An abnormal presentation of the central nervous system in a fetus during a screening examination is an indication for extended diagnosis, the aim of which is to explain the character of such an anomaly (a congenital defect, destructive effect of intrauterine infection or abnormality with reasons that are difficult to explain). Knowledge of normal development sequence of the fetal brain, which is discussed in this paper, is the basis for correct interpretation of imaging findings. Together with the increase in survival of preterm neonates, a high risk of early brain damage is still a problem in this extremely immature population. Therefore, imaging examinations become necessary. The paper presents intrauterine and postnatal risk factors of early brain damage as well as classification of such lesions, of hemorrhagic and hypoxic-ischemic etiology. The diagnosis of the cerebellum damage, which is currently believed to be a significant cause of autism, is emphasized. The evolution of lesions over time is also presented. Moreover, the elements of diagnosis important for prognosis are stressed. The standards of imaging examinations of the central nervous system include the schedule of ultrasound examinations and provide indications for extended diagnosis with the use of magnetic resonance imaging.


The aim of this presentation is to introduce and discuss the key concepts included in the theory of representation connected to the category of fetish and fetishistic scopophilia introduced by Sigmund Freud and developed out later on by Laura Mulvey in 1970s as well as various feminist theorists writing about visual theory from 1980s. The fetish theory entered various fields of visual arts researching the visual perception and representation mainly focusing on the white male active gaze of white feminine passive bodies. Most psychoanalytic theory excludes the very possibility of the existence of female fetishism. But in recent years, the Freudian construction of passive female sexuality and passive female gaze have been severely criticized, and the other-feminine gaze is more often brought to public. The presentation will follow selected works of theorists who discussed and evolved the concepts of gendered and racial gaze, scopophilic gaze or fetishistic gaze developing polemic in works Seeing Differently. A history and theory of identification and the visual arts by Amelia Jones and Female Fetishism. a New Look by Lorraine Gamman. It can be suggested that Freudian phallocentrism has prevented analysts from seeing the otherness evidence before their eyes so the presentation will provide the examples of feminine looking at sexuality in visual works of Carolee Schneemann, Renee Cox, Kozyra and fetish fashion photographer Lanee Bird.


Vibrational spectroscopy, namely near infrared (NIR) and Raman spectroscopy, is based on the interaction between the electromagnetic radiation and matter. The technique is sensitive to chemical and physical properties and delivers a wide range of information about the analyzed sample, but in order to extract the information, multivariate calibration of the spectral data is required. The main goal of this work will be to present in detail the available multivariate calibration strategy for development of NIR and Raman spectroscopic methods, which was successfully applied in pharmaceutics.


Acidification of the Bohemian Forest lakes caused by sulphate and nitrate deposition between the 1950s and 1980s strongly affected benthic and pelagic assemblages of macroinvertebrates. Lake water acidification peaked in the mid-1980s and, along with substantial decrease in acid deposition, has been reversing since then. Chemical recovery of lakes exhibits typical changes in water chemistry, such as a decrease in concentrations of strong acid anions, base cations and aluminium, followed by an increase in pH, acid neutralising capacity and concentration of dissolved organic carbon. However, continuing adverse effects of aluminium delayed the biological recovery for at least a decade and recent assemblages still suffer from acid stress. First signs of biological recovery included colonisation by vagile species, reappearance of some indigenous or acid-sensitive species and decline in abundances of eurytopic acid-tolerant species. This study focuses on eight natural lakes of glacial origin on the Czech side (5) and the German side (3) of the Bohemian Forest. We compare biological recovery of two types of lakes – four partly recovered low-aluminium lakes and four acidic high-aluminium lakes. The main aim is to explore compositional changes of macroinvertebrate assemblages in response to recent changes in lake water chemistry between 2010 and 2015. We also compare recent species richness of aquatic insects to that observed in 1999–2007.


What are the differences in learning styles between students and educators who teach and/or design their e-learning environments? Are there variations in the learning styles of students at different levels of study? How may we use this learning styles data to inform the design in e-learning environments? This paper details mixed-methods research with three cohorts teaching and learning in e-learning environments in higher education: novice undergraduate e-learners, graduate e-learners, and educators teaching in, or designing for, e-learning environments (Willems, 2010). Quantitative findings from the Index of Learning Styles (ILS) (Felder & Silverman, 1988; Felder & Soloman, 1991, 1994) reflect an alignment of the results between both the graduate e-learner and e-educator cohorts across all four domains of theILS, suggesting homogeneity of results between these two cohorts. By contrast, there was a statistically significant difference between the results of the graduate and educator cohorts with those of the undergraduate e-learners on two domains: sensing-intuitive (p=0.015) and the global-sequential (p=0.007), suggesting divergent learning style preferences. Qualitative data was also gathered to gain insights on participants' responses to their learning style results


Numerical solutions of the scalar and elastic wave equations have greatly aided geophysicists in both the forward modelling and migration of seismic wavefields in complicated geologic media. In P- and S-wave propagation, the finite-element method is a powerful tool for determining the effect of structural irregularities on wave propagation. Dependence of the wave equation on both spatial and temporal differentials requires solving both spatial and temporal discretization. In the spatial discretization step in 1D and 2D, piecewise linear basis functions and the Galerkin method are the most commonly used tools. After solving spatial discretization with the finite-element method, the wave equation reduces to an ODE (ordinary differential equation). In this regard, different authors used different ODE solver including Runge-Kutta method and finite-difference method. This paper will familiarize the reader with the diverse approaches of solving temporal discretization. An application of finite-element methods to solve seismic wave motion in linear viscoelastic media (where inelastic strains development depends not only on the current state of the stress and strain but on the full history of their development), using memory variable formalism in spatial discretization step, is one of the reviewed sections.


The relationship between environmental variability and niche overlap is studied for a class of model biological communities in which several species compete on a one-dimensional continuum of resources, e.g., food size. In a strictly unvarying (deterministic) environment, there is in general no limit to the degree of overlap, short of complete congruence. However, in a fluctuating (stochastic) environment, the average food sizes for species adjacent on the resource spectrum must differ by an amount roughly equal to the standard deviation in the food size taken by either individual species. This mathematical result emerges in a nonobvious yet robust way for environmental fluctuations whose variance relative to their mean ranges from around 0.01% to around 30%. In short, there is an effective limit to niche overlap in the real world, and this limit is insensitive to the degree of environmental fluctuation, unless it be very severe. Recent field work, particularly on bird guilds, seems in harmony with the model's conclusion.


Ovarian cancer is one of the most common female malignancies and is the forth leading cause of cancer death in the western world. It is estimated that 3-13% of all ovarian cancers are familial and the tumour suppressor gene, BRCA1, is responsible for almost 90% of all these familial cases. BRCA1 is a tumour suppressor gene which spans 100 kb on chromosome 17q21 and contains 24 exons. The 7.8 kb mRNA encodes a protein of 1863 amino acids. The structure of BRCA1 is not strikingly homologous to other known molecules apart from the presence of a ring zinc finger domain and a 10 amino acid granin motif which are thought to be significant due to fact that they both are conserved in humans and other species studied. The overall aims of this study were to screen and characterise mutations in the BRCA1 gene using genomic DNA obtained from ovarian cancer patients from the West of Scotland. As a result of the information obtained from this study, genetic counselling would be possible for those who have inherited the mutations and for those who have a high risk of developing the same condition. In this study, 48 ovarian cancer patients with a family history of breast and/or ovarian cancer were screened for germline mutations in the BRCA1 gene. The strategy for germline mutation analysis involved the initial amplification of the BRCA1 gene by polymerase chain reaction (PCR) using genomic DNA as a template. After initial amplification, the product was electrophoresed in an 1% agarose gel in order to check for any abnormal alteration in size, quality and quantity of product. If no alteration was identified, further screening of the gene was carried out using the single strand conformational analysis (SSCP) and the protein truncation test (PTT). Any differences in the band pattern, when compared with negative controls (in both techniques) were fully characterised by automated DNA sequencing analysis. Using the strategy described above, 5 different alterations were detected on analysis of BRCA1 coding sequences. Of these, two were novel missense mutations, two were polymorphisms and one was an unclassified variant. The first novel missense mutation was g.3771 A>T, changing serine to cysteine at amino acid position 1218. This mutation is in the granin site at the amino acid positions 1214-1223 and the leucine zipper at amino acid positions 1209-1230. It is well known that cysteine has a very important role in stabilising the three-dimensional protein structure. Two cysteine residues in different parts of the polypeptide chain but adjacent in the three-dimensional structure of a protein can be oxidised to form a disulfide bridge. Disulfide bridges usually occur among secreted proteins and make them less susceptible to degradation. The second novel missense mutation was g.1380 G>A, changing glutamic acid to lysine at the amino acid position 421. This mutation's effect on the BRCA1 protein is unknown. However, this amino acid is conserved in the murine BRCA1 sequence. Two different polymorphisms were also detected in BRCA1 coding sequence. Patient no 28 is thought to be homozygous for polymorphism g.3667 A>G was also checked for possible large deletion within the exon 11. The first polymorphism, g.3667 A>G, was found in four out of forty-eight patients and the second polymorphism, g.4427 T>C, was found in six out of forty-eight patients. These two polymorphisms are the most frequently found in ovarian cancer cases and the normal population. Although, the polymorphisms are generally thought to be a variation in the gene sequence, histopathologicai studies suggest that the aggressiveness of tumour progress, histological type and survival rate may be related to the host variation. In order to establish the normal population frequency, one hundred samples from normal population was also screened. Six out of one hundred for polymorphism g.3667 A>G and 10 out of 100 for polymorphism g.4427 T>C were found positive for these polymorphisms. An insertion of 12 bp of DNA was also found in intron 20 (5'- GTATTCCACTCC-3') at IVS20+60. Three studies suggested that this variant is not present in any of the subject in the control population analysed. It was also reported that this variant did not modify the correct splicing of exon 19-21 by analysing the cDNA obtained from the patient's peripheral blood. It is possible that a relatively large insertion in a region of non-repetitive DNA might affect the kinetics of splicing and result in a lower level of normal mRNA from the mutant allele.


There has been a burgeoning of research in teacher, peer, and self-assessment in terms of reliability and validity, the use of rubrics, the implementation of these kinds of assessments in different academic settings, the effect of demographic variables in these assessments, and the benefits of these assessments. However, the effect of these assessments on subsequent learning has rarely been explored. To fill that void, this study set out to examine the effects of these kinds of assessments on subsequent learning as evidenced by students' final exam scores. Two intact classes were chosen and teacher, peer, and self-assessments were employed in a general English class. The scores achieved on the students' oral presentations exhibited a statistically significant correlation between the teacher awarded scores and those on the final examination of general English proficiency as a course. Peer awarded scores could also predict final exam scores, though not as good as teacher awarded ones. Self-assessment failed to correlate significantly with final exam scores and teacher/peer assessments. The reasons for the findings are discussed further in the paper.


The feminist bell hooks is a staunch critic of sexist, racist, and classist media representations. Despite this, hooks has been called out for being unscholarly and disorganized in her cultural criticism. Through a close reading of hooks' works, this paper attempts to make sense of and organize her cultural criticism frameworks toward a possible system for a critical discourse analysis. Hooks' works are taken apart to examine how the parts fit together to understand the order, interventions, and intellectual motivations of her methods. Certain processes by which these frameworks may be used by scholars and critics for interrogating sex, race, class, and other intersectional representations are also discussed.


This paper reports on a qualitative study of the attitudes of 23 South Australian practitioners in General Practice (GP) towards adopting an unspecified data amalgamating Health Informatics (HI) system. Findings suggest key areas of concern are associated with the potential for diminution of control over change and adoption was primarily influenced by a perceived need to protect the role and value of GPs. If change was seen as involuntary, uncertain or without demonstrable benefit to relevant patient outcomes, the prospect of change tended to manifest as passive or active GP resistance. Findings suggest increased exposure to use of HI systems influences GP perception of both the importance and certainty of potential implementation outcomes. It was concluded that discrete attitudes towards the use of HIS technology could be identified. Determined by contextual GP perceptions of competing managerial, technological and political factors, they are not mutually exclusive and more appropriately seen as a series of developmental and co-existing perspectives.


The study was performed in the Sahelian part of Burkina Faso. The country is subject to difficult climatic conditions, a strong demographic growth and a continuous decrease in soil fertility. The resulting degradation affects the processes which govern ecological systems and leads, on the long run, to a modification of the ecosystems. This is particularly the case of the eolian formations, the only ecological units susceptible of being useful in the area, since they present good infiltration capacity and support the main part of the vegetation. Field measurements (rainfall, runoff, saturated hydraulic conductivity, bulk density, hydraulic conductivity function, soil water content and pressure head) have been done to asses the impacts of the environmental degradation on the hydrodynamic behavior of these formations. Within this context, an experimental device made of seven measurement sites has been installed in three contrasting zones. The results show significant differences in the hydrodynamic behavior of the soils, according to their surface properties. On one hand, the sites located on an erosion crust as well as on a drying crust in transition towards an erosion crust, are characterized by a low infiltration capacity which favors runoff. The quantity of infiltrated water is very low when compared to total precipitation. Water is stored near the soil surface (in the first 30 cm) favoring evaporation in the days following rainfall events. Thus, little water is available for plants. The resulting water stress causes a weak density, or even complete absence of plants which have difficulties to colonize such surfaces. Surface runoff is favored with runoff coefficients ranging from 50 to 80 %. On the other hand, the sites situated on drying crusts are characterized by good hydraulic conductivity and infiltration capacity. The storage of water in the root zone is more important. Water flows deeper into the soil and, occasionally, drains at the reference depth of 50 cm. The runoff coefficients were found to be lower than in the other sites (30 to 40 %). This differentiated behavior is one of the main factors affecting the formation of different landscapes in the area through the existence of a relationship between soil surface properties, the type of landscape and the ratio runoff/infiltration. The sites located on an erosion crust and those in transition towards an erosion crust behave like impluviums, while those situated on drying crusts are more favorable to infiltration. Observation of the evolution of the hydraulic properties of the soil surface shows a progressive alteration that frequently leads to strongly degraded mediums unfavorable to plants. Control and rehabilitation methods considered in the study, namely "restoration" and "mise en defens" have only partial and time-limited effects; they do not make it possible to stop durably degradation or to favor rehabilitation. Among the other measures assessed on the INERA plots, only the restitution to the soil of the beforehand mown plants causes an improvement of the soil surface properties; the restitution causes the formation of an important macroporal system favoring water infiltration and circulation in the soil. The effects of those different measures occur mainly in the first years after their introduction and concern especially vegetation regeneration, soil protection against degradation factors, improvement of hydrodynamic soil properties, reduction of runoff and erosion. They make it possible to slow down soil degradation, but not to stop it definitively. Within this context, proposals of further studies focussed on other measures to control and rehabilitate degraded areas have been suggested, taking into account the specificity of the sahelian zone, the endogenous knowledge of the agro-pastors, as well as socio-economic and ecological conditions.


An open challenge for interaction designers is to find ways of designing software to enhance the ability of novices to perform tasks that normally require specialized domain expertise. This challenge is particularly demanding in areas such as music analysis, where complex, abstract, domain-specific concepts and notations occur. One promising theoretical foundation for this work involves the identification of conceptual metaphors and image schemas, found by analyzing discourse. This kind of analysis has already been applied, with some success, both to musical concepts and, separately, to user interface design. The present work appears to be the first to combine these hitherto distinct bodies of research, with the aim of devising a general method for improving user interfaces for music. Some areas where this may require extensions to existing method are noted.

This paper presents the results of an exploratory evaluation of Harmony Space, a tool for playing, analysing and learning about harmony. The evaluation uses conceptual metaphors and image schemas elicited from the dialogues of experienced musicians discussing the harmonic progressions in a piece of music. Examples of where the user interface supports the conceptual metaphors, and where support could be improved, are discussed. The potential use of audio output to support conceptual metaphors and image schemas is considered.


Escherichia coli EnvZ is a membrane sensor histidine kinase that plays a pivotal role in cell adaptation to changes in extracellular osmolarity. Although the cytoplasmic histidine kinase domain of EnvZ has been extensively studied, both biochemically and structurally, little is known about the structure of its periplasmic domain, which has been implicated in the mechanism underlying its osmosensing function. In the present study, we report the biochemical and biophysical characterization of the periplasmic region of EnvZ (Ala38-Arg162). This region was found to form a dimer in solution, and to consist of two well-defined domains: an N-terminal a-helical domain and a C-terminal core domain (Glu83-Arg162) containing both a-helical and b-sheet secondary structures. Our pull-down assays and analytical ultracentrifugation analysis revealed that dimerization of the periplasmic region is highly sensitive to the presence of CHAPS, but relatively insensitive to salt concentration, thus suggesting the significance of hydrophobic interactions between the homodimeric subunits. Periplasmic homodimerization is mediated predominantly by the C-terminal core domain, while a regulatory function may be attributed mainly to the N-terminal a-helical domain, whose mutations have been shown previously to produce a high-osmolarity phenotype.


BACKGROUND
Lung disease in preterm infants is often complicated with lung edema.

OBJECTIVES
To assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD).

SEARCH STRATEGY
The standard method of the Cochrane Neonatal Review Group were used. Initially, MEDLINE (1966 to November 2001), EMBASE (1974 to November 2001) and the Cochrane Controlled Trials Register (CENTRAL,The Cochrane Library, Issue 4, 2001) were searched. In addition, several abstract books of national and international American and European Societies were hand searched. Updated searches in April 2003, April 2007, and December 2010 did not yield any additional trials.

SELECTION CRITERIA
Included in this analysis are trials in which preterm infants with or developing CLD and at least five days of age were randomly allocated to receive a diuretic acting on the distal renal tubule. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review.

DATA COLLECTION AND ANALYSIS
The standard method for the Cochrane Collaboration described in the Cochrane Collaboration Handbook were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. Parallel and cross-over trials were combined. Whenever possible, baseline and final outcome data measured on a continuous scale was transformed into change scores using Follmann's formula.

MAIN RESULTS
Of the six studies fulfilling entry criteria, most focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy.In preterm infants > 3 weeks of age with CLD, a four week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. A single study showed thiazide and spironolactone decreased the risk of death and tended to decrease the risk for remaining intubated after eight weeks in infants who did not have access to corticosteroids, bronchodilators or aminophylline.

AUTHORS' CONCLUSIONS
In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. However, positive effects should be interpreted with caution as the numbers of patients studied are small in surprisingly few randomized controlled trials.


This article presents strategies to enhance effectiveness in cross-cultural counseling and psychotherapy encounters. A major assumption is that a coherent orientation is needed that includes cultural differences yet transcends these differences and organizes the human experience in the context of individual world views within the framework of existential philosophy. An understanding of one's own world view and the client's world view are key elements in enhancing cross-cultural effectiveness. Other strategies that can enhance cross-cultural counseling and psychotherapy include a discussion on the knowledge of semantic structures of reasoning and an understanding of culture-its premises and its relationship to effectiveness in cross-cultural counseling and psychotherapy.


Since the first implantation of a cardiac pacemaker numerous efforts have been made to develop miniature implantable power devices, which would be able to run continuously for long periods of time without the need for replacement. In this context enzymatic biofuel cells (EBFCs) represent an attractive alternative, as they work at body temperature, are light and easy to miniaturise. Additionally, enzymatic biofuel cells can generate energy from the metabolites already present in physiological fluids, and produce waste products that naturally occur in the human body. With a view to improving the biocompatibility of such devices, the use of highly porous gold (hPG) as a non-toxic high surface area alternative to the carbon nanotube based materials currently used was here investigated. The process for directly depositing hPG onto conductive surfaces was further developed to improve the stability of the deposited hPG films. The possibility of depositing these films on a range of different materials was also investigated. In particular it was shown that hPG films could also be deposited on very low cost materials, such as graphite composites. It was also demonstrated that these hPG electrodes exhibited potential for the direct electro-oxidation of aldehyde group containing sugars. The potential use of hPG electrodes as abiotic glucose sensors was consequently investigated and found to give stable amperometric responses between 0 and 50 mM, with a strong glucose dependant response even at the lowest concentration investigated of 0.5 µM. However, since hPG electrodes were found to be susceptible to a large degree of interference and fouling in biological solutions, the use of glucose oxidase (GOx) on hPG electrodes was investigated in order to increase the specificity and stability of such electrodes in biological systems. A rapid and simple technique for the direct and functional deposition of GOx onto hPG was developed without using foreign electron mediators. These hPG-GOx electrodes were found to act as glucose sensors with extremely high sensitivity (22.7 µA mM-1 cm-2), and a linear response to glucose in a range of between 50 μM and10 mM. Finally EBFCs that exhibit continuous flow through were developed using fast prototyping techniques that employ 3D printed moulds. These EBFCs employed hPG-GOx electrodes coupled with hPG and laccase electrodes in order to generate power from glucose. The continuous and stable power production from a flow through EBFC for up to 30 days was subsequently demonstrated for the first time, with a peak power output of approximately 2 µW.


The cell is certainly one of the most complex and exciting systems in Nature that scientists are still trying to fully understand. Such a challenge pushes material scientists to seek to reproduce its perfection by building biomimetic materials with high-added value and previously unmatched properties. Thanks to their versatility, their robustness and the current state of polymer chemistry science, we believe polymer-based materials to constitute or represent ideal candidates when addressing the challenge of biomimicry, which defines the focus of this review. The first step consists in mimicking the structure of the cell: its inner compartments, the organelles, with a multicompartmentalized structure, and the rest, i.e. the cytoplasm minus the organelles (mainly cytoskeleton/cytosol) with gels or particular solutions (highly concentrated for example) in one compartment, and finally the combination of both. Achieving this first structural step enables us to considerably widen the gap of possibilities in drug delivery systems. Another powerful property of the cell lies in its metabolic function. The second step is therefore to achieve enzymatic reactions in a compartment, as occurs in the organelles, in a highly controlled, selective and efficient manner. We classify the most exciting polymersome nanoreactors reported in our opinion into two different subsections, depending on their very final concept or purpose of design. We also highlight in a thorough table the experimental sections crucial to such work. Finally, after achieving control over these prerequisites, scientists are able to combine them and push the frontiers of biomimicry further: from cell structure mimics towards a controlled biofunctionality. Such a biomimetic approach in material design and the future research it will stimulate, are believed to bring considerable enrichments to the fields of drug delivery, (bio)sensors, (bio)catalysis and (bio)technology.


A new, long-term study of grasslands (see p. 1720) suggests that nitrogen deposition from the burning of fossil fuels and the use of agricultural chemicals may not be helping to mitigate possible global warming after all. Nitrogen "fertilizes" ecosystems, making plants grow bigger, sequestering more carbon aboveground. But nitrogen also favors the growth of fast-growing, invasive species, which aren't very good at fixing carbon in soils.


In this article we explore the creative recontextualization of JOURNEY, WAR, RACE and SPORTS metaphors and discuss their manifestations in multimodal ICT advertisements across time. Our objectives are to discuss (i) the choices of metaphors and related source domains used to describe (e)businesses in two different time periods, (ii) how the highlighting and hiding of features of the source domains remain constant or change, (iii) the relations between modes, and (iv) the discursive strategies for metaphorical creativity. The results of our analysis reflect an interesting shift in the highlighting and hiding of features of the main metaphors and related sources across the two time periods, thus revealing variations in emergent metaphors across time. We argue that these results reflect ongoing social changes which illustrate the contextual basis and motivation of metaphor as a linguistic form of action and creative communication in advertising discourse.


Interaction of T cells with cells of the surrounding milieu may result in activation of one or both partners. In particular, T cell activation following recognition of antigen presented by antigen presenting cells (APCs) triggers a swift rise of intracellular calcium levels within the T cell. Synthetic calcium indicators have been successfully used to monitor the activation status of T cells in vitro. However, these chemical dyes do not persist intracellularly for a sustained period which creates a major challenge for calcium imaging in the living animal. We now present a newly developed fluorescence resonance energy transfer (FRET)-based, genetically encoded calcium indicator (GECI) expressed in (auto)antigen-specific CD4+ T cells to study T cell activation in vivo at real time. Using two-photon microscopy, we explored the responses of retrovirally transduced, GECI-expressing T cells to antigen. In lymph nodes, the administration of exogenous antigen caused an almost immediate arrest of T cells around APCs concomitant with an instant rise of cytosolic calcium levels. In contrast, encephalitogenic T cells entering the leptomeningeal space, one main portal into the central nervous system parenchyma during experimental autoimmune encephalomyelitis, showed elevated intracellular calcium levels while still meandering through the space. This approach enables us for the first time to follow the migration and activation patterns of T cells in vivo during the course of the disease.


Objective
To explore the reaction pattern rules of mouse retinal ganglion cells potential under different wavelengths of light stimulation.

Methods
Thirty SPF grade 3-week-old C57BL/6 mice were used for ex vivo whole mount retina preparation.The cells firing activities were recorded on patch clamp system with on cell touch mode under stimulation of 400 nm, 580 nm and white light, respectively.According to different reactions to different light stimulation, the cells were classified into 400 nm sensitive RGC, 580 nm sensitive RGC and color vision insensitive RGC.Then the cells were further classified according to light ON type, light ON/OFF type or light OFF type.The RGC's baseline firing pattern (baseline firing frequency, burst firing frequency) and light activation firing pattern (response pattern, light response firing frequency, light response firing amplification) were compared among different RGC classifications.

Results
Eighty-two RGCs were recorded in total.The frequency of spontaneous firing activity ranged from 0.00 Hz to 32.33 Hz among different RGCs.400 nm sensitive RGCs were 52(63.41%), 580 nm sensitive RGCs were 29(35.37%) and color vision insensitive RGC was 1(1.22%). OFF type RGC was the main cell type in 400 nm sensitive group (36.29%), and ON/OFF type RGC was the main cell type in 580 nm sensitive group (34.48%). The firing amplification in 580 nm sensitive RGC was (22.93±10.23)Hz, which was significantly higher than (14.44±10.11)Hz in 400 nm sensitive RGC (t=4.060, P=0.044). The firing amplification in 580 nm sensitive ON type RGC was (24.17±8.98)Hz, which was significantly higher than (11.12±10.35)Hz in 400 nm sensitive ON type RGC (t=5.373, P=0.021).

Conclusions
There is no specific firing pattern rules among different light sensitive RGCs.In the future, artificial color vision may be achieved through personalized electric stimulation and learning feedback strategy.

Key words:
Color perception; Retinal ganglion cell; Action potential


We present a generic liquid packaging method for micro-machined drug delivery systems with microneedles. Hollow microneedles are sealed with thin gold membranes at the openings on the needle tip on wafer level. This provides both a seal and an evaporation barrier to the drug delivery system on chip level. In addition, the membranes may also prevent drug delivery through needles that do not pierce the skin tissue. Applying a small voltage to the microneedle chip pressed onto the skin causes an electrochemical dissolving of membranes only at the needles that penetrated the skin tissue. The gold membrane sealed microneedles where tested for two types of operational modes. Opening the membranes by means of pressure showed that a minimum pressure of 125 kPa is needed to burst open the membranes. The removal of the gold membrane seal electrochemically was tested in vitro. The microneedle chip was opened within 2 min in the presence of an electrolyte comparable to the interstitial fluid.


The efficiency of a financial intermediation system is assessed by its ability to achieve allocative efficiency, asset transformation and the subsequent economic development. In case of an Islamic Banking and Finance as an alternate financial intermediation system adherence to the injunction of Islam is also critical. A critical appraisal of the state of contemporary Islamic Banking and finance (IBF) reveals that IBF has neither been able to achieve the aspirations of Islamic rhetoric, nor has been efficient in terms of asset transformation and economic development. This paper is an intuitive pursuit to explore the economic sense of established principles of IBF, and the reasons of the persistent divergence of IBF, being accused to be based on ruses and sophistry. Disentangling the varying viewpoints, the underdevelopment of IBF has been attributed to misinterpretation of Ribā, which has been explicated through a narrow fiqhi and legally deterministic approach. Deeming 'a collaborative and dynamic Ijtihād' as the elixir, this paper insists on the exigency of revisiting the definition of Ribā through a dynamic and collaborative Ijtihādi effort – i.e. a definition that incorporates the modern modes of economic cooperation and the contemporary financial intermediation ecosystem. The paper articulates Ribā in an agency theoretic framework to eschew expropriation of wealth, and assure protection of property rights, to sustain financial stability and economic development.


Ethylene oxide (ETO) is commonly used to sterilize plastic containers, but the effects of residual amounts left after sterilization on protein therapeutics are still not well understood. Here we focus primarily on the factors that influence concentrations of ETO migrating from ETO-treated plastic containers into aqueous solution. A study was designed to investigate the kinetics of this process at various temperatures, and the kinetic data could be fit with a model based on a combination of Fickean diffusion and first-order chemical reaction (to account for observed hydrolysis of ETO). The diffusion and reaction rate constants thus obtained obey Arrhenius-like temperature dependence. These results indicate that for analytical methods involving extraction into water, measurements of residual ETO in a container must account for the effects of ETO hydrolysis. Further, the effects of salt concentration and pH of the fluid in the container on accumulated ETO levels were explored. Finally, interactions of ETO with anti-streptavidin (AntiSA) Immunoglobulin G1 (IgG1) and IgG2 antibodies were studied, with ETO adducts found on all methionine residues when incubated in solutions spiked with ETO at concentrations that could be reached (based on the kinetic studies) in ETO-treated plastic vials. Overall, the likelihood of observable ETO-protein modifications upon storage in ETO-sterilized containers will depend on a complex interplay of protein properties, formulation details, storage conditions, and amount of residual ETO initially in the container.

LAY ABSTRACT
Ethylene oxide (ETO) is commonly used to sterilize plastic containers, but the effects of residual amounts left after sterilization on protein therapeutics are still not well understood. Here we describe experiments exploring the factors that influence concentrations of ETO migrating from ETO-treated plastic containers into aqueous solution over time. Additionally, interactions of ETO with model antibodies were studied, with ETO adducts found on all methionine residues when incubated in solutions spiked with ETO at concentrations that could potentially be reached in ETO-treated plastic vials. Overall, the likelihood of observable ETO-protein modifications upon storage in ETO-sterilized containers will depend on a complex interplay of protein properties, formulation details, storage conditions, and amount of residual ETO initially in the container.


OBJECTIVE
To describe radiographic findings at disease onset and 3-year followup in patients with juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy (JSpA), to assess radiographic progression and its predictors, and to prospectively assess clinical outcome and predictors of persistent disease at 3-year followup.

METHODS
A total of 197 patients with JRA/JSpA were examined every 6 months for 3 years. Radiographic examination was performed at baseline and 3-year followup of knees and ankles (all patients) and of other joints on clinical indication. Remission was defined as minimum 6 months without medication and no clinical signs of active disease.

RESULTS
Radiographic abnormalities were found in 88% of the patients at onset and in 81% after 3 years. Frequency of swelling/osteoporosis decreased and frequency of abnormal growth increased from baseline to followup. Knees, hands, and wrists had most frequently radiographic abnormalities. Radiographic progression occurred in 38% of the patients. Joints with swelling/osteoporosis on radiographs, young age, and a large number of mobility-restricted joints at baseline were predictors of radiographic progression. At 3 years, 26% of the patients were in remission and 75% had been treated with disease-modifying antirheumatic drugs. Reduced well-being, a large number of active joints and negative antinuclear antibody at baseline were predictors of persistent disease after 3 years.

CONCLUSION
After 3 years most patients had radiographic abnormalities and persistent disease. Young age, many affected joints, reduced well-being, and negative antinuclear antibody at onset increased the risk of radiographic progression and persistent disease after 3 years.


The sensitivities of betavoltaic batteries and photovoltaic batteries to series and parallel resistance are studied. Based on the study, an electrode pattern design principle of GaAs betavoltaic batteries is proposed. GaAs PIN junctions with and without the proposed electrode pattern are fabricated and measured under the illumination of 63Ni. Results show that the proposed electrode can reduce the backscattering and shadowing for the beta particles from 63Ni to increase the GaAs betavoltaic battery short circuit currents effectively but has little impact on the fill factors and ideal factors.


Subgrid effects can have a strong influence on flow and transport in oil reservoirs. In this work, a new model for the representation of subgrid terms is introduced and applied to two-phase reservoir flows. The model entails a generalized convection-diffusion treatment of the saturation equation as well as an extended representation for total mobility in the pressure equation. Motivation for the form of the model is provided through a consideration of volume averaging and homogenization results. The numerical computation of the subgrid terms and the implementation of the overall method are described. The accuracy of the new subgrid representation is compared to that of coarse-scale models with no subgrid treatment and to coarse models based on pseudorelative permeabilities. The new model consistently provides more accurate overall coarsescale predictions, relative to reference fine-scale results, than the other coarse-scale models, particularly in cases when the global boundary conditions vary in time.


A study of 95 patients determined the incidence of postoperative venous thrombosis and the effectiveness of simple prophylactic measures. In addition, the accuracy of the radioactive fibrinogen technique for the detection of thrombosis was compared to venography. Deep venous thrombosis was detected in six of 44 (14%) control patients. However, only two of 51 (4%) patients on whom prophylactic measures were applied developed thrombosis. The ages of the patients with thrombosis occurring postoperatively were significantly higher than the ages of the other patients in this study. There was an excellent correlation of the results obtained by the radioactive method with those of venography. Laboratory tests indicated a deficient endogenous fibrinolytic activity in those patients who developed thrombosis.


Using a population-based sample consisting of 401 6- to 12-year-olds, this study examined normative age and sex distributions on motor activity as measured in an actigraphic-based motion tracking system (MTS) and on attention-related functions derived from a Continuous Performance Test (CPT). Specific objectives were to present new knowledge on age-related change in motor activity and to study age effects on changes in motor activity and CPT performance as a function of time on task. Further, continuous relations between the two ADHD symptom domains and CPT performance and motor activity, and importantly, age effects in these relations were examined. CPT performance improved, and level of motor activity decreased with age. Linear associations between the two ADHD symptom domains and several of the CPT and MTS parameters support available research describing the nature of ADHD as a continuous dimension with variable expression throughout the general population. Further, our study is one of the first to provide developmental data using a time on task design, particularly with regard to motor activity. Imperative for ADHD future research are our results showing that age matters in the relation between ADHD behaviours and neuropsychological function.


This paper investigates the hovering efficiency of the wing-actuation parameters of a flapping microaerial vehicle with a two-degree-of-freedom (2-DOF) driving mechanism, using finite-element analysis based on the arbitrary Lagrangian-Eulerian method (ALE-FEA). A 75-mm-long wing and multilinkage mechanism that consisted of thin plates and films was employed. It generated a flapping motion that consisted of horizontal stroke of the wing and twist around its leading edge, which were activated by the rotations of two motors. The application of the ALE-FEA was successfully extended to the structural behavior of the driving mechanism. The behaviors of the linkage mechanism, the wing, and its surrounding airflow were reproduced numerically. Various parameters were obtained, some of which were difficult to measure in real experiments, such as the pressure distribution on the wing. For cases of 25 combinations of wings' twist angles and flapping periods, lift forces and energy requirements for the motors were determined. Based on these results, the most efficient flapping combination that generated 1 gf lift force was calculated. In contrast with the combination that created the strongest lift force, the combination of a larger twist angle and a faster flapping cycle was found to provide the most efficient flight.


Prior work on mobile app reviews has demonstrated that user reviews contain a wealth of information and are seen as a potential source of requirements. However, most of the studies done in this area mainly focused on mining and analyzing user reviews from the US App Store, leaving reviews of users from other countries unexplored. In this paper, we seek to understand if the perception of the same apps between users from other countries and that from the US differs through analyzing user reviews. We retrieve 300,643 user reviews of the 15 most downloaded iOS apps of 2018, published directly by Apple, from nine English-speaking countries over the course of 5 months. We manually classify 3,358 reviews into several software quality and improvement factors. We leverage a random forest based algorithm to identify factors that can be used to differentiate reviews between the US and other countries. Our preliminary results show that all countries have some factors that are proportionally inconsistent with the US.


This research to know influences retail mix is consist of place, product, value, people and communication to satisfaction shops at Indomaret and to know dominant variable influence form variable place, product, value, people and communication to satisfaction of consumer shops at Indomaret.

Research data aplies primary data in the form of questionnaire is containing questions realtes to place, product, value, people and communication to satisfaction of consumer. The data do analyzed to apply doubled linear regression analysis.

Result of calculation showing retail mix that consist variable place, product, value, officer and communications, influential signification in simulant and partial to consumer satisfaction Indomaret. Between variable retail mix which consist variable of place, product, value, officer and communications, variable that is very influential is product variable.

Based on above conclusion, hence suggestion given is remembers most Indonesia consumer sensitive to price, in consequence Indomaret to depress price with breaking long distributor channel causig minimization expense and finally the price of becoming equal to competitor. Brochure full color contains information of product and price does not influence buyer because buyer also will get good broshure from other competitor. Indomaret expected able to give attention and does analysis to the other factor can designed a marketing causing can increase customer satisfaction. In this case, implementation can be doing by adding appearance stand without lessening standard determined, by adding designed touch or accessories matching with local culture so that when customer come feels balmy. Remembers existence of emulation that is enough is height, Indomaret shall increase service level together with the side of customer.


This article studies agricultural history from the perspective of masculinity. It aims to show how early twentieth-century Finnish historical studies ar ticulated manly ideals, mainly by looking at The History of Karelian Tribe in Finland published in 1915 by Vaino Voionmaa. This well-known book, central to Finnish historiography and important for later studies on rural history, dealt with swidden agriculture in the Finnish interior. The article focuses on the intertwining of societal ideals, landscapes, and masculinity and shows the intersection of nationalist, class-based, and racial concep tions of the peasantry. Through this interpretation stressing manly ideals, Voionmaa ascribed the Finnish swidden society, traditionally regarded as primitive, a more recognized place in the nation's history.


A current-mode driving scheme has significant advantages over other competing driving method, and the scheme does not require the time-consuming threshold voltage sampling process used in recent voltage-mode driving methods. Design considerations for compact and uniform channel DACs in current-mode AMOLED display data drivers are addressed in detail. Furthermore, an 8 bit area-efficient cascaded-dividing DAC and a 9 bit segmented DAC are designed in accordance with the suggested DAC design method. The presented DACs perform outstandingly when compared in terms of a composite DAC performance that comprises chip area, power consumption, sampling frequency, and DAC bit resolution.


A new spectral-spatial method for classification of hyperspectral images is proposed. The HSegClas method is based on the integration of probabilistic classification and shape analysis within the hierarchical step-wise optimization algorithm. First, probabilistic support vector machines classification is applied. Then, at each iteration two neighboring regions with the smallest Dissimilarity Criterion (DC) are merged, and classification probabilities are recomputed. The important contribution of this work consists in estimating a DC between regions as a function of statistical, classification and geometrical (area and rectangularity) features. Experimental results are presented on a 102-band ROSIS image of the Center of Pavia, Italy. The developed approach yields more accurate classification results when compared to previously proposed methods.


Leukotriene and prostaglandin production by mouse peritoneal macrophages was investigated. It could be shown that the tumour promoter 12-O-tetradecanoylphorbol-13-acetate, despite initiating the release of prostaglandin E2, had little effect on the release of leukotriene C4-like immunoreactivity. The divalent cation ionophore A 23187 at concentrations between 10(-6) and 10(-8) mol/l initiated prostaglandin as well as leukotriene release. This prostaglandin and leukotriene release could be modulated by drugs. Non-steroidal anti-inflammatory drugs inhibited prostaglandin release but enhanced leukotriene production. The experimental compound BW 755C inhibited prostaglandin and leukotriene production, whereas the antithrombotic compound nafazatrom inhibited the production of leukotriene C4-like immunoreactivity but enhanced the prostaglandin E2 production. Nordihydroguaiaretic acid inhibited prostaglandin and leukotriene production. The results show that the metabolism of arachidonic acid in macrophages via the cyclooxygenase or the lipoxygenase pathway is dependent on the stimulus applied. Both pathways can be inhibited conjointly or selectively by drugs. The experimental system described may be used for assessing the potency of drugs to inhibit the lipoxygenase and the cyclooxygenase pathway of arachidonic acid metabolism.


This volume centres on one of the most dramatic periods of Italian History: 1900-1945. It examines the crisis of the liberal state as it undergoes a process of significant transformation, which starts with a process of modernisation and leads to the totalitarian fascist state. Lyttelton and his international team discuss the social and moral conflicts resulting from modernisation, the two world wars and the fascist regime, considering the issues from both national and international standpoints. The discussion includes the developments and impact of the changes on religion, literature, and the visual arts.


The object of this work was to determine of gonotrophic diel pattern of female Aedes aegypti in laboratory and field conditions. Three day-old female mosquitoes were the fed on chicken blood and transferred to bioassay cages. Four oviposition substrates were offered: paper sulfite, filter, butter and towel. The results showed that filter paper received a significantly higher (40.4%) percentage of deposited eggs than the other oviposition substrates. After their first blood meal, females started to oviposit on the 3rd model day; 35.7% of the total number of eggs deposited. The oviposition diel patterns of females were observed every two hours during the photoperiod in the laboratory and in the field. In the laboratory, the periodicity of oviposition showed that the highest egg deposition occurred during the 9th- 12th h of photophase and 1st - 2nd h of scotophase. In the field, the highest egg deposition occurred during the 9th - 12th h of photophase and 1st - 4th h of scotophase. These results point out that Aedes aegypti showed an oviposition periodicity pattern that can subsidize monitoring and or control of vector insect. itis suggested that ovitraps should be placed in the field during the morning hours since the captures occur during afternoon.


Mobile device are widely used today in MANETs, due to their rich functionality. However, route failure may occur due to lower receive signal strength, mobility, congestion and device failures. Also, the battery life of these devices is very limited and deploying high resource consuming applications such as streaming on these mobile devices, is a challenging task. It is extremely important to efficiently use of the contained resources on these devices when they participate in a mobile ad hoc network. In this paper, we propose an optimization of the cross-layer networking mechanism. Our work focuses on MAC and routing layers of the OSI stack. We propose a cooperation of the routing layer with the MAC layer power-control technique to decrease the energy consumption in transmission within adhoc networks. We propose an energy-conserving multipath routing protocol for adhoc networks lifetime improvement protocol called E-PPAOMDV (Energy aware Predictive Preemptive AOMDV). This protocol is based on new metric to preserves the residual energy of nodes and balances the consumed energy to increase the network lifetime. Also, we propose a mechanism based on Newton interpolation, to distinguish between both situations, failures due to congestion or mobility, and consequently avoiding unnecessary route repair process. The E-PPAOMDV was implemented using NS-2. The simulation results demonstrate the merits of our proposed E-PPAOMDV. Our proposal improves the performance of mobile ad hoc networks by extending the lifetime of the network and decreasing the average consumed energy with approximately 1 to 3%, while the average end-to-end delay is reduced by 33%, normalized routing load by 20 to 27%; also, increasing the packet delivery ratio with approximately 2-10%  and the throughput with 5%  when compared with AOMR-LM.


Objective: Conformity is an important phenomenon to examine as it has the potential to influence a vast majority of people in everyday life, especially with the current technology of social media available. Factors that affect conformity rates have had little examination in the past, but are important to note in order to fully understand this behavior of conformity. I designed this study to observe the potential effects of one such factor, cognitive load, on conformity rates in an online setting with the goal of generalizing results to the effects of social media in our contemporary society. Design: I devised an online survey, with two groups; an experimental group who experienced high cognitive load and a control group who experienced low cognitive load, while tasked with the rating of 10 purposefully unfunny cartoons. My study took place in an online setting using the social media platform of Facebook to gain participants in order to meet the research goal of being able to generalize results to the effects of overstimulation (a form of cognitive load) experienced with social media on conformity rates in society. Main Outcome Measures: I examined high cognitive load as a potential variable in increasing conformity rates to group pressure in an online setting. Results: My analyses showed that high cognitive load did not increase rates of conformity, and the best conclusion is that the null hypothesis cannot be rejected. I did observe a trend that high cognitive load seemed to decrease conformity rates, although the trend was not statistically significant. Conclusion: The results were not significant, therefore the most viable conclusion is that the null hypothesis cannot be rejected. The trend seen is discussed as potentially being related to cognitive rationing and attention theory.


Cross wedge rolling of asymmetric shaft parts has a series of problems such as the difficulty of forming, and the rules of mental flow are not clear until now. Rigid plastic FE models of the asymmetric rolling and symmetric rolling were adopted to analyze the difference of the stress and strain fields of cross section and vertical section in the two rolling processes, which illuminated the rules of the stress and strain fields in the asymmetric rolling process. The research of the stress and strain fields in asymmetric rolling has positive significance for recognizing the forming characteristics and predicting deformation defects in asymmetric rolling process.


Inadequate participant recruitment and retention practices can affect sample representativeness and thus the generalizability of research findings. Retention of research participants has been examined within the literature to some extent; however, there is no consensus on best practice in achieving acceptable results. Furthermore, there is a gap in understanding how to engage and retain women with physical disabilities (WPDs) in research. To address these oversights, we review (1) the significance of retention as a methodological concern, (2) factors that influence the involvement and retention of participants in research, including individual, population, and health-illness considerations, and (3) particular circumstances impacting the inclusion and retention of WPDs in research. On the basis of a review of the literature and our experience with the Healing Pathways randomized controlled trial (RCT), we present a conceptual model to guide culturally sensitive health research implementation with WPDs, and promote the engagement and retention of this group in RCTs and other forms of interventional health research.


The energy audit for a building is a procedure designed mainly to obtain adequate knowledge of the energy consumption profile, identify, and quantify opportunities for energy savings by a cost-benefit analysis and report, clearly and comprehensively, about the obtained results. If the audit is referred to a building with a significant historical and artistic value, a compatibility evaluation of the energy saving interventions with the architectural features should also be developed. In this paper, analysing the case study of a historical building used as public offices in Pisa (Italy), the authors describe how it is possible to conduct an energy audit activity (especially dedicated to the lighting system) and they show how, for this type of buildings, it is possible to obtain significant energy savings with a refurbishment of the lighting system. A total number of seven interventions on indoor and outdoor lighting sub-systems were analysed in the paper. They are characterised by absolute compatibility with the historical and artistic value of the building and they show short payback times, variable between 4 and 34 months, allowing a reduction of the electrical energy consumption for the artificial indoor and outdoor lighting variable from 1.1 MWh/year to 39.0 MWh/year. The followed methodology and the evaluation results described in the paper, although based on a case study, can be extended to numerous historical buildings used as public offices, a recurring situation in the centres of Italian historical cities.


In this paper we highlight issues related to measuring ethnicity and ethnic identity. We base our discussion on an extensive review of the literature and an intensive consultation process undertaken as part of the development of the ethnicity focused strand of a major new UK panel study, Understanding Society. We conclude that ethnic identity is a multi-dimensional concept and its ideal measure would have to be consistent, reliable as well as capture people's perception of their own ethnic identity. One way forward is to design a multiple response question with different dimensions of ethnicity as response options.


Background : flavor enhancing food additives are often added as a flavor enhancer known as MSG that exceed the dose . if the addition of the additive is often done to cause dependence , so it will pose a health hazard to the consumer , such as stomach disorders, allergies , hypertension , asthma , cancer , diabetes , and lower intelligence. Most housewives do not know the information would adversely affect health. Objective : This study aims to describe the level of knowledge of the use of monosodium glutamate ( MSG ) housewife in backwoods village sauleya timbuseng Polongbangkeng northern districts Kab.Takalar. Methods : This is a descriptive study. samples are all housewives in the hamlet village sauleya timbuseng Polongbangkeng northern districts Kab. Takalar , who meet the criteria as much as 49 people . Data on the use MSG knowledge samples obtained by the interview method which uses a questionnaire instrument.the data presented in the from of frequency distribution graphic and narrative. Result : Results of research on the use of knowledge MSG housewives generally less category as many as 25 ( 51.0 % ) , use of MSG housewives generally can not be tolerated as many as 36 ( 73.5 % ). Conclusion : Knowledge of the use of MSG housewife classified as less and use MSG can not be tolerated.


Gel analysis of vaccinia virus particles purified by buoyant [correction of bouyant] density demonstrates a protein with an estimated molecular mass of 59 kDa, which is apparently restricted to the intracellular mature virion (IMV) form. Western blotting (immunoblotting) and immunoprecipitation procedures identify the protein as the vaccinia virus 4c protein, which facilitates occlusion of poxvirus particles within cowpox cytoplasmic inclusions. Western blotting procedures also identify the truncated A-type inclusion protein of vaccinia virus as a specific marker for IMV particles. Kinetic analyses of virion maturation and 4c production suggest that peak enveloped virion production occurs before peak IMV production in the virus replication cycle and that 4c production is concomitant with maturation of IMV. The implications for a distinct and evolutionarily conserved function of IMV in viral pathogenesis are discussed.


ABSTRACT This study investigated the relationship between L2 oral narrative morphosyntactic quality and L2 reading comprehension in a sample of 81 students enrolled in a Canadian French immersion program in Grade 1. Measures of French narrative generation and reading comprehension were administered concurrently. The proportion of utterances in the narratives that were judged to be grammatically acceptable was found to explain unique variance in reading comprehension, controlling for nonverbal intelligence, maternal education, phonological awareness, vocabulary and word reading. The results suggest that even in the earliest stages of L2 literacy acquisition, L2 oral language skills contribute to reading comprehension outcomes. The results of our study suggest that there may be value in providing L2 children with classroom-based story-related experiences that expose them to literate language.


Using the elastic wave continuum model, we investigate the effect of material properties on ballistic thermal transport in a cylindrical nanowire. A comparative analysis for the convexity-shaped and concavity-shaped structure is made. It is found that in the convexity-shaped structure, the material with higher wave velocity in the convexity region can increase the thermal conductance at the lower temperature range; the thermal conductance of the nanowire with higher wave velocity in the convexity region is lower than that of the nanowire with lower wave velocity in the convexity region at the higher temperature range. However, in the concavity-shaped structure, the material properties of the concavity region have less effect on the thermal conductance at the lower temperature range; the material with higher wave velocity in the concavity region can reduce the thermal conductance at the higher temperature range. A brief analysis of these results is given.


BACKGROUND
A guideline for occupational health professionals (OHPs) is developed which provides them with knowledge and skills to optimize their guidance to people with a chronic disease.

OBJECTIVE
Developing a training programme to acquire and apply knowledge and skills provided by the guideline, through a bottom-up approach.

METHODS
First, OHPs training needs were explored using focus groups. Second, learning objectives were formulated by the researchers. Third, experts in the field of education were interviewed to explore relevant training activities. Fourth, researchers integrated all the results into a training programme.

RESULTS
Based on the training needs identified, we formulated 17 learning objectives, e.g. being able to name influential factors and effective interventions, increase the individual client's role, and increase communication with a professionals to enhance work participation of people with a chronic disease. The training activities identified by experts for OHPs to acquire and apply knowledge and skills were: a case study, role play, discussion of best practices and interviewing stakeholders. These were all performed in plenary sessions or small groups.

CONCLUSIONS
Training needs, -activities and learning objectives were integrated into a six-hour training programme. This bottom-up approach can serve as input for others developing training programmes to transfer knowledge and skills to OHPs.


The Iberian Basin or its present-day expression, the Iberian Ranges, was refilled with red bed sediments of alluvial origin during the late Olenekian–Anisian period represented by the Cañizar (Olenekian–Anisian) and Eslida (Anisian) Formations, both commonly known as Buntsandstein facies. In the late part of the Anisian, the Tethys Sea reached the eastern side of the Iberian microplate, represented by the shallow marine facies of the Landete and Cañete Formations, also called Muschelkalk facies. The ichnites studied in this paper belong to the Anisian continental-marine transition in the SE Iberian Ranges. The Cañizar Formation shows the oldest Triassic footprints found in the Iberian Peninsula, consisting in swimming, uncomplete lacertoid three digit Rhynchosauroides traces with possibly resting (cubichnia) and furrowing (pascichnia) Cruziana/Rusophycus due to large triopsids. Specimens from Lacertoïd and Crocodiloïd groups have been collected in the Eslida Formation. Rhynchosauroides sp. is the most representative ichnospecies of the first group, while in the Crocodiloïd group, the presence of Chirotherium barthii Kaup 1835 and Isochirotherium cf coureli (Demathieu 1970) are distinctive. In the Landete Formation specimens are found from Crocodiloïd and Dinosauroïd groups. Brachychirotherium gallicum Willruth 1917, Brachychirotherium sp. and Chirotherium sp. are characteristic of the first one, and 'Coelurosaurichnus' perriauxi and cf Paratrisauropus latus as the most representative of the second group. Some of the specimens described here present ancestors in the Early Triassic and have been described in the Triassic of North America, Italy and France. Possible paleogeographical connections with faunas of SE France can be inferred. Based on different sedimentary structures and plant remains, the footprints are related to fluvial systems within huge flood plains, playa and shallow marine environments, with alternating dry and wet periods. The vertical ichnites distribution during the Anisian shows that the fauna modification was weak at a high clade level. In the Triassic of the Iberian microplate, there are no findings of traces prior to the Anisian, and the footprint content for the Middle Triassic is less diversified than in other neighbouring regions. By comparison with other western Pangea areas, there was a later appearance of the forms after the end-Permian mass extinction event in the studied area.


Recently, adaptive random testing (ART) has been developed to enhance the fault-detection effectiveness of random testing (RT). It has been known in general that the fault-detection effectiveness of ART depends on the distribution of failure-causing inputs, yet this understanding is in coarse terms without precise details. In this paper, we conduct an in-depth investigation into the factors related to the distribution of failure-causing inputs that have an impact on the fault-detection effectiveness of ART. This paper gives a comprehensive analysis of the favourable conditions for ART. Our study contributes to the knowledge of ART and provides useful information for testers to decide when it is more cost-effective to use ART.


A good business is a growing business. The development of business is determined by good relationships with parties concerned, which is customers, markets, and relationships those forces combine to create opportunities for growth. Business development also concern about creating opportunities for that value to persist over the long term and sustain. In other hand, as business organization, company have responsibility to contribute to society where they operate, or called as corporate social responsibility (CSR). One of the aim from CSR activity is to gain sustainability development both for society and company. PT. Heinz ABC Indonesia as a corporation member of Global Kraft Heinz Company which operated in Indonesia have responsible to the community and environment. PT. Heinz ABC Indonesia, as one of the multinational food producers committed to be able to implement the CSR activities with activities related to the fulfillment of food needs in the vicinity. It is embodied in the value of companies committed to becoming "to be best food company, growing better world". The research will focus on sustainable business development through CSR Implementation at PT. Heinz ABC Indonesia. Through CSR implementation, PT. Heinz ABC Indonesia aim to develop the business by focus on environmental and social interrelationships with initiatives to reduce the amount of waste or emissions, resulting in lower costs. Also, developing the business using future benefit from social responsibility will keep in good company and brand image as well.


This report describes tree separate studies that examine the deformability of shredded tire fill material: The first study determined the response of shredded tires to cyclic loading. These tests were conducted in a load frame on both constrained and unconstrained samples and showed that the material became stiffer with increasing load; The second study focused on the long-term creep settlements of constrained and unconstrained samples. The results indicate that creep exists for a period of up to two years after loading; The third study investigated the possible anisotropic properties in the material. A larger modulus of elasticity was found in directions parallel to the layers than in the direction perpendicular to the layers. However, settlements computed using a representative anisotropic shredded tire fill material indicate that the current settlement analysis, based on isotropic shredded tire layers, predicts maximum settlements conservatively.


Eleven samples of the most important pistachio rust (caused by Pileolaria terebinthi (DC.) Cast.,), which causes disease on Beneh (Pistacia atlantica Desf. subsp. mutica (Fisch. & Mey.) Rech. F) and Kasoor ( Pistacia khinjuk Stocks.), were collected from herbarium specimens and pistachio fields at the Pistachio Research Institute in Rafsanjan, Iran. The complete sequences of ribosomal DNA internal transcribed spacers ITS1 and ITS2 (rDNA ITS) from the samples were determined and analysed. In general, very little rDNA ITS sequence variation was observed between rDNA ITS sequences of P. terebinthi samples. The length of the PCR fragments was 621 bp (for ITS1F-ITS4) and 1177 bp (for ITS1F-rust1), and consisted of 67 bp at the 3 end of 18S rDNA, 93 bp of ITS1 region, 154 bp of 5.8S rDNA, 246 bp of the ITS2 region, 57 bp (for ITS1F-ITS4) and 613 bp (for ITS1F-rust1) at the 5 end of the 28S rDNA. Restriction fragment length polymorphisms (RFLPs) of the rDNA-ITS region were used to identify Pileolaria terebinthi . Three strong bands of 105, 134 and 381 bp and five bands of 105, 134, 200, 301 and 437 bp are observed for the fragment of "ITS1F-ITS4" and "ITS1F-rust1", respectively. A PCR-RFLP diagnostic technique provided effective identification of the species by a unique pattern with the specific restriction enzyme XapI (ApoI).


We propose a two-stage non-linear stochastic formulation for the economic dispatch problem under renewable-generation uncertainty. Each stage models dispatching and transmission decisions that are made on subsequent time periods. Certain generation decisions are made only in the first stage and the second stage realizes the actual renewable generation, where the uncertainty in renewable output is captured by a finite number of scenarios. Any resulting supply-demand mis-match must then be alleviated using extra, high marginal-cost power sources that can be tapped in short order. We propose two outer approximation algorithms to solve this nonconvex optimization problem to optimality. We show that under certain conditions the sequence of optimal solutions obtained under both alternatives has a limit point that is a globally-optimal solution to the original two-stage nonconvex program. Numerical experiments for a variety of parameter settings were carried out to indicate the efficiency and usability of this method of large practical instances.


OBJECTIVE
Expiratory films are regarded as being superior to inspiratory films for pneumothorax detection, yet this has not been proved. In the current study, we compared inspiratory versus expiratory chest radiographs for pneumothorax detection.

MATERIALS AND METHODS
Eighty-five paired inspiratory and expiratory radiographs with pneumothoraces and 93 pairs without pneumothoraces were randomly arranged and reviewed independently by three radiologists. A score of 1-5 was assigned for each hemithorax (5 = definite pneumothorax, 1 = definitely no pneumothorax). Results were compared for inspiration and expiration using receiver operating characteristic (ROC) analysis.

RESULTS
The average area under the ROC curves for all readers was .973 for inspiration and .972 for expiration (nonsignificant). McNemar's test and an alpha level of .05 also yielded no significant difference in sensitivity and specificity. Four of the 85 cases were scored as definite pneumothorax on inspiration and as definitely not on expiration by all readers, and three of the 85 cases were scored as definite pneumothorax on expiration and as definitely not on inspiration.

CONCLUSION
Inspiratory and expiratory upright films are equally sensitive for pneumothorax detection. Given the limitations of expiratory films, inspiratory films are recommended as the initial examination of choice for pneumothorax detection.


Diabetes mellitus is a disease characterized by chronic hyperglycemia either due to a lack of secretion of the hormone insulin (Type 1 Diabetes Mellitus, T1DM) or due to impaired action of this hormone (Type 2 Diabetes Mellitus, T2DM). Due to its shortand long-term complications, it is currently one of the major health problems of the economically developed countries and at the same time, one of the first items of healthcare spending. Diabetic patients therefore need regular blood glucose monitoring associated with adequate insulin therapy whose goal is to keep glucose concentration within the normal safe range (70  180 mg/dl), trying to limit excursions in hypoglycemic (20  70 mg/dl), due to shortterm complications, and hyperglycemic range (180  600 mg/dl), due to long-term complications. In order to optimize insulin therapy, and then assess the correct amount of insulin to be administered to the patient, it is necessary to know its insulin sensitivity (SI), i.e. the ability of insulin to stimulate glucose utilization and inhibit its production, specific for each individual and changing during the day. The aim of this thesis is to estimate an index of insulin sensitivity in patients with type 1diabetes by using a recently proposed technique which exploits minimally invasive technologies used by diabetic patients for control therapy. This parameter will be estimated in correspondence of meals over the whole day and, in order to be able to estimate the index of insulin sensitivity even in the presence of meals close, a tool for the estimation of carbohydrates absorbed during the meal (Carbohydrates On Board, COB) will be proposed. In Chapter 1 the glucose-insulin regulatory system, diabetes and its complications, conventional therapy for its control and indices of insulin sensitivity in literature are introduced. In Chapter 2 the experimental protocols applied to the patients and the data available data are presented. In Chapter 3 the recently proposed method for the estimation of SI using minimally invasive technologies and the COB function for the estimation of carbohydrates absorbed during the meal are presented.


The integrin leukocyte function associated antigen 1 (LFA-1) binds the intercellular adhesion molecule 1 (ICAM-1) by its αL-chain inserted domain (I-domain). This interaction plays a key role in cancer and other diseases. We report the structure-based design, small-scale synthesis, and biological activity evaluation of a novel family of LFA-1 antagonists. The design led to the synthesis of a family of highly substituted homochiral pyrrolidines with antiproliferative and antimetastatic activity in a murine model of colon carcinoma, as well as potent antiadhesive properties in several cancer cell lines in the low micromolar range. NMR analysis of their binding to the isolated I-domain shows that they bind to the I-domain allosteric site (IDAS), the binding site of other allosteric LFA-1 inhibitors. These results provide evidence of the potential therapeutic value of a new set of LFA-1 inhibitors, whose further development is facilitated by a synthetic strategy that is versatile and fully stereocontrolled.


Null mutations in the prune gene of Drosophila melanogaster result in prune eye color due to reductions in red pigment accumulation. When one copy of the awd(Killer of prune) mutant gene is present in a prune background, the animals die. The cause of prune/Killer of prune lethality remains unknown. The genomic region characterized for the prune locus is transcriptionally active and complex, with multiple and overlapping transcripts. Despite the transcriptional complexity of the genomic region of prune, accumulated evidence suggests that the prune locus is small and consists of a single transcription unit, since every prune allele to date exhibits both prune eye color and prune/Killer of prune lethality. A functional prune product from a single, full-length cDNA was identified in this study that can rescue both the eye phenotype and prune/Killer of prune lethality. The DNA sequences of several mutant prune alleles along with Western blot analysis of mutant proteins provide convincing evidence that prune mutations are nulls, and that the cDNA identified in this study encodes the only product of the prune locus.


Abstract: Coarse-grained sediments deposited in high-energy environments are usually considered unfavorable to the preservation of fossil tracks. Here we report dinosaur footprints showing good physical preservation, despite being found in coarse-grained sandstones of alluvial origin from the Upper Triassic of Ardèche, southeastern France. The ichnoassemblage, dominated by Grallator isp., raises questions about the processes leading to the formation and preservation of tracks in coarse-grained sediments. The track-bearing surface is a medium- to coarse-grained quartz arenite that is microconglomeratic locally. The tracking surface grain size ranges from 0.2 to 2 mm and numerous pebbles are present. It is overlain by a succession of thin, intercalated layers of claystones and siltstones, themselves covered by a mix of siltstones and coarse-grained sandstones. We interpret this succession as a progressive decrease in energy due to channel migration culminating in channel abandonment, and the establishment of a lower energy setting where the tracking surface formed. Sedimentological and taphonomic observations indicate that the trackmakers walked on fine-grained layers (clay, silt) in which true tracks formed. The passage of the animals along the tracking surface deformed the older coarse-grained sand layers and resulted in the formation of the transmitted undertracks. The fine-grained layer helped record the pedal anatomy of the trackmakers and contributed to protecting the transmitted undertracks from destruction. Overall, we suggest that the fossil footprints were preserved by abiotic processes only, the main factor being the lithological contrast between successive sedimentary layers. The exceptional preservation of those relatively high quality undertracks in coarse-grained deposits contrasts sharply with the prevailing models of true track formation involving fine-grained sediments and microbial mats present in low-energy environments. This mode of undertrack formation may have been relatively frequent elsewhere but potentially overlooked in previous studies.


IP based networks still do not have the required degree of reliability required by new multimedia services, achieving such reliability will be crucial in the success or failure of the new Internet generation. Most of existing schemes for QoS routing do not take into consideration parameters concerning the quality of the protection, such as packet loss or restoration time. In this paper, we define a new paradigm to develop new protection strategies for building reliable MPLS networks, based on what we have called the network protection degree (NPD). This NPD consists of an a priori evaluation, the failure sensibility degree (FSD), which provides the failure probability and an a posteriori evaluation, the failure impact degree (FID), to determine the impact on the network in case of failure. Having mathematical formulated these components, we point out the most relevant components. Experimental results demonstrate the benefits of the utilization of the NPD, when used to enhance some current QoS routing algorithms to offer a certain degree of protection.


The purpose of this paper is to study the impact of beating analysts' forecasts and the impact of analysts' forecast dispersion on the pricing of firms' credit default swaps (CDSs). CDS premium is the compensation required by investors for bearing firms' credit default risk. Sell-side analysts collect market, industry and firm information and provide important information in the form of stock recommendations, stock price targets and accounting number forecasts. For that reason, the information contained in their forecasts may provide additional information to investors to price CDSs. My results show that firms that beat analysts' earnings and revenue forecasts, and firms with less dispersed analysts' earnings and revenue forecasts have on average a reduction in their CDS premia around the earnings announcement date. These effects are stronger for firm that jointly beat the two forecasts and for firms with high risk of default. I also document that the effect of beating analysts' earnings (revenue) forecasts is stronger for firms with more (less) earnings quality.


A set of .fig files, that can be opened by Matlab or Octave, providing all data needed to generate the figures in the report.


Environmental narratives have become an increasingly important area of study in the environmental humanities. Rob Nixon has drawn attention to the difficulties of representing the complex processes of environmental change that inflict 'slow violence' on vulnerable human (and non-human) populations. Nixon argues that a lack of "arresting stories, images and symbols" reduces the visibility of gradual problems such as biodiversity loss, climate change and chemical pollution in cultural imaginations and on political agendas. We agree with Nixon that addressing this representational imbalance is an important mission for the environmental humanities. However, we argue that another aspect of the same imbalance, or representational bias, suggests the inverse of this is also needed—to unpack the ways that complicated and multifaceted environmental phenomena can be reduced to fast, simple, evocative, invasive narratives that percolate through science, legislation, policy and civic action, and to examine how these narratives can drown out rather than open up possibilities for novel social-ecological engagements. In this article we demonstrate the idea of invasive narratives through a case study of the 'invasive alien species' (IAS) narrative in South Africa. We suggest that IAS reduces complex webs of ecological, biological, economic, and cultural relations to a simple 'good' versus 'bad' battle between easily discernible 'natural' and 'non- natural' identities. We argue that this narrative obstructs the options available to citizens, land managers and policy-makers and prevents a more nuanced understanding of the dynamics and implications of biodiversity change, in South Africa and beyond.


The case of Félida X and her 'doubled personality' served in the last quarter of the 19th century as a proving ground for a distinctively French form of psychology that bore the stamp of physiology, including the comparative term normal state. Debates around Félida's case provided the occasion for reflection about how that term and its opposites could take their places in the emerging discursive field of psychopathology. This article centres its analysis on Eugène Azam's 1876–77 study of Félida, and the ways his framing of the case was adopted or critiqued by subsequent researchers. Azam initially deployed the label normal state in a routine manner, in contrast to his use of condition seconde to designate Félida's other state; this pairing served, I argue, to anchor the scientific legitimacy of Félida's extraordinary psychological manifestations. Unpacking the conceptual associations of Azam's use of normal state, we find it marked as qualitatively distinct, temporally fixed, and most of all individualized; this without becoming normative. It was only through responses to and criticism of Azam's study that there emerged a more generalized sense of normality against which pathological (hysteric) subjects' comportment could be contrasted. Félida's case itself constitutes a highly individualized reconfiguration of the concept of a normal state, while the subsequent framing of doubled mental states provides a valuable vantage point from which to consider the articulations between the language of emerging French psychology and its evolving subjects of enquiry.


Specifications which limit the amount of fine material that adheres to coarse aggregates tend to be vague. For example, the Wisconsin state specifications require coarse aggregates used in portland cement concrete to be free of deleterious substances and adherent coatings; however, neither the washing procedure nor the desired end result of aggregate washing is specified. The purpose of this research was to identify which aggregate coatings in Wisconsin are deleterious and to determine what degree they affect concrete durability and strength. To this end, coarse aggregates containing surface coatings were collected throughout the state and characterized with the California cleanness test, methylene blue adsorption test, and x-ray diffraction. Based on the results of these tests, a subset of the sampled aggregates was selected to further study the effects of the coatings on concrete performance. It was hypothesized that coatings containing clay material are more deleterious than coatings containing either dust or carbonate material. The 10-batch mixing plan tested coarse aggregates fiom three different sources and in the following three conditions: (1) coated aggregates that were sampled in the field, (2) washed aggregates that were washed in the laboratory to remove the existing coating, and (3) coated aggregates that were manufactured with dust and clay fines to increase the extent of the coating. The effect of each aggregate coating on concrete performance was assessed by comparing the relative changes in compressive strength, tensile strength, drying shrinkage, freeze-thaw durability, and chloride ion penetrability between batches containing the washed and coated aggregates. The test results confirmed that coatings with high clay contents are iv more deleterious to concrete strength and durability than coatings that consist largely of dust or carbonate material. While the carbonate coatings appeared to slightly improve performance, the clay coatings appeared to significantly decrease strength and durability. Although current washing procedures do not need to be changed, it was recommended that the WisDOT require the California cleanness test whenever aggregate coatings are suspected of influencing strength or durability during concrete construction.


Introduction: Supported Employment (SE) is a strategy that facilitates positive employment outcomes for people with mental disabilities in open labour market settings. SE's cost-effectiveness has been established internationally, but not in South Africa. This paper reports on the cost and affordability of SE services offered to people with mental disabilities in South Africa. Method: A longitudinal descriptive study was used to determine the cost of SE service components utilised by people with mental disabilities, from two programmes in the Western Cape. The utilisation of service elements was captured in 15-minute time units. Data collection continued for 12 months, commencing when a job had been identified and preparation for placement had ensued. Time utilisation data were used to calculate cost, using a government sessional salary (R189/hour) and a medical aid reimbursement rate (R367/hour) of occupational therapists acting as job coaches. Findings: The findings show SE services to be less than 10% of the cost of a monthly disability grant, and 10% - 21% lower than the current subsidy per consumer in a protective workshop. Conclusion: Evidence from the study thus reflects the cost of SE services to people with mental disability as substantially lower than the current government investment in disability grants and protective workshops subsidies. Key words: psychiatric disability; intellectual disability; vocational rehabilitation; reasonable accommodation; return to work


Anaplastic pancreatic carcinoma is a rare form of pancreatic cancer with an extremely poor prognosis. Its diagnosis is often based on surgical specimens and few reports have described the use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for diagnosis. In this study, we examined six patients (mean age, 70.5 years;sex ratio, 1:1) who were diagnosed with anaplastic pancreatic carcinoma using EUS-FNA. The carcinomas were located in the pancreatic head, body, and tail in one, three, and two patients, respectively. The mean tumor diameter was 49.2mm. Five patients opted for best supportive care due to poor performance status and one underwent chemotherapy (GEM+nab-PTX). The median survival was 40.5 (14-98) days. The characteristic imaging findings of anaplastic pancreatic carcinoma, including central necrosis, marginal contrast enhancement, cystic findings, and internal calcification, were frequently observed in the patients. Anaplastic pancreatic carcinoma can also be diagnosed using biopsy tissue;however, a pathologist's consultation is required to differentiate the disease based on imaging findings for an accurate diagnosis.


The Protectorate is arguably the Cinderella of Interregnum studies: it lacks the immediate drama of the Regicide, the Republic or the Restoration, and is often dismissed as a 'retreat from revolution', a short period of conservative rule before the inevitable return of the Stuarts. The essays in this volume present new research that challenges this view. They argue instead that the Protectorate was dynamic and progressive, even if the policies put forward were not always successful, and often created further tensions within the government and between Whitehall and the localities. Particular topics include studies of Oliver Cromwell and his relationship with Parliament, and the awkward position inherited by his son, Richard; the role of art and architecture in creating a splendid protectoral court; and the important part played by the council, as a law-making body, as a political cockpit, and as part of a hierarchy of government covering not just England but also Ireland and Scotland. There are also investigations of the reactions to Cromwellian rule in Wales, in the towns and cities of the Severn/Avon basin, and in the local communities of England faced with a far-reaching programme of religious reform. Patrick Little is Senior Research Fellow at the History of Parliament Trust. The contributors are: Barry Coward, David L. Smith, Jason Peacey, Paul Hunneyball, Blair Worden, Peter Gaunt, Lloyd Bowen, Stephen K. Roberts, and Christopher Durston.


The present study investigates concomitant processes of solid-state disordering and oxidation of simvastatin during milling. The separate dry ball milling of crystalline and amorphous powders of simvastatin were conducted at ambient temperature for 10 and 60 min each. The relative crystallinity was determined using X-ray scattering and oxidative degradation was analyzed using liquid chromatography. The physical and chemical transformations in the milled powder were evaluated using modulated differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy. The disordering during milling of the crystalline powder was found to progressively decrease the crystallinity. For the amorphous starting material, milling for 10 min induced a large extent of recrystallization, while milling for 60 min largely re-amorphized the powder. This solid-state disordering and/or ordering were accompanied by progressive air oxidation during milling. The infrared spectroscopic analysis revealed the molecular manifestations associated with the physicochemical transformations in the disordered solid states. The melting point of simvastatin depressed systematically with the increase in the degree of disorder as well as the degradation. The in situ cooling in DSC of milled samples from their molten state led to the formation of the co-amorphous phase between the drug and degradation products, which showed a consistent increase in glass transition temperature with the increase in the content of degradation products. The study overall demonstrates the solid-state re-ordering and disordering of crystalline and amorphous simvastatin accompanied by chemical degradation as the consequence of the mechano-activation.


With advances in therapeutics for rare, genetic and syndromic diseases, there is an increasing need for objective assessments of phenotypic endpoints. These assessments will preferentially be high precision, non-invasive, non-irradiating, and relatively inexpensive and portable. We report a case of a child with an extensive lymphatic vascular malformation of the head and neck, treated with an mammalian target of Rapamycin (mTOR) inhibitor that was assessed using 3D facial analysis. This case illustrates that this technology is prospectively a cost-effective modality for treatment monitoring, and it supports that it may also be used for novel explorations of disease biology for conditions associated with disturbances in the mTOR, and interrelated, pathways.