Abstract The Demand-Control-Support (DCS) and the Effort-Reward Imbalance (ERI) models assess different psychosocial factors. This study investigates whether a combination of these models increases their ability to predict sickness absence, as compared to results based on each model separately. A cross-sectional study with nursing personnel (N = 1307) in Brazil was performed. Regression analyses were conducted in three stages: analysis of each scale of the models and sickness absences; assessment of the independent association of each model with sickness absences; assessment of the associations of three combinations of models/scales with sickness absences: DC and social support (SS), ERI and overcommitment, and DC and ERI. As regards comparisons between the stress models, ERI was shown to be independently associated with short (up to 9 days) and long (10 days or more) spells of absenteeism. The same result held true for low social support. The combinations DC-ERI and DC-SS were better predictors for short spells than each model/scale separately, whereas for long spells, the combination DC-SS was the best predictor. ERI seems to be a good instrument for predicting absenteeism if used alone, whereas DC performed better when combined with ERI or SS. An improved risk estimation of sickness absences by combining information from the two models was observed.


Phlebography of the internal spermatic vein was performed on 87 patients. In only two cases were slight complications (fever and chill) recorded after the examinations. The patients felt only a little discomfort during the examination. They did not have to be hospitalized before or after the examinations. In a few cases we saw sufficient values distally, at the level of L4-5. We have interpreted these cases as being normal.


In this paper, we analyse the recent principal volatility components analysis procedure. The procedure overcomes several diculties in modelling and forecasting the conditional covariance matrix in large dimensions arising from the curse of dimensionality. We show that outliers have a devastating e↵ect on the construction of the principal volatility components and on the forecast of the conditional covariance matrix and consequently in economic and financial applications based on this forecast. We propose a robust procedure and analyse its finite sample properties by means of Monte Carlo experiments and also illustrate it using empirical data. The robust procedure outperforms the classical method in simulated and empirical data.


The journal publishes original research papers. All papers undergo a thorough double-blind review process. Some issues are devoted to a special focus. The section BISE – Research Paper splits into the following departments (department editors in brackets): 1. Business Engineering and Theories of BISE Design (Winter, Pries-Heje, Goul) 2. Information Systems Engineering (Müller, Lin, Echizen) 3. Information Systems Management & Operations (Bichler, Bhattacharya) 4. Theories for BISE (Heinzl, Leidner) Besides, the journal is organized into the following sections (section editors in brackets): BISE – State of the Art (Buxmann) BISE – Catchword (Sinz) BISE – Profile (Heinzl) BISE – Discussion (Loos) The journal's website http://www.bisejournal.org is managed by Detlef Schoder.


Methamphetamine (MA) dependence is associated with neural abnormalities (e.g., frontal systems neurotoxicity) and corresponding cognitive deficits, including impairment in episodic memory and executive functions. This study evaluated the hypothesis that MA use is associated with impairment in memory for intentions, or prospective memory (ProM), which is an ecologically relevant aspect of episodic memory that involves the execution of a previously encoded intention at an appropriate moment in the future and is known to rely on frontal systems integrity. A total of 39 MA-dependent individuals and 26 demographically similar non-MA-using comparison participants were administered the Memory for Intentions Screening Test (MIST). The MA group performed significantly lower than the comparison participants on overall ProM, an effect that could not be better explained by demographics, psychiatric factors, infectious disease comorbidity, or other substance use disorders. The ProM impairment observed in the MA group was comparable on time- and event-based tasks and was marked by an increased rate of task substitution (i.e., intrusions) and loss of time (e.g., early responding) errors. Within the MA cohort, ProM impairment was associated with executive dysfunction and earlier age at first MA use. Findings suggest that individuals with MA dependence experience difficulty in the strategic components involved in the retrieval of future intentions and are discussed with regard to their implications for everyday functioning.


This paper builds upon current research into the organizational implications of 'modularity'. Advocates of modularity argue that the 'invisible hand' of markets is reaching activities previously controlled through the visible hand of hierarchies. This paper argues that there are cognitive limits to the extent of division of labour: what kinds of problems firms solve, and how they solve them, set limits to the extent of division of labour, irrespective of the extent of the market. This paper analyses the cognitive limits to the division of labour, relying on an in-depth case study of engineering design activities. On this basis, it explains why coordinating increasingly specialized bodies of knowledge, and increasingly distributed learning processes, requires the presence of knowledge-integrating firms even in the presence of modular products. Such firms, relying on their wide in-house scientific and technological capabilities, have the 'authority' to identify, propose and implement solutions to complex problems. In so doing, they coordinate networks of suppliers of both components and specialized competencies.


In the engineering applications area, welding defect is a major hidden danger of structure security. the bending failure process of welded specimens is detected by using AE technique and the data samples of typical welding defect source are collected, and by using wavelet technique the typical AE datas acquired through experiment are analyzed, characteristic information of the typical acoustic emission source such as electromagnetic noise, plastic deformation, micro-crack initiation, crack unsteady expansion and fracture, etc are extracted. A serial acoustic emission source identification methods based on the energy spectrum coefficients of wavelet are established and which can realize accurately distinguishing of different acoustic emission sources, so as to provide a theoretical basis to detect equipment welding defects by acoustic emission technology dynamic in engineering practice.


Neoclassical labor market theories imply that employers will react to binding minimum wages by changing the level of employment. A multitude of studies consider this aspect of minimum wages, yet fail to reach a consensus as to its employment effects. While the employment effects of the minimum wage are certainly important, the empirical literature has not adequately explored the possibility that employers may also adjust non-wage components of the job such as fringe benefits, job safety, and access to training opportunities. We study the effect of minimum wage legislation on fringe benefits (employer provision of health insurance, pension coverage, dental insurance, vacation pay, and training/educational benefits) and working conditions (shift work, irregular shifts, and workplace safety) during the period 1979 to 2000 using the National Longitudinal Survey of Youth and the Current Population Survey. We examine effects of state and federal variation in the minimum wages on groups likely to be affected by the minimum wage. These effects are compared to estimates found for groups unlikely to be affected by minimum wages. Our results indicate no discernible effect of the minimum wage on fringe benefit generosity for low-skilled workers. This conclusion is unchanged whether we use only state level variation or federal and state variation in minimum wages.


The chemokines are a growing family of low m.w., 70- to 80-residue proinflammatory cytokines that operate by interacting with G protein-coupled receptors. Chemokines are involved in cell migration and in the activation of specific leukocyte subsets. Using the Mono Mac 1 monocytic cell line, we show that monocyte chemotactic protein 1 (MCP-1) triggers activation of the Janus kinase 2 (JAK2)/STAT3 pathway and CCR2 receptor tyrosine phosphorylation. Both Ca2+ mobilization and cell migration are blocked in Mono Mac 1 cells by tyrphostin B42, a specific JAK2 kinase inhibitor. Within seconds of MCP-1 activation, JAK2 phosphorylates CCR2 at the Tyr139 position and promotes JAK2/STAT3 complex association to the receptor. This MCP-1-initiated phosphorylation and association to JAK2 is also observed in CCR2B-transfected HEK293 cells. In contrast, when a CCR2B Tyr139Phe mutant is expressed in HEK293 cells, it is not phosphorylated in tyrosine and triggers neither JAK2/STAT3 activation nor Ca2+ mobilization in response to MCP-1. These results implicate the tyrosine kinase pathway in early chemokine signaling, suggesting a key role for this kinase in later events.


In the Vega series of paintings by Vasarely, half spheres bulge out of the plane. We make an attempt to construct transformations that produce this effect. We take a close look at the two spheres in the painting Bull. We visualize parametric stereographic projection and show what parameter choices fit best for the two spheres in the painting. It remains an open issue if Vasarely had the same projection in mind. All the same, the interactive experimental tool can serve as a means to give insight into the mathematical idea behind the painting.


Abstract. Non-thermal echoes in incoherent scatter radar observations are occasionally seen in the high-latitude ionosphere. Such anomalous echoes are a manifestation of plasma instabilities on spatial scales matching the radar wavelength. Here we investigate the occurrence of a class of spatially localized anomalous echoes with an enhanced zero Doppler frequency feature and their relation to auroral particle precipitation. The ionization profile of the E region is used to parametrize the precipitation, with nmE and hmE being the E region peak electron density and the altitude of the peak, respectively. We find the occurrence rate of the echoes to generally increase with nmE and decrease with hmE, thereby indicating a correlation between the echoes and high-energy flux precipitation of particles with a high characteristic energy. The highest occurrence rate of > 20 % is found for hmE  =  109 km and nmE  =  1011. 9 m−3, averaged over the radar observation volume.


2 rearing trials were carried out on a total of 8550 hybrid chicks (White Leghorn) to investigate in which way food mixtures containing reduced levels of crude protein (supplemented or unsupplemented with amino acids) might influence the growth of chicks and young hens. Decreases from 21.5% to 16.5% in the crude protein content of chicken feed and from 15% to 13% in feeds feed to young hens (greater than 8 weeks of life) did not reduce the live weight of birds at the end of the rearing period to any appreciable extent. No clearly defined differences were found to exist between the different types of feed tested concerning the amount of food and energy consumed per unit of weight gain and the mortality rate among the birds; it was shown, however, that the demand for crude protein per unit of weight gain was clearly reduced in birds reared at the lower crude protein level. For young hens receiving the diet poorer in protein the date when the birds began laying was slightly delayed. Otherwise, no statistically significant differences were found to exist between the young birds fed varying levels of crude protein, concerning the age at 50% laying performance and other parameters that are characteristic of the entire laying period (laying performance, weight of individual eggs, food consumption, mortality, fertilization of hatching eggs, hatchability of eggs). It appears that the feeding of a reduced protein diet to chicks and young hens (laying stock) did not have any detrimental effect on the growth and later laying performance of the birds. Apart from the fact that the demand for protein feeds is considerably reduced during the rearing period the costs of feeding per bird can also be cut down.


Quantum phase interference and spin-parity effects are studied in biaxial molecular magnets in a magnetic field at an arbitrarily directed angle. The calculations of the ground-state tunnel splitting are performed on the basis of the instanton technique in the spin-coherent-state path-integral representation, and complemented by exactly numerical diagonalization. Both the Wentzel–Kramers–Brillouin exponent and the pre-exponential factor are obtained for the entire region of the direction of the field. Our results show that the tunnel splitting oscillates with the field for the small field angle, while for the large field angle the oscillation is completely suppressed. This distinct angular dependence, together with the dependence of the tunnel splitting on the field strength, provides an independent test for spin-parity effects in biaxial molecular magnets. The analytical results for the molecular magnet are found to be in good agreement with the numerical simulations, which suggests that even the molecular magnet with total spin is large enough to be treated as a giant spin system.


Solar energy is a renewable and sustainable energy source that has a promising potential for the rapidly growing energy demands across the world. Large scale power generation from the energy of the sun is well established utilizing both direct thermal energy conversion and conversion to electricity via photovoltaic processes. Solar thermal systems have been limited to macro systems, even though they operate at higher efficiency compared to photovoltaic systems. Solar energy harvesting requires the use of collector plates to capture incident radiation. The surface area exposed to incident radiation is critical in solar thermal energy harvesting. In this work, we have integrated micro technology processes and solar thermal energy to design and fabricate a micro solar thermal system for power generation. This work specifically examined surface area enhancement using MEMS-based techniques to maximize solar thermal absorption. Selective absorber coating and enhanced surface areas due to the incorporation of micro structures on the collector substrates were utilized. In this manner, an important component to an autonomous micro power supply is investigated.Advanced microfabrication and electrochemical deposition techniques were employed to generate a selective absorber surface with enhanced surface area on a silicon substrate. Microchannels were used to enhance the surface area on the substrate. The selective absorber coating consists of a bimetallic structure consisting of tin and nickel.Copyright © 2012 by ASME


Oxynotus centrina is considered a rare or uncommon shark species throughout its distribution range. Because of this reason, it is one of the 46 uncommon elasmobranchs in the Mediterranean Sea, which requires filling the knowledge gaps, such as length-weight relations. Based on the analysis of 34 angular rough sharks, the length-weight relations (LWR) of males, females and combined sexes of O. centrina were described as W = 0.216L2.686, W = 0.134L3.041 and W=0.102L3.173, respectively. Total lengths (TL) of females and combined sexes were strongly correlated with total weights (TW); while TL of males was moderately correlated with TW. The b values of LWRs of females and combined sexes (3.041 and 3.173, respectively) were not significantly different from 3.0 (t-test, p>0.10) and indicated positive allometric growth for the examined TL and TW range of O. centrina in the Mediterranean Sea.


Despite the fact that textbooks are central in foreign language learning, only limited research has explored to what extent L2 textbooks support language learning and whether the content in them is relevant from a vocabulary perspective. This study investigates the vocabulary in seven English textbooks used in Swedish primary schools. A corpus has been constructed based on the words in the textbooks. By means of a concordancing software tool, the material has been analyzed by comparing the vocabulary between the books and to words on the New General Service List and in the VP-Kids corpus. The analysis shows that many words in the textbooks occur only occasionally in common everyday language use. It also demonstrates that there is great variation in the number and selection of words across the books indicating that there does not seem to be a common thought behind word selection in textbooks used in Swedish schools.


Hemoglobin E (HbE) is an extremely common structural hemoglobin variant that occurs at high frequencies throughout many Asian countries. It is a β-hemoglobin variant, which is produced at a slightly reduced rate and hence has the phenotype of a mild form of β thalassemia. Its interactions with different forms of α thalassemia result in a wide variety of clinical disorders, whereas its coinheritance with β thalassemia, a condition called hemoglobin E β thalassemia, is by far the most common severe form of β thalassemia in Asia and, globally, comprises approximately 50% of the clinically severe β-thalassemia disorders.


The major modernisation programmes in tax administration confer an ever greater
role on new technologies. Made necessary by the context, the technological solution is
unlike the traditional legal instrument, and will supplement rationales of action different
from previous organisational rationales. ICTs thus speed up change but do not
immediately bring about organisational transformation, as shown by the evolution in the
metiers of agents. Thus the cultural and structural repercussions of ICTs cannot be
isolated from the dynamics of change they are part of.


Increasing world population and limited food resources, has made it inevitable to apply the benefits of modern technology to improve the efficiency of agricultural fields. Automatic plant type identification process is crucial not only to industries related to food production but also to environmentalists and related authorities. It increases productivity, contributes to a better understanding of the relationship between environmental factors and healthy crops. It is expected to reduce the labor costs for farmers and increase the operation speed and accuracy. In this paper, we propose a method to classify the type of plants in a video sequence. Our approach utilizes feature fusion together with color and texture features and support vector machine is used for classification. A variety of feature extraction techniques are employed in W-B, R-G and B-Y color spaces to extract color and textural features. Principal component analysis and t-distributed stochastic neighbor embedding methods are employed for dimension reduction. The performance of the approach is tested on dataset collected through a government supported project, TARBIL, for which over 1200 agro-stations are placed throughout Turkey. 5-fold cross validation technique as well as random test samples are used to test the accuracy of the system.


Variable inductors have a simple structure that consists of only magnetic core and primary dc and secondary ac windings, but can control effective inductance of the secondary ac winding by the primary dc current due to magnetic saturation effect. Hence, the variable inductors can be applied as a var compensator in electric power systems. In a previous paper, a lap-winding type three-phase variable inductor, which has the primary dc and secondary ac windings concentrically arranged on the same leg, was presented. It has a good controllability and low distortion current. This paper describes size and weight reduction of the lap-winding type three-phase variable inductor by focusing on the leg width. First, an initial design method of the leg width considering the influence of the dc-biased magnetization is presented. Next, a detailed design of the leg width for the size and weight reduction of the proposed variable inductor is described. Finally, characteristics of the size- and weight-reduced variable inductor were compared to those of the previous variable inductor. It is demonstrated that the core diameter is reduced by about 6% and the weight is decreased by about 50% in comparison with the previous variable inductor.


The Cham Muslims of Cambodia are descendents of Champa, a once-powerful Hindu-Buddhist kingdom located in modern-day central and southern Vietnam. Champa existed from the second century CE until its complete annexation by its long-time rival, the Dai Viet, in 1832.1 Its gradual loss of territory caused several waves of immigration to Cambodia between the crucial dates of 1471 and 1835 (the start of violent repression against the Cham in their last, and finally also annexed, principality: Panduranga).2 It seems that the first wave allied itself with Cambodia's Malay community, with whom the Cham share ethno-linguistic (as both groups are speakers of Austronesian languages) and cultural (e.g., matrilinear customs) heritage, as well as their status as foreign immigrants. Through this contact, they were Islamized. This article presents an overview of the religious and political development of Cambodia's Cham Muslims, most of whom are Sunnis, from the days of French colonialism up to the present, and shows how this formerly neglected minority became a showcase of Islamic internationalism. Contact persons or interviewees were recommended to me by Dr. Sos Mousine (CMDF, CAMSA, and the Ministry of Agriculture), Set Muhammadsis (CAMSA, CMDF) or Dato Hajji Alwi Muhammad (MAI Terengganu), or were sought out by myself. As I was mainly interested in religious change and the rebuilding of religious infrastructure, I visited many mosques and schools for interviews, which were conducted in English, Arabic, or with a Khmer or Cham translator.


Construction is one of the most dangerous with high prevalence of work-related fatalities and injuries among the high-risk industrial sectors. Concurrently, the construction industry is experiencing workforce demographic changes and shortages of skilled trade/construction workers. This paper provides an overview of the shifting construction workforce and the benefits & exposures from the evolving automated and autonomous machines & equipment (AAM&E) under development for the construction industry. Specifically, this paper describes a synopsis of design methodology and principles of AAM&E associated with human-related factors (e.g., self-efficacy, mental/cognitive workload, situation awareness). Also, this paper discusses potential practical applications and insights on the human-machine interaction/collaboration and key factors for building trust in human-robot teamwork (e.g., rule-based framework, transparency/feedback, observation, predictability). This paper can assist human factors & ergonomics (HFE) and safety professionals who may not be current with this evolving AAM&E technology to pre-plan and design control methods into industrial and construction projects.


New data on the valine molecule (C5H11NO2) fragmentation under the low-energy electron-impact are presented. These data are related to the formation of ionized products due to the ionizing radiation influence on the above amino acid molecule. A series of the fragments produced are identified by applying an extensive DFT-theory approach. The results obtained allowed the principal pathways of the valine molecule fragmentation to be found. The absolute appearance energies of some fragments are both measured experimentally and calculated theoretically. The experimental and theoretical data are compared and analysed.


I am an academic cardiologist whose major research interest is echocardiography and whose entire 35-year career has been spent in Northern California at one institution. My extracurricular career as an expert witness began when my department chairman asked me to help his neighbour, an attorney who was representing a plaintiff and seeking an expert. The pivotal issue was whether liability for a fatal myocardial infarction was attributable to overly aggressive thyroid hormone replacement. It was my opinion that, based on the information contained in the medical records and the current pharmacological parameters, the treating doctor had not prescribed appropriately. The defence witness was a pathologist who stated that "It was only a small infarction and should not have killed him." In deposition, my response cited a substantial body of indisputable scientific evidence supporting the lethality of acute coronary syndromes. Having no counter argument, the defence settled for an undisclosed sum.

From that time, I have been riveted by the interface between law and medicine and have since served as an expert witness at least a 100 times. The cases I have reviewed represent only a fraction of the number of requests received. Time constraints and my interest in particular cases have been the major factors limiting my involvement. While I prefer to testify in defence of my fellow doctors, about 40% of the time I have been retained by a plaintiff's attorney. My professional opinion is not swayed by whichever "side" retains me.

My approach reflects the system used in the United Kingdom, where the duty of the expert is solely to the court. Yet, before reading the impressions of Professor Roger Hall,1 Dr Steven J D Brecker2 and Adrian Whitfield QC,3 I was unaware of the responsibilities of an expert witness in what we in America …


Introduction Severe attacks of neuromyelitis optica spectrum disorder (NMO-SD) are improved by plasma exchange (PLEX) given as an adjunctive therapy. Initial studies failed to demonstrate a delay of PLEX treatment influenced clinical outcome; however PLEX was always used late. We examine the clinical consequences of delay in PLEX initiation on severe optic neuritis and spinal cord attacks in NMO-SD. Methods All of our patients who suffered attacks of NMO-SD, treated in our centre by PLEX, were retrospectively considered for inclusion. Primary outcome was defined as complete improvement. Secondary poor/good outcomes were respectively defined to be the higher/lower third of Delta-Expanded Disability Status Scale (EDSS) (late minus baseline EDSS). Delays from clinical onset to PLEX initiation were categorised for multivariate analysis. Results Of the 60 patients included, NMO-SD criteria (2015) were fulfilled in 92%. One hundred and fifteen attacks were included and received PLEX with a median of 7 days (0–54) after clinical onset. The probability to regain complete improvement continuously decreased from 50% for PLEX given at day 0 to 1%–5% after day 20. Through multivariate analysis, the baseline impairment and PLEX delay were associated with the probability to complete improvement (OR 5.3; 95% CI 1.8 to 15.9). Reducing the PLEX delay also influenced the good secondary outcome but not the poor secondary outcome. Conclusions These results confirm an improved clinical benefit of early initiation of PLEX during severe attacks of NMO-SD. Perceiving PLEX as a rescue therapy only after steroid failure could be deleterious.


Adult caudal blockade has fallen from favor in the anesthesia community. The majority of anesthesia providers now use lumbar epidurals and spinals for surgeries that can be done with caudals. Many claim the procedure is difficult to perform and the outcome of the block is unpredictable. Caudal anesthesia has distinct advantages over lumbar epidurals and spinals and can be done with confidence by anesthetists who are willing to learn the anatomy, basic skills, and limitations entailed in this lost technique.


We describe new implementations of leptonic and hadronic models for the broadband emission from relativistic jets in active galactic nuclei in a temporary steady state. For the leptonic model, a temporary equilibrium between particle injection/acceleration, radiative cooling, and escape from a spherical emission region is evaluated, and the self-consistent radiative output is calculated. For the hadronic model, a temporary equilibrium between particle injection/acceleration, radiative and adiabatic cooling, and escape is evaluated for both primary electrons and protons. A new, semianalytical method to evaluate the radiative output from cascades initiated by internal γγ pair production is presented. We use our codes to fit snapshot spectral energy distributions (SEDs) of a representative set of Fermi-LAT-detected blazars. We find that the leptonic model provides acceptable fits to the SEDs of almost all blazars with parameters close to equipartition between the magnetic field and the relativistic electron population. However, the hard γ-ray spectrum of AO 0235+164, in contrast to the very steep IR–optical–UV continuum, poses a severe problem for the leptonic model. If charge neutrality in leptonic models is provided by cold protons, the kinetic energy carried by the jet should be dominated by protons. We find satisfactory representations of the snapshot SEDs of most blazars in our sample with the hadronic model presented here. However, in the case of two quasars the characteristic break at a few GeV energies cannot be well modeled. All of our hadronic model fits require powers in relativistic protons in the range Lp ∼ 1047–1049 erg s−1.


Psychiatric care in Japan has received criticisms not only within Japan but from other parts of the world. In contrast, the services for the mentally ill in England are considered to be superior, despite serious criticisms. Psychiatric services in Japan and England are compared using government statistics. In Japan, the number of inpatients per 100,000 population has increased from the 1950s, while that of England has decreased since 1954. Since 1972 the prevalence of inpatients has been higher in Japan than in England. The history of psychiatric services in England where, after World War II, deinstitutionalization has been occurring is briefly described. For developing community care of the mentally ill in Japan, alternatives to inpatient care are thought to be important. These include primary care, day care and residential service in the community. Studies on families of mentally ill patients are crucial in community care and, among them, Expressed Emotion (EE) study is promising. Twenty cohort studies on EE and schizophrenic relapse, most of which successfully replicated the relationship between EE of the family and the course of the disease, are reviewed. Finally, some important aspects of EE study in Japan are discussed.


In this study, the harmful effect of Tuta absoluta on different tomato species was investigated. Six tomato genotypes which are Solanum chmielewskii (LA1028), Solanum neorickii (LA0247), Solanum hirsutum (LA777), Solanum pimpinellifolium (LA0722), and Solanum lycopersicum cv. Cuatomate and Solanum lycopersicum cv. Ailsa Craig (LA2838A) species were used as plant material in the study. To determine the incidence of Tuta absoluta on the plants, the egg and larvae were counted weekly by taking 5 leaves from the species. According to eggs and larvae counts, the plants were exposed to 5 types of severe damage while Solanum lycopersicum cv. Cuatomate was found to be later and less effective than the others. These results indicate that this species exhibits antixenosis properties against Tuta absoluta pests and that the other species that have been exposed to earlier and more severe damage lack such property.


The position of the molecular orbitals of polyaniline, relative to the Fermi level, shifts with the doping of polyaniline by both charge donor and charge acceptor species. Sodium as an electron donor, when added to the polyaniline system, results in an increase in electron population in the polyaniline bands but a decrease in density of states near E F . This is evident from the consistent shifts toward the greater binding energy of the occupied as well as unoccupied molecular orbitals, the valence bands and conduction band edges and characteristic core levels. In the case of iodine doping, an electron acceptor, all the states were shifted toward smaller binding energy. These results provide compelling evidence that the molecular orbitals of vapor deposited polyaniline thin films are delocalized. © 2002 American Institute of Physics. @ DOI: 10.1063/1.1484247


Anxiety disorders are chronic illnesses that occur more often in women than men. Previously, we found a significant sex difference in the 5‐year clinical course of uncomplicated panic disorder that was attributable to a doubling of the illness relapse rate in women compared to men. However, we have not detected a sex difference in the clinical course of panic with agoraphobia, generalized anxiety disorder (GAD), or social phobia (SP), which are conditions generally thought to be more chronic than uncomplicated panic disorder. Given that a longer follow‐up period may be required to detect differences in clinical course for more enduring illnesses, we conducted further analyses on this same cohort after a more protracted interval of observation to determine whether sex differences would emerge or be sustained. Data were analyzed from the Harvard/Brown Anxiety Research Program (HARP), a naturalistic, longitudinal study that repeatedly assessed patients at 6 to 12 month intervals over the course of 8 years. Data regarding remission and relapse status were collected from 558 patients and treatment was observed but not prescribed. Cumulative remission rates were equivalent among men and women with all diagnoses. Patients who experienced remission were more likely to improve during the first 2 years of study. Women with GAD continued remitting late into the observation period and experienced fewer overall remission events by 8 years. However, the difference in course failed to reach statistical significance. Relapse rates for women were comparable to those for men who suffered from panic disorder with agoraphobia, GAD, and SP. Again, initial relapse events were more likely to occur within the first 2 years of observation. However, relapse events for uncomplicated panic in women were less restricted to the first 2 years of observation and by 8 years, the relapse rates for uncomplicated panic was 3‐fold higher in women compared with men. Anxiety disorders are chronic in the majority of men and women, although uncomplicated panic is characterized by frequent remission and relapse events. Short interval follow‐up shows sex differences in the remission and relapse rates for some but not all anxiety disorders. These findings suggest important differences in the clinical course among the various anxiety disorders and support nosological distinctions among the various types of anxiety. It may be that sex differences in the clinical course of anxiety disorders hold prognostic implications for patients with these illnesses. Depression and Anxiety 17: 173–179, 2003. © 2003 Wiley‐Liss, Inc.


Aaron Tyler, Islam, the West, and Tolerance: Conceiving Coexistence. New York: Palgrave, 2008. Aaron Tyler's book is about tolerance, coexistence, and reconciling religious and ideological differences. The book begins by giving an excellent background analysis of the points of divergence "between Islam and the West." The author focuses on three broad themes that reflect theoretical and substantial perspectives. First, the modern world is described as characterized by anxious dilemma in the face of post-September 11 trauma. The dark incident of September 11, 2001 has unleashed angry recriminations between the Muslim world and the West. Even though fringe groups and malcontents in the name of Islam have conducted terrorist acts, their misguided acts need not be attributed to Islam. By comparison with Christianity and other religions, Islam is not more violent than the rest. Episodic violence by Muslims in direct reaction to the West's geostrategic interests, such as the "double standard regarding the Palestinian-Israeli question," unquestioning support for the state of Israel, the Iraqi invasion, and cultural invasion in the form of "Western secularism and materialism" may have aroused anger among some extremists. Extremists do not define Islam; Islam, in the fullness of its tenets, is a religion of peace. The apparent unease on the part of the West regarding Islam is an inevitable outcome of Islam seeking to validate itself in the face of globalization driven by Western power and influence. Islam must be tolerated, accommodated, and welcomed by the West. Tolerance, an ancient concept common in the medieval era, that had played a critical role before the liberal ideology came into vogue, is essential today and much more needed than ever before. The author differentiates tolerance from toleration by dismissing toleration as a forced, reluctant, and matter of fact acceptance of the Other. Tolerance is the opposite; it is a willing embrace of the Other without any pretexts or contingencies. Islam's reticence toward ? and skepticism of? Western cultural values needs to be understood from the perspective of tolerance in its authentic rendition. Western consumerism and materialism are perceived by many in the world of Islam as a relentless threat to the survival of the religiocultural values and traditions espoused by the greater Islamic community. The West's postmodern relativism is regarded by many Muslims as intolerant to those traditional Muslim communities that adhere to a system of absolutes (p. 2). Second, the ubiquitous Huntington paradigm about the clash of civilizations, looked at from the point of view of this book, is not without merit. The author agrees with Huntington that "colliding" ideologies have caused cross-cultural misunderstandings and upheavals. Even though Huntington was a nationalist zealot who expressed his pessimism about Islam as a menace to Western civilization, his misgivings concerning multiculturalism on Western terms fit well with Islam's rejection of multiculturalism on Islam's terms. In order to reverse the impending "cultural confrontation", the author argues that "Islam and the West" must learn to "coexist." Against this backdrop, Western intolerance of Islam seeking its own ways of perpetual validation is an obstacle to coexistence. Many Muslims view the West's dissemblance of tolerance as a disingenuous, valueless indifference, where individuals are extracted from their group identities, and a universal strangeness and religious apathy are espoused. Muslims describe the thin conceptualization of tolerance that dominates the West as nothing more than hypocritical relativism or indifference, intolerant of absolute convictions (p. 161). Third, coexistence is the essential antidote to conflict. Historians such as Bernard Lewis identify coexistence as a prudent alternative. Muslims, such as the grand mufti of Syria, and Christian and Jewish religious leaders have identified the indispensability of coexistence. …


Abstract PD-1/PD-L1 inhibitors activate immunological response and have become one of the main modalities of cancer treatment. However, they may result in the immune-related adverse events (irAEs). Immune-related cardiotoxicity is relatively rare but may become fatal. We will present a case of a male patient who experienced immunotherapy-related cardiotoxicity one year after received pembrolizumab treatment. The patient had atypical symptom presentation initially, but his condition deteriorated worsened rapidly and he developed severe cardiac disease. The patient experienced significant relief after corticosteroid treatment. Unfortunately, he experienced a reoccurence of the severe adverse event when discontinuing the use of corticosteroids. Ultimately, larger doses and longer courses of corticosteroid treatment cured the heart damage. Fortunately, we observed that lesions were stable and maintained for a long time after cessation of using pembrolizumab for eight months.


BACKGROUND
Parkinson's disease (PD) is a neurodegenerative disorder associated with caregiver burden. Higher rates of burden are associated with adverse outcomes for caregivers and patients. Our aim was to understand patient and caregiver predictors of caregiver burden in PD from a palliative care approach.

METHODS
We conducted a cross-sectional analysis of baseline data from PD patients and caregivers in a randomized trial of outpatient palliative care at three study sites: University of Colorado, University of Alberta, and University of California San Francisco. The primary outcome measure of caregiver burden, the Zarit Burden Interview (ZBI), was compared against the following patient and caregiver variables: site of care, age, disease/caretaking duration, presence of atypical parkinsonism, race, income, education level, deep brain stimulation status, the Unified Parkinson's Disease Rating Scale (UPDRS) and Edmonton Symptom Assessment System Revised: Parkinson Disease (ESAS) for symptom severity and burden, the Montreal Cognitive Assessment (MoCA) for cognitive function, Quality of Life in Alzheimer's Disease (QOL-AD) scale for patient and caregiver perspectives on patient general quality of life, Parkinson's Disease Questionnaire 39 (PDQ-39) scale for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for patient and caregiver mood, Prolonged Grief Questionnaire, Functional Assessment of Chronic Illness Therapy- Spiritual Well-Being (FACIT-SP) of patient and caregiver, and Palliative Performance Scale for functional status. A stepwise multivariate linear regression model was used to determine associations with ZBI.

RESULTS
A total of 175 patients (70.9% male; average age 70.7±8.1 years; average disease duration 117.2±82.6 months), and 175 caregivers (73.1% female; average age 66.1±11.1 years) were included. Patient spiritual well-being (FACIT-SP Faith subscale, r2=0.024, P=0.0380), patient health-related quality of life (PDQ-39, r2=0.161, P<0.0001), caregiver depression (HADS Depression, r2=0.062, P=0.0014), caregiver anxiety (HADS Anxiety, r2=0.077, P=0.0002), and caregiver perspective on patient quality of life (QOL-AD Caregiver Perspective, r2=0.088, P<0.0001) were significant contributors to ZBI scores.

CONCLUSIONS
Patient and caregiver factors contribute to caregiver burden in persons living with PD. These results suggest targets for future interventions to improve caregiver support.


The San Andreas Fault Observatory at Depth (SAFOD) pilot hole traverses the upper 2 km of a site 1.8 km west of the San Andreas fault (SAF) near Parkfield, California. In order to evaluate the burial and exhumation history of the site and its relationship to the kinematics and mechanics of the SAF, we use 15 apatite fission‐track (FT) and 5 (U‐Th)/He analyses from pilot hole samples to document their thermal history. Sample ages decrease with depth: FT and (U‐Th)/He ages range from ∼60 and ∼31 Ma, respectively, in the upper 800 m of the hole to ∼3 and 1 Ma at the base of the hole (2.2 km depth, 93°C).Thermal modeling of the distribution of FT lengths indicates three events in the last 80 Ma: 1) cooling and exhumation of >60°C that culminated at ∼30 Ma; 2) reheating of ∼50°C from ∼30 to 8–4 Ma, probably as the result of basin subsidence and burial by 1–1.5 km of sediments; and 3) cooling of ∼30°C and estimated Coast Range exhumation of ∼1 km since 8–4 Ma.


Communalism permeates the political, academic, media and everyday discourse in and about India. As a dominant interpretive framework, it expresses a particular politics of interfaith relations that normalises socio-political conflicts and violence intersecting with gender, class and caste relations. These intersections emerge in the experiences, practices and spaces of marginality and violence, revealing both the mechanisms of their normalisation in the context of communal violence and the experience of living within, through and despite it. Everyday life becomes the privileged context for reading communalism in light of a systematic reorganising of the gender-socio-economic governance, and the possibility to interrogate it. Based on an ethnographic study carried out in Hyderabad between 2009 and 2012, the paper reveals a politics of communal violence embedded in everyday social practices. It shows that the gender-socio-economic governance is not parallel to communalism but in fact constitutive of its logic and practices. The paper offers a perspective on how socio-political conflicts become actualised in a social order and how agency within such contexts unfolds as awareness of and action upon the space/possibility of their reconfiguration.


Space-time spectral analysis methods and their applications to large-scale atmospheric waves are reviewed. Space-time spectral analysis resolves transient waves into eastward and westward moving components and is mathematically analogous to rotary spectral analysis which resolves twodimensional velocity vectors into clockwise and anticlockwise components. Space-time spectral analysis can also resolve transient waves consisting of multiple wavenumbers into standing and traveling wave packets. Space-time energy spectra are governed by space-time spectral energy equations which consist of linear and nonlinear energy transfer spectra. Space-time spectra can be estimated by either the lag correlation method, direct Fourier transform method or the maximum entropy method depending on the length of the time record. By use of the modified space-Fourier transform these spectra can be estimated correctly from polar-orbiting satellite data which are sampled globally at different hours of the day. Space-time spectral analysis has been extensively applied to data generated by GFDL general circulation models to determine the wave characteristics, structure and energetics of transient planetary waves, to verify the model with observations and to clarify their generation mechanisms by means of controlled experiments.


In this work, a predictive control framework is proposed for the constrained stabilization of switched nonlinear systems that transit between their constituent modes at prescribed switching times. The main idea is to design a Lyapunov-based predictive controller for each constituent mode in which the switched system operates and incorporate constraints in the predictive controller design which upon satisfaction ensure that the prescribed transitions between the modes occur in a way that guarantees stability of the switched closed-loop system. This is achieved as follows: For each constituent mode, a Lyapunov-based model predictive controller (MPC) is designed, and an analytic bounded controller, using the same Lyapunov function, is used to explicitly characterize a set of initial conditions for which the MPC, irrespective of the controller parameters, is guaranteed to be feasible, and hence stabilizing. Then, constraints are incorporated in the MPC design which, upon satisfaction, ensure that: 1) the state of the closed-loop system, at the time of the transition, resides in the stability region of the mode that the system is switched into, and 2) the Lyapunov function for each mode is nonincreasing wherever the mode is reactivated, thereby guaranteeing stability. The proposed control method is demonstrated through application to a chemical process example.


This is the fifth of a series of papers that are being written as part of a larger project to estimate a small quarterly Global Projection Model (GPM). The GPM project is designed to improve the toolkit to which economists have access for studying both own-country and cross-country linkages. In this paper, we add Indonesia to a previously estimated small quarterly projection model of the US, euro area, and Japanese economies. The model is estimated with Bayesian techniques, which provide a very efficient way of imposing restrictions to produce both plausible dynamics and sensible forecasting properties.


The origin of this research is illuminated by CIBER's exploratory research on Trust in Scholarly Communications conducted in 2012-2013. This study's interest lies with Malaysian academic researchers both as producers and consumers and how they deal with the quality and trust consequences of the digital transition, especially, but not exclusively, the impact of social media and open access publishing on their scholarly communications. This paper reports on a survey on citation behaviour, part of a wider study of gauging quality and trustworthiness in scholarly communication in the emerging digital environment. It focuses on investigating what Malaysian researchers trust or find reliable to cite in their publications. In order to make the study results comparable, we adapted the same questionnaire that CIBER has developed and used in previous surveys. We used surveymonkey.com. a web-based questionnaire which has been widely used for surveys. The questionnaire went online on the 1 October 2014 and closed on the 30 December 2014. More than 400 respondents completed the questionnaire. The answers were analysed quantitatively and then grouped under descriptive headings of the types of reasons for citation provided. Similar to CIBER's study, the motivations for citing were found to be complex and multi-faceted but, in nearly all cases, researchers do regard the authority and trustworthiness of the cited source as an important factor in choosing to cite it. Citing behaviour includes an acknowledgement of useful intellectual content, and this process cannot be separated from the researcher's position in networks of trusted social and research influence. The digital transition has provided tools to help maintain and develop these social networks and it has also made it easier for researchers to investigate the credentials of the sources of documents. Peer-reviewed journals still hold influential. Measures of establishing trust and authority do not seem to have changed profoundly in Malaysia. The digital environment may bring ease and convenience to scholarly communication, but it gives more pressure for scholarly communication on high quality platforms. Looking at the researchers' trust-related views, it is emphasised that academic librarians apply their understanding of scholarly communication towards delivering the right services to meet the needs of the academic community.


Digital technologies and the internet play an increasingly important role in building innovations with a strong social impact  - digital social innovations DSI. Education should support this role and respond at trends as rapid population growth, climate instability, rising poverty, demographic developments. In this paper the role of DSI in inclusive education i.e. in the process of strengthening the capacity of the education systems to reach out to all learners is described. Education for an Inclusive Entrepreneurship i.e. entrepreneurship that contributes to social inclusion to give all people an equal opportunity to start up and operate businesses  should be  included in strategies of all countries. Particularly target groups in the inclusion process are those who are disadvantage and under-represented in entrepreneurship and self-employment, including youth, women, seniors, ethnic minorities and immigrants, disabled people and many other groups. Examples of projects with authors as active partners and developers of DSI in this context are given.


Despite considerable investigation, the mechanism of laser assisted vascular anastomosis remains unknown. Indications suggest that bonding is the result of thermal action, particularly the thermal denaturation of tissue proteins. However, our own work has led us to conclude that dehydration is an important factor. Hence, we have proposed that laser anastomosis is the result of dehydration at the apposed tissue faces, induced by laser irradiation. This was investigated by comparing the properties of bonds created by dehydration with those created by laser. The bonds were created using parameters consistent with laser anastomoses created in vivo. Results revealed that anastomoses created by dehydration were equivalent to those created by laser, with little difference in strength, histology or response to rehydration. The only significant difference (p < 0.02) was mean bond strength created at temperatures above the denaturation temperature of the tissue (548 g cm(-2) by laser, 994 g cm(-2) by dehydration). Given the similarity of bonds created by the two methods, we conclude that the same mechanism (i.e. dehydration) is likely to be responsible for bonding in both cases and therefore that argon laser bonding is mediated by dehydration.


Using the recently proposed echo-enabled harmonic generation (EEHG) free-electron laser (FEL) scheme, it is shown that operating the Shanghai deep ultraviolet FEL (SDUV-FEL) with single-stage to higher harmonics is very promising, with higher frequency up-conversion efficiency, higher harmonic selectivity and lower power requirement of the seed laser. The considerations on a proof-of-principle experiment and expected performance in SDUV-FEL are given.


Objective The aim was to compare intraocular pressure (IOP) changes after laser-assisted in-situ keratomileusis (LASIK) versus photorefractive keratectomy (PRK) in myopic eyes. Background IOP measurement is necessary for diagnosing glaucoma. LASIK and PRK are used for correction of myopia. IOP is underestimated after LASIK and PRK. It is very important to evaluate IOP changes after LASIK and PRK especially in myopic patients, as myopia is a risk factor for primary open-angle glaucoma. Patients and methods A total of 50 patients diagnosed clinically to have myopia were selected. Their ages ranged from 18 to 48 years. A total of 50 eyes were operated using LASIK 1 and 50 eyes were operated using PRK 2. Patients were subjected to corneal topography by pentacam and IOP measurement by Goldmann applanation tonometer (GAT), preoperatively and postoperatively at the end of the first week, the first month, and the third month. Results The mean IOP in LASIK and PRK groups, which was preoperatively 15.86 ± 1.99 and 15.62 ± 2.12 mmHg, respectively, decreased postoperatively to 12.98 ± 1.83 and 12.98 ± 2.03 mmHg, respectively. There is a statistically nonsignificant difference between LASIK and PRK, postoperatively (P = 0.164), whereas there was a statistically highly significant difference between preoperative and postoperative IOP in both LASIK and PRK groups (P = 0.000). Conclusion IOP is underestimated after laser correction. IOP decrease can be dramatic in highly myopic corrections. Preoperative IOP is the single strongest predictor of postoperative IOP change, with eyes with higher preoperative IOP having greater IOP decrease. LASIK correction will lower IOP by ∼1 mmHg because of the effect of the lamellar flap.


ABSTRACT The population distribution grid at fine scales better reflects the distribution of residents and plays an important role in investigating urban systems. The recent years have witnessed a growing trend of applying the nighttime light data to the estimation of population at micro levels. However, using the nighttime light data alone to estimate population may cause the overestimation problem due to excessively high light radiance in specific types of areas such as commercial zones and transportation hubs. In dealing with this issue, this study used taxi trajectory data that delineate people's movements, and explored the utility of integrating the nighttime light and taxi trajectory data in the estimation of population in Shanghai at the spatial resolution of 500 m. First, the initial population distribution grid was generated based on the NPP-VIIRS nighttime light data. Then, a calibration grid was created with taxi trajectory data, whereby the initial population grid was optimized. The accuracy of the resultant population grid was assessed by comparing it with the refined survey data. The result indicates that the final population distribution grid performed better than the initial population grid, which reflects the effectiveness of the proposed calibration process.


Abstract. From 2017 to 2019, an extensive sampling campaign was conducted in Belgian inland and coastal waters, aimed at providing paired data of optical and biogeochemical properties to support research into optical monitoring of aquatic systems. The campaign was focused on inland waters, with sampling of four lakes and a coastal lagoon during the growth season, in addition to samples of opportunity from other four lakes. Campaigns also included the Scheldt estuary over a tidal cycle and two sampling campaigns in the Belgian coastal zone. Measured parameters include inherent optical properties (absorption, scattering and beam attenuation coefficients, near-forward volume scattering function, turbidity), apparent optical properties (Secchi disc depth, substrate and water-leaving Lambert-equivalent bi-hemispherical reflectance), and biogeochemical properties (suspended particulate matter, mineral fraction of particle mass, particle size distribution, pigment concentration, DNA metabarcoding, flow microscopy counts, and bottom type classification). The diversity of water bodies and environmental conditions covered a wide range of system states. The chlorophyll a concentration varied from 0.63 to 382.72 mg m−3, while the suspended particulate matter concentration varied from 1.02 to 791.19 g m−3, with mineral fraction varying from 0 to 0.95. Depending on system and season, phytoplankton assemblages were dominated by cyanobacteria, green algae (Mamiellophyceae, Pyramimonadophyceae), or diatoms. The dataset is available from https://doi.org/10.1594/PANGAEA.940240 (Castagna et al., 2022).


This paper is proposed a transformer less static synchronous compensator (STATCOM) system based on multi-level H-bridge converter with star configuration to compensate the reactive power in transmission system. This proposed system with controller devotes themselves not only to the current loop control but also to the dc capacitor voltage control. With regards to the current loop control, a nonlinear controller based on the passivity-based control theory is used in this cascaded structure of STATCOM. As to the dc capacitor voltage control, overall voltage control is realized by adopting a proportional integral controller. Individual balancing control is achieved by shifting the modulation wave vertically. Also fuzzy logic control controller has used instead of PI controller to have balanced DC-link Voltage. A three phase five-level H-bridge cascaded STATCOM has designed using MATLAB software for theoretical analysis. The dc capacitor voltage can be maintained at the given value effectively using the proposed control.


The purpose of this transcendental phenomenological study was to explore litigious experiences for special education teachers in South Central Pennsylvania. It was known that teachers are not typically required to have courses on school law, but they are required to abide by educational law. This study was guided by the following research question: How do special education teachers in South Central Pennsylvania describe their litigious experiences? It sought to fill a gap in the literature in the area of actual teacher experience with the problem of litigation. Background information was given to show why this issue was a current problem and how this study sought to address the problem, and an examination of current literature was conducted to show how this study filled the current gap. The data for the study relied primarily on participant interviews and public record documentation from 11 participants. When the data was analyzed, four themes emerged: internalized stress, lack of confidence in present knowledge, lack of personal responsibility for the litigation, and guarding against the possibility of future litigious experiences. The implications for these themes were also discussed.


An improvement in the electrical properties of the films is absolutely required for the application of ZnO thin film in electrical devices. And the conventional dry etching process is accompanied by the generation of physical defects, degradation of the properties. The electrical property of direct-patternable, graphene-incorporated ZnO thin film prepared by photochemical solution deposition was improved by N2 atmosphere annealing. Direct-patterning of graphene-incorporated ZnO thin films by photochemical solution deposition was performed without a photoresist or etching process. The transmittance of graphene-incorporated ZnO thin films was similar to ZnO thin film. The transmittance of ZnO thin film was unaffected by annealing atmosphere such as air or N2. The incorporation of graphene slightly decreased the crystallinity of the ZnO thin films and annealing atmosphere did not affect to the crystallinity of ZnO thin films. The resistivity was decreased due to the mobility enhancement because of the π-bond nature of the graphene surface. In addition, N2 atmosphere annealing decreased the resistivity of ZnO thin film than O2 atmosphere annealing due to decreasing of oxidation on the surface. These results suggest that a micro-patterned system can be simply fabricated at low cost and the electrical properties of ZnO thin films can be improved by graphene incorporation and N2 atmosphere annealing.


The role of public extension in the sustainability and development of rural smallholder farmers is central to rural development. Although the benefits of public extension cannot be quantified to justify its funding, it remains pivotal to the success of poor smallholders with low literacy levels. The reports on agricultural extension in Eswatini paints blink picture on public extension. Data was collected on a census of 13 horticultural EOs alongside a snowballed sample of 82 farmers across the Hhohho region. The senior extension staff participated in a group discussion. The EOs were predominantly young males and were not trained in extension service delivery. The farmers were predominantly older females and had low levels of education. The EOs perceived themselves as good in horticultural issues and average in farmer management and agribusiness issues. They faced a number of challenges including work overload, being under-staffed, poorly resourced, inactive farmer groups, inconsistency of farmers' participation, and poor personal welfare. Institutionalising smallholder farmers in the community development plans (CDPs) and organising them into formal groups like cooperatives was identified as the first step towards improving public extension. This should be supported by training of EOs on Extension and business management. This would improve the efficiency of offering extension services and other benefits of collective operations. This would also reduce the EOs required per RDA and will enable the government to improve the welfare and operations of EOs. Keywords: Public extension services, smallholder farmers, extension officers, perceptions


Introduction and Objectives: The present study was done to determine the total number of antepartum and intrapartum fetal deaths; to know the probable etiology and management of the same, and to study the role of antenatal care in prevention of IUFD.
Materials and Method: A prospective study of intrauterine fetal demise and associated maternal factors were studied. All IUFD with singleton pregnancies more than 28 weeks of gestation were included in the study.
Results: The fetal death rate was 25.4 1000 births. Major causes of IUFD were PE and eclampsia (36.19%) and abruption placenta (19.87%). Majority were preterm (56.31%) and birth weight 2.5 kg (72.17%). Risk of IUFD was significantly less in booked patients than in unbooked patients.
Conclusion: Present study showed that majority of IUDs were preventable. Early detection of pre-eclampsia by regular ANCs and its treatment can reduce its complications including IUD and abruption placenta in few cases thereby further reducing the stillbirth rate.

 Keywords: Intrauterine fetal demise, Etiology, Prevention


Peanut plants showing mottling, yellow and necrotic spots on leaves were collected from peanut fields in Golestan province. Electron microscopic studies revealed the presence of flexuous filamentous particles ca. 700 nm in length, which was suggestive of a potyvirus infection. Healthy Nicotiana benthamiana plants mechanically inoculated with sap from infected peanut plants showed mottling, downward leaf curling, and wrinkling of the leaves. The virus was transmitted by Myzus persicae in a non-persistent manner to healthy N. benthamiana, on which symptoms were observed two weeks later. RT-PCR using an Oligo-dT and a NIb primer set resulted in a fragment of about 1093 bp, which comprised the complete coat protein (CP) gene and 3´-non-coding region. Analysis of its CP nucleotide and amino acid sequence revealed 98-99% similarity and 95-99% identity to those of Peanut mottle virus (PeMoV) isolated from other countries, respectively. The molecular data confirmed serological, vector transmission, and electron microscopic findings on the incidence of PeMoV in Iran. Additionally, sequence and phylogenetic analyses of the CP revealed clustering of Iranian PeMoV isolate with Asian/Australian isolates.


This paper considers mathematical optimization for the multistage train formation problem, which at the core is the allocation of classification yard formation tracks to outbound freight trains, subject to realistic constraints on train scheduling, arrival and departure timeliness, and track capacity. The problem formulation allows the temporary storage of freight cars on a dedicated mixed-usage track. This real-world practice increases the capacity of the yard, measured in the number of simultaneous trains that can be successfully handled. Two optimization models are proposed and evaluated for the multistage train formation problem. The first one is a column-based integer programming model, which is solved using branch and price. The second model is a simplified reformulation of the first model as an arc-indexed integer linear program, which has the same linear programming relaxation as the first model. Both models are adapted for rolling horizon planning and evaluated on a five-month historical data set from the largest freight yard in Scandinavia. From this data set, 784 instances of different types and lengths, spanning from two to five days, were created. In contrast to earlier approaches, all instances could be solved to optimality using the two models. In the experiments, the arc-indexed model proved optimality on average twice as fast as the column-based model for the independent instances, and three times faster for the rolling horizon instances. For the arc-indexed model, the average solution time for a reasonably sized planning horizon of three days was 16 seconds. Regardless of size, no instance took longer than eight minutes to be solved. The results indicate that optimization approaches are suitable alternatives for scheduling and track allocation at classification yards.


As an active research field, the self-mixing interferometry (SMI) based on semiconductor lasers (SLs) is a highly promising and emerging technique for non-contact sensing and parameter measurement of SLs. The basic structure of an SMI system consists of an SL, a lens and an external target. When a portion of reflected light from the target travels back to the laser cavity, a new lasing field is built up leading to both amplitude and phase modulations. The modulated output power is called a self-mixing signal which carries the information of both the target and SL's feature parameters. Alpha factor, also known as linewidth enhancement factor, is one of the most important SL's feature parameters. It characterizes the characteristics of SLs, such as the linewidth, the chirp, the injection lock range and the dynamic performances. This paper presents a new method for retrieving alpha factor of SLs by making use of a self-mixing interference (SMI) waveform. According to the well-known Lang-Kobayashi (L-K) theory, the SMI waveform is shaped by multiple parameters, including the alpha, the optical feedback level factor (denoted as C) and other parameters related to the oscillation of the external target. In this work, we build a new equation based on the SMI model derived from the L-K theory, which can be used to calculate the alpha value. In the existing SMI based methods for measuring the alpha factor, the optical feedback level C is limited within a certain narrow range. The proposed method is able to relieve this limitation. The associated simulations and experiments are carried out for verifying the proposed method.


AIM
The ductal carcinoma in situ (DCIS) is a more and more frequent neoplasia, representing over 25% of diagnosed breast cancer in recent surveys.It is particularly interesting as concerns several aspects of which the most important are issues linked to clinical diagnosis and the difficulties of histopathological classification, with evident and important therapeutic implications.

PATIENTS AND METHODS
The authors report their experience about 161 ductal carcinoma in situ of the breast. Guidelines for surgical treatment are: radiological or clinical diagnosis, tumor's extension, histological classification, grading and margin status. At the present the authors prefer breast conserving surgery with tumor margin's study. They report their experience in the last seven years about sentinel lymph node biopsy.

RESULTS
The most frequent histotype resulted comedocarcinoma (61,8%) followed by non comedo (38,2%). Local recurrence after DCIS therapy is 6,1%.

CONCLUSIONS
80-90% of the patients currently treated for DCIS present non-palpable breast lesions at diagnosis. Breast conserving surgery is the first choice and radiotherapy and endocrine therapy are indicated for selected patients.


We present two characterizations of Lagrange interpolation sets for weak Chebyshev spaces. The first of them is valid for an arbitrary weak Chebyshev space U and is based on an analysis of the structure of zero sets of functions in U extending Stockenberg's theorem. The second one holds for all weak Chebyshev spaces that possess a locally linearly independent basis.


In this paper, we formulate a recently proposed qualitative imaging approach named near-field orthogonality sampling method (NOSM) for a general measurement configuration. In the very first version, the NOSM was basically a backpropagation method, which analytically transforms the scattered fields, which is obtained with some specific multiview–multistatic measurement configurations (circular or linear), to reduced scattered electric fields on the sampling domain, which encapsulates the targets. The contributions of this paper are: 1) physical meaning of the reduced scattered field of the NOSM is explained by showing how it approximates the contrast source values in the sampling domain for different generic and limited aperture configurations; 2) the application of the NOSM is generalized to a generic configuration and some comments are made how to reduce the computational complexity and source requirements; 3) the reciprocity of the data is accounted for to improve the performance for limited aperture measurement scenarios; and 4) finally, a useful modified indicator is obtained by relying on the physical meaning of the indicator. The accuracy and stability of the proposed formulations are corroborated with numerical examples for which the excitation-measurement configuration is of limited aperture.


Humans are equipped with many systems to help protect us from bodily harm. One of them is the peripersonal space that tries to help us avoid collisions or minimize the impact of collisions with external objects. This small network in the brain monitors the spaces immediately surrounding individual body-parts such as the face, hands, torso, legs and engages defensive responses such as moving the body-part away from the direction of impact, or closing the eyes in the event that impact is expected on the face. The interesting thing is that the protective zones around the body parts of independent of each other, and the defensive responses they trigger are also specific to protecting that body part. This defensive mechanism was the focus of this thesis. Initially discovered in primates, research is now being conducted in humans to gain an understanding of it. In the first study of the thesis, we show that humans are not only capable of anticipating where they are to expect an approaching object to make contact, but they are also capable of extracting exactly when the contact is to occur. We show that anticipating physical contact from a moving object facilitates the activity of the PPS mechanism. That is, both the action of the peripersonal space network and the anticipation of touch together help us prepare and respond to an object that is likely to come in contact with us. In other studies we looked at the properties of the peripersonal space. When the speed of a looming object increases, the defensive PPS around the body-part also increases, so as to be able to trigger the defensive response effectively sooner. This result is directly in line with what was observed in the neuronal activity of monkeys. Neurons tended to respond sooner when the object approaching the monkey loomed faster. We also show that the peripersonal space network integrates information from multiple senses, such as vision and touch to form its responses. That is, when you are able to both see an object approach you and feel its initial touch you are likely to detect it sooner than if you only saw it or felt its touch. This thesis looked at the effect of our action capability on our ability to estimate the locations of approaching objects. We showed that the better your action capability, the better you are estimating the location of a looming object. We compared video game players with non-video game players in a virtual reality task where they had to prevent a looming ball from making contact with an object standing next to them. We then asked the participants to estimate the location of the ball when it changed colour. We found that video game players were not only more effective at stopping the ball, they were also more accurate at estimating the location of the ball. Non-video game players, were slower at stopping the ball and also consistently judged the ball to be closer to them than it actually was. We see that when we need to interact with a looming object, our ability to effectively interact with it determines our judgement of its location. The results of this thesis demonstrate the effects of the mechanisms that our brain is equipped with to maintain a safety margin around our body.


This innovation is small, lightweight, and consumes very little electricity as it measures the solar energy attenuated by gases and aerosol particles in the atmosphere. A Sun photometer is commonly used on the Earth's surface, as well as on aircraft, to determine the solar energy attenuated by aerosol particles in the atmosphere and their distribution of sizes. This information is used to determine the spatial and temporal distribution of gases and aerosols in the atmosphere, as well as their distribution sizes. The design for this Sun photometer uses a combination of unique optics and a charge coupled device (CCD) array to eliminate moving parts and make the instrument more reliable. It could be selfcalibrating throughout the year. Data products would be down-welling flux, the direct-diffuse flux ratio, column abundance of gas phase constituents, aerosol optical depth at multiple-wavelengths, phase functions, cloud statistics, and an estimate of the representative size of atmospheric particles. These measurements can be used to obtain an estimate of aerosol size distribution, refractive index, and particle shape. Incident light is received at a light-reflecting (inner) surface, which is a truncated paraboloid. Light arriving from a hemispheric field of view (solid angle 2 steradians) enters the reflecting optic at an entrance aperture at, or adjacent to, the focus of the paraboloid, and is captured by the optic. Most of this light is reflected from an inner surface. The light proceeds substantially parallel to the paraboloid axis, and is detected by an array detector located near an exit aperture. Each of the entrance and exit apertures is formed by the intersection of the paraboloid with a plane substantially perpendicular to the paraboloid axis. Incident (non-reflected) light from a source of limited extent (the Sun) illuminates a limited area on the detector array. Both direct and diffuse illumination may be reflected, or not reflected, before being received on the detector array. As the Sun traverses a path in the sky over some time interval, the track of the Sun can be traced on the detector array. A suitably modified Sun photometer might be used to study the dynamics of an environment on another planet or satellite with an atmosphere.


Macroscopic derivation of the entrainment in a supersolid cylinder induced by a surface elastic wave (of small amplitude) propagating along the flexible interface is conducted by considering the nonlinear coupling between the interface and the rarefaction effect. We obtain the critical bounds for zero-volume-flow-rate states corresponding to specific rarefaction measure and wave number which is relevant to the rather small critical velocity or disappearance of supersolid flows reported by Rittner and Reppy.


A very good day to all the Excellences, Distinguished Speakers, Ladies and Gentlemen.
It is our privilege to address you all on behalf of the conference committee and welcome you all to the webinar on Plant Science and Agriculture Webinar organized by Allied Academies in conjunction with the generous support and cooperation from the editorial board members and from the Journal of Plant Diseases & Biomarkers, Journal of Biotechnology and Photochemistry, Journal of Plant Diseases & Biomarkers and Journal of Agricultural Science and Botany.
And we believe that everyone is staying safe and healthy. We hope soon we will overcome this pandemic.
The world is adapting to the new digital era and following the same, we have now moved our events to digital platforms making it easier for the researcher around the globe and all those who could not make it to the Global Events due to economic constraints get access to such meetings.
To begin with, Allied Academies is a 25-year-old organization which has been working with various researchers to make their research work available to the global scientific community. With various journals and 1000+ conferences till date; we have been trying to bring the scientific community close to each other. Towards the same effort, we have gathered here today for the commencements of the virtual meet on Plant Science and Agriculture 2021.


ABSTRACT Effective management of marine environments requires a sound understanding of the relevant physical sedimentary sciences. Environmental impact assessment (EIA) is a key management and decision-making tool employed in Australia for coastal and marine developments. This article examines the veracity of the application of the marine physical sciences within the EIA process, using turbidity measurement and sediment transport pathways as examples. A review of EIA guidance reveals deficiencies in regulation. Turbidity measurement is poorly understood and performed in current practice, while a focus on protecting marine habitats largely ignores those physical sedimentary processes, such as long-term bed-sediment transport pathways, that create and maintain these habitats. Thus evaluations of impacts of offshore activities such as channel dredging and spoil emplacement at sea are fundamentally flawed. An extensive body of scientific knowledge is already available on marine physical processes, and equivalent information for assessments of terrestrial development is routinely taken into consideration. Perhaps practice for the marine environment lags behind that for terrestrial settings or is it a case of 'out of sight – out of mind'? We call on environmental management professionals to increase engagement with the physical processes that determine the quality of marine environments.


Background Iron deficiency is common during pregnancy. Experimental animal studies suggest that it increases cardiovascular risk in the offspring. Objective To examine the relationship between maternal pregnancy dietary and supplement iron intake and hemoglobin, with offspring's arterial stiffness (measured by carotid-radial pulse wave velocity), endothelial function (measured by brachial artery flow mediated dilatation), blood pressure, and adiposity (measured by body mass index), test for mediation by cord ferritin, birth weight, gestational age, and child dietary iron intake, and for effect modification by maternal vitamin C intake and offspring sex. Design Prospective data from 2958 mothers and children pairs at 10 years of age enrolled in an English birth cohort, the Avon Longitudinal Study for Parents and Children (ALSPAC), was analysed. Results 2639 (89.2%) mothers reported dietary iron intake in pregnancy below the UK reference nutrient intake of 14.8 mg/day. 1328 (44.9%) reported taking iron supplements, and 129 (4.4%) were anemic by 18 weeks gestation. No associations were observed apart from maternal iron intake from supplements with offspring systolic blood pressure (−0.8 mmHg, 99% CI −1.7 to 0, P = 0.01 in the sample with all relevant data observed, and −0.7 mmHg, 99% CI −1.3 to 0, P = 0.008 in the sample with missing data imputed). Conclusion There was no evidence of association between maternal pregnancy dietary iron intake, or maternal hemoglobin concentration (which is less likely to be biased by subjective reporting) with offspring outcomes. There was a modest inverse association between maternal iron supplement intake during pregnancy with offspring systolic blood pressure at 10 years.


Nanoparticles have been extensively used to deliver therapeutic drugs to tumor tissues through extravasation from a leaky vessel via enhanced permeation and retention effect (EPR, passive targeting) or targeted interaction of tumor-specific ligands (active targeting). However, the therapeutic efficacy of drug-loaded nanoparticles is hampered by heterogeneous distribution owing to limited penetration in tumor tissue. Inspired by the fact that cancer cells can recruit inflammatory immune cells to support their survival, we developed a click reaction-assisted immune cell targeting (CRAIT) strategy to deliver drug-loaded nanoparticles deep into avascular regions of the tumor. Immune cell-targeting CD11b antibodies are modified with trans-cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 hr results in targeted conjugation of the nanoparticles onto CD11b+ myeloid cells, which serve as active vectors into tumor interiors. We show that the CRAIT strategy allows deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model. The CRAIT strategy does not require ex vivo manipulation of cells and can be applied to various types of cells and nanovehicles.


Some of the recorded properties of a filterable organism (the PAP organism) isolated by Eaton and colleagues from cases of human primary atypical pneumonia suggest that it may be related biologically to the Mycoplasma (pleuropneumonia-like) group. In further investigation of this possibility now reported it was found that the organic gold salt, sodium aurothiomalate, which is known to inhibit certain mycoplasmas, would also inhibit infection with the PAP organism in the hamster and chick embryo lung. Some accepted viruses of a similar order of size to the PAP organism -namely, Nigg's pneumonitis virus of mice (psittacosis group), three strains of influenza virus A, vaccinia and variola viruses-were not inhibited by sodium aurothiomalate. On the other hand, grey lung virus of mice, an organism with some properties resembling those of the PAP organism, was strongly inhibited. Diethyl ether and the antibiotic kanamycin sulphate both inhibited the growth of the PAP organism in chick embryo lung. An intensified Giemsa-staining method revealed small red-purple coccobacillary bodies (later called elementary bodies, EB) in the lungs of chick embryos infected with three different strains of PAP organism isolated, respectively, in 1944, 1954 and 1960 in different parts of the United States. The EB were not seen in uninfected chick embryo lungs. The EB and the antigen of the PAP organism stained by the fluorescent antibody technique occupied essentially the same position in relation to the mesobronchial epithelial cells of chick embryo lung. The formation of both was suppressed in parallel by treatment of inoculum or eggs with diethyl ether, kanamycin sulphate or sodium aurothiomalate. There was a good but not absolute correlation between the presence or absence of EB and antigen in experiments on the growth or survival of the P,4P organism in chick embryos, in cell-free media, and in titrations in eggs.


ABSTRACT Cytokines play crucial roles in curtailing the propagation and spread of pathogens within the host. As obligate pathogens, gammaherpesviruses have evolved a plethora of mechanisms to evade host immune responses. We have previously shown that murine gammaherpesvirus 68 (γHV68) induces the degradation of RelA, an essential subunit of the transcriptionally active NF-κB dimer, to evade cytokine production. Here, we report that the immediately early gene product of γHV68, replication transactivator (RTA), functions as a ubiquitin E3 ligase to promote RelA degradation and abrogate cytokine production. A targeted genomic screen identified that RTA, out of 24 candidates, induces RelA degradation and abolishes NF-κB activation. Biochemical analyses indicated that RTA interacts with RelA and promotes RelA ubiquitination, thereby facilitating RelA degradation. Mutations within a conserved cysteine/histidine-rich, putative E3 ligase domain impaired the ability of RTA to induce RelA ubiquitination and degradation. Moreover, infection by recombinant γHV68 carrying mutations that diminish the E3 ligase activity of RTA resulted in more robust NF-κB activation and cytokine induction than did infection by wild-type γHV68. These findings support the conclusion that γHV68 subverts early NF-κB activation and cytokine production through RTA-induced RelA degradation, uncovering a key function of RTA that antagonizes the intrinsic cytokine production during gammaherpesvirus infection.


BACKGROUND
Special Needs Dentistry (SND) has been recognized as a dental specialty in Australia since 2003 but there have been no studies addressing the profile of patients for specialist care. The purpose of this study is to identify, via referrals received, the profile of patients and quality of referrals at the largest public SND unit in Victoria, Australia.

METHODS
All referrals received over a 6-month period (1 January-30 June 2013) by the integrated SND unit (ISNU) were reviewed prior to allocation to the outpatient clinic (OP), domiciliary (DOM) or general anaesthetic (GA) services.

RESULTS
Six-hundred and eighty-eight referrals were received with the majority for the OP clinic (68.3%), followed by DOM (22.4%) and GA services (9.3%) (χ2  = 360.2, P < 0.001). A referral may have specified more than one special needs condition with the most common category being those who were medically compromised (81.7%). The reasons for referral included lack of compliance (27.2%), further management due to multiple medical conditions or GA services required (9.9%), or for multiple other reasons (62.9%).

CONCLUSIONS
A diverse pattern of SND patients was referred to the ISNU with a majority of referrals having no specific referral reason cited, suggesting poor quality of referrals.


A particle swarm algorithm is proposed to generate optimal assembly sequences for compliant assemblies. Firstly, the liaison graph and the adjacency matrix describe the geometry of the compliant assemblies. An assembly sequence is represented by a character string, whose length is the number of all parts. The conceptual tolerance analysis is used to evaluate feasible sequences. Thereafter, the particle swarm algorithm is presented to generate assembly sequences, in which the elite ratio is applied to improve optimization results. Finally a fender assembly is used to illustrate the algorithm of assembly sequence generation and optimization.


It might not have been foreseen that William Rehnquist would have a marked influence on the Supreme Court's interpretation, construction, and application of the First Amendment's Religion Clauses. And yet, he certainly did. Kent Greenawalt wrote that Rehnquist – or, more precisely, the "Rehnquist Court" – "turned the constitutional law of religion upside down." "[W]e have moved," he reported, "from expansive readings of both of the religion clauses to narrow readings of the Free Exercise Clause and of very important aspects of the Establishment Clause." It is suggested in this paper that in facilitating and guiding the "move[s]" identified by Greenawalt, Rehnquist for the most part "turned the constitutional law of religion" right-side up, rather than "upside down." He left the Court's Religion Clauses doctrine better than it was before, that is, better rooted in the Constitution's text, history, structure, and values than it was when he joined the Court. In any event, that the "move[s]" happened, and that they happened in no small part because of him, seems beyond dispute.Rehnquist was able, for the most part, to exercise both judicial humility in the face of politically accountable actors' attempts to deal with debatable questions of policy and morality – including most of the questions that arise in free-exercise and non-establishment cases – and careful review of measures and actions that might compromise the structural integrity of our Constitution. This paper's appreciative review of his contributions to the Court's Religion Clauses doctrine will, it is hoped, serve as a reminder that cases involving tension or collision between political and religious authority implicate the "first principles" of our constitutional experiment no less than those involving federal interference with the states' appropriate functions or regulatory overreach by Congress.


Thyroid hormone is a pleiotropic hormone with widespread biological actions. For instance, adequate levels of thyroid hormone are critical for the development of different tissues such as the central nervous system, but are also essential for the regulation of metabolic processes throughout life. The biological activity of thyroid hormone depends not only on serum thyroid hormone levels, but is also regulated at the tissue level by the expression and activity of deiodinases, which activate thyroid hormone or mediate its degradation. In addition, thyroid hormone transporters are necessary for the uptake of thyroid hormone into target tissues. With the discovery of monocarboxylate transporter 8 (MCT8) as a specific thyroid hormone transporter and the finding that mutations in this transporter lead to a syndrome of severe psychomotor retardation and elevated serum 3,3',5-tri-iodothyronine levels known as the Allan-Herndon-Dudley syndrome, the interest in this area of research has greatly increased. In this review, we will focus on the molecular aspects of thyroid hormone transporters, including MCT8, MCT10, organic anion transporting polypeptides, and the effects of genetic variation in these transporters.


Over the past 10 years, improvements to the fundamental components in superconducting qubits and the realization of novel circuit topologies have increased the lifetimes of qubits and catapulted this architecture to become one of the leading hardware platforms for universal quantum computation. Despite the progress that has been made in increasing the lifetime of the charge qubit by almost six orders of magnitude, further improvements must be made to climb over the threshold for fault tolerant quantum computation. Two complementary approaches towards achieving this goal are investigating and improving upon existing qubit designs, and looking for new types of superconducting qubits which would offer some intrinsic improvements over existing designs. This thesis will explore both of these directions through a detailed study of new materials, circuit designs, and coupling schemes for superconducting qubits. In the first experiment, we explore the use of disordered superconducting films, specifically Niobium Titanium Nitride, as the inductive element in a fluxonium qubit and measure the loss mechanisms limiting the qubit lifetime. In the second experiment, we work towards the experimental realization of the 0 − π qubit architecture, which offers the promise of intrinsic protection in lifetime and decoherence compared to existing superconducting qubits. In the final experiment, we design and measure a two qubit device where the static σz⊗σz crosstalk between the two qubits is eliminated via destructive interference. The use of multiple coupling elements removes the σz⊗σz crosstalk while maintaining the large σz⊗σx interaction needed to perform two qubit gates.


Despite extensive research in the domain of requirements engineering (RE), companies still struggle with this discipline. Moreover, practitioners are challenged with developing successful products, services, and systems which address the true needs of their customers. This gives rise to a new research field in the domain of RE, namely artifact orientation. According to the literature, this artifact orientation should increase the success of RE significantly. By conducting a literature review and 7 expert interviews, we identified 7 model requirements (MRs) for an artifact-oriented RE model. Furthermore, the results of this paper suggest that existing artifact-oriented RE models do not sufficiently address all identified MRs. In particular, these models lack the combination of traditional RE practices, such as goal orientation, documentation, and traceability with novel agile approaches. Furthermore, there is a need for a more holistic RE which merges the domains of product, service, and software engineering.


An encoder may include a core MDCT filterbank that can be used to implement an advanced audio coding (AAC) algorithm, an AAC-enhanced low delay (ELD) algorithm or both algorithms. For the AAC algorithm, a sequence of input samples is sent directly to the MDCT filterbank to obtain a sequence of output samples. For the AAC-ELD algorithm, the signs of input samples of the sequence of input samples are inverted, the MDCT analysis filterbank is applied to the sign-inverted sequence of input samples to obtain a sequence of output samples, the order of the sequence of output samples is reversed, and the signs of alternating output samples of the sequence of output samples are inverted. Similarly, a decoder may include a core IMDCT synthesis filterbank that can be used to implement AAC-ELD or both AAC and AAC-ELD algorithms. The steps for the decoder are merely the reverse of the encoder.


Protein–protein interactions have become attractive targets for both experimental and therapeutic interventions. The PSD-95/Dlg1/ZO-1 (PDZ) domain is found in a large family of eukaryotic scaffold proteins that plays important roles in intracellular trafficking and localization of many target proteins. Here, we seek inhibitors of the PDZ protein that facilitates post-endocytic degradation of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR): the CFTR-associated ligand (CAL). We develop and validate biochemical screens and identify methyl-3,4-dephostatin (MD) and its analog ethyl-3,4-dephostatin (ED) as CAL PDZ inhibitors. Depending on conditions, MD can bind either covalently or non-covalently. Crystallographic and NMR data confirm that MD attacks a pocket at a site distinct from the canonical peptide-binding groove, and suggests an allosteric connection between target residue Cys319 and the conserved Leu291 in the GLGI motif. MD and ED thus appear to represent the first examples of small-molecule allosteric regulation of PDZ:peptide affinity. Their mechanism of action may exploit the known conformational plasticity of the PDZ domains and suggests that allosteric modulation may represent a strategy for targeting of this family of protein–protein binding modules.


BACKGROUND: Patients undergoing mechanical ventilation in the ICU often receive supplemental oxygen. If not closely monitored, this may lead to hyperoxia. The use of an oxygen-weaning protocol may reduce this risk by pacing the titration of oxygen therapy to patient needs. ICU protocols are correlated with decreased mortality and length of stay and have great potential for cost savings. The goals of this study were to determine whether the oxygen-weaning protocol at a university-affiliated hospital was followed and to measure the length of time respiratory therapists took to wean patients once the oxygen-weaning parameters were met. METHODS: This was a retrospective chart review of subjects > 18 y of age admitted to the medical ICU who underwent intubation and mechanical ventilation and were placed on an oxygen therapy protocol. The following data were collected: demographics, arterial blood gases, the length of time to change FIO2 after meeting weaning parameters, and the percent change in FIO2. RESULTS: Data were collected from 30 subjects. The most common oxygen saturation parameter measured via pulse oximetry (SpO2) used to initiate weaning oxygen was 92%. The mean ± SD FIO2 administered to subjects was 39.6 ± 15.3% prior to extubation. The majority of subjects exhibited adequate oxygenation prior to extubation (mean ± SD): PaO2 99.3 ± 6.7 mm Hg, SaO2 95.1 ± 26.9%. The mean ± SD length of time to the first change in FIO2 from the time a subject met the weaning criteria was 9.1 ± 10.6 h (range 1–39 h; interquartile range 2–13 h). CONCLUSIONS: Subjects admitted to the medical ICU who were intubated, mechanically ventilated, and placed on the oxygen therapy protocol experienced a significant delay in oxygen weaning. Closer monitoring and adherence to the oxygen-weaning protocol should be considered to reduce the potential risk for hyperoxia.