Patient and Informant Views on Visual Hallucinations in Parkinson Disease.

OBJECTIVE Visual hallucinations (VHs) are a very personal experience, and it is not clear whether information about them is best provided by informants or patients. Some patients may not share their hallucinatory experiences with caregivers to avoid distress or for fear of being labeled insane, and others do not have informants at all, which limits the use of informant-based questionnaires. The aim of this study was to compare patient and caregiver views about VHs in Parkinson disease (PD), using the North-East Visual Hallucinations Interview (NEVHI). METHODS Fifty-nine PD patient-informant pairs were included. PD patients and informants were interviewed separately about VHs using the NEVHI. Informants were additionally interviewed using the four-item version of the Neuropsychiatric Inventory. Inter-reliability and concurrent validity of the different measures were compared. RESULTS VHs were more commonly reported by patients than informants. The inter-rater agreement between NEVHI-patient and NEVHI-informant was moderate for complex VHs (Cohen's kappa = 0.44; 95% confidence interval [CI]: 0.13-0.75; t = 3.43, df = 58, p = 0.001) and feeling of presence (Cohen's kappa = 0.35; 95% CI: 0.00-0.70; t = 2.75, df = 58, p = 0.006), but agreement was poor for illusions (Cohen's kappa = 0.25; 95% CI: -0.07-0.57; t = 2.36, df = 58, p = 0.018) and passage hallucinations (Cohen's kappa = 0.16; 95% CI: -0.04-0.36; t = 2.26, df = 58, p = 0.024). CONCLUSION When assessing VHs in PD patients, it is best to rely on patient information, because not all patients share the details of their hallucinations with their caregivers.

What supports students' education in the operating room? A focus group study including students' and surgeons' views.

BACKGROUND AND METHODS We conducted a focus group analysis with students and surgeons on factors which influence medical school students' education in the operating room (OR). The interviews were analyzed using grounded theory. RESULTS The analysis resulted in 18 detailed and easily applyable themes, which were grouped into the four categories: "Students' preparation and organizational aspects", "Learning objectives", "Educational strategies for the teacher", and "Social-environmental aspects". CONCLUSION By including students and surgeons, we were able to extend existing knowledge and enable better understanding of factors influencing teaching in the OR.

Fulminant hepatic and multiple organ failure following acute viral tonsillitis: a case report.

BACKGROUND Pyogenic tonsillitis may often be observed in the general Western population. In severe cases, it may require antibiotic treatment or even hospitalization and often a prompt clinical response will be noted. Here we present an unusual case of progressive multiple organ failure including fulminant liver failure following acute tonsillitis initially mistaken for "classic" pyogenic (that is bacterial) tonsillitis. CASE PRESENTATION A 68-year-old previously healthy white man was referred with suspicion of pyogenic angina. After tonsillectomy, he developed acute liver failure and consecutive multiple organ failure including acute hemodynamic, pulmonary and dialysis-dependent renal failure. Immunohistopathological analysis of his tonsils and liver as well as serum polymerase chain reaction analyses revealed herpes simplex virus-2 to be the causative pathogen. Treatment included high-dose acyclovir and multiorgan supportive intensive care therapy. His final outcome was favorable. CONCLUSIONS Fulminant herpes simplex virus-2-induced multiple organ failure is rarely observed in the Western hemisphere and should be considered a potential diagnosis in patients with tonsillitis and multiple organ failure including acute liver failure. From a clinical perspective, it seems important to note that fulminant herpes simplex virus-2 infection may masquerade as "routine" bacterial severe sepsis/septic shock. This persevering condition should be diagnosed early and treated goal-oriented in order to gain control of this life-threatening condition.

Gesture performance in first- and multiple-episode patients with schizophrenia spectrum disorders

BACKGROUND/AIM Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. METHODS In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. RESULTS Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstrated subtle deficits with a comparable pattern. CONCLUSIONS Subjects with multiple psychotic episodes have severe deficits in gesturing, while only mild impairments were found in first-episode patients independent of age, gender, education and negative symptoms. The results indicate that gesturing is impaired at the onset of disease and likely to further deteriorate during its course.

Fail But Try Again? The Effects of Age, Gender, and Multiple-Owner Experience on Failed Entrepreneurs’ Reentry

We investigate what leads failed entrepreneurs to reenter entrepreneurship by taking a developmental career perspective. Specifically, we hypothesize that the age of failed entrepreneurs has a nonlinear relationship with the likelihood of reentering entrepreneurship that follows different career stages (early, middle, and late). The gender of failed entrepreneurs and multiple-owner experience in the failed firm are hypothesized to be moderators of this relationship. We test our hypotheses using a database consisting of the Swedish population, including 4,761 entrepreneurs who failed between 2000 and 2004. Analyzing their career paths over the years following their failure offers support for our theoretical expectations.

Review of Lodox Statscan in the detection of peripheral skeletal fractures in multiple injury patients

As part of the primary survey, polytrauma patients in our emergency department are examined using the new 'Lodox Statscan' (LS) digital low-radiation imaging device. The LS provides full-body anterior and lateral views based on enhanced linear slot-scanning technology, in accordance with the recommended Advanced Trauma Life Support (ATLS) Guidelines. This study's objectives were to establish whether LS appropriately rules out peripheral bone injuries and to examine whether LS imaging provides adequate information for the preoperative planning of such lesions.

Optimized temperature and deadspace correction improve analysis of multiple breath washout measurements by ultrasonic flowmeter in infants

BACKGROUND: Assessment of lung volume (FRC) and ventilation inhomogeneities with ultrasonic flowmeter and multiple breath washout (MBW) has been used to provide important information about lung disease in infants. Sub-optimal adjustment of the mainstream molar mass (MM) signal for temperature and external deadspace may lead to analysis errors in infants with critically small tidal volume changes during breathing. METHODS: We measured expiratory temperature in human infants at 5 weeks of age and examined the influence of temperature and deadspace changes on FRC results with computer simulation modeling. A new analysis method with optimized temperature and deadspace settings was then derived, tested for robustness to analysis errors and compared with the previously used analysis methods. RESULTS: Temperature in the facemask was higher and variations of deadspace volumes larger than previously assumed. Both showed considerable impact upon FRC and LCI results with high variability when obtained with the previously used analysis model. Using the measured temperature we optimized model parameters and tested a newly derived analysis method, which was found to be more robust to variations in deadspace. Comparison between both analysis methods showed systematic differences and a wide scatter. CONCLUSION: Corrected deadspace and more realistic temperature assumptions improved the stability of the analysis of MM measurements obtained by ultrasonic flowmeter in infants. This new analysis method using the only currently available commercial ultrasonic flowmeter in infants may help to improve stability of the analysis and further facilitate assessment of lung volume and ventilation inhomogeneities in infants.

Color and Scent: How Single Genes Influence Pollinator Attraction

A major function of angiosperm flowers is the recruitment of animal pollinators that serve to transfer pollen among conspecific plants. Distinct sets of floral characteristics, called pollination syndromes, are correlated with visitation by specific groups of pollinators. Switches among pollination syndromes have occurred in many plant families. Such switches must have involved coordinated changes in multiple traits and multiple genes. Two well-studied floral traits affecting pollinator attraction are petal color and scent production. We review current knowledge about the biosynthetic pathways for floral color and scent production and their interaction at the genetic and biochemical levels. A key question in the field concerns the genes that underlie natural variation in color and scent and how such genes affect pollinator preference, reproductive isolation, and ultimately speciation.

Patterns of landscape form in the upper Rhône basin, Central Swiss Alps, predominantly show lithologic controls despite multiple glaciations and variations in rock uplift rates

The development of topography depends mainly on the interplay between uplift and erosion. These processes are controlled by various factors including climate, glaciers, lithology, seismic activity and short-term variables, such as anthropogenic impact. Many studies in orogens all over the world have shown how these controlling variables may affect the landscape's topography. In particular, it has been hypothesized that lithology exerts a dominant control on erosion rates and landscape morphology. However, clear demonstrations of this influence are rare and difficult to disentangle from the overprint of other signals such as climate or tectonics. In this study we focus on the upper Rhône Basin situated in the Central Swiss Alps in order to explore the relation between topography, possible controlling variables and lithology in particular. The Rhône Basin has been affected by spatially variable uplift, high orographically driven rainfalls and multiple glaciations. Furthermore, lithology and erodibility vary substantially within the basin. Thanks to high-resolution geological, climatic and topographic data, the Rhône Basin is a suitable laboratory to explore these complexities. Elevation, relief, slope and hypsometric data as well as river profile information from digital elevation models are used to characterize the landscape's topography of around 50 tributary basins. Additionally, uplift over different timescales, glacial inheritance, precipitation patterns and erodibility of the underlying bedrock are quantified for each basin. Results show that the chosen topographic and controlling variables vary remarkably between different tributary basins. We investigate the link between observed topographic differences and the possible controlling variables through statistical analyses. Variations of elevation, slope and relief seem to be linked to differences in long-term uplift rate, whereas elevation distributions (hypsometry) and river profile shapes may be related to glacial imprint. This confirms that the landscape of the Rhône Basin has been highly preconditioned by (past) uplift and glaciation. Linear discriminant analyses (LDAs), however, suggest a stronger link between observed topographic variations and differences in erodibility. We therefore conclude that despite evident glacial and tectonic conditioning, a lithologic control is still preserved and measurable in the landscape of the Rhône tributary basins.

Deposition and biokinetics of inhaled nanoparticles

Particle biokinetics is important in hazard identification and characterization of inhaled particles. Such studies intend to convert external to internal exposure or biologically effective dose, and may help to set limits in that way. Here we focus on the biokinetics of inhaled nanometer sized particles in comparison to micrometer sized ones.The presented approach ranges from inhaled particle deposition probability and retention in the respiratory tract to biokinetics and clearance of particles out of the respiratory tract. Particle transport into the blood circulation (translocation), towards secondary target organs and tissues (accumulation), and out of the body (clearance) is considered. The macroscopically assessed amount of particles in the respiratory tract and secondary target organs provides dose estimates for toxicological studies on the level of the whole organism. Complementary, microscopic analyses at the individual particle level provide detailed information about which cells and subcellular components are the target of inhaled particles. These studies contribute to shed light on mechanisms and modes of action eventually leading to adverse health effects by inhaled nanoparticles.We review current methods for macroscopic and microscopic analyses of particle deposition, retention and clearance. Existing macroscopic knowledge on particle biokinetics and microscopic views on particle organ interactions are discussed comparing nanometer and micrometer sized particles. We emphasize the importance for quantitative analyses and the use of particle doses derived from real world exposures.

Multiplex assays for biomarker research and clinical application: translational science coming of age

Over the last decade, translational science has come into the focus of academic medicine, and significant intellectual and financial efforts have been made to initiate a multitude of bench-to-bedside projects. The quest for suitable biomarkers that will significantly change clinical practice has become one of the biggest challenges in translational medicine. Quantitative measurement of proteins is a critical step in biomarker discovery. Assessing a large number of potential protein biomarkers in a statistically significant number of samples and controls still constitutes a major technical hurdle. Multiplexed analysis offers significant advantages regarding time, reagent cost, sample requirements and the amount of data that can be generated. The two contemporary approaches in multiplexed and quantitative biomarker validation, antibody-based immunoassays and MS-based multiple (or selected) reaction monitoring, are based on different assay principles and instrument requirements. Both approaches have their own advantages and disadvantages and therefore have complementary roles in the multi-staged biomarker verification and validation process. In this review, we discuss quantitative immunoassay and multiple reaction monitoring/selected reaction monitoring assay principles and development. We also discuss choosing an appropriate platform, judging the performance of assays, obtaining reliable, quantitative results for translational research and clinical applications in the biomarker field.

A two-centre study on facial morphology in patients with complete bilateral cleft lip and palate at nine years of age

The aim of this study was to compare craniofacial morphology and soft tissue profiles in patients with complete bilateral cleft lip and palate at 9 years of age, treated in two European cleft centres with delayed hard palate closure but different treatment protocols. The cephalometric data of 83 consecutively treated patients were compared (Gothenburg, N=44; Nijmegen, N=39). In total, 18 hard tissue and 10 soft tissue landmarks were digitized by one operator. To determine the intra-observer reliability 20 cephalograms were digitized twice with a monthly interval. Paired t-test, Pearson correlation coefficients and multiple regression models were applied for statistical analysis. Hard and soft tissue data were superimposed using the Generalized Procrustes Analysis. In Nijmegen, the maxilla was protrusive for hard and soft tissue values (P=0.001, P=0.030, respectively) and the maxillary incisors were retroclined (P<0.001), influencing the nasolabial angle, which was increased in comparison with Gothenburg (P=0.004). In conclusion, both centres showed a favourable craniofacial form at 9-10 years of age, although there were significant differences in the maxillary prominence, the incisor inclination and soft tissue cephalometric values. Follow-up of these patients until facial growth has ceased, may elucidate components for outcome improvement.

Intratumoral budding as a potential parameter of tumor progression in mismatch repair-proficient and mismatch repair-deficient colorectal cancer patients

In colorectal cancer, tumor budding at the invasive front (peritumoral budding) is an established prognostic parameter and decreased in mismatch repair-deficient tumors. In contrast, the clinical relevance of tumor budding within the tumor center (intratumoral budding) is not yet known. The aim of the study was to determine the correlation of intratumoral budding with peritumoral budding and mismatch repair status and the prognostic impact of intratumoral budding using 2 independent patient cohorts. Following pancytokeratin staining of whole-tissue sections and multiple-punch tissue microarrays, 2 independent cohorts (group 1: n = 289; group 2: n = 222) with known mismatch repair status were investigated for intratumoral budding and peritumoral budding. In group 1, intratumoral budding was strongly correlated to peritumoral budding (r = 0.64; P < .001) and less frequent in mismatch repair-deficient versus mismatch repair-proficient cases (P = .177). Sensitivity and specificity for lymph node positivity were 72.7% and 72.1%. In mismatch repair-proficient cancers, high-grade intratumoral budding was associated with right-sided location (P = .024), advanced T stage (P = .001) and N stage pN (P < .001), vascular invasion (P = .041), infiltrating tumor margin (P = .003), and shorter survival time (P = .014). In mismatch repair-deficient cancers, high intratumoral budding was linked to higher tumor grade (P = .004), vascular invasion (P = .009), infiltrating tumor margin (P = .005), and more unfavorable survival time (P = .09). These associations were confirmed in group 2. High-grade intratumoral budding was a poor prognostic factor in univariate (P < .001) and multivariable analyses (P = .019) adjusting for T stage, N stage distant metastasis, and adjuvant therapy. These preliminary results on 511 patients show that intratumoral budding is an independent prognostic factor, supporting the future investigation of intratumoral budding in larger series of both preoperative and postoperative rectal and colon cancer specimens.

Comprehensive analysis of CpG island methylator phenotype (CIMP)-high, -low, and -negative colorectal cancers based on protein marker expression and molecular features

CpG island methylator phenotype (CIMP) is being investigated for its role in the molecular and prognostic classification of colorectal cancer patients but is also emerging as a factor with the potential to influence clinical decision-making. We report a comprehensive analysis of clinico-pathological and molecular features (KRAS, BRAF and microsatellite instability, MSI) as well as of selected tumour- and host-related protein markers characterizing CIMP-high (CIMP-H), -low, and -negative colorectal cancers. Immunohistochemical analysis for 48 protein markers and molecular analysis of CIMP (CIMP-H: ? 4/5 methylated genes), MSI (MSI-H: ? 2 instable genes), KRAS, and BRAF were performed on 337 colorectal cancers. Simple and multiple regression analysis and receiver operating characteristic (ROC) curve analysis were performed. CIMP-H was found in 24 cases (7.1%) and linked (p < 0.0001) to more proximal tumour location, BRAF mutation, MSI-H, MGMT methylation (p = 0.022), advanced pT classification (p = 0.03), mucinous histology (p = 0.069), and less frequent KRAS mutation (p = 0.067) compared to CIMP-low or -negative cases. Of the 48 protein markers, decreased levels of RKIP (p = 0.0056), EphB2 (p = 0.0045), CK20 (p = 0.002), and Cdx2 (p < 0.0001) and increased numbers of CD8+ intra-epithelial lymphocytes (p < 0.0001) were related to CIMP-H, independently of MSI status. In addition to the expected clinico-pathological and molecular associations, CIMP-H colorectal cancers are characterized by a loss of protein markers associated with differentiation, and metastasis suppression, and have increased CD8+ T-lymphocytes regardless of MSI status. In particular, Cdx2 loss seems to strongly predict CIMP-H in both microsatellite-stable (MSS) and MSI-H colorectal cancers. Cdx2 is proposed as a surrogate marker for CIMP-H.

Negotiating conservation: the construction of meaningful spaces in a world heritage debate

According to one’s personal biography, social background and the resultant degree of affectedness, a person has certain ideas about the meaning of, in our example, a World Heritage Site (WHS), what he or she can expect from it and what his or her relation to it can and should be. The handling of potentially different meaningful spaces is decisive, when it comes to the negotiation of pathways towards the sustainable development of a WHS region. Due to the fact that – in a pluralistic world – multiple realities exist, they have to be taken seriously and adequately addressed. In this article we identified the ways the Jungfrau-Aletsch- WHS was constructed by exploring the visual and verbal representations of the WHS during the decision-making process (1998-2001). The results demonstrate that in the visual representations (images), the WHS was to a large extent presented as an unspoiled natural environment similar to a touristy promotion brochure. Such a ‘picture-book’-like portrait has no direct link to the population’s daily needs, their questions and anxieties about the consequences of a WHS label. By contrast, the verbal representations (articles, letters-to-the-editor, comments) were dominated by issues concerning the economic development of the region, fears of disappropriation, and different views on nature. Whereas visual and verbal representations to a large extent differ significantly, their combination might have contributed to the final decision of the majority of people concerned to support the application for inscription of the Jungfrau-Aletsch-Bietschhorn region into the World Heritage list. The prominence of economic arguments and narratives about intergenerational responsibility in the verbal representations and their combination with the aesthetic appeal of the natural environment in the visual representations might have built a common meaningful space for one part of the population.