentiate between a good clinical and complete response in rectal cancer patients using endoscopy and MRI, since in many patients submillimeter tumor fragments remain below the luminal surface. To detect residual vital tumor tissue in all patients included in this study a technique with a spatial resolution of 0.06mm and an imaging depth of 8.9mm would have been required. Optical imaging techniques offer the possibility of detecting majority of these cases due to the potential of both high-resolution imaging and enhanced contrast between tissue types. These techniques could thus serve as a complimentary tool to conventional methods for rectal cancer response assessment

Мирон Кордуба і українська громада в Москві (штрих до історії візиту 1907 року)

Молодого науковця Мирона Кордубу професор Львівського університету М. Грушевський восени 1907 р. відрядив до Москви з метою опрацювання архівних матеріалів. М. Кордуба активно влився у громадсько-політичне та культурне життя української громади російської столиці. Висвітлено вплив візиту Кордуби на усвідомлення українським студентством Москви своєї ідентичності, розуміння потреби згуртованості та активної позиції у досягненні громадянських та національних прав.Молодого ученого Мирона Кордубу профессор Львовского университета М. Грушевский осенью 1907 г. командировал в Москву с целью изучения архивных материалов. М. Кордуба стал активным участником общественно-политической и культурной жизни столицы. Раскрыто влияние визита Кордубы на степень сплоченности, формирование национального сознания украинского студенчества Москвы.The young scientist Myron Korduba studied historical archives in Moscow in autumn 1907. His civic and cultural activities during this period positively influenced on the unity of Ukrainian student community in Moscow. Lviv scientist helped to identify community goals and methods of obtaining civil and national rights