In memory-based collaborative filtering, the existing methods conduct a prediction based on the overall consistency of two users or items. The major problem with these methods is that it is hard to find users/items that are overall consistent with the test user/item in the system. In addition, these methods are sometimes being over optimistic, and disregard some useful information in user profiles in making a prediction. This paper exposes the drawbacks in these methods and proposes an inference-based recommendation scheme to overcome those drawbacks. This model is based on the fact that any two users may have common interest genres as well as different ones, with the capability of making full use of rating information to capture accurately the relevance between item and user. Experimental results from two popular public datasets, EachMovie and Movielens, show that our approach improves significantly the prediction accuracy.


Introduction There are indications that oxidized low density lipoprotein cholesterol (Ox-LDLC) may play an important role in cardiovascular disease (CVD) events. In most developing countries, the interplay between the different lipid fractions and cigarette smoking has not been studied. This study assessed the effect of cigarette smoking on the alterations in plasma lipid fractions and their associations with the gonadal hormone, testosterone (T). Methods One hundred and sixty male participants, consisting of eighty smokers and eighty apparently healthy non-smokers were recruited. Anthropometric indices and biochemical parameters were determined using standard procedures. Results Significant increases were obtained in plasma total cholesterol (TC), triglyceride (TG), oxidized low density lipoprotein (Ox-LDLC) and Ox-LDLC/TT ratio (p<0.001) in smokers compared with the non-smokers. Plasma high density cholesterol (HDLC) (p<0.001) was significantly reduced in smokers compared with the non-smokers. The plasma mean T result was not significantly different from the non-smokers, but inversely correlated with Ox-LDLC and significantly correlated with the lipids and lipoproteins. Significantly high plasma TC, TG and LDLC (p<0.001) and low HDLC (p<0.001) were also obtained in smokers when co-founding factors such as duration and number of cigarette smoked per day were applied. Conclusion This study showed an inverse correlation between Ox-LDLC and testosterone as well as strong association between the number of tobacco and cigarettes usage per day. These changes in part, could be major causes of premature CVD and decreased fertility in young adults.


Currently, the world of education is entering a disruptive era. Digital-based educational technology. Especially in the distance education model. The technology used is relatively unsophisticated. This study aims to: (1) develop Disruptive Innovation learning media with Augmented Reality with the concept of 3D objects in the form of a Drill Machine; (2) testing the attractiveness of Disruptive Innovation Learning media with Augmented Reality with a 3D Object Concept in the form of a Drill Machine; and (3) testing the effectiveness level of the product being developed. The method used is research and development (R&D), followed by quasi-experimentation to test its effectiveness. Validation consists of two teams of experts, namely e-learning media experts and vocational education material experts. The findings in this study include augmented reality technology based on 3D objects in the form of a drill machine that was developed has a high level of attractiveness and completeness of vocational material. The object-based 3D augmented reality technology in the form of a drill machine that was developed was proven to be able to improve the understanding skills of vocational students in the education era 4.0.


Machimosaurus was a large-bodied durophagous/chelonivorous genus of teleosaurid crocodylomorph that lived in shallow marine and brackish ecosystems during the Late Jurassic. Among teleosaurids, Machimosaurus and its sister taxon 'Steneosaurus' obtusidens are characterized by having foreshortened rostra, proportionally enlarged supratemporal fenestrae and blunt teeth with numerous apicobasal ridges and a shorter anastomosed ridged pattern in the apical region. A recent study on 'S.' obtusidens dentition found both true denticles and false serrations (enamel ridges which contact the carinae). Here, we comprehensively describe and figure the dentition of Machimosaurus, and find that Machimosaurus buffetauti and Machimosaurus hugii have four types of serration or serration-like structures, including both denticles and false denticles on the carinae. The denticles are irregularly shaped and are not always discrete units, whereas the false denticles caused by the interaction between the superficial enamel ridges and the carinae are restricted to the apical region. Peculiarly, the most 'denticle-like' structures are discrete, bulbous units on the apicobasal and apical anastomosed ridges of M. hugii. These 'pseudo-denticles' have never, to our knowledge, previously been reported among crocodylomorphs, and their precise function is unclear. They may have increased the surface area of the apical region and/or strengthened the enamel, both of which would have been advantageous for a durophagous taxon feeding on hard objects such as turtles.


The problem of bilingual education in globalized society is discussed in this article. In this context, the characteristics of society and the role of language as a means of communication are described. Furthermore, this study defends the idea that bilingual education should be based on a critical intercultural perspective. From this idea, it is possible to educate not only in diversity and plurality, but it is also possible to problematize situations of power that maintain relations of inequality among speakers of different languages. The theoretical principles that guide these reflections come from authors such as Grundy (1998), Habermas (1972), Walsh (2010), Freire (1967), Garcia (2009), among others. We hope that this work contributes to the discussion of bilingual education and linguistic policies in Colombia.


For vertical cryogenic tests of Superconducting Radio Frequency (SRF) cavities for particle accelerators, typically many hundreds of liters of liquid helium are required. The location of the superfluid-helium to vapour interphase undergoes significant change during the test. We describe a new technique based on commercially available quartz tuning forks for measuring the ambient conditions of the helium bath and for precisely determining the liquid to vapour interface during a vertical cavity test. It is shown that transition from the superfluid phase to vapour as well as to the normal-fluid phase can be unambiguously determined. The experimental results are analysed with existing theories of superfluidity, using an approach for the hydrodynamics of oscillating objects immersed into a viscous medium.


The purpose of this article is to discuss the significance of academic collaboration within cardiovascular medicine and surgery, in both clinical and research settings, at a major academic institution in Europe.


Cell surface receptors survey and relay information to ensure the development and survival of multicellular organisms. In the model plant Arabidopsis thaliana, the Catharanthus roseus RLK1-like receptor kinase FERONIA (FER) regulates myriad of biological processes to coordinate development, growth and responses to the environment. We recently showed that FER positively regulates immune signaling by controlling the ligand-induced complex formation between the leucine-rich repeat receptor kinase (LRR-RK) FLAGELLIN SENSING 2 (FLS2) and its co-receptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1/SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3 (BAK1/SERK3). In this context, FER function is inhibited by binding of its peptide ligand RAPID ALKALINIZATION FACTOR 23 (RALF23). However, the mechanisms by which FER regulates FLS2-BAK1 complex formation remain unclear. Here, we show that FER-dependent regulation of immune signaling is independent of its kinase activity, indicating that FER rather plays a structural role. FER has been proposed to bind directly to the plant cell wall, but we found that a FER mutant unable to bind pectin is still functional in regulating immune signaling. Instead, FER- and cell wall-associated LEUCINE RICH REPEAT-EXTENSIN proteins are required for this regulation. Using high-resolution live-imaging and single-particle tracking, we observed that FER regulates FLS2 plasma membrane nanoscale dynamics, which may explain its role in controlling ligand-induced FLS2-BAK1 association. We propose that FER acts as an anchoring point connecting cell wall and plasma membrane nano-environments to enable the nucleation of pre-formed receptor/co-receptor complexes at the cell surface.


Lithospheric extension is sited, preferentially, along orogenic belts because they have a thicker continental crust, contain structural inhomogeneities, and suffer extensional orogenic collapse caused by body forces resulting from isostatically compensated elevation and sharp elevation gradients. Collapse occurs especially where rapid advective thinning of the shortened thermal boundary conduction layer occurs beneath an orogen and causes rapid uplift. Where boundary forces are compressional, extension is balanced by radial thrusting to form oroclinal loops around collapsed extensional basins. Where, as in the disruption of Pangea, boundary forces change rapidly from compressional to tensional, body force collapse is continued by general extension which may lead to continental splitting. Even where overall convergence is continuing, orogenic collapse may be enhanced by subduction rollback into small remnant oceans. The extensional collapse of orogens offers a partial explanation for why oceans cyclically close and reopen in roughly the same places, preservation of very high pressure metamorphic rocks, for the return of orogenic large crustal thicknesses to normal without very much erosional denudation with the widespread preservation of supracrustal sequences, high temperature metamorphic assemblages and the minimum-melting granite suite.


A 56-year-old man developed allergic interstitial nephritis and deterioration of preexisting chronic renal failure after receiving diazepam. On discontinuation of diazepam, kidney function returned to the baseline level and itching, eosinophilia, and eosinophiluria subsided. A causative correlation between allergic interstitial nephritis and diazepam is suggested.


Abstract:Advocating the perspective of emotive history, this article looks at two examples of emotive archiving—the assembly of artifacts, photographs, oral interviews, and documents that record the feelings of Mexican immigrants as an inspiration for family members. The commitment and creativity of the archivist (usually a woman) is a feminist act of empowerment and an expression of love and honor to the subject of the archive, while the innermost feelings of the memorialized individual, often repressed from fear of apprehension and deportment, are expressed openly, forming a model for younger family members.


Resource allocation could be influenced by various dynamic elements, such as the skills of engineers and the growth of skills, which requires managers to find an effective and efficient tool to support their staffing decision-making processes. Rescheduling happens commonly and frequently during the project execution. Control options have to be made when new resources are added or tasks are changed. In this paper we propose a software project staffing model considering dynamic elements of staff productivity with a Genetic Algorithm (GA) and Hill Climbing (HC) based optimizer. Since a newly generated reschedule dramatically different from the initial schedule could cause an obvious shifting cost increase, our rescheduling strategies consider both efficiency and stability. The results of real world case studies and extensive simulation experiments show that our proposed method is effective and could achieve comparable performance to other heuristic algorithms in most cases.


We perform simulations in a simple model that aims to mimic the hydrodynamic evolution of a relativistic fluid during a cosmological first-order phase transitions. The observable we are concerned with is hereby the spectrum of gravitational radiation produced by colliding fluid shells. We present simple parameterizations of our results as functions of the wall velocity, the duration of the phase transition and the latent heat. We also improve on previous results in the envelope approximation and compare with hydrodynamic simulations.


1 Nine cases of accidental poisoning of children with sneezing powder are reported. Symptoms, besides sneezing, included gastrointestinal disturbances and syncope, whilst examination demonstrated bradycardia and hypotension. 2 The powder, as supplied, carried no information on its constituents but Veratrum alkaloids were identified on analysis. The signs and symptoms observed were compatible with poisoning from these compounds. 3 As a result of these observations, it was possible to trace the manufacturers and a change was made to a safer formulation. This example emphasises the value of toxicovigilance by Poison Control Centres.


AIM
The aim of the study was to investigate the relationship between the clinical evidence of foot deformities in spina bifida occulta and the associated neurophysio-logical damage.

METHODS
The authors studied 47 patients with foot deformities (37 flat foot, 10 pes cavus) and vertebral cleft, variably associated with enuresis, midline cutaneous lesions, and further orthopaedic deformities. An electrophysiological evaluation was performed in an attempt to investigate the peripheral nervous system in greater detail, including conventional motor and sensory nerve conduction, F-wave recording and electromyogram (EMG) testing.

RESULTS
The peroneal nerve F wave latency was longer in patients with pes cavus than in those with flat foot (P<0.04). Conversely, the posterior tibial nerve F-wave latency was longer in patients with flat foot than in those with pes cavus (P<0.02). Needle EMG showed large amplitude motor unit potentials during voluntary recruitment in all patients, suggesting a neurogenic origin of these EMG changes. Neurophysiological study makes it possible to distinguish between myogenic and lower motor neuron involvement. The existence of some degree of spinal cord dysraphism may be pathophysiologically associated with foot deformities.

CONCLUSION
Children with foot deformities and clinical evidence of occult spinal dysraphism should have a neuro-physiological assessment in order to obtain an early diagnosis and avoid ineffective foot surgery.


The aim of this paper was to shake up the entrepreneurship ideal by problematizing what seems to have become naturalized, i.e. the ideologized tale of optimism associated with entrepreneurship. We have chosen a particular group of entrepreneurs (one usually and typically excluded in not only popular discourse but also in mainstream entrepreneurship literature), and we have chosen a typical Western society, one that firmly ascribes to neoliberal ideas. We have brought into play Dutch institutional stories with those of female ethnic entrepreneurs to see if these institutions sustain the presupposed view and to find out how these women consequently 'deal' with such presuppositions, and how and at what particular aspects they resist them. Since centre-margin positionalities are central to our investigations we have turned to deconstruction analysis as an inspirational source for our analysis. Our analysis portrays how the centred ideas about entrepreneurship and the positive powers attributed to it do not hold; it demonstrates the incoherence of this centre rather than confirming its position. We have been able to establish that the hegemonic, positive discourse on entrepreneurship in general and with women of ethnic minority origin specifically indeed resonates in these institutions' stories, mostly in its non-reflexivity and ideological prejudices.


Objective The main objectives of this study were to use the effect of information framing (different expressions of the same issue, e.g., positive messages and negative messages) to explore key factors that influence the attitude of and intention of the public toward wearing masks and to understand the internal and external factors of intervention on information framing perception. Methods This study performed an online questionnaire survey to explore the influence of demographic characteristics, information framing, social norms, and information credibility on the attitude of the public toward masks and their intention to wear them. Results (1) Information framing had a significant impact on the attitudes of people toward masks and their intention to wear them, and the persuasion effect of gain-framed messages was higher than that of loss-framed messages. (2) Gender, income, occupation, educational background, and residence have no significant difference in attitude and intention to wear masks. There was a significant correlation between age and wearing of masks (p = 0.041 < 0.05). (3) Social norms affected people's perception of information framing and their attitude toward wearing masks, but only the impact of loss-framed messages on intention was significant. (4) Information framing affected people's perception of information credibility, which had a positive impact on their intention to wear masks; however, information credibility only had a significant impact on attitude toward wearing masks under the gain-framed messages and played an intermediary role. Conclusion The impact of information framing on the attitude of people toward masks and their intention to wear them varies. Individuals involved in the publicity of health information related to this issue should pay attention to the influence of information framing and content on the public wearing masks as a means of enhancing public health awareness.


The classical computer vision methods can only weakly emulate some of the multi-level parallelisms in signal processing and information sharing that takes place in different parts of the primates' visual system thus enabling it to accomplish many diverse functions of visual perception. One of the main functions of the primates' vision is to detect and recognise objects in natural scenes despite all the linear and non-linear variations of the objects and their environment. The superior performance of the primates' visual system compared to what machine vision systems have been able to achieve to date, motivates scientists and researchers to further explore this area in pursuit of more efficient vision systems inspired by natural models. In this paper building blocks for a hierarchical efficient object recognition model are proposed. Incorporating the attention-based processing would lead to a system that will process the visual data in a non-linear way focusing only on the regions of interest and hence reducing the time to achieve real-time performance. Further, it is suggested to modify the visual cortex model for recognizing objects by adding non-linearities in the ventral path consistent with earlier discoveries as reported by researchers in the neuro-physiology of vision.


This research note compares sequential and concurrent web-mail mixed-mode approaches and incentives for a survey on US consumers' use of financial products, especially when their finances are tight. The sample (n = 2,000) was drawn from credit bureau data. We examine the effects on response rates, survey costs, and possible nonresponse bias in an experiment varying two factors in a 2x2 design: (1) using concurrent or sequential web and then mail survey modes, and (2) different incentive amounts given to initial survey nonrespondents ($5 versus $10). The sequential (web-first) design had a significantly lower response rate (3.9 percent) at week five—before the paper questionnaire was mailed—than the concurrent group (11.0 percent). This difference was nearly fully eliminated by the end of the field period. The higher incentive brought in slightly more respondents in the concurrent arm and slightly fewer respondents in the sequential arm, but neither difference is statistically significant. Compared with the sample frame, respondents in both groups were generally older and had many of the characteristics that come from being older: higher credit scores, more open credit cards, lower credit card utilization, greater likelihood of having a mortgage, and lower likelihood of being delinquent on credit card payments. Given the lower initial response rate and the need for more follow-up mailing, the sequential mixed-mode approach resulted in a higher cost per complete survey.


Combination with high throughput screening, combinatorial organic synthesis of diverse libraries of biologically active compounds has revolutionized the drug discovery process. Although combinatorial organic synthesis on solid supports is a useful approach, several groups are focusing their research efforts on liquid-phase combinatorial synthesis by using soluble polymer supports for generation of libraries. This macromolecular carrier (PEG), in contrast to an insoluble matrix, is soluble in different kinds of organic solvents and has a strong tendency to precipitate in some particular solvents. Liquid-phase combinatorial synthesis is a unique approach since homogeneous reaction conditions can be applied, while product purification similar to the solid-phase method can be carried out by simple filtration and washing. This strategy retains the advantages of classical solution-phase chemistry and solid-phase polymer-supported synthesis. Moreover, the smart designation of traceless linkers approach and the utilization of microwave technology on combinatorial chemistry improve the reaction's condition, time and results. This review, first, presents the history of soluble polymer supports in the synthesis of combinatorial libraries; and then, some selected examples from our laboratory are introduced.


A contemporary pathology of science is outlined. This pathology suggests that "previous knowledge" drastically limits innovative thinking in science. In very raw "Bayesian" terms it is affirmed that a too rich and flexible a priori knowledge is detrimental to the appreciation of novelty coming from experimental results by both lowering the relative weight assigned to a posteriori contrasting evidence and adapting potentially revolutionary findings to an already existing frame.


Lakes and reservoirs are considered sentinels of climate and anthropogenic changes. Lakes and reservoirs surface water storage is an essential hydrological variable but poorly known as this information is scarce. Earth Observation data are a reliable source of information to overcome this scarcity. Among these, the combined use of satellite images, to derive water extent, and radar altimetry, which enables to estimate water levels, provides valuable information on water storage changes. Here, we used Synthetic Aperture Radar images from Sentinel-1 and radar altimetry data from Sentinel-3 to monitor the water volume changes of Lake Bracciano from 2016 to 2021. This lake was affected by a water crisis in 2017 and the water supply to the city of Rome (Italy) was interrupted September 2017 to preserve its ecosystem. Hence, we demonstrate how Sentinel-1 and Sentinel-3 data can be useful to monitor water extent and level, which can be profoundly changed by the climate crisis.


ABSTRACT We report a case of Epstein-Barr virus (EBV) primo infection with the development of successive infectious mononucleosis, hemophagocytic lymphohistiocytosis, and B-cell lymphoproliferative disorder in a patient treated with azathioprine for Crohn's disease. This case report suggests that specific EBV-related clinical and virological management should be considered when treating a patient with inflammatory bowel disease with azathioprine.


This obituary of Siro Lombardini recalls his scientific, operative and public activities and gives an obviously preliminary appraisal of his main innovative contributions to a surprisingly long list of economic issues such as: theory of the firm and markets, supply and demand disequilibrium, modern monopolies and economic growth, disequilibrium growth and computational economics, national and regional planning. Of particular relevance is also the attention he devoted to the great financial crisis of 1987 which he closely compared with the great slump of 1929, with annotations that have become almost prophetic if one thinks of the current depression. A final section is devoted to his numerous elaborations on the scope and moral aspects of economics.


The purpose of this research is to provide a systematic review on the flipped classroom (FL) approach in English language teaching (ELT) in Vietnam in terms of the trends and the key results, based on 12 published articles. A content analysis method was employed to analyze the collected papers. The findings indicated that the implementation of flipped learning appeared to gradually increase in Vietnam since 2017 and remain its prosperity in the higher education context. Also, the results revealed that a variety of research methods were used in selected articles; however, the most common one was the mixed method. Moreover, grammar and speaking skills were the two basic language skills being commonly studied. Additionally, the flipped learning was shown to not only produce an improvement on learners' achievement but also positively affect their perspectives toward its application. The findings also pointed out some challenges and benefits concerning the utilization of the FC in ELT in Vietnam. Finally, some suggestions were provided to educators and future scholars.


The number of clinical specimens containing β-lactam-resistant Pseudomonas aeruginosa isolates is increasing. However, whether resistance is associated with reduced fitness is still uncertain in clinical Pseudomonas aeruginosa isolates. In this study, we aimed to determine whether β-lactam resistance conferred a fitness cost in Pseudomonas aeruginosa. Growth rate, extracellular slime production, elastase activity, proteolytic activity, LasA protease activity, biofilm formation, and pairwise in vitro competition experiments were investigated in a collection of 11 isogenic, β-lactam-susceptible and -resistant (≥8-fold increase in minimum inhibitory concentration (MIC)) pairs of P. aeruginosa clinical isolates; each pair was recovered from a different patient treated with β-lactam antibiotics. All β-lactam-resistant Pseudomonas aeruginosa isolates showed a significant reduction in elastase activity. In addition, 90.9% (10/11) of β-lactam-resistant Pseudomonas aeruginosa isolates were associated with markedly lower growth rate and proteolytic activity, and 81.8% (9/11) of β-lactam-resistant Pseudomonas aeruginosa isolates had less extracellular slime production, compared to susceptible isolates. Meanwhile, LasA protease activity and biofilm formation ability were variable among isolates. Pairwise in vitro competition experiments showed that 72.7% (8/11) of β- lactam-susceptible strains could outgrow resistant strains. In conclusion, resistance development with β-lactam exposure confers a fitness cost, resulting in a decreased invasion potential, while the effect on viability varied. Thus, the potential for the dissemination of β-lactam-resistant Pseudomonas aeruginosa clinical isolates should not be underestimated.


The properties of deductive systems in Hilbert algebras are treated. If a Hilbert algebra H considered as an ordered set is an upper semilattice then prime deductive systems coincide with meet-irreducible elements of the lattice DedH of all deductive systems on H and every maximal deductive system is prime. Complements and relative complements of DedH are characterized as the so called annihilators in H.


The density derived electrostatic and chemical (DDEC/c3) method is implemented into the onetep program to compute net atomic charges (NACs), as well as higher-order atomic multipole moments, of molecules, dense solids, nanoclusters, liquids, and biomolecules using linear-scaling density functional theory (DFT) in a distributed memory parallel computing environment. For a >1000 atom model of the oxygenated myoglobin protein, the DDEC/c3 net charge of the adsorbed oxygen molecule is approximately -1e (in agreement with the Weiss model) using a dynamical mean field theory treatment of the iron atom, but much smaller in magnitude when using the generalized gradient approximation. For GaAs semiconducting nanorods, the system dipole moment using the DDEC/c3 NACs is about 5% higher in magnitude than the dipole computed directly from the quantum mechanical electron density distribution, and the DDEC/c3 NACs reproduce the electrostatic potential to within approximately 0.1 V on the nanorod's solvent-accessible surface. As examples of conducting materials, we study (i) a 55-atom Pt cluster with an adsorbed CO molecule and (ii) the dense solids Mo2C and Pd3V. Our results for solid Mo2C and Pd3V confirm the necessity of a constraint enforcing exponentially decaying electron density in the tails of buried atoms.


In this paper, we study interference networks with local views, where each node only knows the channel gains of h hops around them, leading to mismatched knowledge about the network. For networks with a local view, we propose a new sub-network scheduling called Maximal k-Clique Scheduling (MCS). A key benefit of MCS is that it can be explicitly constructed and hence easier to analyze compared to prior subgraph schedulers. Our main result is that MCS can be used to bound the performance from above and below of a more complex sub-graph scheduling algorithm, known as Maximal Independent Graph Scheduling (MIGS), which in many cases does not have a known explicit construction.


A photoelectrochemical (PEC) cell based on a series-connected photocathode and photoanode made of particulate semiconductors is a potentially scalable and inexpensive device for renewable solar hydrogen production via PEC water splitting without any external power supply. The realisation of such PEC devices hinges on the development of photoelectrodes that operate at a small applied voltage. In this study, solid solutions of La5Ti2CuS5O7 (LTC) and La5Ti2AgS5O7 (LTA) were synthesised, and their physical, optical, and PEC properties in the water splitting reaction were discussed. LTC and LTA formed a La5Ti2Cu1−xAgxS5O7 solid solution (LTC1−xAx) over the whole compositional range. The indirect bandgap energy of LTC1−xAx changed nonlinearly with respect to composition, attaining its minimum value (ca. 1.8 eV) at a composition of x ≈ 0.16. Photoelectrodes of Al-doped LTC1−xAx solid solution powder fabricated using the particle transfer method exhibited a photocathodic response regardless of the Ag content. 1%Al-LTC0.9A0.1 photocathodes exhibited the best PEC properties in the hydrogen evolution reaction and yielded a hypothetical half-cell solar-to-hydrogen energy conversion efficiency of 0.25% at +0.6 V vs. RHE, three times higher than the previously reported 1%Sc-LTC. In addition, 1%Al-LTC0.9A0.1 photocathodes were fairly stable at +0.7 V vs. RHE without any protective modifications. Owing to the positive operational electrode potential of 1%Al-LTC0.9A0.1, unassisted PEC water splitting was accomplished using series-connected photoelectrodes made of 1%Al-LTC0.9A0.1 and BaTaO2N, particulate semiconductors with absorption edge wavelengths of 710 and 660 nm, respectively, at a Faradaic efficiency of unity and a solar-to-hydrogen energy conversion efficiency of approximately 0.1%.


The Global Financial Crisis has been one of the most significant
economic shocks since the Great Depression. As the Crisis intensified,
there was a large fall in markets' capacity to accept risk. The result was
a situation of tight credit conditions and in some cases dysfunctional
markets, accompanied by a general loss of confidence. This dissertation
explores some of the forces that have been working to mitigate the
negative effects in the aftermath of the Crisis.
The first chapter analyses the role played by central bank forwardlooking
communication in shaping markets' expectation. To this aim,
we propose a new index of central bank's verbal guidance, which measures
the communication about future based on the frequency of future
verbs in monetary policy statements. The purpose is to test whether and
the extent to which verbal guidance might be considered an additional
policy instrument. We consider the case of the European Central Bank
(ECB) and follow a two-steps procedure. First, we analyze the main
determinants of our index and estimate the unexpected component.
Second, we investigate the effects of the identified innovation of verbal
guidance on daily changes of forward money markets rates between
September 2007 and December 2015. Our results show that financial
markets' expectations on future short-term interest rates react to a
shock of communication about future: the effect is negative and larger
for higher horizons, after controlling for the standard policy rate shock
and the announcement of unconventional monetary policies. This
suggests that the verbal guidance may be considered an additional policy instrument.
The second chapter provides evidence about the tightening credit
conditions faced by the private sector in Italy in the aftermath of the
Global Crisis and analyses the role played by social capital. Since
social capital is a key determinant of trust, it should positively affects
the supply of credit, in particular during crises when confidence is
under stress, as it was for the financial turmoil of 2008. To investigate
whether and the extent to which social capital mitigated the credit
rationing following the Crisis, we compare the probability of approving
a loan requests lodged by over half a million Italian non-financial
corporations before and after the default of Lehman Brothers (from
January 2007 to June 2010). We find that firms headquartered in
high-social capital provinces suffered less: while during the Crisis
the probability of loan approval declined for all firms, for those ones
headquartered in high-social-capital areas the decline was half that of
low-social-capital areas, indicating that social capital smoothed the
impact of the shock. Moreover, consistent with theory, we find that
social capital conveys its mitigating effect on credit rationing in cases in
which the reciprocal trust, because of the lack of information, matters
more.


Honeycomb with good mechanical properties and low density are the top priorities in material selection. Therefore, the facesheet thickness is a factor that contributes to it as it made up most of the weight in the structure. Appropriate thickness can optimize the mechanical performance. However, the sandwich composite may associate to high density if the facesheet is of high thickness yet deteriorate the mechanical properties as an overall. As the facesheet is attached to the sandwich structure via matrix, the peeling properties for various facesheet thickness is investigated. The facesheet thickness in terms of one to five layers are glued to the rubber wood core. The structures are tested for its peeling strength under vertical 90° test according to the ASTM standard. The optimal number of facesheet with good peeling strength is discussed.


OBJECTIVES
This study was designed to investigate the frequency of requests for computed tomography (CT) examination of the spinal column and pelvis in our emergency orthopedic department, the reasons of requests, and the rates of positive and negative CT examinations.

METHODS
We retrospectively reviewed patients for whom a request for CT examination was made by the emergency orthopedic department within a year (September 2005- 2006). The reasons for CT requests, findings in CT reports, and age and sex of the patients were recorded. Findings unrelated and related to the original request denoted a negative and positive CT examination, respectively.

RESULTS
Of 24,378 admissions to our emergency orthopedic department, a CT scan was requested in 1,295 patients (5.3%). In 817 patients (63.1%), CT examination involved the pelvis or the spinal column. Of these, 418 CT scans (51.2%) yielded a negative result. The mean age of the patients with a negative CT scan was significantly lower than those having a positive CT scan (40.7 vs 45.1 years; p=0.001). There was no significant difference with respect to sex between patients having negative and positive CT findings (p=0.670). Compared to pelvis CT scans, the frequency of negative CTs was significantly higher for spinal column examinations (p<0.001). The incidence of negative CT scans for upper thoracic and cervical vertebrae was significantly higher than that found for lower thoracic and lumbar regions (p<0.001).

CONCLUSION
The high incidence of negative CT scans documented for pelvic and spinal column examinations underlines the need for measures to avoid superfluous CT requests in emergency departments.


The aim of the article is to conduct a comparative analysis of the quality of government (QoG) in Lithuania (treated as a single NUTS 2 region) and in Polish Voivodships (16 NUTS 2 regions). The analysis of the quality of government was conducted on the basis of indicators quality of government in the European regions developed twice, in 2010 and in 2013, by the Quality of Government Institute in Gothenborg. The results of the performed analyzes show that in both cases the quality of government in Lithuania and in Poland was relatively low, and as regards the quality of government, Lithuania was placed very low in the ranking of the 17 analyzed NUTS 2 regions. The article is of theoretical and empirical nature. The theoretical part is dedicated to presenting public tasks implemented by self-government units in Lithuania and in Poland along with the concept of the QoG. The empirical part contains description of the methodology of research and results of conducted comparative analysis. The article is concluded with a summary, in which the main conclusions from the study are presented.


Abundance data from a 6-year study (1988–1993) of harbour seals (Phoca vitulina) were used to control for seasonal changes in haulout behaviour and assess the effect of temperature and other weather conditions on haulout numbers at a site in Scotland. A significant relationship between Julian day and haulout numbers was consistent between years. In some years, there was also a significant relationship between ambient temperature and haulout numbers, but examination of the residuals around the relationship between haulout numbers and Julian day revealed no evidence for a consistent effect of temperature, wind speed, or wind-chill adjusted temperatures. A weak negative relationship between haulout numbers and both precipitation and cloud cover did exist, but these variables explained little of the variation in seal numbers.


In 1897, the architect Ernesto Basile was commissioned to design the new Chamber in the Italian Parliament. Basile visualised a long painted frieze crowning the Chamber. The assignment was given to the painter Aristide Sartorio who executed it between 1908 and 1911. The frieze is 105 meters long, 3.75 high, and consists of 50 panels painted on canvas. In 1998 the frieze was examined closely and several problems regarding its state of conservation became evident, such as the loss of elasticity of the canvas and the widespread tendency of the paint film to become detached. In order to study the problem and plan the restoration for the entire frieze, it was decided to do a pilot restoration on only one of the 50 panels. The restoration was carried out in an equipped environment inside the Parliament, during the period 2003- 2004. Based on the studies carried out over the two years, it was possible to plan the restoration of the entire frieze, which was completed in one year: from 2006 to 2007. The panels were taken to a Roman studio exclusively dedicated to this restoration. It was not possible to do the restoration in situ as it would have created a disturbance in the working of the Parliament. The panels painted by Sartorio with a particular technique based on oil and wax, were treated with BEVA 371, reactivated with heat using a flat, low pressure table, and with a heated curved low pressure table specially designed by us. Using the same system and cloth bands, the edges of the panels were reinforced and then placed on their original frames. Finally, the veil of greasy particulate matter that had deposited over a century was removed. The restoration, directed by the Architectural Superintendency of Rome, was preceded and accompanied by numerous scientific research studies on the colors, canvas, color medium, wood and microclimate of the frieze. An extensive detailed color photographic documentation recorded all the phases of the restoration.


Mixing in heterogeneous flows depends on the interplay between the generation of gradients by velocity fluctuations and their dissipation by diffusion. One of the key questions concerns the range of scales for which a scalar can be considered well mixed. The spreading scale σ(t) quantifies the global size of the transported plume. Since the heterogeneity induces incomplete mixing inside the plume, this scale is not relevant for quantifying mixing. Yet, no alternative scale have been defined for this purpose. Therefore, we define the mixing scale e(t) as the upper limit for which the concentration distribution is well mixed. We discuss different methods to estimate e from a concentration field and study numerically its temporal evolution in heterogeneous porous media. For homogeneous flow fields, e^2(t) evolves linearly in time and e(t) is equal to the characteristic plume size σ(t). For highly heterogeneous flows, this behaviour breaks down and e(t) is much smaller than σ(t). We find that the mixing scale e(t) evolves subdiffusively over a large range of times. We attribute this behaviour to the wide distribution of velocity gradients, which implies that the competition between diffusion and the velocity field shear action is non-local. Since the characteristic plume size σ(t) evolves superdiffusively, the mixing and spreading scales diverge, implying the persistence of incomplete mixing. This result is of particular importance for upscaling reactive transport, for which the existence of such a mixing scale generally needs to be assumed.


Complications of spine surgery are common in surgical practice and practitioners should be aware of the multiple risks related to these operations as well as of the means to prevent them. To present day in Belgium, the patient has to support the evidence of a fault resulting from medical malpractice in case of legal dispute. The authors remind the foundations of the medical responsibility applied to the surgery of the spine in Belgium, although it is well known that any surgical damage does not necessarily result from an error or from a surgical misconduct, and that therefore, the surgeon is not always responsible for the damage in the absence of a proven fault in the legal sense.


We propose a learning framework, named Multi-Coordinate Cost Balancing (MCCB), to address the problem of acquiring point-to-point movement skills from demonstrations. MCCB encodes demonstrations simultaneously in multiple differential coordinates that specify local geometric properties. MCCB generates reproductions by solving a convex optimization problem with a multi-coordinate cost function and linear constraints on the reproductions, such as initial, target, and via points. Further, since the relative importance of each coordinate system in the cost function might be unknown for a given skill, MCCB learns optimal weighting factors that balance the cost function. We demonstrate the effectiveness of MCCB via detailed experiments conducted on one handwriting dataset and three complex skill datasets.


Four varieties of paddy were soaked in hot water, drained, roasted in an industrial roaster, tempered, flaked and passed through roller. Moisture content reduced from about 35% in paddy to 11–13% in the flakes. Equilibrium moisture content was high (83–85%) in roller pass flakes compared to edge runner flakes. Total amylose equivalent varied from 21 to 23% in flakes of edge runner (ER) while that of roller pass were ~22%. Soluble amylose varied from 10 to 14% in flakes of ER and 11 to 13% in flakes of ER+RP. Protein contents were high in ER flakes, but reduced to an extent of 6 to 30% in roller pass flakes. Significant changes in phosphorus, vitamins; riboflavin and niacin contents w ere not recorded among two types of flakes. Pasting profile parameters indicated that the initial viscosity ranged from 280 to 550 BU in all flakes. Peak viscosity was low compared to initial value in all flakes with exception in MTU 1001 variety. Swelling power remained almost same in both type of flakes, however the solubility was high in BPT 5204 variety in ER + RP flakes. In MTU 1001, the solubility in ER flakes was high compared to ER + RP flakes. Considerable nutrient losses occurred in the flakes obtained after passing through the rollers, except whitening of the flakes.


The structure and connexions of Reissner's fibre have been studied in the rat by means of scanning and transmission electron microscopy. The fibre was found to arise from a series of filaments, each of which was formed by a structure forming the juxta-aqueductal surface or lining of the subcommissural organ. This structure was termed 'apical spherical protrusion' and was found to be rich in rough endoplasmic reticulum. The fibre was firmly attached at its rostral end to the subcommissural organ, at its middle to the ventral surface of the termination of the aqueduct and finally to the calamus scriptorius of the fourth ventricle. It was held in a state of considerable tension between these three points and attached to it were numerous cilia from the ependymal lining. In sections examined by TEM the fibre appeared to be totally amorphous in structure, with erythrocytes and other debris attached to it.


In this paper, we propose an iterative source error correction (ISEC) decoding scheme for deep-learning-based joint source-channel coding (Deep JSCC). Given a noisy codeword received through the channel, we use a Deep JSCC encoder and decoder pair to update the codeword iteratively to find a (modified) maximum a-posteriori (MAP) solution. For efficient MAP decoding, we utilize a neural network-based denoiser to approximate the gradient of the log-prior density of the codeword space. Albeit the non-convexity of the optimization problem, our proposed scheme improves various distortion and perceptual quality metrics from the conventional one-shot (non-iterative) Deep JSCC decoding baseline. Furthermore, the proposed scheme produces more reliable source reconstruction results compared to the baseline when the channel noise characteristics do not match the ones used during training.


In this study, we present a new driving method to generate traveling waves in a finite plate for application to piezoelectric motors. Due to resonant modes which dominate the vibration of finite structures, methods to reduce resonant effects such as using an electric sinker or driving at a non-resonant frequency have been reported. To take advantage of natural resonance and to increase driving efficiency, a new method entitled gated two-frequency-two-mode (G-TFTM) was developed. A piezoelectric bimorph of 1.1 g weight with two rectangular actuators was implemented to verify the design concept. One actuator was operated at a first bending mode and the other actuator operated at a second bending mode with a phase difference. The driving signal was gated to generate an intermittent excitation to provide the periodic propulsion. To determine the profile of the induced traveling wave, an analytical solution was derived and a numerical model was used. Using these design tools, we experimentally verified that traveling waves can be generated using a G-TFTM method. A 0.1-g object can be moved at a speed of 3.31 mm/s under the condition of a 70-to-20 voltage ratio and a 137 deg phase difference. The moving direction was found to be reversed by changing the phase to −43 deg. The experimental and numerical data are detailed in this paper to demonstrate the feasibility of this G-TFTM method.


Visual Abstract Background and objectives Patients receiving in-center hemodialysis treatment face unique challenges during the coronavirus disease 2019 (COVID-19) pandemic, specifically the need to attend for treatment that prevents self-isolation. Dialysis unit attributes and isolation strategies that might reduce dialysis center COVID-19 infection rates have not been previously examined. Design, setting, participants, & measurements We explored the role of variables, including community disease burden, dialysis unit attributes (size and layout), and infection control strategies, on rates of COVID-19 among patients receiving in-center hemodialysis in London, United Kingdom, between March 2, 2020 and May 31, 2020. The two outcomes were defined as (1) a positive test for infection or admission with suspected COVID-19 and (2) admission to the hospital with suspected infection. Associations were examined using a discrete time multilevel time-to-event analysis. Results Data on 5755 patients dialyzing in 51 units were analyzed; 990 (17%) tested positive and 465 (8%) were admitted with suspected COVID-19 between March 2 and May 31, 2020. Outcomes were associated with age, diabetes, local community COVID-19 rates, and dialysis unit size. A greater number of available side rooms and the introduction of mask policies for asymptomatic patients were inversely associated with outcomes. No association was seen with sex, ethnicity, or deprivation indices, nor with any of the different isolation strategies. Conclusions Rates of COVID-19 in the in-center hemodialysis population relate to individual factors, underlying community transmission, unit size, and layout.


This article reports on shifts and continuities in policy relating to disabled people and the administrative apparatus of federal disability policy under the Rudd government (2007–10). It begins with a brief historical overview of disability policy in Australia. It then gives particular attention to highlighting the contentious and dramatic changes to disability policy which were instigated by the Howard government (1996–2007). Following this, attention is focused on the major developments in disability policy and administration with the election of the Rudd Labor government in 2007. Through this discussion, we demonstrate the ways the altered vocabularies, practices and instruments of the state have manifested in relation to disability policy in Australia, ultimately shaping opportunities for either inclusion or exclusion at the national level among disabled people.


Importance Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment. Objective To independently assess the effects of nicotine dependence and stimulation of the nicotinic acetylcholine receptor on the ability to interpret valence information (reward sensitivity) and subsequently alter behavior as reward contingencies change (cognitive flexibility) in a probabilistic reversal learning task. Design, Setting, and Participants Nicotine-dependent smokers and nonsmokers completed a probabilistic reversal learning task during acquisition of functional magnetic resonance imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent from cigarette smoking for 12 hours for all sessions. In a fully Latin square fashion, participants in both groups underwent MRI twice while receiving varenicline and twice while receiving a placebo pill, wearing either a nicotine or a placebo patch. Imaging analysis was performed from June 15, 2015, to August 10, 2016. Main Outcome and Measures A well-established computational model captured effects of smoking status and administration of nicotine and varenicline on probabilistic reversal learning choice behavior. Neural effects of smoking status, nicotine, and varenicline were tested for on MRI contrasts that captured reward sensitivity and cognitive flexibility. Results The study included 24 nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years) and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years). Computational modeling indicated that abstinent smokers were biased toward response shifting and that their decisions were less sensitive to the available evidence, suggesting increased impulsivity during withdrawal. These behavioral impairments were mitigated with nicotine and varenicline. Similarly, decreased mesocorticolimbic activity associated with cognitive flexibility in abstinent smokers was restored to the level of nonsmokers following stimulation of nicotinic acetylcholine receptors (familywise error–corrected P < .05). Conversely, neural signatures of decreased reward sensitivity in smokers (vs nonsmokers; familywise error–corrected P < .05) in the dorsal striatum and anterior cingulate cortex were not mitigated by nicotine or varenicline. Conclusions and Relevance There was a double dissociation between the effects of chronic nicotine dependence on neural representations of reward sensitivity and acute effects of stimulation of nicotinic acetylcholine receptors on behavioral and neural signatures of cognitive flexibility in smokers. These chronic and acute pharmacologic effects were observed in overlapping mesocorticolimbic regions, suggesting that available pharmacotherapies may alleviate deficits in the same circuitry for certain mental computations but not for others. Trial Registration clinicaltrials.gov Identifier: NCT00830739


Through a brief examination of neo-Marxist and neo-Weberian arguments it is demonstrated that the class nature of the new middle class has yet to be established. The paper goes on to show that as well as differences arising out of material conditions (i.e. class differences), inequalities based on expectations of entitlement or norms are also significant in capitalist society. Weber's treatment of status has not encouraged an adequate understanding of the concept, and an alternative is outlined. The paper then argues that the differences between the so-called new middle class and the working class are reasonably understood on a number of criteria as differences between status groups which form part of a single class. Not only does this approach remove a number of difficulties from accounts of the salariat, it also helps explain the different political alignments of social collectivities.


ABSTRACT Objective: Despite the frequent occurrence of depressive symptoms in children and adolescents with autism spectrum disorder (ASD), few studies have investigated the relationship between depressive symptoms and adaptive functioning. The present study explored the impact of depressive symptoms on different domains of adaptive functioning in children and adolescents with ASD. Methods: Depressive symptoms and adaptive functioning were analyzed in 62 children and adolescents with ASD (20 females) and 36 children and adolescents (15 females) with typical development between 5 and 18 years of age. Results: After controlling for IQ, age and sex, higher depressive symptoms predicted lower functioning in the social domain among children and adolescents with ASD. Depressive symptoms did not significantly predict communication or daily living skills. Conclusions: These findings highlight the relevance of depression in social adaptive function in ASD and emphasize the importance of assessing depressive symptomatology when evaluating social skills and planning treatment for children and adolescents with ASD.


Genomic DNA from 23 patients with isolated growth hormone (GH) deficiency (12 males and 11 females: heights -4.9 +/- 1.4 SDS) was screened for GH gene deletions by restriction endonuclease analysis of polymerase chain reaction amplification products. Three unrelated patients had typical features of severe GH deficiency and deletions (6.7 kb in two and 7.6 kb in one) of the GH gene. The two patients with 6.7-kb deletions developed growth-attenuating anti-GH antibodies whereas the patient with the 7.6-kb deletion continued to grow with GH replacement therapy. Our finding that 3/23 (approximately 13%) Brazilian subjects had GH gene deletions agrees with previous studies of severe isolated GH deficiency subjects in other populations. Two of three subjects (67%) with deletions developed blocking antibodies despite administration of exogenous GH at low doses. Interestingly, only 1/10 of cases with affected relatives or parental consanguinity had GH-1 gene deletions.


Systems thinking is an indispensable tool in comprehending and analyzing real-world phenomena. Observed processes are naturally composed of many interconnected components which ought to be studied jointly rather than individually. Engineering systems thinking is a very valuable skill, which helps to successfully execute multi-disciplinary projects. In high-tech companies that deal with complex and dynamic systems projects, the need for engineers with high systems thinking skills is growing. Engineers with high systems thinking skills are able to understand the big picture and the project in its entirety, both functionally and conceptually, without necessarily knowing all of the small details. Systems thinking enables understanding the entire system beyond its components, and clarifies the importance of the isolated component as part of the system as a whole. Systems thinking helps understand how sub-systems connect to one whole system, and provides solutions for the client's specifications and requirements. In addition, systems thinking enables perceiving the inter-relationships and mutual influence among the system's components and other systems. The current study examined the development of systems thinking among engineers and engineering students. In addition, the personality traits of engineers with high systems thinking skills were examined by the Myers-Briggs Type Indicator (MBTI) personality type test. This article also presents the initial results of the development of a new systems thinking study course, taught as a pilot course to industrial and management engineering students. It seems that engineers with certain personality traits can acquire or improve their systems thinking capabilities through a gradual, long-term learning process and by acquiring the necessary tools. Additionally, the study includes recommendations for the continuation of ongoing research on developing systems thinking.


The SO+ molecular ion has been detected radioastronomically via the J = §—*§ rotational transitions, whose rest frequencies were determined by earlier laboratory spectroscopic studies. This ion was detected in seven interstellar sources, including both giant molecular clouds and a cold dark cloud, and thus appears to be very widely distributed in the Galaxy and to play an important role in interstellar chemistry. We have obtained rotational spectra of HCO+ in a wide variety of vibrational states in three isotopic forms, leading to the equilibrium structural parameters that are consistent to a high degree in redundant determinations. These results will be compared to similar structures we have obtained for HCN and HNC. The high bending vibrational states observed for HCO+ and HCN exhibit the effects of Stark broadening due to the electric fields present in the discharge plasmas. The effects observed for ions against neutrals will be compared, as will those for normal glow discharges against those for magnetically confined abnormal discharges.


Osteoarthritis (OA) is the most common chronic joint disease in the world. Pathological changes in all joint tissues are the impetus for considering OA as a disease of the joint 'as an organ', resulting in joint failure. Although the management of OA remains under-provided, this book provides a new insight on the future of gene therapy after going through the preceding advances in therapeutic discoveries. An overview of the role of gene therapy in other rheumatic diseases was considered. This book presents a comprehensive description of the basics of OA and gene therapy with in-depth discussion. It provides advanced information of such a mysterious and interesting therapeutic approach. The book is designed to provide a useful and informative overview for rheumatology students and professionals and the material included is sufficient to serve as a reference for clinicians dealing with OA patients. The readers will take a worthy idea on the disease, updates in medical treatments and the advanced concepts in its management. This book should prove useful in throwing light on gene therapy and its role in OA, and in implementing these updates to improve human health and quality of life.


Aims To analyse all studies discussing effectiveness and safety (adverse events (AEs)) of chloral hydrate as a sedative drug in children undergoing diagnostic and/or treatment painless procedures. Methods A systematic literature review of MEDLINE (1948–January 2012), EMBASE (1980–January 2012), COCHRANE (from 1974 to January 2012) and CINAHL (from 1974 to January 2012). The search terms used included "chloral hydrate" and "children or infant or pe*diatric* or neonate or adolescence or adolescences or adolescent" and "sedation". The search was limited to the studies that assessed chloral hydrate safety and efficacy in children, up to 18 years, undergoing painless procedures. Retrieved articles were reviewed and data were abstracted using standardised data collection. Trial quality was assessed using the Jadad score for RCTs and STROBE scoring checklist for observational studies. Results Of the 76 articles identified, 60 met the inclusion criteria for analysis of AEs. Hypoxia is the most commonly reported AE, incidence rate of 5.1 per 100 children. Many cases (528) were mild (SpO2 90–95%), 3.5 per 100. Moderate hypoxia (SpO2 <90%) was seen in 247 cases, 1.6 per 100, and was completely reversible after using simple manoeuvres, such as supplemental oxygen therapy. There were no deaths, however eight serious respiratory AEs all required medical interventions and/or hospitalisation. Hypoxia was more common in infants under two years (8.0 per 100 children). The second most frequently reported adverse event was vomiting, risk of 2.9 per 100 children. 58 studies met the inclusion criteria for the analysis of clinical effectiveness. The success rate of painless procedural sedations was variable (range 50%–100%). The success rate (up to 100%) was higher for shorter imaging procedures such as CT imaging versus (81%) for MRI. Conclusions The systematic review suggests that chloral hydrate is a safe and effective agent for painless procedural sedation. The moderate incidence of hypoxia emphasises the importance of monitoring children during sedation, especially infants, and that the sedation should be conducted by a practitioner confident in resuscitation.


Testicular hypogonadism, or androgen deficiency, is defined as a clinical condition resulting from failure of the testes to produce physiologic levels of testosterone and a normal number of spermatozoa because of disruption of the hypothalamic-pituitary-gonadal axis. Testosterone deficiency (TD) is defined as a serum level less than 300 ng/dL on a morning total testosterone test. It is estimated that more than one-third of men 45 years and older have testosterone deficiency. Associated symptoms include decreased libido, erectile dysfunction, decreased physical stamina and strength, depressed mood, fatigue, increased visceral adiposity, sleep disturbance, and/or poor concentration and memory. These conditions have a direct relationship with cardiometabolic parameters, including insulin resistance, hypertension, hyperlipidemia, and endothelial dysfunction in aging men. No single sign or symptom defines TD. Controversy exists relative to the benefits versus risks of testosterone replacement therapy in men with testicular hypogonadism. Benefits include improvements in the symptoms related to deficiency as well as cardiometabolic parameters, yet recent retrospective and observational trials have suggested an increased risk of cardiovascular mortality without a proven direct cause-and-effect relationship.


Body temperature affects many aspects of reptilian behavior and physiology, but its effect on hormonal secretion has been little studied, especially in snakes. Major objectives of this study were to determine if acute changes in body temperature during confinement influenced plasma corticosterone levels and if initial body temperatures upon capture in the field were related to baseline corticosterone levels in water snakes (Nerodia sipedon). Water snakes were bled upon capture in the field and after one hour of confinement in a cooled, control, or heated incubator. Since little is known about the potential metabolic changes in response to stress in reptiles, plasma triglyceride levels were also measured. Upon completion of the field study, snakes were housed for 5-8 days without food to determine the effect of chronic stress on both corticosterone and triglyceride levels. Plasma corticosterone concentrations were measured using enzyme-linked immunosorbant assay (ELISA) and plasma triglycerides were determined enzymatically. In the field, experimental alterations of body temperature during confinement had no effect on corticosterone levels. Similarly, there was no correlation between initial body temperature and baseline plasma corticosterone concentrations. However, post-confinement corticosterone levels were approximately three-times greater in females than males. Plasma triglyceride levels were not affected by temperature treatment, confinement, or sex. Compared to field values, both baseline and post-confinement corticosterone levels were elevated after the chronic stress of short-term laboratory housing but triglyceride levels decreased. Overall, these results indicate that sex but not body temperature has a major influence on the adrenocortical stress response in Nerodia sipedon.


Some previous researches proved the positive association between family ownership and firm value or companies' performance. Contrary with these results, Jiang and Peng (2011) found that Indonesia is one of the country in which family ownership structure has a negative association with firm value. Moreover, Claessen et al. (2000), stated that as of 16.6% of Indonesia's public companies are controlled by a single majority shareholder. Claessens et al. (2000) also stated that higher entrenchment occurred in Indonesia together with Philipina and Thailand. Besides that the low law enforcement and the lowest corruption index in Indonesia (Jiang & Peng 2011), add opportunity to the majority to expropriate the minority. Therefore, this research aims to prove that there is a negative association between family ownership structure and firm value in which negative entrenchment of the majority to minority exists. This study shows that family ownership has a significant negative effect on firm value at significance level of 10%.


We attempted to determine whether the inhibition of renin release from rat kidney cortical slices by alpha adrenoceptor agonists is mediated by activation of alpha-1 and/or alpha-2 adrenoceptors, and to investigate the role of calcium in the mechanisms of this inhibition. Norepinephrine (NE), methoxamine (ME) and phenylephrine (PE) produced a concentration-dependent inhibition of renin release from rat kidney cortical slices, whereas clonidine was without effect. NE-, ME- and PE-induced inhibition of renin release was blocked by prazosin, which was 2 or 3 orders of magnitude more potent than yohimbine. The inhibitory effects of NE, ME and PE on renin release from the slices were abolished by removal of calcium from the incubation medium. Calcium antagonists, verapamil and nifedipine, attenuated the responses of renin release to NE, ME and PE, in a concentration-dependent manner. The inhibitory effects of NE, ME and PE on renin release were blocked significantly by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, but not by N-(6-aminohexyl)-1-naphthalenesulfonamide, which has virtually no calmodulin antagonistic activity. These findings suggest that alpha adrenoceptor agonists inhibit renin release from rat kidney cortical slices mainly via alpha-1 adrenoceptors and that calcium influx followed by the activation of the calcium-calmodulin system is involved in the above inhibition.


PoweRline Intelligent Metering Evolution (PRIME) is a Narrowband Powerline Communication (NB-PLC) technology widely deployed in the last mile of Advanced Metering Infrastructure (AMI) in Spain (Iberdrola, Union Fenosa), which is also quickly spreading globally. The present paper addresses the evaluation of the two medium access control mechanisms used in this technology: the Shared Contention Period (SCP), where all nodes content to access the channel; and the Contention Free Period (CFP), where time slots are reserved in order to guarantee some transmission opportunities. Whereas the SCP is the default behavior given its simplicity, the use of the CFP may be necessary when using applications that require a given level of Quality of Service (QoS). The paper first describes how the CFP has been implemented according to the standard in the PRIME network simulator SimPRIME. Moreover, the paper asseses how combining different number of nodes in the SCP and CFP affects the network performance in a series of illustrative scenarios. Results from simulations point out that, when all nodes transmit together in the SCP, it yields better network performance than using the CFP in general; and especially in highly populated networks. However, the paper also highlights trade-off solutions that allow guaranteeing QoS to certain nodes without compromising the performance of the rest of the network. Additionally, the paper proposes an amendment to the standard to increase the number of nodes that can use the CFP under the previous assumption.


The main objective of this study was to determine quantitatively euchromatin/heterochromatin (EU/HET) ratios of cell nuclei in the adventitia of 2 weeks streptozotocin induced diabetic rats combined with acridine orange (AO) ultracytochemistry. Specimens of the aorta above and below the orificium of the a. renalis were treated with AO and then prepared for electron microscopy. Images of 295 nuclei randomly selected from 180 ultrathin sections were analysed by a computer assisted image analyser method. The findings that surface areas of euchromatin portions and those of total nuclei are dependent variables (correlation coefficients 0.93-0.99), however, the EU/HET ratios and total surface areas are independent variables are essential prerequisites for an efficient application of this method. Determinations of EU/HET ratios revealed that populations of AO labeled cell nuclei consistently have higher ratios (2.17-3.38) than nuclei not labeled by AO (1.26-2.12). On the basis of 2583 nuclei counted AO positive cell nuclei were found to increase from 12% in control to 23% in diabetic rats. Changing EU/HET ratios are interpreted in terms of differential RNA synthetic activity enhanced in the early diabetic state. For these cells AO serves as a specific nuclear marker.


Collections documentation systems are powerful frameworks for organising, producing and controlling cultural knowledge. Drawing on the findings from the Australian Research Council Linkage project Reconceptualising Heritage Collections (University of Western Sydney and Powerhouse Museum, Sydney, Australia) and research undertaken using the museum's Palestinian collections through wikis and focus groups with constituencies in Australia, Israel and Palestine, we illustrate the highly political and fluid nature of the meanings and values existent around objects; and how now, in a networked complex world, non-linear interactions are occurring across transnational borders. These interactions sit uneasily with conventional museum practice. The collections became visible mechanisms to confront the complex relations and politics of borders between the museum and everyday life. 'Cosmopolitics', in terms of its political, ethical, cosmological and transnational outlook along with cultural complexity, enables an exploration of the dynamics and the shifting borders of an emerging complex museum. Ideas for the future imaginary of these interactions are further explored through the pathway of chaos theory.


Objective: In India, increasing prevalence of multi-drug resistant tuberculosis (MDR) has aggravated the control of tuberculosis problem. In many urban and semi-urban regions of India, no surveillance data of multidrug resistance in Mycobacterium tuberculosisis available. Methods: A surveillance study on multidrug resistance was carried out in semi-urban and rural regions in and around Nashik City of Maharashtra, India. The surveillance study was conducted in this region found that the prevalence of combined resistance to first and second-line anti-tuberculosis drugs is remarkably high. The isolates of M. tuberculosis was identified and subjected to drug susceptibility testing. The patterns of drug susceptibility of isolates of M. tuberculosis during the periods 2000 and 2004 were compared with drug susceptibility patterns of the organisms during the period 2008 to 2011. Results: The 260 isolates identified as M. tuberculosis show mean drug resistance prevalence of 45.6% for more than any two drugs and the MDR rate as 37% in the years 2000 to 2004 whereas 305 isolates of the organism show mean drug resistance prevalence of 30.2% and the MDR rate as 25% in the years 2008 to 2011. Conclusion: The researcher found that, though the prevalence of multidrug resistance to the drugs tested is remarkably high, it has come down noticeably during the past seven years due to efforts of State Government and strict implementation of treatment guidelines of WHO by the physicians. J Microbiol Infect Dis 2013; 3(1): 12-17


Airborne ground penetrating radar systems allow for carrying out snowpack surveys in complex terrain. Ultra wideband radars operate within the lower part of the microwave band and are suitable for measurements of snow depth and layering in a time-saving and safe manner. We have developed a complete radar system based on a commercial UWB radar sensor, custom designed antennas and a single board acquisition computer in all weighing 4 kg and fitting (without antennas) into a 30 x 25 x 15 cm3 box. The radar is capable of measurements with a frequency range from 0.95 6 GHz, giving roughly 5 cm slant range resolution and an unambiguous range in air of 5.75 m. The radar can be carried by an octocopter drone with a wingspan of 1.5 m, flying autonomously at an altitude of 1 m above the snow surface. In this paper we present the characteristics and specification of our drone-borne radar system and show results from two different campaigns. We were able to resolve snow stratigraphy in great detail in a dry snowpack, identifying the most prominent layers. Our second example shows the system's capabilities of detecting a person buried under 1.5 m of wet snow.


Abstract: As part of the Western NSW Aboriginal Smoking Project (1995) a self–administered questionnaire surveyed regional Aboriginal health workers (AHWs) about their tobacco use and their awareness of smoking related health issues. The aim was to provide baselineinformation to guide the development of project interventions. The majority of respondents smoked. Among the smokers most said that they would like to quit smoking, and all said that they had tried to quit. All the smokers were interested in assistance to help them quit, and were interested in assistance to help them help others in their communities to quit. AHWs are a professional group whose smoking rates might typify that of their communities, and in the future they might provide indications of smoking trends in their communities.


The Customer Equity and Lifetime Management (CELM) solution is based on a decision-support system that offers marketing managers a scientific framework for the optimal planning and budgeting of targeted marketing campaigns to maximize return on marketing investments. The CELM technology combines advanced models of Markov decision processes (MDPs), Monte Carlo simulation, and portfolio optimization. MDPs are used to model customer dynamics and to find optimal marketing policies that maximize the value generated by a customer over a given time horizon. Lifetime value optimization is achieved through dynamic programming algorithms that identify which marketing actions, such as cross-selling, up-selling, and loyalty marketing campaigns, transition customers to better value and loyalty states. The CELM technology can also be used to simulate the financial impact of a given marketing policy using Monte Carlo simulation. This allows marketing managers to simulate several targeting scenarios to assess budget requirements and the expected impact of a given marketing policy. The benefits of the solution are illustrated with the Finnair case study, where CELM has been used to optimize marketing planning and budgeting for Finnair's frequent-flyer program (FFP).


The COVID-19 pandemic had many new post-viral sequelae some of which are yet to be detected. In our case series, we are presenting five patients with different ages, medical backgrounds, and presentations, who were diagnosed with Post COVID-19 Graves' disease at Royal Hospital from January to December of 2020. The main reason behind this case series is to highlight the variability of presentation and the duration between exposure to the virus and the presentation. In addition, due to the similarity in the presentation of some of the symptoms between COVID-19 infection and Graves' Disease, most of those patients were delayed in getting the proper diagnosis of COVID-19-induced Graves' disease. Hence, this case series can aid in alerting primary care doctors for early detection of such cases and regular follow-up, which can positively impact our national healthcare system.


Testicular germ cell tumors obtained from 44 patients were immunohistochemically studied using anti-neuron specific enolase (NSE) antibody. The level of NSE in the serum was also measured in 9 patients before and after extirpation of the tumor. As for tumor cells of seminoma, 19 of 20 pure seminomas and all 9 of mixed type were positive for NSE. On the contrary, a spermatocytic seminoma was NSE-negative. As for embryonal carcinomas, some tumor cells were NSE-positive in 13 of 15 of mixed type. In yolk sac tumor, a few tumor cells were also NSE-positive in 8 of 21 of both pure and mixed types. Some NSE-positive cells were found in teratomatous components of 10 of 14 mature and immature teratomas of both pure and mixed types. These were in neural cells, chondrocytes, and glandular epithelial cells. Spermatogonia in 5 normal testes were NSE-positive. NSE level in the serum was elevated before extirpation and decreased after extirpation in 4 of 5 cases of seminoma of pure type and in 1 of 2 of mixed type which included seminomatous elements. All of these cases were either in the advanced stage or had a rather large primary tumors. Immunohistochemical study of testicular germ cell tumors using anti-NSE antibody may facilitate histological diagnosis, and serum NSE level may be useful for monitoring the clinical course as well as for clinical diagnosis of seminoma.


Is there a trade-off of scholarly research productivity when faculty members found or join for-profit firms? This paper offers an empirical examination of this question for a subpopulation of biomedical academic scientists who received research funding from the US National Institutes of Health (NIH). In this study, we are able to distinguish between permanent versus temporary employment transitions by entrepreneurial faculty members and examine how their journal article publication rates change using individual-level panel data. We find that the biomedical scientists who eventually choose to found or join a for-profit firm were more productive during their careers in academe than a randomly selected control group of their NIH peers. When they pursue entrepreneurship in the private sector, however, their scholarly productivity falls. Those entrepreneurial faculty members who return to academe are not as productive as they were before their entrepreneurial experience in terms of journal publications.


Language usage changes over time, and this can impact the effectiveness of NLP systems. This work investigates methods for adapting to changing discourse during crisis events. We explore social media data during crisis, for which effective, time-sensitive methods are necessary. We experiment with two separate methods to accommodate changing data: temporal pretraining, which uses unlabeled data for the target time periods to train better language models, and a model of embedding shift based on tools for analyzing semantic change. This shift allows us to counteract temporal drift by normalizing incoming data based on observed patterns of language change. Simulating scenarios in which we lack access to incoming labeled data, we demonstrate the effectiveness of these methods for a wide variety of crises, showing we can improve performance by up to 8.0 F1 score for relevance classification across datasets.


Objective: The study was designed to determine (1) the pharmacokinetic (PK) profile of dexmethylphenidate (d-MPH) after oral administration of three dosage strengths of a new treatment containing d-MPH and a novel prodrug, serdexmethylphenidate (SDX); (2) the dose proportionality of the different SDX/d-MPH dosages; and (3) the steady-state PK profile of d-MPH and SDX after multiple dosing of SDX/d-MPH. Methods: Twenty-three healthy volunteers (aged 18–55 years) under fasted conditions received in a crossover design SDX/d-MPH 26.1/5.2 mg (Treatment A), 39.2/7.8 mg (Treatment B), and 52.3/10.4 mg (Treatment C) for a total d-MPH hydrochloride equivalent dose of 20, 30, and 40 mg, respectively. After a 96-hour washout period, all participants received four consecutive daily doses of SDX/d-MPH 52.3/10.4 mg. Blood samples were collected for measurement of plasma d-MPH and SDX and for PK analysis. Results: Administration of all three doses of SDX/d-MPH resulted in a rapid rise and slow decline in the plasma concentration of d-MPH. For Treatments A, B, and C, mean (± standard deviation) maximum concentrations (Cmax) were 7.1 ± 2.1, 9.8 ± 2.8, and 13.8 ± 3.8 ng/mL, and overall exposures (AUC0−last) were 97.2 ± 28.8, 142.5 ± 41.2, and 199.8 ± 57.2 h*ng/mL, respectively. Dose-normalized Cmax, AUC0–last, and AUC0–inf for d-MPH were similar when comparing the high and low doses versus the middle dose. Power model regression analysis revealed that Cmax and AUC0–inf proportionally increased with an increase in SDX/d-MPH dose. In the multiple-dose study, d-MPH reached steady state before the third dose, and SDX after the first dose. Conclusion: The PK profile of SDX/d-MPH is characterized by a rapid rise and a gradual decline in d-MPH concentration, with proportional Cmax and AUC0–inf across doses. The PK attributes of SDX/d-MPH may optimize symptom control from early morning to early evening, while the demonstrated dose proportionality may facilitate initial dose titration and ongoing dose adjustment.


Whether climatic changes in high latitudes of the Northern Hemisphere since the last glaciation have effects on the Tibetan Plateau monsoon, and the variation characteristics of the Plateau monsoon itself are still not solved but of great significance. The 22-m high-resolution Ioess-paleosol sequence in the Hezuo Basin on the northeastern Tibetan Plateau demonstrates that the Plateau winter monsoon experienced a millennial variation similar to high latitude Northern Hemisphere, with cold events clearly correlated with Heinrich events but less for the warm events (Dansgarrd-Oeschger events). It may indicate that the climate system at high latitudes in the Northern Hemisphere had played an important role in both the Plateau monsoon and the high-level westerlies. On 10^4 year scale, there are two distinct anomalous changes, which are not found in the records from high latitude northern hemisphere, revealed by the loess grain size in the Hezuo Basin. One is that there was a considerable grain size increase at -36 kaBP, suggesting an abrupt enhancement of the Plateau winter monsoon at that time; the other is that, during 43--36 kaBP, the grain size decreased distinctly, indicating a notable weakening of the Plateau winter monsoon around that period. Both of the two anomalies suggest that the Tibetan climate may have been controlled by some other factors, besides the high latitude climatic changes in the Northern Hemisphere.


Haber + past participle (PP) is an example of a resultative construction that evolved into a perfect form, known as the present perfect. This form derived from the Latin periphrastic perfect, which was "a possessive construction consisting of transitive habere followed by a direct object and agreeing past passive participle" (Lopez-Couso & Seoane 2008: 135-136). It was originally used similarly to tener + PP, which in modern peninsular Spanish may signify the present result of a past action (Harre 1991; Kato 1993), and also shared the same formal characteristics as tener + PP. Furthermore, this construction has grammaticalized as the default past perfective in the peninsular variety of Spanish (Schwenter & Torres Cacoullos 2008), following the perfect to perfective path of grammaticalization (Bybee et al. 1994; Squartini & Bertinetto 2000). The current study considers whether tener + PP is following the same evolution as haber + PP by diachronically extending into the realm of the perfect. 550 tokens of tener + PP and 1083 of haber + PP were extracted from the Corpus de Referencia del Espanol Actual (CREA). All tokens were coded for several variables in order to determine if tener + PP expresses any of the four primary uses of the perfect (Dahl 1985:132, Comrie 1976: 56-61). The data were then analyzed using the statistical program Goldvarb X. Results indicate that tener + PP remains principally a resultative form, as it most frequently occurs with several factors indicative of resultative uses. However, uses of this construction with psychological, perception, and communicative verbs, as well as frequency adverbs, non-specific temporal reference, and without a direct object, are indicative of an extension to perfect uses. These first steps are consistent with accounts of the evolution of the Romance habeo (Pinkster 1987, Vincent 1982, Benveniste 1968) and the Old English perfect (Carey 1994, 1995) from resultative constructions. This working paper is available in University of Pennsylvania Working Papers in Linguistics: http://repository.upenn.edu/pwpl/


The fire incident in Santa Maria, Brazil, where died 242 people, 123 injuries, repeated aspects already found in similar tragedies in other countries and showed the difficulty of learning with these aspects regard to accident prevention. The disaster occurred when a pyrotechnic component used by a music band emitted heat that reached the polyurethane ceiling, which ignited. This study aimed to analyze systemically the Santa Maria nightclub fire to describe different aspects whose interaction led to the accident. The assembled maps allowed us to conclude that there was an insufficient mechanism of action coordination for accident prevention. It was possible to show that besides the nightclub's design problems, such as a lack of alternative unobstructed rescue routes, emergency signaling, agility in emergency response, other contributing factors were material weaknesses, lack of training of firefighters and first responders responsible for preventing injuries resulting from the burning of the coating material used for soundproofing the club. Accident analysis based on the AcciMap helped reveal the systemic nature of the complex network of causal factors involved in the fire at the club.


Abstract : Clean and Boost (Apex Dental Materials) is a novel surface treatment solution designed to be used in place of phosphoric acid to increase the bond strength of self-etch adhesives to enamel and more effectively remove contaminants (e.g., handpiece lubricant) from the tooth surface. Simplicity (Apex Dental Materials) is a self-etch bonding agent with acidic monomers that reportedly eliminates concerns about bonding to enamel. The purpose of this study was to evaluate the effect of surface exposure, surface treatment, or bonding agent on the bond strength of composite to enamel. The crowns of 120 bovine incisors were mounted. For surface exposure, half of the specimens were exposed to the water spray of a high-speed handpiece after cleaning/lubrication with an automatic handpiece system and the other half had only water spray. For surface treatment, one third of the specimens were etched with 34% phosphoric-acid gel, one third were treated with Clean and Boost, and one third were untreated. Self-etch bonding agents(Simplicity or Clearfil SE Bond, Kuraray) were applied and light cured. Composite was placed into a mold and light cured (n=10). The specimens were stored in water for 24 hours at 37C and tested in shear. Data were analyzed with a 3-way ANOVA/Tukeys to evaluate the effects of surface exposure, surface treatment, or bonding agent on the bond strength of composite to enamel (alpha=0.05). A significant difference was found based on surface treatment (p=0.023),or bonding agent (p0.001), but not on surface exposure (p=0.057) with no significant interactions(p0.21). Phosphoric-acid etch resulted in greater bond strength than no surface treatment. The use of Clean and Boost was not significantly different from phosphoric acid or no treatment. Simplicity had significantly lower bond strengths to enamel than Clearfil SE Bond. Handpiece spray exposure had no significant effect on bond strength to specimens.


Non-chrome-tanned (chrome-free) leather has gradually gained commercial importance, particularly for automobile upholstery applications. UV and heat resistance are very important qualities for automobile applications. We developed an environmentally friendly finishing process that will improve the UV- and heat resistance of automobile upholstery leather. Tocopherol (Vitamin E) is a potent free radical scavenger and highly protective agent for collagen fibers against UV damage. We previously reported that the application of tocopherol to the grain layer of chrome-tanned leather improved its durability. The current study focuses on non-chrome-tanned leather made with a glutaraldehyde tanning process. We applied tocopherol to the grain layer of that leather and also studied the addition of tocopherol to the fatliquoring drums. Following exposure in a Fade-Ometer, the treated samples were evaluated by colorimetry and mechanical testing for the efficacy of UV- and heat resistance. A polarizing microscope equipped with a Berek compensator was employed to determine the birefringence of the untreated and treated leather collagen fibers to determine the treatment effects on the degree of orientation. Data showed that leather coated with tocopherol exhibited significant improvement in tensile strength retention and color fading resistance against UV radiation and heat. Leather fatliquored with tocopherol, however, did not show a similar improvement.


Chronic obstructive pulmonary disease (COPD) is a complex condition involving chronic inflammation of the airways (chronic bronchitis) and destruction of airways parenchyma (emphysema). It is characterized by progressive airway limitation that is not fully reversible. Although the precise mechanisms of disease remains unclear, it has been thought that noxious materials, such as gases caused by smoking, may play role in the pathogenesis of the disease. However, only 15-20% of smokers developed COPD and non-smokers have also developed the disease, suggesting that other determinants may be involved the disease onset and other contributing factors may be exist. One such factor may be autoimmunity. COPD is accepted as an inflammatory disorder with evidence of circulating autoantibodies against variety of targets. Natural autoantibodies (nAAbs) are autoantibodies found in the circulation of healthy individuals without development of autoimmunity and they are considered to play a role in immune regulation and act as a protector in healthy individuals. However it has been suggested that nAAbs, under circumstances, may shift to be pathological autoantibodies.

The aim of the study was to investigate nAAbs in healthy individuals in relation to COPD. To achieve the project aim; firstly ELISA was used to detect reactivity of IgG , IgM and IgA nAAbs in 23 healthy non-smoker individuals to four auto antigens. However, ELISA technique has some limitations. It requires high sample volume and takes considerable time. In order to perform our goal, that is to investigate 37 auto antigens and screen numerous healthy individuals and COPD patients' samples in the limited time of this PhD project, a high throughput, multiplexed assay was required.

Therefore, we moved to develop an antigen microarray platform that would be a high throughput technique that is rapid, accurate, automated and highly sensitive. Before applying this technique, quality control experiments were performed to optimize the procedures, including testing different slides surface coatings, investigating numerous blocking buffers, as well as series of validatory tests to determine if the assay was both accurate and reproducible.

The optimization results showed that a combination of aminosilane coated slides and I-block buffer performed well and gave high signal intensity and low backgrounds. Validation tests were performed for the optimized technique and showed no cross reactivity occurred, coefficient of variation (CV%) was acceptable, and the limit of detection (LoD) was satisfactory.

This validated technique was used to then screen natural autoantibody responses to a range of autoantigens in healthy non-smokers and COPD samples. The study compared purified and unpurified IgG Abs in healthy individuals and COPD patient samples and showed significance differences in reactivity of IgG Abs in most auto antigens investigated in healthy subjects. Conversely, no significance differences were detected in autoantibody responses to most auto antigens investigated in COPD patients samples suggesting serum components may be involved in controlling the auto reactivity of natural IgG Abs in healthy individuals.

Natural IgM Abs was also investigated against 37 auto antigens in healthy individuals and COPD patient samples and the results showed various pattern of reactivity of IgM Abs to all auto antigens suggesting that natural IgM Abs may play a role in controlling the auto reactivity of natural IgG Abs in healthy individuals. This control may be achieved via either anti-idiotypic activity of the natural IgM Abs or could be in part dependent on the competitive binding of IgM Abs to the auto antigens.

Regarding comparison of autoantibody responses to 37 auto antigens in COPD patients compared to healthy individuals, the results showed there was a significance increased in reactivity for both IgG and IgM auto antibodies in COPD group compared to healthy subjects for Elastin, ATS 0.02/sm, HNRPD, HNRP2B1, Keratin8, PL-12, Vimentin, BPI, Vitronectin, Collagen V and Lactoferrin. This suggests that these auto antigens have the potential to be used as a diagnostic biomarker for the detection of COPD or tracking disease progression.

In conclusion, nAAbs showed various pattern of reactivity to all auto antigens investigated in this study with high levels observed in reactivity of purified IgG Abs in healthy individuals. This suggests that a serum component may be involved in regulation of auto reactivity of natural IgG Abs in normal conditions. This thesis has also developed a rapid, inexpensive, broad-spectrum antigen microarray technology, which may have an important future role in monitoring the levels of nAAbs and early diagnosis of COPD.