Large deviations for heavy-tailed random elements in convex cones

We prove large deviation results for sums of heavy-tailed random elements in rather general convex cones being semigroups equipped with a rescaling operation by positive real numbers. In difference to previous results for the cone of convex sets, our technique does not use the embedding of cones in linear spaces. Examples include the cone of convex sets with the Minkowski addition, positive half-line with maximum operation and the family of square integrable functions with arithmetic addition and argument rescaling.

Multimorbidity in adult asylum seekers: a first overview

PRINCIPALS Over the last two decades, the total annual number of applications for asylum in the countries of the European Union has increased from 15,000 to more than 300,000 people. The aim of this study was to give a first overview on multimorbidity of adult asylum seekers. METHODS Our retrospective Swiss single center data analysis examined multimorbidity of adult asylums seekers admitted to our ED between 1 January 2000 and 31 December 2012. RESULTS A total of 3170 patients were eligible for the study; they were predominantly male (2392 male, 75.5% versus 778 female, 24.5). The median age of the patients was 28 years (range 28-82). The most common region of origin was Africa (1544, 48.7%), followed by the Middle East (736, 23.6%). 2144 (67.6%) of all patients were not multimorbid. A total of 1183 (37.7%) of our patients were multimorbid. The mean Charlson comorbidity index was 0.25 (SD 1.1, range 0-12). 634 (20%) of all patients sufferem from psychiatric diseases, followed by chronic medical conditions (12.6%, 399) and infectious diseases (4.7%, 150). Overall, 11% (349) of our patients presented as a direct consequence of prior violence. Patients from Sri Lanka/India most often suffered from addictions problems (50/240, 20.8%, p<0.0001). Infectious diseases were most frequent in patients from Africa (6.6%), followed by the Balkans and Eastern Europe/Russia (each 3.8%). CONCLUSION The health care problems of asylum seekers are manifold. More than 60% of the study population assessed in our study did not suffer from more than one disease. Nevertheless a significant percentage of asylum seekers is multimorbid and exhibits underlying psychiatric, infectious or chronic medical conditions despite their young age.

Assessment of Collimator Jaw Optimization in Reducing Normal Tissue Irradiation with Intensity Modulated Radiation Therapy

Purpose: To evaluate normal tissue dose reduction in step-and-shoot intensity-modulated radiation therapy (IMRT) on the Varian 2100 platform by tracking the multileaf collimator (MLC) apertures with the accelerator jaws. Methods: Clinical radiation treatment plans for 10 thoracic, 3 pediatric and 3 head and neck patients were converted to plans with the jaws tracking each segment’s MLC apertures. Each segment was then renormalized to account for the change in collimator scatter to obtain target coverage within 1% of that in the original plan. The new plans were compared to the original plans in a commercial radiation treatment planning system (TPS). Reduction in normal tissue dose was evaluated in the new plan by using the parameters V5, V10, and V20 in the cumulative dose-volume histogram for the following structures: total lung minus GTV (gross target volume), heart, esophagus, spinal cord, liver, parotids, and brainstem. In order to validate the accuracy of our beam model, MLC transmission measurements were made and compared to those predicted by the TPS. Results: The greatest change between the original plan and new plan occurred at lower dose levels. The reduction in V20 was never more than 6.3% and was typically less than 1% for all patients. The reduction in V5 was 16.7% maximum and was typically less than 3% for all patients. The variation in normal tissue dose reduction was not predictable, and we found no clear parameters that indicated which patients would benefit most from jaw tracking. Our TPS model of MLC transmission agreed with measurements with absolute transmission differences of less than 0.1 % and thus uncertainties in the model did not contribute significantly to the uncertainty in the dose determination. Conclusion: The amount of dose reduction achieved by collimating the jaws around each MLC aperture in step-and-shoot IMRT does not appear to be clinically significant.

Functions and intramolecular interactions of ribosomal RNA in decoding of termination codons

Two regions in the 3$\prime$ domain of 16S rRNA (the RNA of the small ribosomal subunit) have been implicated in decoding of termination codons. Using segment-directed PCR random mutagenesis, I isolated 33 translational suppressor mutations in the 3$\prime$ domain of 16S rRNA. Characterization of the mutations by both genetic and biochemical methods indicated that some of the mutations are defective in UGA-specific peptide chain termination and that others may be defective in peptide chain termination at all termination codons. The studies of the mutations at an internal loop in the non-conserved region of helix 44 also indicated that this structure, in a non-conserved region of 16S rRNA, is involved in both peptide chain termination and assembly of 16S rRNA.^ With a suppressible trpA UAG nonsense mutation, a spontaneously arising translational suppressor mutation was isolated in the rrnB operon cloned into a pBR322-derived plasmid. The mutation caused suppression of UAG at two codon positions in trpA but did not suppress UAA or UGA mutations at the same trpA positions. The specificity of the rRNA suppressor mutation suggests that it may cause a defect in UAG-specific peptide chain termination. The mutation is a single nucleotide deletion (G2484$\Delta$) in helix 89 of 23S rRNA (the large RNA of the large ribosomal subunit). The result indicates a functional interaction between two regions of 23S rRNA. Furthermore, it provides suggestive in vivo evidence for the involvement of the peptidyl-transferase center of 23S rRNA in peptide chain termination. The $\Delta$2484 and A1093/$\Delta$2484 (double) mutations were also observed to alter the decoding specificity of the suppressor tRNA lysT(U70), which has a mutation in its acceptor stem. That result suggests that there is an interaction between the stem-loop region of helix 89 of 23S rRNA and the acceptor stem of tRNA during decoding and that the interaction is important for the decoding specificity of tRNA.^ Using gene manipulation procedures, I have constructed a new expression vector to express and purify the cellular protein factors required for a recently developed, realistic in vitro termination assay. The gene for each protein was cloned into the newly constructed vector in such a way that expression yielded a protein with an N-terminal affinity tag, for specific, rapid purification. The amino terminus was engineered so that, after purification, the unwanted N-terminal tag can be completely removed from the protein by thrombin cleavage, yielding a natural amino acid sequence for each protein. I have cloned the genes for EF-G and all three release factors into this new expression vector and the genes for all the other protein factors into a pCAL-n expression vector. These constructs will allow our laboratory group to quickly and inexpensively purify all the protein factors needed for the new in vitro termination assay. (Abstract shortened by UMI.) ^

How useful is the ultrastructural study of the cilia of the respiratory tract in the diagnosis of an immotile cilia syndrome?

The immotile cilia syndrome (ICS) comprises a range of congenital defects of the ciliary apparatus most probably transmitted by autosomal recessive inheritance. Because cilia occur mainly in the respiratory and genital tract, the clinical symptoms of ICS are most commonly chronic sinusitis, bronchitis, bronchiectasis and male sterility. The syndrome can be associated with a situs inversus and is then called Kartagener's syndrome. We studied the ciliary ultrastructure in airway biopsies of 5 patients suffering from chronic upper and lower respiratory tract infections. With the single exception of one female patient with confirmed ICS diagnosis (Kartagener's syndrome) the etiology of the recurrent infections was unknown. The following ciliary defects were observed: missing dynein arms, radial spoke defects, missing nexin links, microtubular transpositions, compound cilia, supernumerary, absent, or incomplete microtubules, lack of ciliary orientation and various abnormal patterns of microtubular arrangement. In no instance did a patient show only a single anomaly; defects were always combined. Missing dynein arms, radial spoke defects and microtubular transpositions have frequently been described as lesions specific for ICS. Whenever these lesions were found simultaneously in both the respiratory and genital tracts, their genetic origin cannot be doubted. In our confirmed ICS patient the outer dynein arms were not missing but were reduced in number and length in a large number of cilia. The biopsy was, however, obtained from the heavily infected maxillary sinus and it is known that inflammation can lead to a loss of dynein arms. In the light of our investigations and of a review of the published cases of ciliary anomalies, it is concluded that none of the above defects in itself is specific for ICS. They may all occur as secondary lesions or sporadically as varieties in otherwise healthy subjects. It therefore appears questionable whether ICS can be diagnosed from the ciliary ultrastructure of a single airway biopsy. Assessment of ICS cannot be based simply on the ultrastructural demonstration of a particular ciliary defect, but necessitates additional considerations particularly regarding the origin of the biopsy, the sampling procedures and quantitation of defects. It appears necessary to investigate samples from different parts of the airways and quantitatively analyze the prominent lesions.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Caries-preventive effectiveness of fluoride varnish as adjunct to oral health promotion and supervised tooth brushing in preschool children: a double-blind randomized controlled trial.

OBJECTIVES To evaluate the effect of biannual fluoride varnish applications in preschool children as an adjunct to school-based oral health promotion and supervised tooth brushing with 1000ppm fluoride toothpaste. METHODS 424 preschool children, 2-5 year of age, from 10 different pre schools in Athens were invited to this double-blind randomized controlled trial and 328 children completed the 2-year programme. All children received oral health education with hygiene instructions twice yearly and attended supervised tooth brushing once daily. The test group was treated with fluoride varnish (0.9% diflurosilane) biannually while the control group had placebo applications. The primary endpoints were caries prevalence and increment; secondary outcomes were gingival health, mutans streptococci growth and salivary buffer capacity. RESULTS The groups were balanced at baseline and no significant differences in caries prevalence or increment were displayed between the groups after 1 and 2 years, respectively. There was a reduced number of new pre-cavitated enamel lesions during the second year of the study (p=0.05) but the decrease was not statistically significant. The secondary endpoints were unaffected by the varnish treatments. CONCLUSIONS Under the present conditions, biannual fluoride varnish applications in preschool children did not show significant caries-preventive benefits when provided as an adjunct to school-based supervised tooth brushing with 1000ppm fluoride toothpaste. CLINICAL SIGNIFICANCE In community based, caries prevention programmes, for high caries risk preschool children, a fluoride varnish may add little to caries prevention, when 1000ppm fluoride toothpaste is used daily.

Ethics, Interrupted: Community and Impersonality in Levinas

Despite the influence of Emmanuel Levinas’s ethics on the rethinking of community in post-identitarian terms (most prominently in the work of Maurice Blanchot, Alphonso Lingis, and, to a lesser extent, Jean-Luc Nancy), the question of community remains a problematic spot in Levinas’s own philosophy. I would argue that, instead of grounding a new thinking of community, the dyadic relation of Same and Other poses a structural problem when trying to open the ethical relation to the wider realm of others while keeping radical difference in place. As external observer and guarantor of justice, for instance, is the Third excluded a priori from the ethical relation? Is community always only another term for the political? Or, as Levinas himself puts it in Otherwise Than Being: “What meaning can community take on in difference without reducing difference?” Identifying in the notion of impersonality a way to access Levinas’s thought on community, this paper aims at rethinking the scene of address and the ethical relation in terms of displacement, dislocation and interruption.

Nonthymoma-associated exfoliative dermatitis in 18 cats.

BACKGROUND Exfoliative dermatitis has been described in cats as a paraneoplastic skin disease associated with thymoma. There are anecdotal reports of cases without thymoma, with various suspected aetiologies. HYPOTHESIS/OBJECTIVES To identify common features, underlying causes, response to therapy and outcome of nonthymoma-associated exfoliative dermatitis in cats. METHODS Retrospective analysis was carried out of cases presented to dermatology referral centres or cases submitted for histopathological examination. Detailed historical and clinical data were obtained and evaluated statistically. Histopathology was reviewed in a blinded fashion by three dermatopathologists, and PCR for herpesvirus was performed. RESULTS Eighteen cats fulfilled all inclusion criteria. There was no sex, age or breed predisposition. All cats presented with severe generalized (77%) or multifocal exfoliation (23%); 12 cats were severely depressed. In all cats, thymoma was excluded radiographically and feline leukaemia virus tests were negative. Additional imaging procedures in 14 cats and postmortem examination in two cats did not detect neoplasia. Histopathology revealed interface dermatitis, mural interface folliculitis and sebaceous adenitis indistinguishable from findings in thymoma-associated cases. PCR for herpes DNA was negative. No aetiology was identified. Treatment in 12 cases consisted of immunosuppressive doses of corticosteroids and/or ciclosporin; one responded to antibiotics, one to shampoo, two went into spontaneous remission, and two did not receive any therapy and were euthanized. CONCLUSIONS AND CLINICAL IMPORTANCE Nonthymoma-associated exfoliative dermatitis in cats is clinically and histopathologically indistinguishable from thymoma-associated cases. Most cases benefit from immunosuppressive therapy; therefore, an immunopathological response to an undefined trigger is suspected.

What are the metacognitive costs of young children's overconfidence?

Children typically hold very optimistic views of their own skills but so far, only a few studies have investigated possible correlates of the ability to predict performance accurately. Therefore, this study examined the role of individual differences in performance estimation accuracy as a global metacognitive index for different monitoring and control skills (item-level judgments of learning [JOLs] and confidence judgments [CJs]), metacognitive control processes (allocation of study time and control of answers), and executive functions (cognitive flexibility, inhibition, working memory) in 6-year-olds (N=93). The three groups of under estimators, realists and over estimators differed significantly in their monitoring and control abilities: the under estimators outperformed the over estimators by showing a higher discrimination in CJs between correct and incorrect recognition. Also, the under estimators scored higher on the adequate control of incorrectly recognized items. Regarding the interplay of monitoring and control processes, under estimators spent more time studying items with low JOLs, and relied more systematically on their monitoring when controlling their recognition compared to over estimators. At the same time, the three groups did not differ significantly from each other in their executive functions. Overall, results indicate that differences in performance estimation accuracy are systematically related to other global and item-level metacognitive monitoring and control abilities in children as young as six years of age, while no meaningful association between performance estimation accuracy and executive functions was found.

Disparate Wages in a Globalized World

This study uses wage data from the UBS Prices and Earnings survey to highlight Disparate Wages in a Globalized World from di↵erent perspectives. This wage data is characterised by remarkable consistency over the last 40 years, as well as unusual global comparability. In the first chapter we analyse the convergence hypothesis for purchasing power adjusted wages across the world for 1970 to 2009. The results provide solid evidence for the hypotheses of absolute and conditional convergence in real wages, with the key driver being faster overall growing wage levels in lower wage countries compared to higher wage countries. At the same time, the highest skilled professions have experienced the highest wage growth, while low skilled workers’ wages have lagged, thus no convergence in this sense is found between skill groups. In the second chapter we examine deviations in international wages from Factor Price Equalisation theory (FPE). Following an approach analogous to Engel (1993) we find that deviations from FPE are more likely driven by the higher variability of wages between countries than by the variability of di↵erent wages within countries. With regard to the traditional analysis of the real exchange rate and the Balassa-Samuelson assumptions our analysis points to a larger impact on the real exchange rate likely stemming from the movements in the real exchange rate of tradables, and only to a lesser extent from the lack of equalisation of wages within countries. In the third chapter our results show that India’s economic and trade liberalisation, starting in the early 1990s, had very di↵erential impacts on skill premia, both over time and over skill levels. The most striking result is the large increase in wage inequality of high-skilled versus low-skilled professions. Both the synthetic control group method and the di↵erence-in-di↵erences (DID) approach suggest that a significant part of this increase in wage inequality can be attributed to India’s liberalisation.

Computer Vision-Based Carbohydrate Estimation for Type 1 Diabetic Patients Using Smartphones

Background: Individuals with type 1 diabetes (T1D) have to count the carbohydrates (CHOs) of their meal to estimate the prandial insulin dose needed to compensate for the meal’s effect on blood glucose levels. CHO counting is very challenging but also crucial, since an error of 20 grams can substantially impair postprandial control. Method: The GoCARB system is a smartphone application designed to support T1D patients with CHO counting of nonpacked foods. In a typical scenario, the user places a reference card next to the dish and acquires 2 images with his/her smartphone. From these images, the plate is detected and the different food items on the plate are automatically segmented and recognized, while their 3D shape is reconstructed. Finally, the food volumes are calculated and the CHO content is estimated by combining the previous results and using the USDA nutritional database. Results: To evaluate the proposed system, a set of 24 multi-food dishes was used. For each dish, 3 pairs of images were taken and for each pair, the system was applied 4 times. The mean absolute percentage error in CHO estimation was 10 ± 12%, which led to a mean absolute error of 6 ± 8 CHO grams for normal-sized dishes. Conclusion: The laboratory experiments demonstrated the feasibility of the GoCARB prototype system since the error was below the initial goal of 20 grams. However, further improvements and evaluation are needed prior launching a system able to meet the inter- and intracultural eating habits.

GoCARB in the Context of an Artificial Pancreas

Background: In an artificial pancreas (AP), the meals are either manually announced or detected and their size estimated from the blood glucose level. Both methods have limitations, which result in suboptimal postprandial glucose control. The GoCARB system is designed to provide the carbohydrate content of meals and is presented within the AP framework. Method: The combined use of GoCARB with a control algorithm is assessed in a series of 12 computer simulations. The simulations are defined according to the type of the control (open or closed loop), the use or not-use of GoCARB and the diabetics’ skills in carbohydrate estimation. Results: For bad estimators without GoCARB, the percentage of the time spent in target range (70-180 mg/dl) during the postprandial period is 22.5% and 66.2% for open and closed loop, respectively. When the GoCARB is used, the corresponding percentages are 99.7% and 99.8%. In case of open loop, the time spent in severe hypoglycemic events (<50 mg/dl) is 33.6% without the GoCARB and is reduced to 0.0% when the GoCARB is used. In case of closed loop, the corresponding percentage is 1.4% without the GoCARB and is reduced to 0.0% with the GoCARB. Conclusion: The use of GoCARB improves the control of postprandial response and glucose profiles especially in the case of open loop. However, the most efficient regulation is achieved by the combined use of the control algorithm and the GoCARB.

Consistent nuclear expression of thyroid transcription factor 1 in subependymal giant cell astrocytomas suggests lineage-restricted histogenesis.

Thyroid transcription factor 1 (TTF-1) is encoded by the NKX2-1 homeobox gene. Besides specifying thyroid and pulmonary organogenesis, it is also temporarily expressed during embryonic development of the ventral forebrain. We recently observed widespread immunoreactivity for TTF-1 in a case of subependymal giant cell astrocytoma (SEGA, WHO grade I) – a defining lesion of the tuberous sclerosis complex (TSC). This prompted us to investigate additional SEGAs in this regard. We found tumor cells in all 7 specimens analyzed to be TTF-1 positive. In contrast, we did not find TTF-1 immunoreactivity in a cortical tuber or two renal angiomyolipomas resected from TSC patients. We propose our finding of consistent TTF-1 expression in SEGAs to indicate lineage-committed derivation of these tumors from a regionally specified cell of origin. The medial ganglionic eminence, ventral septal region, and preoptic area of the developing brain may represent candidates for the origin of SEGAs. Such lineagerestricted histogenesis may also explain the stereotypic distribution of SEGAs along the caudate nucleus in the lateral ventricles.

An inter-regional assessment of concentrations and δ13C values of methane and dissolved inorganic carbon in small European lakes

Methane (CH4) and carbon dioxide emissions from lakes are relevant for assessing the greenhouse gas output of wetlands. However, only few standardized datasets describe concentrations of these gases in lakes across different geographical regions. We studied concentrations and stable carbon isotopic composition (δ13C) of CH4 and dissolved inorganic carbon (DIC) in 32 small lakes from Finland, Sweden, Germany, the Netherlands, and Switzerland in late summer. Higher concentrations and δ13C values of DIC were observed in calcareous lakes than in lakes on non-calcareous areas. In stratified lakes, δ13C values of DIC were generally lower in the hypolimnion due to the degradation of organic matter (OM). Unexpectedly, increased δ13C values of DIC were registered above the sediment in several lakes. This may reflect carbonate dissolution in calcareous lakes or methanogenesis in deepwater layers or in the sediments. Surface water CH4 concentrations were generally higher in western and central European lakes than in Fennoscandian lakes, possibly due to higher CH4 production in the littoral sediments and lateral transport, whereas CH4 concentrations in the hypolimnion did not differ significantly between the regions. The δ13C values of CH4 in the sediment suggest that δ13C values of biogenic CH4 are not necessarily linked to δ13C values of sedimentary OM but may be strongly influenced by OM quality and methanogenic pathway. Our study suggests that CH4 and DIC cycling in small lakes differ between geographical regions and that this should be taken into account when regional studies on greenhouse gas emissions are upscaled to inter-regional scales.