Title of Document: CHARACTERIZATION OF THE IMMUNE RESPONSE INDUCED BY NON-PATHOGENIC MYCOBACTERIA IN MACROPHAGES AND DENDRITIC CELLS Amro Youssef Bohsali, PhD, 2012 Directed By: Associate Professor, Volker Briken, PhD, Cell Biology and Molecular Genetics The capacity of the host to mount an effective immune response (IR) is crucial for the protection against invading pathogens. The apoptotic and proinflammatory responses of infected cells are important innate immune mechanisms. Consequently, the ability of persistent intracellular pathogens, such as the human pathogen Mycobacterium tuberculosis (Mtb), to inhibit infection-induced apoptosis of macrophages is important for its virulence in the host. Facultative-pathogenic mycobacterial species, like M. kansasii (Mkan), can cause disseminating disease in individuals with immune deficiencies. In contrast, non-pathogenic mycobacteria, like M. smegmatis (Msme), are not known to cause disseminating disease even in immunocompromised individuals. We hypothesized that this difference in phenotype could be explained by the strong induction of an innate IR by non-pathogenic mycobacteria. Here we analyze the mechanisms by which non-pathogenic mycobacteria induce a strong IR in their macrophage and dendritic cell (DC) host, specifically the induction of host cell apoptosis and the host inflammasome response via the secretion of IL-1β. The comparison of two non-pathogenic mycobacterial species (Msme and Mkan) with two facultative-pathogenic mycobacterial species (M.kan and M. bovis BCG) demonstrated that only the non-pathogenic mycobacteria induce strong apoptosis in murine bone marrow derived macrophages (BMDM) and dendritic cells (BMDC), which was dependent upon caspase-3 activation and TNF secretion. Consistently, BMDMs responded by secreting relatively large amounts of TNF and by upregulating the expression of Il-12. We also demonstrated that Msme infection of BMDCs strongly induces the secretion of IL-1β. This induction was dependent upon the presence of functional ASC and was partially independent of NLRP3. Interestingly this induction was also partially dependent on AIM2 and IFN-β. This AIM2-dpendent induction was observed in infection with non-pathogenic and opportunistic mycobacteria, and attenuated but not virulent Mtb. Surprisingly, caspase-1/11 deficient BMDCs still secreted substantial but reduced amounts of IL-1β upon Msme infection. In conclusion, we demonstrate a strong induction of the innate IR by nonpathogenic mycobacteria as measured by host cell apoptosis, and IL-12 / TNF / IL-1β cytokine induction. We also demonstrate the partially caspase-1/11 and NLRP3 independent, partially AIM2-dependent, but ASC-dependent IL-1β secretion in Msme infected BMDCs. Our findings support the hypothesis that the strong induction of the innate IR is a major reason for the lack of pathogenicity in non-pathogenic mycobacteria. CHARACTERIZATION OF THE IMMUNE RESPONSE INDCUED BY NONPATHOGENIC MYCOBACTERIA IN MACROPHAGES AND DENDRITIC CELLS


This study presents the results from recent intense marine geophysical surveys conducted offshore of southwestern Taiwan. Mud volcanoes and gassy sediments have been identified along chirp sonar and seismic reflection profile data. The distribution of gassy sediments and mud volcanoes has been compiled, showing these features extending from the accretionary wedge to the passive China continental margin. Submarine mud volcanoes could be grouped into four main clusters in the accretionary wedge province: offshore Kaohsiung, adjacent to the Kaoping Submarine Canyon, near the head of the Fangliao Submarine Canyon and along the Yung-An Lineament. Each cluster is composed of a few to more than 10 submarine mud volcanoes. Their origin could be related to gas hydrate dissociation with rising highpressure fluid along faults or mud diapir piercing the seafloor. These gassy sediments and mud volcanoes could be formed by fluids escaping from dewatering sedimentary layers of mud diapirs, or along faults and fractures where free gases or gases dissociating from hydrates migrate to the seafloor.


We present spatially resolved long-slit spectroscopy from the Southern African Large Telescope to examine the spatial extent of the narrow-line regions (NLRs) of a sample of eight luminous obscured quasars at 0.10 < z < 0.43. Our results are consistent with an observed shallow slope in the relationship between NLR size and L[O iii], which has been interpreted to indicate that NLR size is limited by the density and ionization state of the NLR gas rather than the availability of ionizing photons. We also explore how the NLR size scales with a more direct measure of instantaneous active galactic nucleus power using mid-IR photometry from the Wide Field Infrared Explorer, which probes warm to hot dust near the central black hole and so, unlike [O iii], does not depend on the properties of the NLR. Using our results as well as samples from the literature, we obtain a power-law relationship between NLR size and L8 μm that is significantly steeper than that observed for NLR size and L[O iii]. We find that the size of the NLR goes approximately as , as expected from the simple scenario of constant-density clouds illuminated by a central ionizing source. We further see tentative evidence for a flattening of the relationship between NLR size and L8 μm at the high-luminosity end, and propose that we are seeing a limiting NLR size of 10–20 kpc, beyond which the availability of gas to ionize becomes too low. We find that , consistent with a picture in which the L[O iii] is dependent on the volume of the NLR. These results indicate that high-luminosity quasars have a strong effect in ionizing the available gas in a galaxy.


1 The present study was designed to evaluate the protective effects of the nitric oxide (NO)‐generating compounds l‐arginine (l‐Arg) and sodium nitroprusside (SNP) on oxidative stress markers in streptozotocin (STZ)‐diabetic rats. 2 Diabetes was induced after a single intraperitoneal injection of STZ (60 mg/kg). Rats were divided into non‐diabetic (control), diabetic and treated diabetic groups. The treated diabetic groups were supplemented with l‐Arg (300 mg/kg), SNP (3 mg/kg per day) or glibenclamide (0.6 mg/kg per day) orally for 4 weeks. 3 At the end of the experiment, fasted rats were killed by cervical decapitation. Blood was collected for estimation of glucose, haemoglobin, glycosylated haemoglobin (HbA1c), total cholesterol, high‐density lipoprotein–cholesterol and triglycerides. Thiobarbituric acid‐reactive substances (TBARS; an index of lipid peroxidation), superoxide dismutase, glutathione peroxidase, catalase, nitrate/nitrite (NOx) and reduced glutathione (GSH) were estimated in liver and kidney homogenates. 4 A significant increase was observed in plasma glucose levels and HbA1c, with a concomitant decrease in haemoglobin levels, in diabetic rats. These alterations reverted back to near normal after treatment with the NO‐generating compounds. A loss of bodyweight, polydipsia, polyphagia and elevated levels of serum cholesterol and triglycerides were observed in diabetic rats. Hyperglycaemia was accompanied by a significant increase in tissue TBARS and a decrease in NOx, GSH and anti‐oxidant enzymes, whereas, supplementation with l‐Arg and SNP significantly reduced TBARS levels and increased GSH and anti‐oxidant enzyme activities. Linear regression analysis indicated that blood glucose and TBARS were had a significant positive correlation with HbA1c, whereas a negative correlation was observed between GSH and NOx. 5 It is concluded that NO‐generating compounds improve most of the biochemical abnormalities and anti‐oxidant levels in diabetic rats. The beneficial effects of NO‐generating compounds can be attributed to the generation of NO and/or enhanced anti‐oxidant enzyme activities.


Polymorphic variation in the human serotonin transporter (SERT; 5‐HTT) gene resulting in a lifelong increase in SERT expression is associated with reduced anxiety and a reduced risk of affective disorder. Evidence also suggests that sex influences the effect of this polymorphism on affective functioning. Here we use novel transgenic mice overexpressing human SERT (hSERT OVR) to investigate the possible influence of sex on the alterations in SERT protein expression and cerebral function that occur in response to increased SERT gene transcription. SERT binding levels were significantly increased in the brain of hSERT OVR mice in a region‐dependent manner. The increased SERT binding in hSERT OVR mice was more pronounced in female than in male mice. Cerebral metabolism, as reflected by a quantitative index of local cerebral glucose utilization (iLCMRglu), was significantly decreased in many brain regions in hSERT OVR female as compared with wild‐type female mice, whereas there was no evidence for a significant effect in any region in males. The ability of hSERT overexpression to modify cerebral metabolism was significantly greater in females than in males. This effect was particularly pronounced in the medial striatum, globus pallidus, somatosensory cortex, mamillary body, and ventrolateral thalamus. Overall, these findings demonstrate that the influence of a lifelong increase in SERT gene transcription on cerebral function is greater in females than in males and may relate, in part, to the influence of sex on genetically driven increases in SERT protein expression. © 2009 Wiley‐Liss, Inc.


Post-polymerisation modification of poly(glycidyl methacrylate) (PGMA) through the nucleophilic ring opening reactions of the pendent epoxide groups allows for the installation of a variety of functionalities onto the reactive scaffold. The primary modification processes involve amine-epoxy, thiol–epoxy, azide-epoxy, acid-epoxy, and hydrolysis reactions. In all cases, sequential post-synthesis modification reactions can also be carried out if multiply-functionalised polymers are required. This, in particular, includes reactions of the hydroxyl group(s) that come into being through the initial oxirane ring-opening reaction. The overall flexibility of these functionalisations, coupled with the commercial availability of glycidyl methacrylate monomer, its controlled polymerisation behaviour through free radical polymerisation methods and high shelf life of the resulting polymers makes PGMA one of the most adaptable reactive scaffolds in polymer chemistry. In this review article, our aim is to discuss the fundamental aspects of the epoxy ring-opening reactions and highlight the utilitarian nature of PGMA by addressing the range of chemistry that has been used to transform this simple structure into a plethora of customised functional polymers.


In recent years the role of the myofibroblast in corneal wound healing has been extensively studied. The transformation of the corneal keratocyte to the fibroblast and myofibroblast phenotypes is a critical process in normal and pathologic corneal wound healing. This review will introduce this important transformation and its role in corneal wound healing and pathology.


In this chapter the term probiotics is used in a broad sense to include the use of various different microbes in veterinary strategies aimed at manipulation or replacement of intestinal microbes. The reduction in the incidence of diarrhea by probiotics has frequently been studied because this problem is of the utmost importance for farm animals. Neonatal farmhouse animals including piglets often have an insufficiency of stomach acid, which is the first line of defense against bacterial invasion. Microbes of all types, including bacteria, viruses, archaea, fungi, and protozoans, colonize and persist in the intestinal tract of farm animals. Genomic analysis of differential gene expression in microbes and higher organisms has been greatly facilitated by the development of DNA microarrays. This technology has been exploited to monitor global intestinal transcriptional responses to the colonization of germ free mice with Bacteroides thetaiotaomicron, a prominent member of the normal murine and human intestinal microbiota. This study showed that this commensal was able to modulate expression of host genes participating in diverse and fundamental physiological functions, including nutrient absorption, mucosal barrier fortification, xenobiotic metabolism, angiogenesis, and postnatal intestinal maturation. Recent in vitro studies have suggested that probiotics can have protective effects on cytokine-induced apoptosis or permeability changes, attenuate epithelial inflammatory responses, and reduce invasion or adherence of pathogens.


An implicit equation for the oscillation threshold of stimulated Brillouin scattering from Raman amplified signals in fibers with external feedback is derived under the assumption of no depletion. This is compared to numerical investigations of Raman amplification schemes showing good agreement for high reflectivities. For low reflectivities and high attenuation or long fibers, the assumption of no depletion is shown not to be valid. In these cases the effects of the depletion on the self-pulsation is examined.


When policymakers design programs and policies, they often want to understand why individuals engage in particular behaviors. Collecting survey data about respondents' reasons for their behavior presents important challenges, and there is little methodological research on this topic. We conducted an experiment to investigate the best practices for asking questions about respondents' reasons for their behavior. We embedded a split ballot experiment in a face-to-face survey of 608 entrepreneurs in Ethiopia. Respondents were asked questions about why they did not engage in three business practices (advertising, sharing product storage, and switching suppliers). When asked these questions, respondents were randomly assigned to one of three conditions: close-ended questions, open-ended questions with interviewer probing, and open-ended questions without probing. Respondents endorsed more responses when asked close-ended (versus open-ended) questions. Close-ended responses produced higher rates of socially undesirable responses and fewer "other" responses. Notably, probing had no effect on the number or types of responses given. Our results suggest some best practices for asking respondents questions about reasons for their behavior.


Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.


Federal, State, and local agencies share keen interests in appraising the Nation's water resources and in seeking solutions to waterrelated problems. The U.S. Geological Survey (USGS) Federal-State Cooperative Water-Resources Program was initiated in 1895 to address the diversity in missions and areas of responsibility of various agencies through joint planning and funding of hydrologic data collection, investigations, and research. During the 100-year history of the cooperative program, the USGS has performed many data-collection and investigation activities in cooperation with a variety of State and local agencies to help meet their goals and to carry out the principal mission of the Water Resources Division of the USGS--to further the understanding of water reSources throughout the Nation. The .cooperative program represents almost 50 percent of USGS water-related activities in Nebraska and is a vital component in addressing water issues of local, State, and National interest.


Ivan T. Berend. History Derailed: Central and Eastern Europe in the Long Nineteenth Century. Berkeley: University of California Press, 2003. xix, 330 pp. Illustrations. Maps. Tables. Bibliography. Index. $39.95, hardcover.This synthesis of nineteenth-century Central and Eastern European history by Ivan T. Berend complements his two other works on the history of this region in the twentieth century and thus provides us with the complete authorial vision of the region's modern history. The value of this book is increased by the fact that, in comparison with a few general works dealing with the region in the twentieth century, there had been a definite lack of generalizing narratives about the area's nineteenth century. This wonderfully written book is the first synthetic work on East Central Europe's nineteenth century that has managed equally successfully to integrate social, cultural and political aspects of the region's history.Since the task of this book was to give the region its proper nineteenth-century history, the author avoids wading into hot discussions on the region's discursive construction and its political implications. Berend does believe that there are some objective features shared by all parts of the region and allowing one to speak about Central Eastern Europe. In his opinion, the countries of this region faced similar economic, social and political problems-all deriving from the developmental lag between them and Western Europe, they designed similar responses to these problems, and they faced similar consequences. Berend's Central and Eastern Europe consists of Austria-Hungary (usually excluding Austria proper), the Balkans (usually excluding Greece), and Poland.The book starts with an explanation of how the basis for the distinctiveness of the region was laid down in the early modern period. By the beginning of the "long" nineteenth century the region's leading intellectuals were well aware of their own countries' backwardness. Just as for these intellectuals, for Berend the most important distinctive features of the region can be revealed through comparing it with the Western European "core." Every chapter begins with a brief outline of the developments in Western Europe against which trends in Eastern and Central Europe are discerned and measured.First the author looks at culture. Here the differences between Eastern and Western Europe seem less unbridgeable than in social or political structures. Local thinkers were part of European intellectual life. At the centre of Berend's story is the epoch of Romanticism, which, he believes, in the ease of Central Eastern Europe was conflated with Enlightenment. This particular intellectual blend gave birth to the phenomenon crucial for understanding most of the region's developments throughout the modern period, namely-to nationalism. The author believes that romanticism left its imprint not only on this nationalism but on the totality of the region's mental pattern throughout the whole long nineteenth century.Nationalism was the intellectual movement guiding political responses in theregion to the challenges of the West. Despite the fact that the author is well aware of difficulties in distinguishing between "good" civic and "bad" ethnic nationalisms, he believes that because of their belatedness and the specific social structure of the region, the local nationalisms differed significantly from the civic and democratic nationalisms of the West. …


Shrimp trawlers in the Barents Sea use a Nordmøre sorting grid ahead of a small-mesh codend to avoid bycatch while catching shrimps efficiently. However, small fish can still pass through the grid to enter the codend, which increases their risk of being retained. In this study, we quantified the selectivity of a standard Nordmøre grid used together with one of two different codend designs, namely a diamond mesh codend with square mesh panels and a codend with a square mesh sorting cone section, for deep-water shrimp (Pandalus borealis), redfish (Sebastes spp.), and American plaice (Hippoglossoides platessoides). For the first time, the selective properties of these two alternative designs were estimated and compared to those of a Nordmøre grid used together with a 35-mm diamond mesh codend, which is the compulsory gear used in the fishery today. With this traditional codend, the size selectivity of both bycatch species showed the expected characteristic bell-shaped size selection pattern, with low retention probability of very small fish and bigger fish but with high retention probability of certain sizes of juveniles. Using the square mesh sorting cone significantly reduced the maximum retention risk of redfish. The maximum retention with the diamond mesh codend with square mesh panels was estimated to be 14% lower than that of the traditional codend, but the difference was not statistically significant. The two alternative codend designs did not result in any significant reduction in bycatch of American plaice.


This paper presents two algorithms used to derive Aerosol Optical Depth (AOD) from a synergy of satellite and ground-based observations, as well as aerosol transport model output. The Spinning Enhanced Visible Infrared Radiometer (SEVIRI) instrument on board Meteosat Second Generation (MSG) allows us to monitor aerosol loading over land at high temporal and spatial resolution. We present the algorithms which were fed with the data acquired via the SEVIRI channel 1, and also channels 1 and 3 in conjunction. In both cases, the surface reflectance is the most important parameter that should be estimated during the retrieval process. The surface properties are estimated during days with a low AOD (less than 0.1 at 500 nm) based on the radiance measured by the SEVIRI detector and aerosol optical properties modeled with the aerosol transport model or measured by the MODIS sensor. For data from the model and the MODIS, ground-based stations equipped with a sun photometer have been applied to correct the AOD fields using the optimal interpolation method. By assuming that surface reflectance at the SEVIRI resolution changes slowly over time, the AOD has been computed. Comparison of the SEVIRI AOD with the sun photometer observations shows good agreement/correlation. The mean bias is small (an order of 0.01–0.02) and the root mean square (rms) is about 0.05 for both one- and two-channel methods. In addition, the rms for the one-channel method does not change with the AOD.


The thesis reviews the literature concerning the high- and low-strain fatigue
which is pertinent to the nucleation of cracks during cyclic stressing.
The methods of investigating the crack nucleation process are discussed with the
disadvantages of each method stated. The thesis deals mainly with the examination
of the cracks by surface replication and electron microscopy.
A direct carbon replica technique is described which allows the results of
macroscopic as well as microscopic deformation to be followed during both low
and high strain fatigue. The microscopic deformation (slip) produced an overall
macroscopic deformation producing an undulating surface topography with accompanying
grain rotations and displacements. The stereoscopic electron micrographs
prepared from OFHC copper subjected to fatigue at room temperature have
shown that the grain boundaries slip at their common interface at the surface
when subjected to a cyclic shear strain. [Continues.]


The actual performance of programs on modern processors that employ deep memory hierarchies is closely related to the performance of the memory subsystem. Compiler optimizations aimed at improving cache locality are critical in realizing the performance potential of powerful processors. For scientific applications, several loop transformations have been shown to be useful in improving both temporal and spatial locality. Recently, there has been some work in the area of data layout optimizations, i.e., changing the memory layouts of multi-dimensional arrays from the languagedefined default such as column-major storage in Fortran. These memory layout optimizations affect the spatial locality characteristics of loop nests. This paper presents a technique based on integer linear programming (ILP) that attempts to derive the best combination of loop and data layout transformations. Prior attempts to unify loop and data layout transformations for programs consisting of a sequence of loop nests have been based on heuristics not only for transformations for a single loop nest but also for the sequence in which loop nests will be considered. The ILP formulation presented here obviates the need for such heuristics. Experimental results on a MIPS RlOOOO based system demonstrate the benefits of this approach, and show that the use of the ILP formulation does not increase the compilation time significantly.


Atytosia lineata was successfully hybridized with Cajanus cajan using the latter as female patent. Reciprocal crosses were not successful. The characters of C. cajan, viz., fugacious stiplues, absence of pigmentation on the standard petal, deciduous petals, absence of hairs on the pods, non-shattering nature of pods reddish brown seed color without mottles and absence of strophiole on the seeds were recessive to those of. A.lmtata. The meiotic behaviour of the hybrid was regular exceptfor minor abnormalities. Two bivalents frequently showed heteromorphism and there was a reduction in the chiasma frequency during diakmesis and metaphase-I. A few laggards and irregular distribution of chromosomes to the poles during anaphase-I was noticed in s few cells. On the basis of plant morphology, crossability, hybrid fertility and meiotic behaviour, A. lineata comes very close to C. cajan.


This study focuses on the production of handmade and machinemade jewellery in three
sites in India: Noida Export Processing Zone (NEPZ), Delhi and Medinipur. It draws
from and contributes to two strands of literature and extends them. One is the gendered
literature on export processing zones (EPZs) and export oriented industries (EOIs). The
other is the literature on globalisation, feminisation and flexibility.
The thesis poses two major research questions. First, how are jobs in jewellery
production constituted as masculine or feminine? Second, how do masculinised and
feminised jobs relate to flexibility?
The evidence I use to answer these questions is based on materials collected in the course
of two field trips to India, of nine months and two months duration between 1996-1998.
A questionnaire survey, non-participant observation and semi-structured interviews were
used as methods of data collection.
Contrary to much of the literature on EPZs, machinemade jewellery production in NEPZ
is predominantly male with 25% female work participation, and handmade jewellery
production in NEPZ is entirely male with no female work participation. Handmade
jewellery in Delhi has a marginal representation of women as family workers. Only in
handmade chain production in the villages of Medinipur is the female labour
predominant, in the form of hidden women homeworkers, constituting 64% of the labour
time. My study shows that the gender division of labour is not a fixed or given entity but
a product of discursive and material practices, which are reproduced through discourses
into which different actors invest, and which feed into the gendered subjective identities
of these actors. The study breaks down the assumption of a formal labour market in
EPZs. There is a wide prevalence of male child labour and subcontracting in all three
sites of handmade jewellery production. Contrary to the literature on EPZs and EOIs
which show that it is the feminised jobs that are flexible, in machinemade jewellery
production in NEPZ there is a slight feminisation of flexibility but it is not very
significant. In the handmade jewellery sector in NEPZ and Delhi, labour market
flexibility is occurring with a largely masculinised labour force. In Medinipur all labour
is flexible and since there is greater representation of women in the labour time, there is
some feminisation of flexibility. So no clear linkage can be drawn between the
feminisation of jobs and flexible labour within the jewellery industry in India thus
complicating the debates on feminisation and flexibility. The study underlines the
importance of localised industry studies which are not bounded by a particular space.


We used the Binomial Options Pricing Model (BOPM) implemented on a Graphics Processing Unit (GPU) to calculate the value of European and American options, of both put and call type. The advantage of using a GPU over a CPU is that a GPU has many more processing-cores than a CPU and can perform more calculations simultaneously. This, of course, also implies limitations. The result was compared with both the exact value and with the value obtained using a Central Processing Unit (CPU). The CPU-code was implemented using C++ and the GPU-code was implemented using NVIDIA's programming language CUDA. It turns out that the value obtained using the GPU is for the most part almost consistent with both the exact value and the value obtained using a CPU. Undergraduate thesis


Introduction and Objectives Delivery of pulmonary rehabilitation (PR) and self-management (SM) support programmes to patients living with chronic obstructive pulmonary disease (COPD) is emphasised in national guidelines, but these interventions are not always routinely available. One potential explanation for the lack of implementation could be the poor patient participation and retention reported in the literature. We conducted a systematic review to determine a true estimate of participation and dropout rates. Methods Studies were identified from eight electronic databases including MEDLINE. Controlled clinical trials of structured SM, PR and health education (HE) programmes for COPD were included. Data extraction included 'participant flow' data using the Consolidated Standards of Reporting Trials (CONSORT) statement and its extension to pragmatic trials. Patient 'participation rates' (study participation rate (SPR), study dropout rate (SDR) and intervention dropout rate (IDR)) were calculated using prior definitions consistent with CONSORT Random effects logistic regression analysis was conducted to examine effects of four key study characteristics on participation rates. Results 56 quantitative studies (51 randomised controlled trials, three quasi-experimental and two before-after studies) evaluated PR (n=31), SM (n=21) and HE (n=4). Reports of participant flow were generally incomplete; 'numbers of potential participants identified' were only available for 16%, and 'numbers assessed for eligibility' for only 39% of studies. Although 'numbers eligible' were better reported (77%), we were unable to calculate SPR for 23% of studies. Overall we found 'participation rates' for studies (n=43) were higher than previous reports; only 19% of studies had less than 50% SPR and just over one third (34%) had a SPR of 100%; SDR and IDR were less than or equal to 30% for around 93% of studies. There was no evidence of effect of study characteristics on participation rates. Conclusion Unlike previous reports, we found high participation and low dropout rates in studies of PR or SM support for COPD Previous studies adopted different participation definitions; some reported proportions without stating definitions clearly, obscuring whether proportions referred to the study or the intervention. Clear, uniform definitions of patient participation in studies are needed to better inform the wider implementation of effective interventions.


Europeans,
particularly northern and eastern Europeans, are unusually colored. Their hair
can be not only black but also brown, flaxen, golden, or red, and their eyes
not only brown but also blue, gray, hazel, or green. Their skin is pale, almost
like an albino's. This color scheme is more developed in women than in men and
seems to have been selected for its visual properties, particularly brightness
and novelty. Sexual selection is a likely cause. It favors eye-catching colors
and, if strong enough, can produce a color polymorphism, i.e., whenever a
visible feature becomes differently colored through mutation, the new color
will spread through the population until it loses its novelty value and becomes
as frequent as the original one. Such selection is consistent with 1) the many
alleles for European hair and eye color; 2) the high ratio of nonsynonymous to
synonymous variants; and 3) the relatively short time over which this color
diversity developed. Sexual selection will target women if they outnumber men
on the mate market. Among early modern humans, such imbalances resulted from 1)
a low polygyny rate (because few men could provide for a second wife and her
children) and 2) a high risk of early male death (because long hunting distances
increased exposure to environmental hazards). Sexual selection of women was
stronger at latitudes farther from the equator, where men were less polygynous
and more at risk of death while hunting. It was strongest on continental
steppe-tundra, where men provided for almost all family food needs by pursuing
herds of reindeer and other herbivores over long distances. Although this type
of environment is now fragmentary, it covered until 10,000 years ago a much
larger territory—the same area where, today, hair and eyes are diversely
colored and skin almost milk white.


Background: Identifying potential drug candidates through Ligand-based virtual screening is often associated with processing of huge amount of data and hence is a computational intensive task. Ultrafast Shape Recognition (USR) algorithm has been reported as a faster alternative for molecular shape comparison which maps the chemical structure of query ligand into its shape moment vector to find novel chemical scaffolds in chemical compound libraries. The USR algorithm however was devoid of the ability to discriminate ligand molecules according to their pharmacokinetic features. Methods: To overcome this discrepancy, a modification in the existing USR algorithm called DUSR (Distributed Ultrafast Shape Recognition) was carried out where chemical compounds were screened on the basis of their drug-likeliness properties prior to the molecular shape comparison followed by shape complementarity momentum measure. The DUSR due to its Hadoop implementation acts as a faster approach than the existing standalone tools, utilizing the MapReduce algorithm supporting the high throughput screening of million conformers in a much reduced time span. We further demonstrated the utility of DUSR on dataset of 2 million ligand molecules by running shape comparison based searching job on standalone and multisystem Hadoop platforms. Results: The result suggested that DUSR completed its job in 1h 15 m 41s, 0 h 23 m 41s and 0h13m 22s sec for 2038924 molecules on Hadoop standalone mode, 3-nodes cluster & 5-nodes cluster of distributed commodity hardware respectively.


Background and aims: Encouragement of employee's loyalty along with considering the justice principles in organizational climate result in the attitudinal health. The attitudinal encouragement is essential for employees' productive and effective performance in organizations. On the basis of this issue, in this research, the role of loyalty and justice was analyzed on employee's attitudinal health (in the form of commitment and satisfaction). Methods: Current research is a correlational research. Statistical populations were 700 employees of a organization related to the petroleum ministry. From them, 246 persons were selected for answering to the research questionnaires using simple random sampling. Research questionnaires were: reward and encouragement of loyalty with 3 items, distributive justice with 6 items, procedural justice with 6 items, affective commitment with 5 items and job satisfaction with 4 items. Data were analyzed with the use of Pearson's correlation coefficient and structure equation modeling. Results: Results showed that there are positive significant relations between reward and encouragement of loyalty (0.757 and 0.66 respectively) with distributive and procedural justice. Therefore first research hypothesis was verified. The study of second research hypothesis showed that distributive justice is a complete mediator variable in relation between reward and encouragement of loyalty with job satisfaction. Finally the results of third research hypothesis showed that procedural justice has not a mediator role in relation between reward and encouragement of loyalty with affective commitment. Conclusion: The results of this research revealed that for encouragement of attitudinal health in satisfaction and commitment domains, employee's loyalty must be rewarded in a just and equity manner.


Fires shape the biogeochemistry and functioning of many ecosystems, and fire frequencies are changing across much of the globe. Frequent fires can change soil carbon (C) and nitrogen (N) storage by altering the quantity and chemistry of plant inputs through changes in plant biomass and composition as well as the decomposition of soil organic matter. How decomposition rates change with shifting inputs remains uncertain because most studies focus on the effects of single fires, where transient responses may not reflect responses to decadal changes in burning frequencies. Here, we sampled seven sites exposed to different fire frequencies. In four of the sites, we intensively sampled both soils and plant communities across four ecosystems in North America and Africa spanning tropical savanna, temperate coniferous savanna, temperate broadleaf savanna, and temperate coniferous forest ecosystems. Each site contained multiple plots burned frequently for 33–61 years and nearby plots that had remained unburned over the same period replicated at the landscape scale. Across all sites, repeatedly burned plots had 25–185% lower bulk soil C and N concentrations but also 2–10fold lower potential decomposition of organic matter compared to unburned sites. Soil C and N concentrations and extracellular enzyme activities declined with frequent fire because fire reduced both plant biomass inputs into soils and dampened the localized enrichment effect of tree canopies. Examination of soil extracellular enzyme activities revealed that fire decreased the potential turnover of organic matter in the forms of cellulose, starch, and chitin (P < 0.0001) but not polyphenol and lignin (P = 0.09), suggesting a shift in soil C and N cycling. Inclusion of dC data from three additional savanna sites (19–60 years of altered fire frequencies) showed that soil C losses were largest in sites where estimated tree inputs into soils declined the most (r = 0.91, P < 0.01). In conclusion, repeated burning reduced C and N storage, consistent with previous studies, but fire also reduced potential decomposition, likely contributing to slower C and N cycling. Trees were important in shaping soil C and N responses across sites, but the magnitude of tree effects differed and depended on how tree biomass inputs into soil responded to fire.


Impacts of an American Anthropology Field School on the Host Communities in Barbados Although a significant amount of research has been done recently on the effects studying abroad has on students, very little research has examined the effects students and terms abroad programs have on host families and communities. To help address this gap in the literature, this thesis examines the impact American students in an anthropology field school in Barbados have on the families and communities they live among. This field school in question has been running since 1983 and has enrolled 68 students. Every other year approximately ten students participate. During their eleven week stay, students live with families in the northern part of the island, each student in a different village. The students spend the majority of their time interacting with their host families and members of the community while learning about the specific village they live in and Barbadian culture in general.


(NOTE: Each chapter begins with an Introduction, and concludes with Exercises and References.) I. GETTING STARTED. 1. Aspects of Multivariate Analysis. Applications of Multivariate Techniques. The Organization of Data. Data Displays and Pictorial Representations. Distance. Final Comments. 2. Matrix Algebra and Random Vectors. Some Basics of Matrix and Vector Algebra. Positive Definite Matrices. A Square-Root Matrix. Random Vectors and Matrices. Mean Vectors and Covariance Matrices. Matrix Inequalities and Maximization. Supplement 2A Vectors and Matrices: Basic Concepts. 3. Sample Geometry and Random Sampling. The Geometry of the Sample. Random Samples and the Expected Values of the Sample Mean and Covariance Matrix. Generalized Variance. Sample Mean, Covariance, and Correlation as Matrix Operations. Sample Values of Linear Combinations of Variables. 4. The Multivariate Normal Distribution. The Multivariate Normal Density and Its Properties. Sampling from a Multivariate Normal Distribution and Maximum Likelihood Estimation. The Sampling Distribution of 'X and S. Large-Sample Behavior of 'X and S. Assessing the Assumption of Normality. Detecting Outliners and Data Cleaning. Transformations to Near Normality. II. INFERENCES ABOUT MULTIVARIATE MEANS AND LINEAR MODELS. 5. Inferences About a Mean Vector. The Plausibility of ...m0 as a Value for a Normal Population Mean. Hotelling's T 2 and Likelihood Ratio Tests. Confidence Regions and Simultaneous Comparisons of Component Means. Large Sample Inferences about a Population Mean Vector. Multivariate Quality Control Charts. Inferences about Mean Vectors When Some Observations Are Missing. Difficulties Due To Time Dependence in Multivariate Observations. Supplement 5A Simultaneous Confidence Intervals and Ellipses as Shadows of the p-Dimensional Ellipsoids. 6. Comparisons of Several Multivariate Means. Paired Comparisons and a Repeated Measures Design. Comparing Mean Vectors from Two Populations. Comparison of Several Multivariate Population Means (One-Way MANOVA). Simultaneous Confidence Intervals for Treatment Effects. Two-Way Multivariate Analysis of Variance. Profile Analysis. Repealed Measures, Designs, and Growth Curves. Perspectives and a Strategy for Analyzing Multivariate Models. 7. Multivariate Linear Regression Models. The Classical Linear Regression Model. Least Squares Estimation. Inferences About the Regression Model. Inferences from the Estimated Regression Function. Model Checking and Other Aspects of Regression. Multivariate Multiple Regression. The Concept of Linear Regression. Comparing the Two Formulations of the Regression Model. Multiple Regression Models with Time Dependant Errors. Supplement 7A The Distribution of the Likelihood Ratio for the Multivariate Regression Model. III. ANALYSIS OF A COVARIANCE STRUCTURE. 8. Principal Components. Population Principal Components. Summarizing Sample Variation by Principal Components. Graphing the Principal Components. Large-Sample Inferences. Monitoring Quality with Principal Components. Supplement 8A The Geometry of the Sample Principal Component Approximation. 9. Factor Analysis and Inference for Structured Covariance Matrices. The Orthogonal Factor Model. Methods of Estimation. Factor Rotation. Factor Scores. Perspectives and a Strategy for Factor Analysis. Structural Equation Models. Supplement 9A Some Computational Details for Maximum Likelihood Estimation. 10. Canonical Correlation Analysis Canonical Variates and Canonical Correlations. Interpreting the Population Canonical Variables. The Sample Canonical Variates and Sample Canonical Correlations. Additional Sample Descriptive Measures. Large Sample Inferences. IV. CLASSIFICATION AND GROUPING TECHNIQUES. 11. Discrimination and Classification. Separation and Classification for Two Populations. Classifications with Two Multivariate Normal Populations. Evaluating Classification Functions. Fisher's Discriminant Function...nSeparation of Populations. Classification with Several Populations. Fisher's Method for Discriminating among Several Populations. Final Comments. 12. Clustering, Distance Methods and Ordination. Similarity Measures. Hierarchical Clustering Methods. Nonhierarchical Clustering Methods. Multidimensional Scaling. Correspondence Analysis. Biplots for Viewing Sample Units and Variables. Procustes Analysis: A Method for Comparing Configurations. Appendix. Standard Normal Probabilities. Student's t-Distribution Percentage Points. ...c2 Distribution Percentage Points. F-Distribution Percentage Points. F-Distribution Percentage Points (...a = .10). F-Distribution Percentage Points (...a = .05). F-Distribution Percentage Points (...a = .01). Data Index. Subject Index.


Generally, native listeners of a target language are better at understanding foreign-accented speech than any other type of listener, with one possible exception: if the listener speaks the same mother tongue as the speaker, e.g. when Chinese speakers and listeners communicate in English, the information transfer may be more successful than with a native English listener. We review literature data, and present results of our own in an attempt to come up with the optimal quantification of this socalled interlanguage speech intelligibility effect. We argue that the benefit is best quantified in relative terms, as the residual in a linear model that remains after the main effects of speaker and hearer language background have been included.


Magnetic resonance imaging (MRI) is one of the most outstanding developments in medical diagnosis in recent decades. It is used in a wide range of clinical imaging applications, and is particularly effective for producing high quality images of soft tissues. It should therefore be well-suited to evaluating complications arising in patients with orthopaedic metal implants which are considered safe for MRI scanning. However, the presence of the metal produces large variations in the magnetic field, and the resulting images have significant artifacts. Performing accurate fat suppression near metal implants remains an unsolved challenge in MRI. The ability to use multipoint fat suppression techniques close to metal would be greatly beneficial, as it would allow for easier diagnosis of certain soft tissue complications through contrast-enhanced imaging. To succeed, multipoint techniques require a robust and accurate method for estimating the magnetic field variation induced by the metal. Existing methods tend to fail near the boundary of the metal where the field is rapidly varying. This thesis explores new methods for estimating the phase shift due to the magnetic field variation in the three-point Dixon technique near metal. The problem of phase unwrapping in regions where the phase varies rapidly is investigated. Magnetic field variation simulations are used throughout for developing and assessing these new methods. The most significant contribution presented is the development and evaluation of the Phase Onion Peeling (POP) algorithm. POP is a novel approach to phase estimation in the three-point Dixon technique. POP estimates the phase across a two-dimensional slice using a set of closed paths which enclose the implant boundary. The phase is first estimated at the outer edges of the slice. The method incrementally works inwards along a set of adjacent paths, finishing at the boundary of the implant. The phase along each path is represented by a Fourier series, and the coefficients for each path are estimated by minimising an objective function. The main advantage of POP over existing techniques is that the phase unwrapping problem is converted to one of parameter estimation. POP was tested on data acquired from three phantoms and seven human participants, with results presented and evaluated. POP is shown to have superior performance compared to existing phase unwrapping methods


Article History: Received: 10 Sep. 2016 Accepted: 9 Mar. 2017 Drilling Operations are exposed to a variety of hazards, some of which may be location and activity dependent and each could pose different risk from different paths. Drilling operation may be vulnerable to hurricanes in one region and be exposed to Geohazards in another. However, there are other hazards, (e.g. corrosion, age degradation, poor maintenance), which equally affects every rig. Identifying what can go wrong and their likelihood and possible consequences provides insight into vulnerability of the operation and helps to generate mitigation options. Filtering and Ranking risk contributors enable to decide priorities and to focus on the most important risk contributors. This paper offers a framework to identify, assess, prioritize, and manage drilling risks, which includes: (1) a holistic approach to risk identification; (2) prioritization of a large number of risk influencing factors or risk scenarios; (3) structured elicitation of experts' opinion and effective integration of experts judgment into qualitative and quantitative analyses to supplement limited data availability; (4) extreme and catastrophic event analysis; and (5) use of multi-objective framework to evaluate risk management priorities.


Multiple independent runs of an evolutionary algorithm in parallel are often used to increase the efficiency of parameter tuning or to speed up optimizations involving inexpensive fitness functions. A GPU platform is commonly adopted in the research community to implement parallelization, and this platform has been shown to be superior to the traditional CPU platform in many previous studies. However, it is not clear how efficient the GPU is in comparison with the CPU for the parallelizing multiple independent runs, as the vast majority of the previous studies focus on parallelization approaches in which the parallel runs are dependent on each other (such as master-slave, coarse-grained or fine-grained approaches). This study therefore aims to investigate the performance of the GPU in comparison with the CPU in the context of multiple independent runs in order to provide insights into which platform is most efficient. This is done through a number of experiments that evaluate the efficiency of the GPU versus the CPU in various scenarios. An analysis of the results shows that the GPU is powerful, but that there are scenarios where the CPU outperforms the GPU. This means that a GPU is not the universally best option for parallelizing multiple independent runs and that the choice of computation platform therefore should be an informed decision. To facilitate this decision and improve the efficiency of optimizations involving multiple independent runs, the paper provides a number of recommendations for when and how to use the GPU.


Avionics Sensor Health Assessment is a sub-discipline of Integrated Vehicle Health Management (IVHM), which relates to the collection of sensor data, distributing it to diagnostics/prognostics algorithms, detecting run-time anomalies, and scheduling maintenance procedures. Real-time availability of the sensor health diagnostics for aircraft (manned or unmanned) subsystems allows pilots and operators to improve operational decisions. Therefore, avionics sensor health assessments are used extensively in the mil-aero domain. As avionics platforms consist of a variety of hardware and software components, standards such as Open System Architecture for Condition-Based Maintenance (OSA-CBM) have emerged to facilitate integration and interoperability. However, OSA-CBM is a platform-independent standard that provides little guidance for avionics sensor health monitoring, which requires onboard health assessment of airborne sensors in real-time. In this paper, we present a distributed architecture for avionics sensor health assessment using the Data Distribution Service (DDS), an Object Management Group (OMG) standard for developing loosely coupled high-performance real-time distributed systems. We use the datacentric publish/subscribe model supported by DDS for data acquisition, distribution, health monitoring, and presentation of diagnostics. We developed a normalized data model for exchanging the sensor and diagnostics information in a global data space in the system. Moreover, Extensible and Dynamic Topic Types (XTypes) specification allows incremental evolution of any subset of system components without disrupting the overall health monitoring system. We believe, the DDS standard and in particular RTI Connext DDS, is a viable technology for implementing OSA-CBM for avionics systems due to its real-time characteristics and extremely low resource requirements. RTI Connext DDS is being used in other major avionics programs, such as FACETM and UCS. We evaluated our approach to sensor health assessment in a hardware-in-the-loop simulation of an Inertial Measurement Unit (IMU) onboard a simulated General Atomics MQ-9 Reaper UAV. Our proof-of-concept effectively demonstrates real-time health monitoring of avionics sensors using a Bayesian Network –based analysis running on an extremely low-power and lightweight processing unit.


Benchmarking is a common way to evaluate the effectiveness of finite state machine (FSM) low-power methodologies. The serious problem in the existing standard benchmarks is that power-related characteristics are not provided, and therefore these benchmarks are not complete for reliable evaluation and comparison of low-power methods and tools. To address this problem, this paper introduces the coefficient of variation, which is very useful for quantitative analysis of power-related features of an FSM, and for indicating the power optimization opportunity of the corresponding circuit. Based on the coefficient of variation, input-sensitivity analysis of the whole standard benchmark set is conducted. It reveals that the benchmark set is input-data dependant, and the set is insufficient for low-power FSM researches due to the limited coverage of power-related characteristics.


Modern Korean fiction is to a large extent a literature of witness to the historic upheavals of twentieth-century Korea. Often inspired by their own experiences, contemporary writers continue to show us how individual Koreans have been traumatized by wartime violence - whether the uprooting of whole families from the ancestral home, life on the road as war refugees, or the violent deaths of loved ones. "The Red Room" brings together stories by three canonical Korean writers who examine trauma as a simple fact of life. In Pak Wanso's "In the Realm of the Buddha," trauma manifests itself as an undigested lump inside the narrator, a mass needing to be purged before it consumes her. The protagonist of O Chong-hui's "Spirit on the Wind" suffers from an incomprehensible wanderlust - the result of trauma that has escaped her conscious memory. In the title story by Im Ch'or-u, trauma is recycled from torturer to victim when a teacher is arbitrarily detained by unnamed officials. Western readers may find these stories bleak, even chilling, yet they offer restorative truths when viewed in light of the suffering experienced by all victims of war and political violence regardless of place and time.


Book synopsis: Justice as Welfare provides an egalitarian account of distributive justice by rethinking notions of welfare. It first considers possible forms of decentered welfare to promote communal and individual autonomy rather than the bureaucratic, centralized market-oriented control. Next, it uses theoretical resources to rethink the conventional notions of solidarity that support welfare.

Drawing on recent work in continental philosophy, Justice as Welfare suggests that welfare requires a notion of social ontology. It provides both an account of the existential context of communal risk sharing and a framework to think about desire, value, and opportunity. Noting present political and economic realities, it suggests that international strategies to control 'flight capital' are necessary to create and maintain egalitarian welfare.

Justice as Welfare aims to present a convincing theoretical account of welfare as social justice and to show how this requires the assertion of democratic control over economic and social reproduction at both national and international levels. This philosophically informed argument about egalitarian justice will appeal to anyone researching issues of social welfare, political theory, and applied political philosophy.


This descriptive study attempts to document the diversity of intraseasonal oscillations (ISO) propagative and spatial patterns, as inferred from outgoing longwave radiation (OLR) variability. Main ISO events over the Indo‐Pacific Warm Pool are first extracted using a local mode analysis (LMA) applied on the 20–120‐d filtered OLR on the 1979–2008 period. One hundred and sixty‐nine individual ISO are detected. Their propagative patterns are then objectively regrouped into a few types using a hierarchical agglomerative classification. Three alternative partitionings are retained, depending on the level of details expected from the typology. ISO events first regroup naturally into two well‐separated classes, identifying boreal summer northward‐propagating events and boreal winter eastward‐propagating ones. Retaining a larger number of classes shows that the diversity of the ISO patterns is primarily modulated by the seasonal cycle, with the most pronounced convective perturbations roughly located at the latitude of the Inter‐tropical Convergence Zone in the tropics. When a sufficient number of types are considered, one can obtain several types of ISO events for a given season. Apart from seasonality, the variability in the ISO appears to be related to surface conditions, such as sea surface temperature. Analysis of the differences between the types suggests that the 'canonical' ISO, often considered in the literature, is actually rather rare and moderately representative of the propagative events taken individually.


This work highlights the problem of the presence of the termites Reticulitermes lucifugus and Kalotermes flavicollis, detected in an area of the historic center of Florence (Italy). Pest management was immediately undertaken by a specific monitoring program to determine the status of the infestation, identifying the critical elements and their potential impact on the structures involved, as well as outlining the necessary control measures. Analyzing the area, several colonies of both termite species were detected, some located within the wooden flooring of a gym and some others outdoor, in tree stumps and in necrosated roots at the base of some trees. Two episodes of collapsed tall trees were also reported. Termites were detected also in other areas of the city of Florence, such as the Cascine park and the Boboli garden, where many trees were clearly infested by K. flavicollis . This work allowed to realize that problems with termite infestations could be higher than expected, by seriously threatening the historical and artistic heritage of the city and by causing trees weakening in public areas, thus also threatening the people safety. Taking into account these findings, we suggest to extend the termite survey to the entire city and to establish a working group, with multidisciplinary competences, able to develop a proper prevention and control program aimed at the protection of cultural heritage and management of tree health in public parks.


Hiroshi Sugimoto began to photograph his Dioramas series, a body of work that spans almost four decades, when he moved to New York City from Japan in 1974. While looking at the galleries in the American Museum of Natural History, he noticed that if he looked at the dioramas with one eye closed, the artificial scenes--prehistoric humans, dinosaurs, and taxidermied wild animals set in elaborately painted backgrounds--looked utterly convincing. This visual trick launched his conceptual exploration of the photographic medium, which continues today. Through his career, Sugimoto has addressed the photograph's power to create a history. He has said, "photography functions as a fossilization of time." In the Dioramas series, Sugimoto persuades the viewer that the photographer has captured a lived moment in time, although each scene is an elaborately crafted fiction. Hiroshi Sugimoto: Dioramas narrates a story of the cycle of life, death and rebirth, from prehistoric aquatic life to the propagation of reptile and animal life to homo sapiens' destruction of the earth--and then to a renewal of the earth, where flora and fauna flourish without man. Here Sugimoto writes his own history of the world, an artist's creation myth.


Model-checkers are powerful tools that can find individual traces through models to satisfy desired properties. These traces provide solutions to a number of problems. Instead of individual traces, software testing needs sets of traces that satisfy coverage criteria. Finding a trace set in a large model is difficult because model checkers generate single traces and use a lot of memory. Space and time requirements of modelchecking algorithms grow exponentially with respect to the number of variables and parallel automata of the model being analyzed. We present a method that generates a set of traces by iteratively invoking a model checker. The method mitigates the memory consumption problem by dynamically building partitions along the traces. This method was applied to a testability case study, and it generated the complete trace set, while ordinary model-checking could only generate 26%.


Anthony Amsterdam's article, Perspectives On The Fourth Amendment is one of the best, if not the best, law review article written on the Fourth Amendment. Thus, Minnesota Law Review on its hundredth anniversary fittingly recognizes and honors Professor Amsterdam's article in its Symposium edition, "Standing on the Shoulders of Giants: Celebrating 100 Volumes of the Minnesota Law Review." I am flattered that the Law Review invited me to participate in this Symposium.Specifically, my article connects two perspectives from Amsterdam's article — the Fourth Amendment's concern with discretionary police power and the Framers' vision of the Fourth Amendment to bar arbitrary and ruleless searches and seizures — to an aspect of modern American society that affects millions of people: traffic stops by the police. This past Term, the Supreme Court decided Rodriguez v. United States. At issue was whether the Fourth Amendment "tolerates a dog sniff conducted after the completion of a traffic stop." The Court, in a 6-3 ruling, held that "a police stop exceeding the time needed to handle the matter for which the stop was made" violates the Fourth Amendment. While certainly a temporary victory for Mr. Rodriguez, I submit that Rodriguez is a vexing decision on several fronts. As I will explain, Rodriguez is a significant ruling because it rejects the argument that police can prolong a traffic stop to pursue a drug investigation. At the same time, however, Rodriguez blesses two troublesome investigative techniques that have been utilized in the country's seemingly never-ending "War on Drugs" and that are, in my view, inconsistent with Fourth Amendment freedoms and contrary to Professor Amsterdam's insights on the amendment.Rodriguez v. United States explained that the Fourth Amendment tolerates certain unrelated investigations that do not lengthen a roadside detention. Rodriguez's endorsement of police questioning was unnecessary and regrettable. It was gratuitous because the issue before the Court — whether police can detain a motorist to use a drug-sniffing canine after the completion of a traffic stop — had nothing to do with unrelated questioning during a traffic stop. The Court's comments were lamentable for two reasons. First, the practice of questioning motorists about matters unrelated to the traffic stop is inconsistent with the same legal framework the Court relied upon to invalidate the detention and dog sniff at issue in Rodriguez. Second, there was no reason for the Court to provide its imprimatur on a criminal investigative technique that police regularly use to arbitrarily interrogate motorists during routine traffic stops.On a deeper level, Rodriguez's dicta about police questioning during traffic stops is disappointing for its failure to appreciate the fundamental value of the Fourth Amendment. As Professor Amsterdam has taught us, "the fourth amendment is quintessentially a regulation of the police – that, in enforcing the fourth amendment, courts must police the police." More specifically, Professor Amsterdam's article teaches that controlling the discretionary power of officers while they are effectuating searches and seizures is essential to protecting Fourth Amendment freedoms. Police seize millions of Americans every year during traffic stops. Traffic stops are rife with the potential for arbitrary and discriminatory police power. "Once an officer stops a motorist for a traffic offense, the officer has the discretion to transform that traffic stop into an investigation of other serious crimes without the check of reasonable suspicion or probable cause." If the Justices want to protect the Fourth Amendment rights of millions of American motorists, they should recognize that police interrogation of motorists about subjects unrelated to the reason for the traffic stop provides police with unchecked discretion to pursue a criminal investigation and is beyond the scope of an ordinary traffic stop. This Article proceeds in two parts. Part I explains the result and legal reasoning of Rodriguez. It also explains the legal standard, first announced in 1968, that courts have traditionally used to judge the constitutionality of police conduct during investigative detentions, which includes traffic stops. Part II discusses recent rulings of the Court that have been read to authorize police to pursue criminal investigative practices – such as dog sniffs and interrogation unrelated to the reason for the stop – during ordinary traffic stops, provided those practices do not prolong the traffic stop. Part II also explains why those rulings – Illinois v. Caballes, Muehler v. Mena, and Arizona v. Johnson – have been misread and misapplied to allow arbitrary police interrogation during routine traffic stops.


In this study, how to define the dynamic reliability of nuclear power plant is first discussed and then development of reliability monitor for safety related subsystem in PWR is conducted by considering the redundancy of safety system in new concept of risk monitor system. New concept of risk monitor system of Nuclear Power Plant (NPP) is based on the idea of plant Defence-in-Depth (DiD) risk monitor and reliability monitor to monitor what degree of safety functions incorporated in plant's system is maintained by multiple barriers of DiD. The reliability monitor has been developed by implementing the Plant DiD risk monitor's conditions. The example analysis is conducted by using GO-FLOW program, a computer code to evaluate dynamic reliability of system, to obtain the dynamic reliability curve of the containment spray system in PWR. It is shown by GO-FLOW analysis that the redundant system configuration increases the reliability of the system.


Those who reject the 97% expert consensus on human-caused global warming often invoke Galileo as an example of when the scientific minority overturned the majority view. In reality, climate contrarians have almost nothing in common with Galileo, whose conclusions were based on empirical scientific evidence, supported by many scientific contemporaries, and persecuted by the religious-political establishment. Nevertheless, there's a slim chance that the 2–3% minority is correct and the 97% climate consensus is wrong.


Aiming to evaluate the protective effect of garlic on aspirin induced peptic ulcer in comparison with misoprostol and omeprazole drugs and its possible mechanisms. Forty white male albino rats were used. Total acid content, ulcer area/mm2, histological study, mucosal & serum Total Antioxidant Capacity (TAC) by calorimetry and mucosal & serum PGE2 and serum TNF-α by ELISA were assayed. Titrable acidity and total acid output decreased in garlic, misoprostol and omeprazole treated groups. Garlic, misoprostol and omeprazole improved gastric mucosa and decreased ulcer formation and ulcer area/mm2. Aspirin decreased PGE2 in gastric mucosa and serum. Co-administration of garlic to aspirin significantly increased PGE2 near to normal in gastric mucosa. Aspirin significantly increased serum TNF-α than control and other groups. Garlic is suggested to protect the stomach against ulcer formation induced by aspirin by reducing gastric acidity, ulcer area, improve gastric mucosa, increasing PGE2 and decreasing TNF-α.


Gabapentin (1), a widely prescribed anticonvulsant used to treat epilepsy and neuropathic pain. This work describes the synthesis of two potential Gabapentin impurities as per USP and EP. Gabapentin impurity B; 2-(1-cyanocyclohexyl) acetic acid (2) was synthesized by oxidative dehydrogenation of Gabapentin API using trichloroisocyanuric acid. Impurity E; 1-(carboxymethyl) cyclohexanecarboxylic acid (3) was obtained by acid hydrolysis of 2. These impurities are characterized by IR, mass spectral data, HPLC RRT and H NMR


The DIAS-ESTEC Ultra-Heavy Cosmic Ray Experiment (UHCRE) flew on board the Long Duration Exposure Facility
(LDEF) spacecraft in low earth orbit for 69 months. The experiment consisted of a large number (~2 0 0 ) of solid-state nuclear track detector stacks and its objective was to determine the charge abundance spectrum o f ultra-heavy (Z >70) galactic cosmic rays at energies of a few GeV/nucleon. Many hundreds of such ultra-heavy cosmic rays were detected, including 35 actinides (Z > 8 8 ), making this the largest sample of such data to date.

An overview of our current knowledge of the ultra-heavy cosmic-ray flux is presented in Chapter 1. Charge, energy and isotopic spectra are examined and the clues they present to cosmic-ray origin discussed. Current theories of fractionation of the cosmic-ray source matter during transport and suggested sources o f such matter are outlined. The possible insights provided by ultra-heavy cosmicray measurements are then suggested. Chapter 2 discusses the configuration o f the UHCRE and the LDEF spacecraft. Solid-state nuclear track detectors, detector processing and data extraction are discussed. Chapter 3 contains information on detector calibration and error analysis and discusses a Monte-Carlo simulation o f the apparatus used to corroborate the error estimates. Chapter 4 describes the corrections performed on the raw data for detector bias, detector-processing anomalies and fragmentation within the apparatus. The final charge-abundance spectra are presented. Chapter 5 outlines the conclusions which can be drawn from the data, comparing the results with theoretical predictions and other spacebased observations. The experiment's impact on theories o f the origin of the cosmic rays is discussed.


The objective of the paper is to compare the perspectives of both external audit clients and auditors themselves with respect to the nature and significance of two behavioural factors, the client-auditor working relationship and auditor accessibility, which have been identified in the literature as affecting client-initiated auditor changes. A mixed methodology was employed using both online questionnaires and semi-structured interviews. On the part of audit clients, a questionnaire was sent to a random sample of 350 Malta-based companies, out of which 74 responses were received. Seven of the companies also backed up their responses with an interview. On the part of practitioners, a questionnaire was sent to 668 warranted auditors, out of which 124 responses were received. Four of these practitioners also backed up their responses with an interview. Both auditors and clients recognise the importance of clients establishing sound working relationships with all auditing parties - such relationships to include elements such as mutual trust, auditor objectivity and competence - but particularly with the audit manager (as per clients) and audit partner (as per auditors). Both parties also attached high importance to auditor accessibility, this mostly signifying being ready to offer their clients immediate help whenever necessary. Clearly accessibility is not determined by physical presence as much as auditors think, but by each party being reached and responsive with ease, more so during office hours, and increasingly by e-mail. Auditors seem to be more focused on abiding by professional standards, while allotting less importance to other attributes evidently more appreciated by clients, such as personality ones including communication skills. Auditors have to work more on the non-professional aspects of both behavioural factors if they are to secure a higher probability of being reappointed.


Surveys in many academic fields ask respondents to recall the number of events that occurred over a specific period of time with the goal of learning about the mean frequency of these events among the population. Research has shown that the choice of the recall period, particularly the length, affects the results by influencing the cognitive recall process. We combine experimental recall data with use data to learn about this relationship in the context of consumer payments, specifically for the mean frequency of use of the four most popular payment instruments (cash, credit card, debit card, check). Overall, our analysis suggests that day-based recall is inefficient, with mean-squared errors of population estimates minimized for longer recall periods, although the optimal recall period differs among payment instruments. In addition, for cash, we develop a model relating recalled values to individual frequency of use in order to study the relationship between demographic variables and accuracy at different recall lengths. We find little link between demographic characteristics and accuracy of different recall periods for an individual.


1. The urine dopamine response to intravenous frusemide (30 mg) was investigated in 15 salt replete male volunteers. The effects of oral indomethacin (100 mg) and oral carbidopa (100 mg) given before intravenous frusemide were studied in the same group of subjects. 2. Frusemide produced a significant increase in urine dopamine output within 15 min. 3. Indomethacin attenuated the natriuretic and renin responses to frusemide, but did not alter urine dopamine output. 4. Carbidopa lowered urine dopamine to undetectable levels, but did not significantly affect the natriuretic and renin responses to frusemide. 5. We conclude that urine dopamine excretion after frusemide is not directly related to increased sodium excretion or renin response and it is not mediated by the prostaglandins. In addition, dopamine does not contribute to the renal actions of frusemide under normal conditions.


BACKGROUND: Scant information is available on the prevalence of restless legs syndrome (RLS) among patients with chronic kidney disease (CKD) on hemodialysis and its correlation with peripheral iron status. This study was carried out to estimate the prevalence of RLS among patients with chronic renal failure on hemodialysis and to correlate the presence of RLS with peripheral iron status. METHODS: Adults diagnosed with CKD were studied. Demographic details, comorbid illness, and the number of years diagnosed with CKD and on dialysis were noted. RLS was diagnosed based on the International RLS Study Group criteria. Severity of RLS was assessed by international restless legs scale (IRLS) severity score. The presence of RLS was correlated with peripheral iron status. RESULTS: The mean age of 116 subjects was 50.7±13.6 years. Of the total subjects, 79 (68.1%) were men. The mean body mass index of the subjects was 22.02±3.5kg/m2. The subjects had CKD for a mean duration of 3.5±3.2 years and were dialyzed for 2.5±2.3 years. The prevalence of RLS was found to be 10.3% (12/116). Five subjects each had mild and moderate RLS by IRLS severity score and two had severe RLS. All 12 patients with RLS were hypertensive. Hemoglobin and serum ferritin levels were higher in patients with RLS as compared to those who were RLS negative with CKD. CONCLUSION: RLS was previously undiagnosed in this population. Considering RLS, peripheral iron measures are of questionable validity in patients on hemodialysis. Measures to early diagnosis and prompt treatment should be taken, as RLS is known to cause impairment of daytime functioning, disturbed sleep, and increased mortality.


Title of Thesis: RECLAIMING THE ANNAPOLIS WATERFRONT:
Towards an Architecture of Place

Name of Degree Candidate: Ryan D. Kautz

Degree and Year: Master of Architecture, 2003

Thesis Directed by: Thomas L. Schumacher, FAAR, Professor

Annapolis, Maryland is one of the nation's most important historic cities, and the character of its historic core remains much as it did over two hundred years ago. Despite this fact, the most unique amenity that Annapolis offers has suffered from the effects of the automobile and poor planning. The Annapolis waterfront has been developed over the past fifty years as a series of poorly designed buildings and parking lots that take little advantage of their location adjacent to the water. For a city known as "America's Sailing Capital," the Annapolis waterfront does not live up to expectations.

This thesis proposes to entirely redesign the Annapolis waterfront. A new Visitors Center will be a focal point in the City Dock area, providing a center for information, education, and entertainment. The new waterfront will also incorporate a hotel, retail, restaurants, offices, residential, and parking facilities, as well as landscaped parks and plazas.

The challenge of this thesis is to explore how contemporary architecture can blend effortlessly into a vernacular context of fifty, one hundred, and two hundred year old buildings. The true measure of success in this endeavor is not in creating buildings that stand out as objects, but rather in creating modern buildings that seem to be as much a part of the background fabric as the historical context.


Adaptive autonomous (AA) agents are able to make their own decisions on when and with whom to share their autonomy based on their states. Whereas dependability gives evidence on whether a system, (e.g. an agent team), and its provided services are to be trusted. In this paper, an initial analysis on AA agents with respect to dependability is conducted. Firstly, AA is modeled through a pairwise relationship called willingness of agents to interact, i.e. to ask for and give assistance. Secondly, dependability is evaluated by considering solely the reliability attribute, which presents the continuity of correct services. The failure analysis is realized by modeling the agents through Petri Nets. Simulation results indicate that agents drop slightly more tasks when they are more willing to interact than otherwise, especially when the fail-rate of individual agents increases. Conclusively, the willingness should be tweaked such that there is compromise between performance and helpfulness.


Atmospheric correction over turbid and productive waters continues to be problematic and often results in excessive errors in retrieved water-leaving radiance and bio-geo-physical products. This may be likely due to overestimation of La + Lra (atmospheric signal due to aerosol and Rayleigh scattering) in the visible and thus reduction in Lw which appears as an elevated pigment concentration. Spectral models for reconstructing the atmospherically distorted data are developed and their results are thoroughly validated with in-situ data from a wide range of waters. Good agreement was found between the retrieved products and in-situ data. Our results indicate that the new spectral models have the potential to improve the accuracy of ocean colour retrievals in optically complex waters, and can become an important part of the processing of data from ocean colour sensors (e.g., Ocean colour monitor OCM2) with only two near-infrared bands (i.e., 765 and 865 nm).


Issues in Green Criminology: confronting harms against environments, humanity and other animals aims to provide, if not a manifesto, then at least a significant resource for thinking about green criminology, a rapidly developing field.

It offers a set of specially written introductions and a variety of current and new directions, wide-ranging in scope and international in terms of coverage and contributors. It provides focused discussions of current and cutting edge issues that will influence the emergence of a coherent perspective on green issues. The contributors are drawn from the leading thinkers in the field. The twelve chapters of the book explore the myriad ways in which governments, transnational corporations, military apparatuses and ordinary people going about their everyday lives routinely harm environments, other animals and humanity.

The book will be essential reading not only for students taking courses in colleges and universities but also for activists in the environmental and animal rights movements. Its concern is with an ever-expanding agenda − the whys, the hows and the whens of the generation and control of the many aspects of harm to environments, ecological systems and all species of animals, including humans. These harms include, but are not limited to, exploitation, modes of discrimination and disempowerment, degradation, abuse, exclusion, pain, injury, loss and suffering. Straddling and intersecting these many forms of harm are key concepts for a green criminology such as gender inequalities, racism, dominionism and speciesism, classism, the north/south divide, the accountability of science, and the ethics of global capitalist expansion.

Green criminology has the potential to provide not only a different way of examining and making sense of various forms of crime and control responses (some well known, others less so) but can also make explicable much wider connections that are not generally well understood. As all societies face up to the need to confront harms against environments, other animals and humanity, criminology will have a major role to play. This book will be an essential part of this process.


This article highlights the federal government's role as a collector and arbiter of scientific knowledge of "the Indian," in projects directed by Lewis Cass, Albert Gallatin, and Henry R. Schoolcraft; examines the linguistic precursor to biological essentialism; demonstrates white philologists' reliance on Native tutors, some of whom also entered scientific and policy debates; and suggests why the federal government began moving toward English-only instruction even as biological notions of race gained ascendance. During the removal debates, Indian languages focused the attention of men of letters, statesmen, and the broader public. Peter S. Du Ponceau and Cass argued over the grammatical character of the "American languages," with the former praising them and the latter attacking those tongues and the "philanthropic" philology. At stake was the future of Indian affairs and inquirers explored Native languages for evidence of Indians' intellectual and moral capacity to be assimilated into U.S. society. In denying that language corresponded to social condition, Du Ponceau suggested that all Indians spoke according to a uniform, unchanging, and unique "plan of ideas." He and other participants in the debate, such as Wilhelm von Humboldt and Schoolcraft, began to define, linguistically, a distinct and fixed "Indian mind." Scholars of the early republic and antebellum era who wish to study scientific definitions of race must come to terms with linguistic ideas, which requires confronting the intercultural encounters, intellectual exchanges, and institutions through which they emerged.


Applications often re-transmit the same data, such as digital certificates, during repeated communication instances. Avoiding such superfluous transmissions with caching, while complicated, may be necessary in order to operate in low-bandwidth, high-latency wireless networks or in order to reduce communication load in shared, mobile networks. This paper presents a general framework and an accompanying software library, called ``Authenticated Statement Exchange'' (ASE), for helping applications implement persistent caching of application-specific data. ASE supports secure caching of a number of pre-defined data types common to secure communication protocols and allows applications to define new data types to be handled by ASE. ASE is applicable to many applications. The paper describes the use of ASE in one such application, secure group chat. In a recent real-use deployment, ASE was instrumental in allowing secure group chat to operate over low-bandwidth satellite links.


In this paper a bank of velocity filters is devised to be used for isolating a moving object with specific velocity (amplitude and direction) in a sequence of frames. The approach used is a 3-D FFT based experimental procedure without applying any theoretical concept from velocity filters. Accordingly, each velocity filter is built using the spectral signature of an object moving with specific velocity. Experimentation reveals the capabilities of the constructed filter bank to separate moving objects as far as the amplitude as well as the direction of the velocity are concerned. Accordingly, weak objects can be detected when moving with different velocity close to strong vehicles. Accelerating objects can be detected only on the part of their trajectory they have the specific velocity. Problems which arise due to the discontinuities at the edges of the frame sequences are discussed.


Purpose: To evaluate the association between chronological age and mineralization of third molar teeth in a sample from the Northeast region of Brazil.
Methods: A sample of 173 digitized panoramic radiographs were selected from a total of 2,442 panoramic radiographs obtained over a period of 6 months at a private Dental Radiology service, in the city of Joao Pessoa, PB, Brazil. The patients were aged from 5.5 to 21 years, and a calibrated examiner made the evaluation using the classification proposed by Demirjian. Data were analyzed by using an adjusted multiple linear regression model considering age as a response variable. The level of significance adopted was 0.05.
Results: Gender and stage of calcification were significantly correlated associated with age. There was no effect of gender on mineralization of the teeth. Between the two consecutive stages of calcification of third molar teeth, the mean increase in age varied by 16 months.
Conclusion: The results suggest that the development of the third molar teeth is similar in both sexes. Calcification of third molars may be an auxiliary tool in the study of chronological age.


Abstract Based on three recently published books on climate justice, this article reviews the field of climate ethics in light of developments of international climate politics. The central problem addressed is how idealised normative theories can be relevant to the political process of negotiating a just distribution of the costs and benefits of mitigating climate change. I distinguish three possible responses, that is, three kinds of non-ideal theories of climate justice: focused on (1) the injustice of some agents not doing their part; (2) the policy process and aiming to be realistic; and (3) grievances related to the transition to a clean-energy economy. The methodological discussion underpinning each response is innovative and should be of interest more generally, even though it is still underdeveloped. The practical upshot, however, is unclear: even non-ideal climate justice may be too disconnected from the fast-moving and messy climate circus.


Crowdfunding enables project initiators to obtain money from unknown supporters worldwide to finance their business ideas. To receive funding, an adequate and effective communication between project initiators and supporters is very important. However, traditional marketing activities' high costs are often unaffordable. Therefore, guerrilla marketing represents an unconventional and inexpensive way to gain reach and popularity, especially if done via social media. Research has largely neglected the ways different marketing activities and social media influence crowdfunding success. The contribution of our work-inprogress is that we provide a theoretical and integrative understanding of how guerrilla marketing has an influence on crowdfunding success via social media. We derive a preliminary model on crowdfunding success from literature and test it against seven cases of crowdfunding campaigns which employed guerrilla marketing in their social media campaigns. Subsequently, using inductive case analysis, we extend the current understanding of crowdfunding success to an initial research model.


Vagueness exists amongst Christians regarding what it is like to experience divine guidance practically. This problem is aggravated by conflicting perspectives on the will of God, whether or not his will is discoverable, and how Christians are to go about seeking it. This article seeks to reveal what we can reasonably expect to experience when God speaks, by considering perspectives on the will of God as well as its discoverability, and the levels of awareness and certainty of divine communication as evidenced by selected biblical characters. The article shows that the ways in which Christians experience divine direction are as unique and varied as each individual relationship with God is unique and varied. It shows, furthermore, that we should have, as our primary concern, a focus upon fostering a deep and intimate relationship with God, out of which direction and instruction will naturally and invariably flow. Finally, it shows that the primary way in which God communicates with us today is by means of the subtle and unobtrusive guidance and direction of our hearts and minds by the Holy Spirit.


The taste of food is heightened by seasoning, and food prepared with the right mixture of spices is one of the major human pleasures and as such a matter of huge economic dimension. It is therefore no wonder that the trade in spices has been of vast historical importance and a major driving force in the late medieval contacts between the East and West.1 The chemicals responsible for the gustatory and olfactory pleasures of spices are secondary metabolites elaborated by plants primarily for their defence.1 By some strange perversion, many humans have learned to enjoy low doses of these toxic chemicals, and in so doing ensure the success and survival of the plants producing spices.1

What are the mechanisms whereby we sense spices, and what do they have to do with functional disorders of the gastrointestinal (GI) tract? Even one decade ago, nobody could envisage that a large family of closely related ion channels act as molecular sensors for distinct spices, yet also detect other sensory modalities including pain.2 The pioneer that triggered this avalanche of discoveries was the "capsaicin receptor", now termed TRPV1 which stands for "transient receptor potential vanilloid 1" ion channel. Responsible for the piquancy of red pepper ( Capsicum spp.), the vanilloid capsaicin in its pure form is one of the most painful chemicals we know. It was the Hungarian pharmacologist Nicolas Jancso who in the middle of the 20th century first recognised that capsaicin acts specifically on nociceptive afferent neurons.3 The exploration of this unique pharmacological profile of capsaicin led, in 1997, to the identification of TRPV1 as the molecular sensor of capsaicin, selectively expressed by unmyelinated and some thinly myelinated primary afferent neurons.4

The capsaicin receptor belongs to the superfamily of transient receptor potential (TRP) ion channels, so named …


On October 5, 2011, the Supreme Court will hear oral arguments in Hosanna-Tabor Evangelical Lutheran Church & School v. EEOC, a case in which the Court will consider the existence and nature of the so-called "ministerial exception": the judicial doctrine that gives churches legal immunity in employment discrimination cases brought by "ministerial" employees. The case promises to be one of the more important church-state decisions in recent years. In conjunction with the second Annual Law and Religion Roundtable, the Northwestern University Law Review Colloquy will be publishing several pieces on the case.In this contribution to the Colloquy, I argue strongly in favor of the ministerial exception, concluding that it is a necessary part of a principle fundamental not only to the Religion Clauses, but to the Western church-state settlement more broadly: that, in an important sense, church and state each represent separate distinct sovereigns or jurisdictions. Whatever else that settlement means, it requires at a minimum that the state cannot involve itself in questions related to the selection and status of church leaders or members.I argue, however, that our focus on the question of power is inadequate. More important, perhaps, than the question whether the ministerial exception ought to exist is how we ought to behave if it does. Supporters of the ministerial exception – and I count myself among them – are morally obliged to give thought to how churches ought to behave toward their employees in cases in which those employees may be entitled to no legal remedy. I argue that the ministerial exception should be thought of as a responsibility or burden for churches, not just a license to act without legal consequence. Furthermore, where the law treats churches and other "First Amendment institutions" as entitled to a substantial degree of legal autonomy, we ought to think carefully about the role of both debate within the institution and public criticism of that institution in encouraging sound and responsible conduct by those actors. There are good reasons to champion the kind of institutional autonomy and pluralism represented by the ministerial exception, and to avoid thinking of the state as the font of all power and the solution to all problems; but taking that step requires us to think much more carefully about institutional responsibility, and about the civic duty of citizens to monitor and critique our key non-state institutions. Hosanna-Tabor should mark the beginning of an important conversation, not the end.


Importance Testosterone initiation increased substantially in the United States from 2000 to 2013, especially among men without clear indications. Direct-to-consumer advertising (DTCA) also increased during this time. Objective To investigate associations between televised DTCA and testosterone testing and initiation in the United States. Design, Setting, and Population Ecologic study conducted in designated market areas (DMAs) in the United States. Monthly testosterone advertising ratings were linked to DMA-level testosterone use data from 2009-2013 derived from commercial insurance claims. Associations between DTCA and testosterone testing, initiation, and initiation without recent baseline tests were estimated using Poisson generalized estimating equations. Exposures Monthly Nielsen ratings for testosterone DTCA in the 75 largest DMAs. Main Outcomes and Measures (1) Rates of new serum testosterone testing; (2) rates of testosterone initiation (in-office injection, surgical implant, or pharmacy dispensing) for all testosterone products combined and for specific brands; and (3) rates of testosterone initiation without recent serum testosterone testing. Results Of 17 228 599 commercially insured men in the 75 DMAs, 1 007 990 (mean age, 49.6 [SD, 11.5] years) had new serum testosterone tests and 283 317 (mean age, 51.8 [SD, 11.3] years) initiated testosterone treatment. Advertising intensity varied by geographic region and time, with the highest intensity seen in the southeastern United States and with months ranging from no ad exposures to a mean of 13.6 exposures per household. Nonbranded advertisements were common prior to 2012, with branded advertisements becoming more common during and after 2012. Each household advertisement exposure was associated with a monthly increase in rates of new testosterone testing (rate ratio [RR], 1.006; 95% CI, 1.004-1.008), initiation (RR, 1.007; 95% CI, 1.004-1.010), and initiation without a recent test (RR, 1.008; 95% CI, 1.002-1.013). Mean absolute rate increases were 0.14 tests (95% CI, 0.09-0.19), 0.05 new initiations (95% CI, 0.03-0.08), and 0.02 initiations without a recent test (95% CI, 0.01-0.03) per 10 000 men for each monthly ad exposure over the entire period. Conclusions and Relevance Among US men residing in the 75 designated market areas, regional exposure to televised direct-to-consumer advertising was associated with greater testosterone testing, new initiation, and initiation without recent testing.