Using Bayesian Multilevel Models to Control for Multiplicity among Means

It is well known that the Type I error rate will exceed α when multiple hypothesis tests are conducted simultaneously. This is known as Type I error inflation. The probability of committing a Type I error grows monotonically as the number as the number of hypothesis being tested increases. A class of methods, known as multiple comparison procedures, has been developed to combat this issue. However, in turn for maintaining the Type I error rate below α, multiple comparison procedures sacrifice power to correctly reject false hypotheses. The loss of power is exacerbated when variance heterogeneity is present. In the case of making multiple comparisons among means, a possible alternative to multiple comparison procedures is to use Bayesian multilevel models to control for Type I error inflation. Bayesian multilevel models reduce the risk of committing a Type I error by shrinking all means towards the grand mean, in turn, making it more difficult to declare any mean significantly different from one another. To compare the performance of multiple comparison procedures and Bayesian multilevel models, a Monte Carlo simulation study, in which the number of hypotheses and variance heterogeneity was manipulated, was conducted. The results indicated that the Bayesian multilevel models maintain the Type I error rate at α and display greater power than the traditional methods when a large number of hypotheses are tested. When the number of hypotheses tested were small, the Bayesian models were not able to maintain strong control of the Type I error rate. Adviser: Rafael J. De Ayal

Stomatal regulation by microclimate and tree water relations: interpreting ecophysiological field data with a hydraulic plant model

Dynamics in microclimate and physiological plant traits were studied for Pubescent oak and Scots pine in a dry inner-alpine valley in Switzerland, at a 10 min resolution for three consecutive years (2001-2003). As expected, stomata tended to close with increasing drought in air and soil. However, stomatal aperture in oak was smaller than in pine under relatively wet conditions, but larger under dry conditions. To explore underlying mechanisms, a model was applied that (i) quantifies water relations within trees from physical principles (mechanistic part) and (ii) assumes that signals from light, stomatal aperture, crown water potential, and tree water deficit in storage pools control stomata (systemic part). The stomata of pine showed a more sensitive response to increasing drought because both factors, the slowly changing tree water deficit and the rapidly changing crown water potential, closed the stomata. By contrast, the stomata of oak became less drought-sensitive as the closing signal of crown water potential was opposed by the opening signal of tree water deficit. Moreover, parameter optimization suggests that oak withdrew more water from the storage pools and reduced leaf water potentials to lower levels, without risking serious damage by cavitation. The new model thus suggests how the hydraulic water flow and storage system determines the responses in stomatal aperture and transpiration to drought at time scales ranging from hours to multiple years, and why pine and oak might differ in such responses. These differences explain why oaks are more efficient competitors during drought periods, although this was not the case in the extremely dry year 2003, which provoked massive leaf loss and, from July onwards, physiological activity almost cease

Annealing tests of in-pile irradiated oxide coated U–Mo/Al–Si dispersed nuclear fuel

Authors do acknowledge the MERARG team for their experimental work (CEA) and F. Charollais, J. Noirot and finally B. Kapusta for their advices and comments. This study was supported by a combined Grant (FRM0911) of the Bundesministerium für Bildung und Forschung (BMBF) and the Bayerisches Staatsministerium für Wissenschaft, Forschung und Kunst (StMWFK).U–Mo/Al based nuclear fuels have been worldwide considered as a promising high density fuel for the conversion of high flux research reactors from highly enriched uranium to lower enrichment. In this paper, we present the annealing test up to 1800°C of in-pile irradiated U–Mo/Al–Si fuel plate samples. More than 70% of the fission gases (FGs) are released during two major FG release peaks around 500°C and 670°C. Additional characterisations of the samples by XRD, EPMA and SEM suggest that up to 500°C FGs are released from IDL/matrix interfaces. The second peak at 670°C representing the main release of FGs originates from the interaction between U–Mo and matrix in the vicinity of the cladding

Pine and mistletoes: how to live with a leak in the water flow and storage system?

The mistletoe, Viscum album, living on Scots pine (Pinus sylvestris) has been reported barely to regulate its transpiration and thus heavily to affect the gas exchange of its host. The extent of this mistletoe effect and its underlying mechanism has, so far, only been partially analysed. In this study, pine branches with different mistletoe infestation levels were investigated by sap flow gauges and analysed with a modelling approach to identify the mistletoe-induced stomatal regulation of pine and its consequences for the water and carbon balances of the tree. It was found that Viscum album barely regulates its stomata and that pines consequently compensate for the additional water loss of mistletoes by closing their own stomata. Despite the reduced stomatal aperture of the needles, the total water loss of branches with mistletoes increased. Furthermore, the increasingly closed stomata reduced carbon assimilation for the pine. Such a negative effect of the mistletoes on pine's stomatal conductance and carbon gain was particularly strong during dry periods. Our study therefore suggests that mistletoe-induced stomatal closure is a successful mechanism against dying from hydraulic failure in the short term but increases the risk of carbon starvation in the long term. With the current conditions in Valais, Switzerland, a tree with more than about 10-20% of its total leaf area attributable to mistletoes is at the threshold of keeping a positive carbon balance. The currently increasing mistletoe abundance, due to increasing mean annual temperatures, is therefore accelerating the ongoing pine decline in many dry inner-Alpine valley

Wirksamkeit der selektiven Lasertrabekuloplastik bei Patienten mit unzureichender Augendrucksenkung unter maximaler Therapie

Zusammenfassung: Hintergrund: Hauptziel der Glaukomtherapie ist die Senkung des Intraokulardruckes (IOD). Ziel dieser prospektiven Studie war es, die IOD-senkende Wirkung der selektiven Lasertrabekuloplastik (SLT) bei Patienten unter maximaler medikamentöser Therapie (MMT) zu untersuchen. Spezielles Augenmerk wurde auf eine mögliche Wechselwirkung mit Pseudophakie oder Prostaglandintherapie (PGT) gelegt. Material und Methoden: Bei 30Patienten mit primärem Offenwinkelglaukom, Normaldruckglaukom und Pseudoexfoliationsglaukom mit unzureichender IOD-Senkung unter MMT wurde eine SLT über 360° Zirkumferenz durchgeführt. Verlaufskontrollen fanden nach 1Tag sowie nach 1, 3, 6, 9 und 12Monaten statt. Die IOD-senkende Therapie wurde über 3Monate unverändert weitergeführt. Ergebnisse: Die mittlere Verlaufsbeobachtungszeit betrug 11,97 ± 3,1Monate. Der mittlere IOD vor SLT war 19,60 ± 4,69mmHg. Die mittlere IOD-Senkung war −19,95 ± 17,14% nach 1Monat (p<0,001) sowie −14,07 ± 23,57% nach 12Monaten (p=0,003). Patienten mit einem höheren präoperativen IOD hatten eine stärker ausgeprägte Drucksenkung (R2=0,482; p<0,001). Phake Patienten hatten eine signifikant ausgeprägtere IOD-Senkung im Vergleich zu pseudophaken Patienten (-4,55±4,45mmHg bzw. +2,75±6,75mmHg; p=0,010). Patienten ohne PGT hatten eine statistisch knapp nicht signifikant ausgeprägtere IOD-Senkung im Vergleich zu Patienten mit PGT (-7,40±4,72mmHg bzw. -2,48±5,22mmHg; p=0,066). Vier Patienten benötigten einen weiteren IOD-senkenden Eingriff. Schlussfolgerung: Bei Patienten unter MMT kann durch eine SLT der IOD bis zu 1Jahr noch signifikant gesenkt werden. Die IOD-senkende Wirkung ist bei phaken Patienten mit hohem Ausgangsdruck am stärksten ausgepräg

The [4+2]‐Cycloaddition of α‐Nitrosoalkenes with Thiochalcones as a Prototype of Periselective Hetero‐Diels–Alder Reactions—Experimental and Computational Studies

The [4+2]‐cycloadditions of α‐nitrosoalkenes with thiochalcones occur with high selectivity at the thioketone moiety of the dienophile providing styryl‐substituted 4H‐1,5,2‐oxathiazines in moderate to good yields. Of the eight conceivable hetero‐Diels–Alder adducts only this isomer was observed, thus a prototype of a highly periselective and regioselective cycloaddition has been identified. Analysis of crude product mixtures revealed that the α‐nitrosoalkene also adds competitively to the thioketone moiety of the thiochalcone dimer affording bis‐heterocyclic [4+2]‐cycloadducts. The experiments are supported by high‐level DFT calculations that were also extended to related hetero‐Diels–Alder reactions of other nitroso compounds and thioketones. These calculations reveal that the title cycloadditions are kinetically controlled processes confirming the role of thioketones as superdienophiles. The computational study was also applied to the experimentally studied thiochalcone dimerization, and showed that the 1,2‐dithiin and 2H‐thiopyran isomers are in equilibrium with the monomer. Again, the DFT calculations indicate kinetic control of this process

Quantum Statistics and Slow Neutron Scattering by Gases

A surprisingly simple expression in ``closed form'' for the cross section d2σ/dΩdϵ for the scattering of thermal neutrons (including polarized neutrons) from an ideal quantum gas is derived. This result extends the work of Van Hove on the quantum gas. An expansion is obtained for dσ/dϵ. The case of elastic scattering is treated separately. From these expressions is obtained a criterion for ignoring the statistics of the scatterer in favor of classical (Boltzmann) statistics. This criterion should have some validity for weakly interacting systems. It is shown that the effects of statistics on the neutron cross section for a helium‐4 gas range from 5% or less for the noninteracting gas up to as much as 40% for the interacting system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70882/2/JCPSA6-47-12-4923-1.pd

Axonemal Lumen Dominates Cytosolic Protein Diffusion inside the Primary Cilium

Transport of membrane and cytosolic proteins in primary cilia is thought to depend on intraflagellar transport (IFT) and diffusion. However, the relative contribution and spatial routes of each transport mechanism are largely unknown. Although challenging to decipher, the details of these routes are essential for our understanding of protein transport in primary cilia, a critically affected process in many genetic diseases. By using a high-speed virtual 3D super-resolution microscopy, we have mapped the 3D spatial locations of transport routes for various cytosolic proteins in the 250-nm-wide shaft of live primary cilia with a spatiotemporal resolution of 2 ms and &lt;16 nm. Our data reveal two spatially distinguishable transport routes for cytosolic proteins: an IFT-dependent path along the axoneme, and a passive-diffusion route in the axonemal lumen that escaped previous studies. While all cytosolic proteins tested primarily utilize the IFT path in the anterograde direction, differences are observed in the retrograde direction where IFT20 only utilizes IFT, and approximately half of KIF17 and one third of α–tubulin utilizes diffusion besides IFT

Globotrioasylsphingosine levels and optical coherence tomography angiography in fabry disease patients

Background: To date, there are no studies associating the dried blood spot (DBS) levels of globotrioasylsphingosine (lysoGb3) with quantitative optical coherence tomography angiography (OCTA) parameters in Fabry disease (FD) patients. Here, we aimed to investigate the association between OCTA vessel density (VD), vessel length density (VLD) with DBS lysoGb3. Methods: A retrospective, single center analysis of all consecutive FD patients enrolled at the Department of Ophthalmology of the University Hospital of Zurich from December 1st, 2017 to September 9th, 2020. An association between VD and VLD detected by OCTA and lysoGb3 was investigated using a linear mixed model. Results: A total of 57 FD patients (23 male, 34 female; 109 eyes) were included. Forty-one patients suffered from the classic phenotype and 16 from the later-onset phenotype. Lys-oGb3 inversely correlated with VD and VLD in both the superficial (VD: p = 0.034; VLD: p = 0.02) and deep capillary plexus (VD: p = 0.017; VLD: p = 0.018) in the overall FD cohort. Conclusions: Our study shows an association between lysoGb3 and OCTA VD and VLD. This supports the hypothesis that quantitative OCTA parameters might be useful as diagnostic biomarkers for evaluating sys-temic involvement in FD, and possibly other diseases